Lung Cancer NCCN Guidelines 2010,

NCCN Guidelines for Patients™

Version 2010

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also available at NCCN.com

In honor and memory of Dana Reeve

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Table of ContentsMap of the NCCN Member Institutions .......................................................................................................... 3About the NCCN Guidelines for Patients™ .................................................................................................... 4About the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) .............................................. 4Non-Small Cell Lung Cancer Panel ................................................................................................................ 6Introduction ................................................................................................................................................ 7Making Decisions about Lung Cancer Treatment ............................................................................................. 8Lung Cancer Staging ................................................................................................................................... 9T Categories ............................................................................................................................................... 9N Categories ............................................................................................................................................ 10M Categories ........................................................................................................................................... 11

Treatment Pathways for Non-Small Cell Lung Cancer Initial Evaluation and Clinical Stage ............................................................................................................ 12Stage I and II Pretreatment Evaluation .......................................................................................................... 14Stage I and II and IIIA Treatment ................................................................................................................. 15Stage IIB and IIIA Pretreatment Evaluation .................................................................................................... 16Stage IIB and IIIA Treatment ........................................................................................................................ 17Stage IIIA and Separate Nodule(s) Pretreatment Evaluation ............................................................................ 18Stage IIIA (T1-3, N2) Treatment ................................................................................................................... 19Separate Nodule(s) and Stage IV, IIIA (T4, N0-1) Treatment ........................................................................... 20Stage IIIB (T1-3) Evaluation and Initial Treatment ........................................................................................... 21Stage IIIB and Stage IV Evaluation and Initial Treatment ................................................................................. 22Stage IV Evaluation and Initial Treatment ...................................................................................................... 23Follow-Up, Recurrence, and Widespread Disease ......................................................................................... 24Therapy For Recurrence and Widespread Disease ........................................................................................ 25General Principles of Pathologic Evaluation and Treatment ............................................................................. 27Cancer Survivorship Care .......................................................................................................................... 28Lung Cancer Prevention and Screening ........................................................................................................ 29

Discussion Version 2010 ............................................................................................................................ 30

Glossary .................................................................................................................................................. 53

NCCN Member Institutions ........................................................................................................................ 71

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Map of NCCN Member InstitutionsThe National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.

Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

UCSF Helen Diller FamilyComprehensive Cancer Center

Stanford Comprehensive Cancer Center

City of Hope Comprehensive Cancer Center

Huntsman Cancer Institute at the U. of Utah

UNMC Eppley CancerCenter at The NebraskaMedical Center

St. Jude Children’s Research Hospital/U. of Tennessee Cancer Institute

U. of Alabama at Birmingham Comprehensive Cancer Center

Duke Comprehensive Cancer Center

H. Lee Moffitt Cancer Center & Research Institute

Memorial Sloan-Kettering Cancer Center

Fox Chase Cancer Center

The Sidney KimmelComprehensive CancerCenter at Johns Hopkins

Roswell Park Cancer Institute

U. of Michigan Comprehensive Cancer Center

Robert H. Lurie Comprehensive Cancer Center of Northwestern U.

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

The University of Texas MD Anderson Cancer Center

Siteman Cancer Center at Barnes-Jewish Hospitaland Washington U. School of Medicine

Dana-Farber/Brigham and Women’s Cancer CenterMassachusetts General Hospital Cancer Center

Vanderbilt-IngramCancer Center

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About the NCCN Guidelines for Patients™

The National Comprehensive Cancer Network® (NCCN®) aims to provide people with cancer and the general public state-of-the-art cancer treatment information in easy-to-understand language. The NCCN Guidelines for Patients™, based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), are meant to help you when you talk with your doctor about treatment options that are best for you. These guidelines do not replace the expertise and clinical judgment of your doctor.

About the NCCN Guidelines™

The NCCN Guidelines are the most comprehensive and most frequently updated clinical practice guidelines available in any area of medicine. These guidelines provide information that many doctors follow to make sure their decisions for people with cancer are well informed. The NCCN Guidelines are developed by 43 different NCCN Guidelines Panels composed of nearly 900 world-leading experts from each of the NCCN Member Institutions. Cancer is treated by teams of doctors and other health professionals who work together to diagnose and treat cancer. NCCN Guidelines Panels are multidisciplinary, which means they include experts in different fields reflecting the way cancer is treated. These fields include medical oncology, surgical oncology, radiation oncology, pathology, radiology, nursing, and social work. Recommendations in the NCCN Guidelines are based on evaluation of evidence from clinical trials that are published in the medical literature. Most of the panel members who develop the NCCN Guidelines perform both clinical research and treat people with cancer. The members of each NCCN Guideline Panel specialize in the specific tumors and diseases discussed in that NCCN Guideline. Some NCCN Guidelines Panels also have patient advocates to bring the patient’s perspective to the panel discussions. NCCN Guidelines Panel Members volunteer more than 15,000 hours each year to revising and updating the NCCN Guidelines to reflect new data and clinical information.

The NCCN Guidelines are used by doctors in academic centers and community practices to inform their decisions when diagnosing and treating people with cancer. The NCCN Guidelines encompass 97 percent of the tumors encoun-tered in oncology practices, and these guidelines are continually updated as new information becomes available. With the NCCN Guidelines, doctors and patients have access to the same treatment regimens used by NCCN Guidelines Panel Members when they treat their patients. The decisions of the expert panel are based on scientific data coordinated with expert judgment. Community physicians may or may not perform research, but by using the NCCN Guidelines, they have information about the latest evidence from clinical trials and insights to the expertise found at leading cancer centers.

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By showing the standard of care, guidelines can reduce variation in how patients are treated and help make sure everyone gets the best care for them. However, no one treatment is right for everyone. Clinical research shows that some treatments are better for a particular disease than others. Similarly, studies have demonstrated that different patients with the same cancer may need different treatments. In many cases, patient preference is important especially when selecting among several effective treatments each with different side effects. Recommendations included in the NCCN Guidelines are those that NCCN doctors feel are most useful based on the evidence published in medical journals and their own experience treating patients. Therefore, even if a treatment is part of the NCCN Guidelines, it may not be the right treatment for all people with cancer or all people with that particular cancer. This is because each patient has a specific medical history and individual circumstances.

On the other hand, not including a particular treatment in the NCCN Guidelines only means that there is not strong enough evidence at this time to support using it as part of standard practice. In some cases, there may be ongoing clinical trials to determine whether the treatment is effective. Many new treatments are available because patients have participated in clinical trials. Additionally, new treatments that are not yet part of standard practice may only be available in clinical trials. You can discuss whether a clinical trial might be right for you with your doctor.

The NCCN Guidelines for Patients™ translate the information that doctors use to help you and your family understand your treatment options. They empower you to discuss treatment choices with your health care team and make cancer care decisions that are right for you. For the most up-to-date versions of the NCCN Guidelines for Patients™, visit NCCN.com.

A diverse group of experts from NCCN Member Institutions developed the NCCN Guidelines for Non-Small Cell Lung Cancer. Listed on page 6 are the NCCN Guidelines Panel Members whose recommendations for treatment are featured in these NCCN Guidelines for Patients™.

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Non-Small Cell Lung Cancer PanelDavid S. Ettinger, MD / Chair The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Wallace Akerley, MD Huntsman Cancer Institute at the University of Utah

Hossein Borghaei, DO, MS Fox Chase Cancer Center

Andrew Chang, MD University of Michigan Comprehensive Cancer Center

Richard T. Cheney, MD Roswell Park Cancer Institute

Lucian R. Chirieac, MD Dana-Farber/Brigham and Women’s Cancer Center

Thomas A. D’Amico, MD Duke Comprehensive Cancer Center

Todd L. Demmy, MD Roswell Park Cancer Institute

Ramaswamy Govindan, MD Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Frederic W. Grannis, Jr., MD City of Hope Comprehensive Cancer Center

Leora Horn, MD, MSc, FRCPC Vanderbilt-Ingram Cancer Center

Thierry Jahan, MD UCSF Helen Diller Family Comprehensive Cancer Center

Anne Kessinger, MD UNMC Eppley Cancer Center at The Nebraska Medical Center

Ritsuko Komaki, MD The University of Texas MD Anderson Cancer Center

Feng-Ming Kong, MD, PhD, MPH University of Michigan Comprehensive Cancer Center

Mark G. Kris, MD Memorial Sloan-Kettering Cancer Center

Lee M. Krug, MD Memorial Sloan-Kettering Cancer Center

Inga T. Lennes, MD Massachusetts General Hospital Cancer Center

Billy W. Loo, Jr., MD, PhD Stanford Comprehensive Cancer Center

Renato Martins, MD, MPH Seattle Cancer Care Alliance

Janis O’Malley, MD University of Alabama at Birmingham Comprehensive Cancer Center

Raymond U. Osarogiagbon, MD, FACP University of Tennessee Cancer Institute

Gregory A. Otterson, MD The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

Jyoti D. Patel, MD Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Mary Pinder - Schenck, MD H. Lee Moffitt Cancer Center & Research Institute

Katherine M. Pisters, MD The University of Texas MD Anderson Cancer Center

Karen Reckamp, MD, MS City of Hope Comprehensive Cancer Center

Gregory J. Riely, MD, PhD Memorial Sloan-Kettering Cancer Center

Eric Rohren, MD, PhD The University of Texas MD Anderson Cancer Center

Scott Swanson, MD Dana-Farber/Brigham and Women’s Cancer Center

Douglas E. Wood, MD Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

Stephen C. Yang, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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IntroductionThese NCCN Guidelines for PatientsTM: Non-Small Cell Lung Cancer are designed as a resource to assist patients with cancer when discussing treatment options with their doctors. These guidelines do not replace the expertise and clinical judgment of the doctor.

There are several different subtypes of cancer that arise in the lung, which are categorized according to how the tumor cells appear under a microscope. These guidelines specifically address the non-small cell lung cancer subtype. It is also important to understand that cancers that start in other parts of the body, for example, the breast or intestines, can spread to the lung. While some people may still refer to this as “lung cancer,” it is treated differently than cancers that arise in the lung. Therefore, treatment of cancer that spreads to the lung is included in the individual NCCN Guidelines for Patients™ that corresponds to where the tumor first started (e.g., breast cancer).

The NCCN Guidelines for Patients™: Non-Small Cell Lung Cancer are designed to make cancer treatment more understandable. These guidelines apply to most but not all people with non-small cell lung cancer. Their relevance to you and your treatment will depend on your general health and personal circumstances. The guidelines include several important parts:

• An overview of important questions and issues to discuss with your doctor.

• Staging tables that drive the decisions about the best treatments. Your doctor can tell you which stage applies to your cancer.

• The pathways which outline the step-by-step treatment decisions from diagnosis through all phases of treatment and survivorship. Once you know the stage of your cancer, simply follow the arrows corresponding to that stage to view the treatment recommenda-tions as set forth by the NCCN Guidelines Panel for Non-Small Cell Lung Cancer. These pathways are simplified versions of the pathways that doctors use in thinking about how to treat non-small cell lung cancer; however the content is still quite technical.

• Background information is provided in the Discussion section to help you understand this complicated information about non-small cell lung cancer. It includes the tests used in your medical evaluation, factors that lead doctors to recommend one treatment plan over others for a particular patients, description of the treatments themselves and how combinations of treatments are used together to provide the best possible outcomes, and the types of follow up needed after treatment is completed.

• A discussion of each of the pathways is provided, and

• Inevitably, you will encounter unfamiliar words and concepts, either in these guidelines or when talking with your doctor, so a glossary of cancer terms is included. These terms are shown in italics on the first mention in text.

These guidelines are complicated because non-small cell lung cancer is a complex disease. Many users will find that it is convenient to move from one part of the guidelines to another and back again rather than reading from beginning to end. The table of contents can help you navigate from one area to another easily.

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Making Decisions about Lung Cancer TreatmentA diagnosis of lung cancer is overwhelming for both patients and their families. A variety of tests will be recommended, followed by a discussion of treatment options, all of which will certainly lead to questions that patients will want to ask their cancer care team. However, it can be hard to know where to start to ask questions, and some patients and families may feel intimidated when talking to physicians. Therefore, it can be helpful to consider some general issues as you read through this guideline to help create a question list. Below are common issues associated with treatment of non-small cell lung cancer. • Make sure you know the type of lung cancer you have, as this guideline only discusses non-small cell lung cancer.• When making decisions about treatment, it is helpful to ask about the benefits, risks, and side effects of each treatment and how these can

be managed. • You may want to consider getting a second opinion from another lung cancer specialist before deciding on treatment.• Ask the doctor about the best way to prepare for treatment and how to stay healthy while receiving it in order to speed recovery. - Ask about available support services, such as specially trained social workers and psychologists who understand the

special needs of patients with cancer and their families. - Cancer support groups are very helpful and groups are available for both patients and loved ones; you may want to

consider joining one. - Ask how you can help yourself remain fit and healthy: diet, exercise, acupuncture, vitamins, imagery, massage, etc.• Feel free to ask the doctor whether he or she uses treatment guidelines, such as the NCCN Guidelines or other recognized

clinical practice guidelines.• Ask the doctor specific questions about treatment options, such as: - How long it will take to complete all of the treatments? - Will I be able to work or perform other normal activities during treatment? - Will the side effects of treatment be temporary or permanent? - What is the chance that the cancer will come back? - How much will the treatment cost and how can I find out how much my insurance will cover?• You may want to ask the doctor whether participating in a clinical trial would be helpful (see page 39).• If you smoke, it is important to stop now. Talk to your doctor or call 1-800-QUIT NOW (1-800-784-8669) to find a “Quitline” in your area.• You might want to discuss living wills or advanced directives with your cancer care team.• Treatment options for lung cancer consist of surgery, radiation therapy, chemotherapy, and targeted therapy, which can

be given in different orders, or combinations, according to the tumor stage. You will probably want to know which treatments you will receive and in what order they will be given.

• Your treatment will depend on how large your tumor is and whether it involves other parts of the lung or lymph nodes or has spread beyond the lungs. This is called the stage of your lung cancer (see Lung Cancer Staging, page 9). The cancer stage is important to know because treatment will be based on it. For this reason, the treatment pathways in this guideline are also organized by stage.

To be sure you have the most up-to-date version of these NCCN Guidelines for Patients™, visit the NCCN patient website (NCCN.com).

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Lung Cancer StagingThere are four general categories of treatment for non-small cell lung cancer: surgery, radiation therapy, chemotherapy, and targeted therapy. These therapies can be used in different orders and combinations. A key factor in determining how to best combine these options is the stage of the cancer. The stages of lung cancer can be broadly subdivided into stages I, II, III, and IV. Each of these stages (I–IV) defines tumors that have similar prognoses and can be treated in the same general way. Each tumor stage contains tumors with specific combinations of tumor size (T), lymph node involvement (N), and metastases (M). Different imaging tests (see page 12) are initially used to stage the cancer, often followed by biopsy techniques to confirm the imaging results. After this workup has been completed, the cancer can be categorized according to its stage and specific TNM status. To follow the treatment pathways, it is important to know both the cancer stage and TNM classification. Below is more detailed information on the definitions of the T, N, and M categories and cancer staging.

T CategoriesT categories are based on the size of the lung cancer, its location within the lungs, and its spread to nearby tissues.

Tis: Cancer is found only in the layer of cells lining the air passages and has not spread into other lung tissues. This stage is also known as carcinoma in situ.

T1: The cancer is 3 cm or smaller in size, surrounded by lung or visceral pleura (membranes that surround the lungs), and does not affect the main branches of the airways. T1 is further subdivided into:

• T1a cancer is 2 cm or smaller • T1b cancer is larger than 2 cm and smaller or equal to 3 cm

T2: The cancer is larger than 3 cm but no larger than 7 cm in greatest dimension with any of the following features: • It involves a main bronchus but is not closer than 2 cm to the point where the trachea (windpipe) branches into the left and

right main bronchi. • It has spread to the membranes that surround the lungs. • The cancer may partially block the airways, but this has not caused the entire lung to collapse or pneumonia to develop.

T2 is further subdivided into: • T2a cancer is larger than 3 cm but smaller or equal to 5 cm • T2b cancer is larger than 5 cm but smaller or equal to 7 cm

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T3: The cancer is larger than 7 cm in greatest dimension, with any of the following features: • It has spread to the chest wall, the diaphragm (breathing muscle that separates the chest from the abdomen), the mediastinal pleura

(membranes surrounding the space between the lungs), or parietal pericardium (membranes of the sac surrounding the heart). • It involves a main airway, and it is closer than 2 cm to the point where the trachea (windpipe) branches into the left and right main

airway but does not involve this area. • It has grown into the airways enough to cause one lung to entirely collapse or to cause pneumonia of the entire lung. • There is a separate tumor nodule in the same lobe.

T4: The cancer has one or more of the following features: • It has spread to the mediastinum (space behind the chest bone and in front of the heart), heart, blood vessels near the heart,

trachea (windpipe), nerve near the trachea, esophagus (tube connecting the throat to the stomach), backbone, or point where the windpipe branches into the left and right main airway.

• Two or more separate tumor nodules are present in a different lobe of the same lung.

N CategoriesN categories depend on which, if any, of the lymph nodes near the lungs are affected by the cancer.

N0: The cancer has not spread to lymph nodes. N1: The cancer has spread to the lymph nodes either in the lung or located around the area where the bronchus enters the

lung. Affected lymph nodes are present only on the same side as the cancerous lung. N2: The cancer has spread to subcarinal lymph nodes (around the point where the windpipe branches into the left and right

bronchi) or to lymph nodes in the mediastinum. Affected lymph nodes are on the same side of the cancerous lung. N3: The cancer has spread to lymph nodes near the collarbone on either side, and/or to hilar or mediastinal lymph nodes on

the side opposite the lung with the tumor.

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M CategoriesM categories depend on whether the cancer has spread to any distant tissues and organs.

M0: No distant cancer spread. M1: Cancer has spread to one or more distant sites. Sites considered distant include other lobes of the lungs, lymph nodes

further than those mentioned in N stages, and other organs or tissues such as the liver, bones, or brain. M1 is further subdivided into the following categories:

• M1a: Include any of the following: - Separate tumor nodules in a contralateral lobe - Tumor nodules on the lining of the lung surface (i.e., pleura) - Fluid around the lungs or heart that contains cancer cells (i.e., pleural or pericardial effusion) • M1b: Distant spread

This explanation of staging will help to determine what path you should follow throughout the next several pages of treatment pathways. Be sure to refer to the discussion section if you need clarification on any of the information within the pathways.

Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is theAJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerInitial Evaluation and Clinical StageInitial Evaluation and Clinical Stage (For more detailed information, see page 43)

CLINICAL STAGE(ASSESSMENT)

ADDITIONAL PRETREATMENT EVALUATION

Patient has been diagnosed with non-small cell lung cancer based on test results

·Pathology review or description of cells and tissues made by a pathologist based on microscopic features

·Medical history (i.e., cough, chest pain, weight loss) and physical exam to assess general health and cancer symptoms

·Series of images known as a CT scan of the chest, upper abdomen, and adrenal glands

·Complete blood count, also called CBC. A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood.

·Blood chemistry tests, a procedure in which a sample of blood is examined to measure the amounts of certain substances made within the body

·Counseling on stopping smoking

Staging is usually based on the size of the tumor (T), whether lymph nodes contain cancer (N), and whether the cancer has spread from the original site to other parts of the body (M).

Additional testing may be required prior to receiving treatment based upon the stage of your cancer.Review the staging tables with your doctor to determine your clinical stage. Follow the appropriate treatment pathway for your specific clinical stage

TESTS AND EXAMS FOR THE DIAGNOSIS OF NON-SMALL CELL LUNG CANCER

See Staging Table (p. 13)

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NCCN Guidelines for Patients™: Non-Small Cell Lung Cancer

Pretreatment Evaluation

T1ab N0 M0 See page 14

Stage IB T2a N0 M0 See page 14

Stage I T1ab–T2a N0 M0 See page 14

Stage II T1ab–2a N1 M0 See page 14

Stage II T2b N0 M0 See page 14

Stage IIB T2b N1 M0 See page 14

Stage IIB T3 N0 M0 See page 14

Stage IIB T3 N0 M0 See page 16

Stage IIIA T3 N1 M0 See page 16

Stage IIIA T1–3 N2 M0 See page 18

Separate nodule T1–3 M0 See page 18

Stage IIIB T1–3 N3 M0 See page 21

Stage IIIB T4 extension N2–3 See page 22

Stage IV Any T Any N M1a See page 22

Stage IV Any T Any N M1b - single See page 23

Stage IV Any T Any N M1b - multiple See page 23

Clinical Stage T category N category M category

Stage IA

The first step is to determine the clinical stage of your lung cancer with the help of your doctor. Lung cancer staging definitions are provided on pages 9-11. Next, follow the page listed for the pretreatment evaluation that corresponds with your stage.

T4 N0-N1

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage I and II Pretreatment Evaluation (For more detailed information, see page 44)

PRETREATMENT EVALUATION

Mediastinal nodes contain cancer

No cancer found in mediastinal nodes

See Initial Treatment and Adjuvant Treatment (p. 15)

Operable

Inoperable because of health status

See Stage IIIA (p. 19)

Stage IIIB (p. 21)or

Stage IA a(peripheral T1ab, N0)

Stage IB (peripheral T2a, N0) bStage I (central T1ab–T2a, N0)

Stage II (T1ab–2a, N1; T2b, N0)Stage IIB (T2b, N1; T3, N0)

aBased on the CT scan of the chest: Peripheral refers to the outer third of the lung. bBased on the CT scan of the chest: Central refers to the inner two thirds of the lung.cPositive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node

needs to be tested.

�Lung function test (if not previously done) A test used to measure how well the lungs work, also known as pulmonary function test or PFT

�Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs

�Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes

�Endobronchial ultrasound (EBUS) if appropriate

�PET/CT scan

�Lung function test (if not previously done) A test used to measure how well the lungs work, also known as pulmonary function test or PFT



�Endobronchial ultrasound (EBUS) if appropriate

c�PET/CT scan�Brain MRI (stage ll, and possibly stage IB)

Potentially curative radiation therapy


c

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage I and II and IIIA Treatment (For more detailed information, see page 44)

Observe

Surgery to remove remaining cancer (preferred)orRadiation therapy

d Chemoradiation with additional chemotherapy

ADJUVANT (ADDITIONAL) TREATMENT

Surgery to remove tumor and search for spread in nearby lymph nodes

INITIAL TREATMENT

Observeor

eChemotherapy if high-risk of recurrence

Surgery to remove remaining cancer followed by chemotherapyorRadiation with additional chemotherapy

Chemotherapy and radiation therapy

Stage IIA (T1ab-T2a, N1)Stage IIB (T3, N0; T2b, N1)

Stage IA (T1ab, N0)

Stage IIIA(T1-3, N2)

Stage IB (T2a, N0);Stage IIA(T2b, N0)

Tumor removed, but cancer at edges of specimen

Tumor removed, no cancer at edges of specimen







d

therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently.

ePatients who may be at a higher risk for recurrence are those whose cancer characteristics include: poorly differentiated tumor, these are tumors that lack the structure and function of normal cells and tend to grow at a faster rate, or large tumor size, or cancer has spread.

Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation

Surgery to remove remaining cancer followed by chemotherapyor

dChemoradiation with additional chemotherapy

Chemotherapy with or without radiation therapy

CLINICAL STAGE SURGICAL MARGINS

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIB and IIIA Pretreatment Evaluation (For more detailed information, see page 46)

cPositive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested.


Stage IIB (T3, N0) Stage IIIA (T3, N1; T4, N0-N1)

·Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT

·Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs

·Endobronchial ultrasound (EBUS)

·Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes

·MRI of the brain, spine, and uppermost section of the chest

c·PET/CT scanCancer has spread to distant sites outside the chest

See Treatment for Widespread Disease Metastasis (p. 23)

Cancer is growing into the main breathing tubes or into the mediastinum (area between the lungs) and has not spread outside the chest

See Treatment (p. 17)

Cancer is growing into the chest wall and has not spread outside the chest


Cancer is in the uppermost section of the chest (superior sulcus) and has not spread outside the chest



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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIB and IIIA Treatment (For more detailed information, see page 46)

Surgery followed by chemotherapy

Complete definitive (full dose) RT and chemotherapy

Surgery with chemotherapy

Chemotherapy if not given as initial treatment

INITIAL TREATMENT ADJUVANT (ADDITIONAL) TREATMENT

Preoperative concurrent

dchemoradiation

Concurrent chemoradiation as

dprimary treatment

Surgical reevaluation

Surgery (preferred)or Concurrent

dchemoradiationor Chemotherapy

Surgery

Tumor can be completely removed with surgery



Cancer is growing into the main breathing tubes or into the mediastinum (area between the lungs) and has not spread outside the chest


Tumor cannot be completely removed with surgery

dChemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently.

Preoperative concurrent

dchemoradiationTumor cannot be completely removed with surgery



See Follow Up (p. 24)

Surgery to remove remaining cancer and chemotherapy if not given as initial treatmentor

gChemoradiation with additional chemotherapy if not given as initial treatment




Tumor may not be completely removed with surgery


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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIIA and Separate Nodule(s) Pretreatment Evaluation (For more detailed information, see page 46)

Cancer cannot be completely removed with surgery

Stage IIIA(T1–3, N2)

PRETREATMENT EVALUATION MEDIASTINAL BIOPSY FINDINGS AND RESECTABILITY

No cancer found in lymph nodes

Cancer found in lymph nodes on the same side of chest as the tumor

Cancer found in lymph nodes on the other side of the chest from the tumor

See Stage IIIB (p. 21)



Cancer has spread outside the chest (metastatic disease)

See Treatment forWidespread Disease Metastasis (p. 23)

Separate lung nodule(s) (secondary tumor) (Stage IIB, IIIA, IV)




�Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT


�Mediastinoscopy or biopsy of lymph nodes with fine needle through trachea or esophagus

�MRI of the brainc�PET/CT scan



�Mediastinoscopy or biopsy of lymph nodes with fine needle through trachea or esophagus



Cancer has spread to distant sites outside the chest (metastatic disease)

See Treatment for Widespread Disease Metastasis (p.23)

Main tumor and separate tumor(s) in other lung

Main tumor and separate tumor(s) in the same lung


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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIIA (T1-3, N2) Treatment (For more detailed information, see page 47)

ADJUVANT (ADDITIONAL) TREATMENT

See Appropriate Guideline p. 15 or p. 16

Chemotherapy and radiation therapy

Cancer stops growing

Cancer grows

Radiation therapy (if not given) with or without chemotherapy

Surgery with or without chemotherapy and radiation therapy

INITIAL TREATMENT

�Brain MRI, if not previously done

c�PET/CT scan, if not previously done

Surgery

See Appropriate Guideline According to Stage (p.15)

N0–1

N2

MEDIASTINAL BIOPSY FINDINGS AND RESECTABILITY

T1-3, N0No cancer found in lymph nodes

T1-2, T3Cancer found in lymph nodes on the same side of chest as tumor without invasion

Surgery to remove tumors and mediastinal lymph nodes



d Chemoradiation with additional chemotherapy

T3Cancer found in lymph nodes on the same side of chest as tumor with invasion

No evidence of distant spread of disease

Cancer has spread to distant sites

�Brain MRI, if not previously done

c�PET/CT scan, if not previously done

No evidence of distant spread of disease

Cancer has spread to distant sites


Chemotherapy together with full dose radiation therapyorShort course of chemotherapy with or without radiation therapy Cancer has spread

to distant sites


Chemotherapy together with full dose radiation therapy

See Follow Up (p.24)


Tumor cannot be completely removed with surgery




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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerSeparate Nodule(s) and Stage IV, IIIA (T4, N0-1) Treatment (For more detailed information, see page 47)

INITIAL TREATMENT ADJUVANT (ADDITIONAL) TREATMENT

Surgery

dConcurrent chemoradiation Chemotherapy

Stage IIIA (T4, N0-1) Not removable by surgery, no pleural effusion (fluid in the tissue between wall of the lung and chest)

Separate lung tumor, in same lung

Treat as two primary lung tumors if both curable

Stage IV, M1a:Separate tumor in opposite lung See Evaluation (p. 12)

Chemotherapy

Chemoradiation (if possible)





d

therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently.

Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIIB (T1-3) Evaluation and Initial Treatment (For more detailed information, see page 47)

PRETREATMENT EVALUATION INITIAL TREATMENT

Stage IIIB (T1–3, N3)

See Appropriate Guideline for Initial treatment for stage I–IIIA (p. 13)

Chemotherapy


�Biopsy of any suspicious lymph node(s) to check for cancer in the mediastinum or other side of the chest, supraclaicular (above the collarbone), or in the neck or elsewhere

�MRI of the brainc�PET/CT scan Cancer has spread to distant sites

outside the chest (metastatic disease)


Tests and biopsies find no additional cancer in suspicious areas

The suspicious lymph node on the other side of the chest from the tumor or chest wall contains cancer




Concurrent dchemoradiation

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IIIB and Stage IV Evaluation and Initial Treatment (For more detailed information, see page 48)

PRETREATMENT EVALUATION INITIAL TREATMENT

Cancer found in suspicious lymph node(s) on the opposite side of chest

No cancer detected in suspicious lymph node(s) on the opposite side of chest

No cancer found in lymph nodes on same side of chest

See Treatment of Stage IIIA (p. 18)

Cancer found in lymph nodes on same side of chest


Cancer has spread to distant sites outside the chest (metastatic disease)

No cancer cells detected in fluid


Cancer cells found in fluid

Remove chest fluid and possibly remove fluid around heart.Thorcoscopy may be needed to check for spread of cancer in the lining of the chest cavity


Chemotherapy

Chemotherapy Stage IIIB (T4 extension, N2–3)

Stage IV, M1a: pleural or pericardial effusion (fluid in the tissue of the chest or around the heart)

�Biopsy of any suspicious lymph node to check for cancer in the mediastinum (space between the lungs) or other side of the chest, supraclaicular (above the collarbone), or in the neck or elsewhere





See Appropriate Guideline for Initial Treatment (p. 13)


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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerStage IV Evaluation and Initial Treatment (For more detailed information, see page 48)

See Systemic Therapy (p. 25)


INITIAL TREATMENT

A tumor is found in the brain

Surgery to remove brain lesion followed by whole-brain radiation therapy with or without stereotactic radiosurgery (A type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery)orStereotactic radiosurgery (SRS) with or without whole-brain radiation therapy

Cancer has spread to one adrenal gland(confirm findings with needle biopsy or resection)

Localized therapy (surgery or radiation therapy) to treat adrenal lesion if lung lesion appears curableorSee Systemic Therapy (p. 25)

T1-2, N2; T3, N1-2; Any T, N3; T4, Any N

T1-2, N0-1; T3, N0

Surgery to remove the lung lesion followed by chemotherapyor Stereotactic radiosurgery to the lung tumororChemotherapy followed by surgery to remove lung lesion

Treat as indicated by symptoms

See Systemic Therapy (p. 25)

Stage IV, M1b: with a single tumor in a distant site

Stage IV, M1b: disseminated






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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerFollow Up, Recurrence, and Widespread Disease (For more detailed information, see page 49)

No treatmentorChemotherapy

FOLLOW UP THERAPY FOR RECURRENCE AND METASTASIS

Cancer has not spread

Cancer returned in or near the lungs

Cancer returned outside the chest in a distant site

Cancer returned inside air passages causing partial or complete blockage

Recurrent cancer can be completely removed by surgery

Cancer returned in the superior vena cava (large vein in the chest)

Cancer is causing severe bleeding into the air passages

·Laser/stent/other surgery·Brachytherapy (internal radiation)·External-beam radiation therapy·Photodynamic therapy (light therapy)

·Surgery to remove the tumor·External-beam radiation therapy

·External-beam radiation therapy·Placement of a stent (supportive

tube inside vein to keep it open)

·External-beam radiation therapy·Brachytherapy (internal radiation)·Laser or surgery to remove the tumor·Photodynamic therapy (light therapy)·Embolization (block the flow of blood

to the tumor)

Spread to distant organs causing localized symptoms

Cancer spread to many areas of the brain

Spread to bones causing pain and/or fractures

Only one tumor in a distant organ

External-beam radiation therapy to relieve symptoms

·External-beam radiation therapy to relieve symptoms and surgery to prevent/repair fractures if needed

·Consider bisphosphonate therapy (drug therapy to strengthen bones)

See with a single tumor in a distant site (p. 23)

Stage IV, M1b:

Cancer is widespreadSee Systemic Therapy and Best Supportive Care (p. 25)

Cancer returned in mediastinal lymph node

Concurrent chemoradiation (if radiation not previously given)

No evidence of disease, stages I-IV:·Medical history and

physical exam to assess general health and cancer symptoms with a contrast-enhanced chest CT every 4-6 mo for 2 y, then history and physical exam and a non-contrast-enhanced chest CT annually

·Counseling on stopping smoking

·PET or brain MRI is not indicated for routine follow up

Cancer spread outside the chest to distant site(s)

External-beam radiation therapy to relieve symptoms

See Systemic Therapy and Best Supportive Care (p. 25)

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerTherapy For Recurrence and Widespread Disease (For more detailed information, see page 50)

Continuation of current regimen until disease progression or

i Continuation maintenance bevacizumab or cetuximab jor pemetrexed

or i Switch maintenance

gpemetrexed or erlotinib or jdocetaxel

or Observation

Good general health (performance status 0-1)

Poor general health (performance status 3-4)

hErlotinib for EGFRgrowth factor receptor) mutation-positive tumorsorBest supportive care

(epidermal

Systemic therapy

and best supportive care

THERAPY FOR RECURRENCE AND WIDESPREAD DISEASE

eChemotherapyorBevacizumab with

fchemotherapy (if criteria metor

gCisplatin/pemetrexed (if criteria met)orCetuximab/vinorelbine/cisplatinor

hErlotinib for EGFR (epidermal growth factor receptor) mutation-positive tumors

FIRST-LINE THERAPY

Intermediate general health (performance status 2)

Cetuximab/vinorelbine/cisplatinor

eChemotherapyor

hErlotinib for EGFR (epidermal growth factor receptor) mutation-positive tumors

TUMOR RESPONSE

Cancer continues to grow and spread See Progressive Disease (p. 26)

Cancer shrinks or does not spread (cycle 1, cycle 2 )

Therapy continued for total of 4-6 cycles (total)

Cancer shrinks or does not spread

eCisplatin or carboplatin have been proven effective in combination with any of the following agents: paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, etoposide, vinblastine, pemetrexed.

fBevacizumab with chemotherapy is used only for patients with non-squamous NSCLC. Bevacizumab should not be given by itself unless as maintenance if initially used with chemotherapy. Bevacizumab should be given until progression.

gPemetrexed is not recommended for squamous histology.hNon-small cell lung cancer is tested for specific tumor markers for example EGFR. Results are used to guide selection of drugs.iMaintenance therapy may be given after 4-6 cycles of chemotherapy for patients with tumor response (cancer shrinks or does not spread) who have not progressed. Continuation maintenance refers to the use of at least one of the agents given in the first line. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line regimen

jNon-small cell lung cancer can be one or more different types of cells in the lung. These are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The cell type can guide selection of drug therapy

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerTherapy For Recurrence and Widespread Disease (For more detailed information, see pages 50-51)

Good to intermediate general health (performance status 0-2)


Best supportive careor Clinical trial

PROGRESSIVE DISEASE

kPatients with a performance status of 3 were included in the National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) trial BR.21. Erlotinib may be considered for PS 3 and 4 patients with EGFR mutation. .See Performance Status explanation (page 32)

General health remains goodDifferent therapy:

DocetaxelorPemetrexedor

kErlotiniborPlatinum-based drug with one other chemotherapy drug (if erlotinib given as first-line)

kErlotinib

Best supportive care

SECOND-LINE THERAPY THIRD-LINE THERAPY

Cancer continues to grow and spread

Good to intermediate general health (performance status 0-2)


Best supportive care

Cancer continues to grow and spread

General health worsens

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerGeneral Principles of Pathologic Evaluation and Treatment

General Principles of Pathologic Evaluation�The purpose of examining the tissue removed during a biopsy or surgery is to classify the type of lung cancer, determine the extent of

invasion, assess the edges of the specimen are free of cancer or if any cancer cells remain in the surgical margins, and determine the molecular abnormalities of lung cancer that may be able to predict for sensitivity and resistance to epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKI).

�The World Health Organization (WHO) tumor classification system provides the foundation for tumor diagnosis, patient therapy, and clinical studies.

�The surgical pathology report should include the histologic classification published by the WHO for lung cancer.

General Principles of Surgical Therapy�Determination of whether a tumor can be removed by surgery should be performed by board-certified thoracic surgeons who perform lung

cancer surgery as their main duty in their practice.�Complete surgical removal is preferred over ablation (destruction of a body part or tissue or its function). �It is important that the overall treatment plan be discussed and decided, along with all necessary imaging tests prior to any non-emergency

treatment.

General Principles of Radiation Therapy�Radiation therapy can be offered as additional therapy for operable patients whose cancer can be completely removed with surgery.�Radiation therapy may be offered as the primary local treatment for patients in order to shrink the tumor so they can have surgery.�Radiation therapy is an important component of palliative treatment for patients with incurable disease. It can be given locally in the chest

area as well as to distant sites outside the chest as palliative care for stage IV patients with widespread disease.

General Principles of Chemotherapy or Chemoradiation�Chemotherapy is also referred to as systemic therapy.�In patients with early stage lung cancer, chemotherapy/chemoradiation is recommended as additional therapy for patients high-risk features

or if there is cancer in the edges of the surgical specimen.�Chemotherapy/chemoradiation may be given to shrink a tumor prior to surgery this is referred to as induction or neoadjuvant therapy.�For advanced or widespread disease, chemotherapy prolongs survival, improves symptom control, and improves over all quality of life. May

be given as first-line therapy, maintenance therapy, second-line therapy and even third-line therapy.�Chemotherapy may be used as maintenance therapy. Continuation maintenance refers to the use of at least one of the agents given in first

line therapy to patients who have received 4-6 cycles and have not had disease progression. Switch maintenance refers to using a different chemotherapy agent, not included as part of the first-line combination to patients who have received 4-6 cycles and have not had disease progression.

�Second- or third-line therapy is for patients who have experienced disease progression during or after first-line therapy.�Best supportive care should be provided to patients with poor performance status and progressive disease during any stage of the treatment.

Treatment recommendations should be made after joint consultation and/or discussion by a multidisciplinary team including surgical oncologists, radiation oncologists, medical oncologists, pulmonologists, and diagnostic radiologists.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerCancer Survivorship Care

NSCLC Long-Term Follow-up Care�Cancer Surveillance

�Medical history and physical and a contrast-enhanced chest CT scan every 4-6 months for 2 years, then follow-up and a non-contrast-enhanced chest CT scan every year.

�Smoking status assessment at each visit, counseling and referral for cessation as needed.

�Immunizations�Annual flu shot�Pneumococcal vaccination with revaccination as appropriate

1Counseling Regarding Health Promotion and Wellness�Maintain a healthy weight�Adopt a physically active lifestyle (Regular physical activity: 30

minutes of moderate intensity physical activity on most days of the week)

�Consume a healthy diet with emphasis on plant sources�Limit consumption of alcohol if you consume alcoholic beverages

Additional Health Monitoring�Routine blood pressure, cholesterol and glucose monitoring �Bone health: Bone density testing as appropriate �Dental health: Routine dental examinations�Routine sun protection

Resources�National Cancer Institute Facing Forward: Life After Cancer Treatment

http://www.cancer.gov/cancertopics/life-after-treatment/allpages

1ACS Guidelines on Nutrition and Physical Activity for Cancer Prevention ( Accessed November 18, 2009)

2Memorial Sloan-Kettering Cancer Center Screening Guidelines: (Accessed November 24, 2009)3American Cancer Society Guidelines for Early Detection of Cancer:

(Accessed November 24, 2009)

http://www.cancer.org/docroot/PED/content/PED_3_2X_Diet_and_Activity_Factors_That_Affect_Risks.asp?sitearea=PEDhttp://www.mskcc.org/mskcc/html/65279.cfm

http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp?sitearea=PED

2,3Cancer Screening Recommendations�These recommendations are for average risk individuals and

high risk patients should be individualized.�Colorectal Cancer: For men and women, colonoscopy every

10 years (preferred) or fecal occult blood test (FOBT) annually and flexible sigmoidoscopy every 5 years, beginning at age 50See NCCN Colorectal Cancer Screening Guidelines

�Prostate Cancer: For men-annual prostate specific antigen (PSA) testing beginning at age 50; for African American males and those with family history of prostate cancer, PSA testing beginning at age 40. See NCCN Prostate Cancer Early Detection Guidelines

�Breast Cancer: For women-monthly self breast exam (SBE) beginning at age 20 (optional); annual clinical breast exam (CBE) beginning at age 25; annual mammogram beginning at age 40.See NCCN Breast Cancer Screening Guidelines

�Cervical Cancer: Annual cervical cytology testing for women up to age 30; after age 30, annual cervical cytology testing or cervical cytology testing every 2-3 years (if 3 negative/satisfactory annual cervical cytology tests) or cervical cytology and HPV-DNA testing. If both negative, testing every 3 years.See NCCN Cervical Cancer Screening Guidelines

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerLung Cancer Prevention and Screening

�More than 90 percent of cases are caused by voluntary or involuntary (second hand) cigarette smoking. Smoking harms nearly every organ in the body.

�Reports from the Surgeon General on both active smoking and second-hand smoke show that both cause lung cancer. (These reports are available on-line at .) The evidence shows a 20 to 30 percent increase in the risk of lung cancer from second-hand smoke exposure associated with living with a smoker (To review the evidence on-line go to .) Every person should be informed of the health consequences, addictive nature, and risk of dying posed by tobacco consumption and exposure to tobacco smoke and effective legislative, executive, administrative, or other measures should be contemplated at the appropriate governmental level to protect all persons from exposure to tobacco smoke. (To obtain more information on-line visit the website

).

�Further complicating this problem, tobacco products which cause lung cancer, also contain the highly addictive substance, nicotine. Reduction in the number of deaths caused by lung cancer will require widespread implementation of the Agency for Healthcare Research and Quality (AHRQ) Guidelines to identify, counsel, and treat patients who are addicted to nicotine. (To read more visit

)

�Patients who are current or former smokers have a very high risk of developing lung cancer. The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer are not yet established for these patients. When possible, these patients should be encouraged to enroll in prevention trials.

�At the present time, the NCCN Guidelines Panel recommends that high-risk individuals participate in a clinical trial evaluating CT screening. If a trial is not available or the high-risk individual is not eligible for participation in a clinical trial, then the individual should go to a center of excellence with expertise (in radiology, pathology, cytology, thoracic surgery, and general expertise in lung cancer treatment) to discuss the potential risks and benefits before having a screening CT.

http://www.cdc.gov/tobacco/data_statistics/sgr/2004/pdfs/executivesummary.pdf

www.surgeongeneral.gov/library/secondhandsmoke/report/executivesummary.pdf

www.who.int/tobacco/framework/final_text/en/

www.ahrq.gov/clinic/cpgsix.htm .

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010

Introduction

Anatomy of the Lungs: Relevant Aspects

The lungs are 2 sponge-like organs located on either side of the heart in the chest cavity. The right lung is divided into 3 lobes, while the left lung only has 2. This is because the heart takes up more space on the left side of the chest than the right. When air is inhaled, it first travels into the trachea (windpipe) and then passes deeper into the bronchi of the lungs, which are the main airways of the lungs. The bronchi divide into smaller and smaller airways. Finally, the inhaled air ends up in tiny sac-like structures, called the alveoli. In the alveoli, the air comes into contact with the blood vessels that line the thin walls of these structures. Oxygen then passes through the walls of the alveoli and enters the blood stream, while carbon dioxide, a waste product, leaves the blood stream, enters the alveoli, and is exhaled. Most lung cancers start in the lining of the bronchi, but they can also begin in other areas, such as the trachea, smaller airways, or alveoli. The lining around the lungs, called the pleura, helps protect the lungs and allows them to move with each breath. There are 2 parts of the pleura: the visceral pleura, which is attached to the lung, and the parietal pleura, attached to the chest wall. Normally they are attached together.

Lymph is a clear fluid that contains tissue waste products and immune system cells. Lymph fluid circulates throughout the body in vessels similar to veins, called lymphatic vessels, which transport the fluid into structures called the lymph nodes. Lymph nodes are located around the bronchi and in the mediastinum, the area between the lungs; they are also a common site for lung cancer to spread. Whether or not the lymph nodes contain cancer cells has a major impact on treatment options. For example, if lymph nodes are involved, surgery may be combined with chemotherapy or radiation therapy. Therefore, evaluation of the status of the lymph nodes either through imaging tests, such as PET/CT scans or CT scans, or actually taking a small piece of the lymph node to examine under a microscope (called a biopsy) is an important part of the initial evaluation for lung cancer. Furthermore, the spread of cancer cells to the lymph nodes indicates a greater likelihood of spread to other areas of the body. The importance of the status of lymph nodes in the staging of lung cancer is elaborated upon in Lung Cancer Staging, page 9.

Types of Lung Cancer Most cancers are named after the part of the body where the cancer first starts. Thus, lung cancer begins in the lungs. Cancer that starts in a different part of the body can spread, or metastasize, to the lungs but that cancer is still named according to where it first developed. For example, breast cancer can spread to the lungs but is called metastatic breast cancer, not lung cancer. These guidelines only address a specific type of lung cancer, non-small cell lung cancer (NSCLC), which is the most common type of lung cancer, accounting for approximately 85% of lung cancers. There are 3 subtypes within NSCLC, which can be distinguished by size, shape, and chemical make-up when examined microscopically:

• squamous cell carcinoma (cancer)

• adenocarcinoma (including bronchioloalveolar carcinoma)

• large cell undifferentiated carcinoma

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THE DIAGNOSIS OF NON-SMALL CELL LUNG CANCER

Medical History and Physical Exam

Lung cancer may first be suspected based on findings from a lung x-ray or scans performed for other reasons. Alternately, lung cancer can be suspected based on specific symptoms related to the lungs, such as a persistent cough. The first step a doctor takes in diagnosing lung cancer is performing a physical exam and taking a medical history, which consists of questions about the patient’s health and other risk factors that increase the risk for lung cancer, such as smoking. Any of the symptoms displayed in Table 1 should be reported to a doctor right away.

Table 1 Important Symptoms*

Localized (Lung-Related) Symptoms Symptoms due to Metastasis or Spread

A cough that does not go away Bone pain

Chest pain, often made worse by deep breathing Weakness or numbness of the arms or legs

Shoulder pain with numbness in some fingers; Dizziness with (or without) a droopy eyelid

Hoarseness Yellow coloring of the skin and eyes (jaundice)

Weight loss and loss of appetite Lumps near the surface of the body, caused by cancer spread-ing to lymph nodes (often in the neck or above the collarbone)

Bloody or rust-colored sputum (spit or phlegm) Clusters of symptoms (paraneoplastic syndromes) that can point to a possible lung cancer

Shortness of breath

Fever without a known reason

Infections that keep coming back, such as bronchitis and pneumonia

New wheezing

Headaches, dizziness; change in vision or speech

Seizures

*As derived from the American Cancer Society.

A medical history and physical exam will give the physician a general overview of the state of a patient’s health, as well as determine if there are other health problems, such as emphysema or heart problems. If cancer is found, knowing about additional health problems will be important for determining the best cancer treatment.

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Performance Status If chemotherapy is an available treatment option, it is important for the physician to assess the patient’s general health to determine if they can tolerate the side effects of chemotherapy or other treatments, which can be severe. This assessment is called a performance status and is most commonly based on a scale called the Eastern Cooperative Oncology Group (ECOG) Performance Scale, which ranks the general health of people with cancer on a scale of 0 to 4. A rank of 0 means that the patient has no symptoms and is able to do the same daily activities he or she could do before being diagnosed with cancer. At the other end of the scale, a rank of 4 means that the patient cannot take care of his or her daily self-care activities, such as feeding, bathing, dressing, or going to the bathroom, and cannot get out of bed. A rank of 3 means that the patient can do some self-care activities but spends more than half of his or her waking hours in bed because of feeling sick or weak. In the treatment pathways, “good health” refers to an ECOG performance scale ranking of 0 to 1, intermediate health is 2, while “poor health” is a ranking of 3 or 4.

Imaging Imaging tests are an initial part of lung cancer workup used to determine the size and extent of the tumor. Imaging is a term that collectively describes all the different tests that produce an image of an area inside the body, such as the lungs. Imaging tests for lung cancer include a chest x-ray and other, more sophisticated, tests such as the computed tomography (CT) scan or magnetic resonance imaging (MRI). Additional imaging tests, such as a positron emission tomography (PET) scan or bone scan, use very small doses of radioactive material to produce an image A PET scan can be combined with a CT scan (PET/CT) to better determine the location of an abnormality. Technicians will perform these tests, which are then read by radiologists. Imaging tests will be performed throughout lung cancer treatment as routine follow-up to assess response of the tumor to treatment and to check for any recurrence. Further information for the above-mentioned imaging tests is discussed in the following sections.

CT Scan Computed or computerized tomography (CT), also referred to as a CT or CAT scan, is commonly used to image the lungs as part of the initial evaluation of lung cancer; it is also often used to image other parts of the body, such as the brain and liver, to determine the tumor’s size and location and to identify enlarged lymph nodes. A CT scanner looks like a large box with a hole in the center, creating the effect of a short tunnel. If you have a CT scan, you will lie still on a table that is moved into the center of the tunnel, and the x-ray tube will rotate around you taking a series of pictures from different angles. You may hear slight buzzing, clicking, or whirring sounds. A technician will be sitting in a separate room to operate the scanner. Although you will be alone in the examination room, the technician will be able to see, hear, and speak with you at all times.

Sometimes a dye, known as contrast material, is injected into a vein (i.e., an intravenous injection or IV) in order to produce a more detailed image. Some people may experience a reaction to the contrast that feels like a flushing sensation during the injection and a metallic taste in the mouth. Some people may have a mild allergic reaction, such as hives. In very rare cases, some people will have very severe reactions, such as wheezing or trouble breathing that requires further treatment. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

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MRI Scan Magnetic resonance imaging (MRI) scans use radio waves and a powerful magnet linked to a computer to create detailed pictures of areas inside the body. MRIs are especially useful for imaging the brain, spine, soft tissues of the joints, and inside the bones. Similar to a CT scan, a liquid contrast material may be injected into a vein in order to improve the image.

In an MRI scan, you will be asked to lie absolutely still on a table that will move to the center of the MRI machine. The inside of the machine is like a well-lit tunnel, and you will hear the MRI machine making a knocking noise as it moves around you. The technician may give you ear plugs or head phones if this noise is disturbing. Patients should tell the technician if they have significant problems with claustrophobia. Some radiology departments have different types of MRI machines that are open at the top to minimize claustrophobia, and some people may benefit from a sedative before the exam. Like a CT scan, you will be alone in the examination room, but the technician will be able to see, hear, and talk to you during the procedure.

Bone Scan Bone scans help show if cancer has spread to the bones. You will get a low dose injection of radioactive material (usually called technetium diphosphonate), which causes no long-term effects. The injected radioactive substance is attracted to diseased bone cells throughout the entire skeleton. A special gamma camera will take pictures of the radioactive material in the bones. Areas of diseased bone will be seen on the bone scan image as dense, gray to black areas, called “hot spots.” These areas may suggest the presence of metastatic cancer, but they could also suggest the presence of arthritis, infection, or other bone diseases, which can cause a similar pattern.

PET/CT Scan A PET/CT scan is a unique type of image because the PET component provides information on how the tumor is functioning, while the CT com-ponent provides information on where the tumor is located. The PET scan uses a form of sugar (glucose) that contains a radioactive atom, which is injected intravenously. Because tumors typically require more energy than normal cells, the tumor will absorb more of the radioactive sugar. Using a special camera to detect the radiation, areas of tumor will show up as bright spots on the image. The CT component of the scan will then show exactly where the tumor is located. PET/CT scans are commonly used in the initial evaluation of lung cancer, particularly to determine whether or not the cancer has spread to the lymph nodes between the lungs, as well as to distant sites such as the liver, bone, or adrenal glands.

Procedures Used to Diagnose and Check for Spread of Lung Cancer

As previously discussed in the staging section (page 9), the initial evaluation of lung cancer is designed to determine the tumor’s size and loca-tion. The imaging tests previously described accomplish this by providing an image of the cancer and its surrounding anatomy. However, before making final treatment decisions, oncologists typically want to confirm the imaging results with a biopsy. A pathologist will examine the specimen collected and determine if cancer cells are present. If you have any questions about the results of your pathology report or diagnostic tests, do not hesitate to ask your doctor. You can also get a second opinion on the pathology report, called a pathology review, by having the tissue specimen sent to a consulting pathologist at an NCCN Member Institution (to find an institution, visit NCCN.com) or another laboratory recommended by your physician.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010There are a variety of ways that cells can be collected for microscopic examination, depending on the tumor location. These are described in the following sections.

Sputum Cytology Lung cancer develops in the lining of the airways, and cancer cells shed from the tumor become mixed in with mucus, also known as sputum, that is normally present in the lungs. Therefore, a sample of phlegm (mucus coughed up from the lungs) is examined under the microscope to see if cancer cells are present. This is called a sputum cytology.

Biopsy Techniques A biopsy refers to the removal of a sample of the tumor for examination by a pathologist. To obtain a specimen of the tumor, a procedure known as a fine-needle aspiration biopsy may be performed by an interventional radiologist by inserting a needle into the tumor and extracting tumor cells. To safely insert the needle, the interventional radiologist will use an imaging procedure to guide the placement of the needle into the tumor. For example, CT scans can be used to direct needle placement between the ribs and into the lung. If the tumor is near the windpipe (i.e., trachea) or lower (i.e., by the bronchi), a lighted flexible tube called a bronchoscope (see Bronchoscopy, below) can be placed down the throat to help guide the needle safely through the wall of the windpipe and into the tumor for sampling. This biopsy technique is often used if a prior imaging study finds enlarged lymph nodes where the windpipe branches into the right and left lungs. Sometimes it may be easiest to gain access to the enlarged nodes through the esophagus, the tube that extends down into the stomach. Radiologists also use sound waves (also called ultrasound) to guide biopsies through the windpipe or esophagus.

Bronchoscopy A bronchoscopy is a procedure that uses a bronchoscope to examine the inside of the trachea, bronchi, and lungs. This test is performed to examine the lining of the airways to determine if additional tumors are present; biopsies can then be taken from the lining of the airway. Additionally, a bronchoscope is used to provide access to lymph nodes near the airways. Once the correct spot has been identified with the help of an imaging procedure, then a needle can be placed through the wall of the airway into the target lymph node for sampling.

MediastinoscopySometimes the initial imaging tests, such as a CT or PET/CT scan, will identify enlarged nodes in the mediastinum. Evaluation of the lymph nodes in this area, called the mediastinal lymph nodes, is a very important part of the initial evaluation for lung cancer. It is important for physicians to biopsy these nodes to determine if they are cancerous because other conditions, such as infection, can also cause the nodes to become en-larged. The best way to reach these lymph nodes is by mediastinoscopy, a procedure similar in concept to a bronchoscopy since both involve the use of a hollow, lighted tube. However, unlike a bronchoscopy where the tube is placed in the airway, for a mediastinoscopy the tube is placed under the breastbone (sternum), through a small incision at the base of the neck. Special instruments operated through this tube are then used to take a biopsy from the enlarged nodes along the windpipe and the major airways.

ThoracoscopyLike bronchoscopy and mediastinoscopy, a thoracoscopy involves the use of a lighted tube to provide the physician a way to look directly into the

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010body. A thoracoscopy uses a thin, lighted tube to look at the space between the lungs and chest wall, allowing the doctor to see tumors on the surface of the lungs. The doctor can also take a biopsy of any suspicious areas through the use of the tube using specially designed tools.

ThoracentesisThe outside lining of the lung that separates the lung and the chest wall is called the pleura. If cancer is present in the pleura, fluid may fill up between the lung (visceral pleura) and chest wall (parietal pleura), which can cause shortness of breath. However, other conditions can cause fluid build-up, including infection or some heart conditions. Therefore, if fluid is present, it is important to collect a sample for examination under a microscope to determine if cancer cells are present. This procedure is called a thoracentesis and involves placing a syringe between the ribs into the chest cavity and sucking out a sample of the fluid. If there is a lot of fluid, its removal can help improve breathing.

Blood Tests Certain blood tests are often done to see if the lung cancer has spread, or metastasized, to the liver or bones and to determine the overall health of vital organs, such as the liver or kidneys. These tests include a complete blood count (CBC) and blood chemistry. A CBC determines whether the patient’s blood has the correct number of various cell types. Doctors repeat this test regularly in patients treated with chemotherapy because these drugs temporarily affect blood-forming cells of the bone marrow. Spread of cancer to the liver and bones may cause certain chemical abnormalities in the blood. Blood chemistries are used to monitor the function of the kidneys and liver.

Types of Treatment for Non-Small Cell Lung Cancer After a diagnosis of non-small cell lung cancer, there will be a lot to think about. The oncologist will help patients decide the best way to treat or manage cancer. Lung cancer treatment planning is very complex and there may be more than 1 treatment to choose from. The basic options for treatment include surgery, chemotherapy, radiation therapy, or targeted therapy, and each is described in detail below. Treatment may include various combinations of these therapies. A team of cancer care professionals should be available to discuss the options.

Patients should not feel rushed into making a decision; in fact, patients should feel free to get a second opinion on the proposed treatment plan or to find a cancer care team that they feel most comfortable with. (However, before making plans, it can be wise to check with the patient’s health insurance company’s policy regarding second opinions.) If the first doctor has done tests, the results can be sent to the second doctor so patients will not have to undergo them again.

SurgeryOne of the first considerations of treatment is whether or not the lung tumor can be removed with surgery. Determination of surgical eligibility and type of surgery should be completed by a board-certified thoracic surgeon with extensive experience performing lung cancer surgery. The surgeon will determine surgical eligibility based on the size and location of the tumor and if nearby lymph nodes are involved. In general, surgery is not an option if the tumor has spread beyond the lungs to distant organs, such as the bones, brain, or liver. If the tumor is large or involves the adjacent lymph nodes, surgery may be delayed until after an initial cycle of chemotherapy and radiation therapy (chemoradiation) to shrink the tumor. This sequencing of therapy will depend on stage and TNM classification (pages 9–11).

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The extent of surgery will also depend on the tumor size and the overall health of your lungs. A wedge resection (segmental resection) removes the portion of the lung that includes the tumor and some surrounding tissue. If a lobe (section) of the lung is removed, the surgery is called a lobectomy. If the entire lung is removed, the surgery is called a pneumonectomy. Video-assisted thoracic surgery is a relatively new minimally invasive surgical procedure that is done primarily at large academic cancer centers.

Surgery may not be an option if breathing problems, such as emphysema, are present. Pulmonary function tests are always done before surgery to determine if the patient’s lungs can tolerate surgery. The lung tissue that is removed is called the surgical specimen, which is sent to a pathologist for examination. The pathologist will check to see whether all the tumor has been removed by looking at the edge, or margin, of the specimen. If the tumor is present at the margin, it is likely that not all the tumor was removed. The status of the surgical margins is an important part of treatment planning after surgery.

Lung operations are performed while the patient is asleep under general anesthesia, and a hospital stay of about 1 week is usually needed. The patient will have some pain after the surgery because the surgeon will have to cut or spread the ribs to reach the lungs. There are many ways to control this pain (see Palliative and Supportive Care, page 51).

After surgery, people who do not have lung problems other than the cancer can often return to their normal activities after a lobe or even an entire lung is removed. However, if they have other diseases, such as emphysema or chronic bronchitis (common among heavy smokers), they may find that their shortness of breath gets worse.

Radiation Therapy Radiation therapy uses high-energy rays, such as x-rays, to kill or shrink cancer cells. The radiation may come from outside the body (external-beam radiation therapy) or from radioactive materials placed directly in the tumor (internal or implant radiation, also called brachytherapy). External radiation is most often used to treat lung cancer. Radiation therapy is often part of the initial treatment of lung cancer either before or after surgery. Before surgery, it is used to shrink the tumor so that surgery can remove the entire tumor, or if the tumor is near other organs or blood vessels. After surgery, radiation therapy may be considered if there is concern that the surgery did not remove all the tumor. The radiation therapy will then be aimed directly at the tumor and does not have widespread antitumor effects. This contrasts with chemotherapy, which circulates throughout the body. For this reason, radiation therapy is called a local therapy, while chemotherapy is called a systemic therapy.

Chemotherapy Chemotherapy refers to the use of drugs to kill cancer cells. The drugs are usually injected intravenously while a few drugs are given by mouth, called oral chemotherapy. Once the drugs enter the bloodstream, they can reach all parts of the body, which is why chemotherapy is referred to as systemic therapy. Thus, chemotherapy can be used not only to shrink the tumor in the lung, but also to treat tumor cells that have spread outside the lung.

Different chemotherapies attack tumor cells in different ways; therefore, several drugs are often combined for a multi-pronged attack (combination chemotherapy). A specific drug combination is called a chemotherapy regimen. Doctors who prescribe these drugs (called medical oncologists)

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010give chemotherapy in cycles, with each period of treatment followed by a recovery period. Chemotherapy cycles generally last about 21 to 28 days, and multiple cycles are typically given. For example, when chemotherapy is used as part of the initial treatment, treatment usually lasts for 4 to 6 cycles. When chemotherapy is used to treat lung cancer that has spread outside the lungs, the treatment can continue until there is no further improvement. Chemotherapy is not recommended for patients in poor health (performance status 3–4). Advanced age is not a barrier to treatment, as long as the patient is not in poor health.

When given as part of the initial treatment, the timing of chemotherapy in relationship to surgery is given specific names. When chemotherapy is given before surgery to shrink the size of the tumor, the therapy is referred to as induction therapy or neoadjuvant chemotherapy. Adjuvant therapy is given after surgery to reduce the risk that the cancer will recur or spread outside the lung. Chemotherapy may also be combined with radiation therapy in a variety of ways. This combination therapy is discussed further in the Combination Therapy section on page 39.

Chemotherapy can also be given after initial therapy has been completed if the tumor recurs or spreads outside the lungs. Different chemotherapy regimens may be used; the first regimen used is called first-line therapy, followed by second-line therapy, if necessary. Chemotherapy may also be administered as maintenance therapy for patients who have received 4 to 6 cycles of chemotherapy and have had a good response and/or stable disease, and whose cancer has not progressed. There are 2 types of maintenance therapy: continuation maintenance and switch maintenance therapy. Continuation maintenance therapy refers to the use of at least one of the agents given in first-line therapy. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line treatment.

Designed to kill tumor cells, chemotherapy will also affect normal cells, producing temporary side effects, including loss of appetite, nausea and vomiting, mouth sores, and hair loss. Because chemotherapy can damage the blood-producing cells of the bone marrow, a decrease in white blood cells can increase the risk of infection, while a shortage of blood platelets can cause bleeding or bruising after minor cuts or injuries, and a decrease in red blood cells (low blood hemoglobin levels) can lead to fatigue. An important part of cancer care is the prevention and treatment of these side effects. Drugs are available to treat nausea and vomiting, and the cancer care team will make frequent checks to monitor blood counts. Growth factors may be prescribed to boost blood counts to reduce the risk for infection or bleeding if the white blood cell counts or platelets drop too low.

Patients can also experience long-term effects from anticancer drugs such as premature menopause, infertility, or heart or lung damage.

The cancer care team will discuss any potential side effects with you before treatment starts and will carefully monitor the patient’s health to prevent and treat any complications that may arise. However, patients must be sure to let the doctors or nurses know of any complications that arise during treatment, not just those experienced during an office visit.

The drug combinations, or regimens, most frequently used for therapy immediately before or after surgery (i.e., neoadjuvant or adjuvant therapy) are cisplatin (Platinol®) combined with one of the following:

• Docetaxel (Taxotere®)

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010• Etoposide (Toposar®; Vepesid®)

• Gemcitabine (Gemzar®)

• Vinblastine

• Vinorelbine (Navelbine®)

• Pemetrexed (Alimta®)

When appropriate, some patients will receive carboplatin, another platinum-based drug, instead of cisplatin.

If the lung cancer recurs or metastasizes, chemotherapy is the principle treatment. Patients are given first-line chemotherapy and this is continued until the tumor no longer responds, at which point a new combination of drugs will be considered, known as a second-line therapy. Drugs com-monly used for first-line chemotherapy are similar to the ones used for initial therapy at surgery and include cisplatin or carboplatin in combina-tion with any of the following drugs: docetaxel, etoposide, gemcitabine, irinotecan (Camptosar®), paclitaxel (Taxol®), vinblastine, or vinorelbine. Erlotinib (Tarceva®), a type of targeted therapy (see below), is also an option for first-line therapy. In patients who cannot tolerate combination chemotherapy, single-agent chemotherapy (using just one drug) can be used. However, chemotherapy is not recommended for patients in poor general health (performance status 3–4).

Second-line chemotherapy includes all the drugs discussed above, and also:

• Docetaxel alone

• Erlotinib alone (see Targeted Therapy, below)

• Pemetrexed alone

Targeted Therapy In the past few years, lung cancer research has focused on a new class of drugs called “targeted therapy,” which are drugs designed to specifi-cally attack cancer cells and interfere with their ability to grow. Targeted therapy can be combined with chemotherapy for lung cancer that has spread beyond the lungs. One such drug is erlotinib, which is unique because the tumor tissue can be tested first to see if the tumor cells have the target that predicts successful treatment with erlotinib. Erlotinib is taken by mouth, and common side effects include skin rash and diarrhea.

Bevacizumab (Avastin®) is another targeted therapy which specifically targets blood vessels and is designed to choke off the blood supply to the tumor. A side effect of bevacizumab is bleeding, which means it should not be used in patients who are coughing up blood. Care must be taken when this drug is given to those whose cancer has spread to the brain or who are on blood thinners (anticoagulants). Other rare but serious side effects include blood clots and high blood pressure. Bevacizumab is given intravenously every 3 weeks along with chemotherapy. Cetuximab

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(Erbitux®) is designed to interrupt the growth of tumor cells and, similar to other targeted therapies, is combined with chemotherapy. It is given intravenously, and common side effects include skin rash or diarrhea.

Combination Therapy Lung cancer is often initially treated with combination therapy; that is, the combination of surgery with chemotherapy, or radiation therapy, or both, given either before or after surgery. Chemotherapy and radiation therapy can be combined together in several different ways, referred to as chemoradiation. For example, chemotherapy and radiation therapy can be given sequentially. Typically the chemotherapy is given before the radiation therapy, but sometimes the radiation therapy may come first. Occasionally, additional chemotherapy alone will be given after chemoradiation. Concurrent chemoradiation is when chemotherapy and radiation therapy are given together. In the treatment pathways concurrent chemoradiation is described as “chemotherapy together with radiation therapy.” The T and N status of the tumor are used to determine whether combination therapy is needed.

Treatment recommendations should be made after a joint consultation and/or discussion by a multidisciplinary team including thoracic surgeons, radiation oncologists, medical oncologists, pulmonologists, pathologists, and diagnostic radiologists.

Complementary and Alternative Therapies Complementary and alternative therapies and complementary and integrative medicine are therapies of proven or unproven efficacy that have been used to promote wellness, to manage symptoms associated with cancer and its treatment, or to treat cancer. When properly combined with standard cancer treatments, some complementary therapies can enhance wellness and quality of life, but others may be harmful during or after treatment for cancer.

If you are undergoing cancer treatment, it is important that you tell your cancer care team of any alternative therapies that you are participating in for 2 key reasons: 1) your cancer care team can help you determine which therapies may be helpful and which have no benefit; and 2) some therapies could potentially interfere with your medical treatment or cause side effects that will limit the effectiveness of your treatment.

About Clinical Trials Clinical trials are carefully controlled research studies that test whether a new treatment is safe and how effective it is or examine new ways of diagnosing or preventing a disease. Clinical trials may also focus on refining existing “standard” therapies. Most of the advances in cancer therapy have been the result of the participation of patients in clinical trials. NCCN endorses participation in clinical trials, and for patients, there are several advantages to participating. First, patients will receive state-of-the-art cancer care according to a very specific plan of treatment. Second, physicians who participate in clinical trials are aware of the newest cancer treatments, keep careful track of all of the results of treatment—both good and bad—and compare their results with other colleagues to further refine treatment strategies. After a diagnosis of lung cancer, patients have many decisions to make, and one of them may be whether or not to participate in a clinical trial.

Following is a brief overview of clinical trials. If you have lung cancer, talking to your health care team, your family, and your friends can help you make the best treatment choice for you.

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The Purpose of Clinical Trials Clinical trials are done to get a closer look at promising new treatments or procedures in patients. A clinical trial is only planned and begun when there is good reason to believe that the treatment, test, or procedure being studied may be better than the one used currently. Treatments used in clinical trials are often found to have real benefits and may go on to become tomorrow’s standard treatment. NCCN is strongly commit-ted to clinical trials and believes that the best management for any patient with cancer is in a clinical trial.

Clinical trials can focus on many things, such as:

• New uses of drugs that are already approved by the U.S. Food and Drug Administration (FDA). For example, drugs that are used in one type of cancer may be tested in another type of cancer, or different drugs may be combined together.

• Different ways of administering chemotherapy, such as using oral drugs instead of IVs.

• New drugs that have not yet been approved by the FDA, where research is being done to determine the best dosage that balances the side effects with effectiveness.

• Different types of radiation therapy, designed either to decrease the side effects of radiation therapy or allow higher, more effective doses of radiation or both.

• Different types of surgery, some designed to be more “minimally invasive” to permit a faster recovery or to use different tools to destroy tumors, such as lasers.

• Alternative medicines, such as herbs and vitamins.

• New diagnostic tests, such as genetic tests, to determine which patients are the best candidates for certain therapies or to determine whether a particular chemotherapy regimen is likely to be effective for a certain subset of patients.

• Medicines or procedures to relieve symptoms or improve comfort.

Phases of Clinical Trials There are 4 phases of clinical trials, which are numbered I, II, III, and IV, and are described below, using the example of a drug therapy.

Phase I Clinical Trials: The purpose of a phase I study is to find the best way to give a new treatment to patients safely. The cancer care team will closely watch patients for any harmful side effects.

In phase I studies, the drug has already been tested in lab and animal studies, but the drug needs to be tested in humans to understand the opti-mal dose balanced against the potential side effects. Since phase I trials represent the earliest type of trial in humans, most patients in these trials have not been successfully treated with other “standard” chemotherapies. Doctors start by giving very low doses of the drug to the first patients and increase the doses for later groups of patients until side effects appear or the desired effect is seen. Doctors are hoping to help patients, but the main purpose of a phase I trial is to test the safety of the drug. If a drug is found to be reasonably safe in phase I studies, it can then be tested in a phase II clinical trial.

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Phase II Clinical Trials: These studies are designed to determine if the drug works for a specific type of cancer, such as non-small cell lung cancer. Frequently, phase II trials involve new combinations of drugs. Patients are closely watched for an effect on the cancer, which is often de-termined with different imaging studies (i.e., x-rays, CT, or MRI) to see if the tumor is shrinking. The cancer care team also looks for side effects.

Phase II trials are done in larger groups of patients when standard treatments aren’t working. If a drug or combination of drugs is found to be effective in phase II studies, it can be tested in a phase III clinical trial.

Phase III Clinical Trials: Phase III studies involve large numbers of patients. Often, these are randomized clinical trials, which means that patients are randomly put in 1 of 2 (or more) treatment groups. One group (called the control group) receives the standard, most accepted treatment. Other groups get the new treatment or treatments being studied. Neither the patient nor physician can pick which group they want to be in, which may make some patients uneasy. However, the doctor will explain the exact rationale for the clinical trial and the risks and benefits of being assigned to either group. All patients in phase III studies are closely watched. The study will be stopped early if the side effects of the new treatment are too severe or if one group has much better results than the others.

Phase III clinical trials are usually needed before the FDA will approve a new drug for use by the general public.

Phase IV Clinical Trials: Once a new drug has been approved by the FDA and is available for all patients, it may be studied in phase IV studies in very large numbers of patients with different types of cancer. In this setting, more can be learned about short-term and long-term side effects and safety of the drug. For example, some rare side effects may only become apparent in phase IV studies. Doctors can also learn more about how well the drug works, and if it might be helpful when used in other ways, such as in combination with other treatments.

Deciding to Enter a Clinical Trial If you have lung cancer and are interested in taking part in a clinical trial, you should begin by asking your doctor if the clinic or hospital participates in clinical trials. In order to interpret the results of a clinical trial, all the participants must be similar in terms of the tumor status and general health, so the physician can be certain that any improvement in outcome is the result of treatment and not due to different patient or tumor characteristics. Therefore, you will need to meet certain requirements in order to take part in any clinical trial. However, whether or not you enroll in a clinical trial is completely up to you.

Anyone participating in a clinical trial will need to sign a document called an “informed consent.” This informed consent describes the study in detail and outlines the potential risk and benefits. Your doctors and health care team will explain all the details of the clinical trial, and why it may be right for you. Your signature on the informed consent document means that you understand the risk and benefits and agree to participate in the clinical trial. However, the informed consent does not mean that you must stay committed to the clinical trial; you can leave the clinical trial whenever you want for any reason. It is also important to understand that participating in a clinical trial does not keep you from getting any other medical care you may need.

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To find out more about clinical trials, talk to your cancer care team. Among the questions you should ask are:

• Is there a clinical trial that I could take part in?

• What is the purpose of the study?

• What kinds of tests and treatments does the study involve?

• What does this treatment do? Has it been used before?

• Will I know which treatment I receive?

• What is likely to happen in my case with, or without, this new treatment?

• What are my other choices and their pros and cons?

• How could the study affect my daily activities?

• What side effects can I expect from the study? Can the side effects be controlled?

• Will I have to stay in the hospital? If so, how often and for how long?

• Will the study cost me anything? Will any of the treatment be free?

• If I am harmed as a result of the research, what treatment would I be entitled to?

• What type of long-term follow up care is part of the study?

• Has the treatment been used to treat other types of cancers?

People interested in clinical trials can also get a list of current trials by calling the National Cancer Institute’s Cancer Information Service toll free at 1-800-4-CANCER (1-800-422-6237) or by visiting the NCI clinical trials website at www.cancer.gov/clinicaltrials.

Other Things to Consider During and After Treatment

Every patient’s reaction to a cancer diagnosis is different. Some patients may wish to defer entirely to the cancer care team and become minimally involved in treatment decisions. Others will want their family members to be involved in treatment decisions, while others will want to take charge themselves. However, if you are a person with cancer, becoming actively involved in your care may improve your cancer care and recovery. For example, if you are aware of the side effects of treatment, you may be able to alert your cancer care team more promptly if problems emerge. It is also important to follow the scheduling of both chemotherapy and radiation therapy; missed appointments or doses can

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010affect the overall success of your treatment. Understanding the treatment and what it is trying to accomplish may make it easier to follow all the detailed instructions and appointments that you will receive.

Good nutrition and an overall healthy lifestyle are also important factors in treatment. In particular, if you smoke, it is important that you take steps to stop smoking now. Quitting will improve your overall health, and the full return of your sense of smell may help you enjoy a healthy diet during recovery. If you use alcohol, limit how much you drink. Have no more than 1 or 2 drinks per day. Good nutrition can also help you get better after treatment. Eat a nutritious and balanced diet, with plenty of fruits, vegetables, and whole grain foods. If you are having nutrition problems, ask your cancer care team if you may benefit from talking with a dietician.

Cancer treatment can be exhausting, both emotionally and physically. For example, fatigue is a side effect of both chemotherapy and radiation therapy, and lung cancer itself can cause fatigue. Therefore, it is important to get plenty of sleep at night. You will probably have many family members and friends who are eager to help; take advantage of their offers, but make sure you allow yourself plenty of time on your own during the day, if need be. You may have special strengths, such as a history of excellent nutrition and physical activity, a strong family support system, or a deep faith, and these strengths may make a difference in how you respond to cancer treatment. There are also experienced professionals in mental health services, social work services, and pastoral services who may assist you and your family in coping with your illness.

A cancer diagnosis and its treatment is a major life challenge, with an impact on you and everyone who cares for you. Before you get to the point where you feel overwhelmed, consider attending a meeting of a local support group.

ExPLANATION OF TREATMENT PATHWAYS

Initial Evaluation and Clinical Stage (based on page 12)The treatment pathways that accompany this text begin with a diagnosis of non-small cell lung cancer followed by the initial clinical evaluation or workup. The workup begins with a medical history and physical exam, with a focus on symptoms that may help determine if the cancer has spread outside the lung. A review of the patient’s overall health and biopsy results will also be done. The tumor will also be staged based on its size, location, and spread to other sites, such as the lymph nodes or other organs (TNM Classification). For example, a chest CT scan will help to stage the tumor by showing its size and location and will allow the doctor to evaluate the lymph nodes within the chest. If the nodes are enlarged, they may contain cancer cells that have spread from the lung tumor.

If the cancer has metastasized, other common sites include the liver and adrenal glands; these should also be examined and blood tests should be ordered to check their functionality. Blood tests will also be recommended to check how well your liver and kidneys are working and to make sure your blood cell counts are not too low. Low blood cell counts or problems with internal organs could mean a higher risk for problems and side effects of certain lung cancer treatments, so these tests must be done before your treatment begins. Additional blood test results can suggest that the cancer has spread outside the lung. Depending on the results of the medical history, evaluation of symptoms, and physical exam, extra testing of the heart, lungs, kidneys, or other organs may be needed to check whether a patient is likely to have serious problems from certain lung cancer treatments. If the patient is a smoker, smoking cessation counseling should be recommended because it is crucial to the outcome of cancer treatment.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010Results from this initial clinical evaluation are used to determine the cancer stage, and based on this, additional tests may be needed before treatment is started to determine if the cancer has spread. These tests may include imaging studies (MRI scans, bone scans) or biopsies of the lungs, lymph nodes, or other organs. The cancer stage may change after the results of biopsies and surgery are available.

Stage I and II Pretreatment Evaluation (based on page 14)This treatment pathway focuses on the evaluation of stage I and some stage II cancers. These tumors are generally small and there may be spread to the lymph nodes from the lung. For more detailed information on staging, refer to pages 9–12.

For clinical stage T1 or T2, and N0 or N1, the guidelines recommend tests and scans to figure out if surgery is a good treatment option. These tests include a pulmonary function test to measure how well the lungs take in and exhale air and how efficiently they transfer oxygen into the blood. A bronchoscopy is done to look for cancer in other parts of the lungs or to get tissue for biopsy and diagnosis. It is also important to deter-mine if the cancer has spread to nearby lymph nodes, which could affect whether surgery is a good treatment option. Treatment options used to check for cancer spread are a mediastinoscopy, which checks whether cancer has spread to the mediastinal lymph nodes, and an ultrasound. An ultrasound can also be used to evaluate lymph nodes by placing the ultrasound device down the throat (esophagus) or bronchi. The PET/CT scan also shows mediastinal lymph nodes, as well as spread anywhere else in the body. An MRI of the brain is only recommended if stage II cancer is present, to rule out spread to the brain.

If there is no cancer in the mediastinal nodes and the cancer can be removed with surgery, treatment is discussed on page 15.

If there is no cancer in the mediastinal nodes or no distant spread but surgery cannot be performed because of other medical conditions, radia-tion therapy is an option that may provide a cure. Limited surgery is also an option.

If cancer is found in the mediastinal nodes, the tumor stage will be changed to stage III, and surgery may or may not be a good option. See the treatment pathway on page 19 that fit the correct T and N categories.

Stage I, II, and IIIA Treatment (based on page 15)If the initial results of the tests and scans show that the cancer has not spread, surgery is recommended to remove the tumor and see how far it has grown and may have spread. The surgeon will make every effort to completely remove the tumor, since this offers the best chance for a cure. Lymph nodes near the lungs will also be removed and checked for cancer cells. More therapy, consisting of additional surgery, radiation therapy, or chemotherapy, will typically be considered if the surgeon was unable to remove the entire tumor, if there are positive margins, or if there is a high risk that the tumor has metastasized.

As previously discussed, radiation therapy and surgery are referred to as local therapies because they do not treat cancer that has spread outside the lung. Chemotherapy is a systemic therapy that can kill microscopic cancer cells that have spread beyond the lung because it enters the blood-stream. Thus, chemotherapy is more strongly recommended as the tumor size increases because a larger tumor size or spread to nearby lymph nodes is associated with a greater risk of spread beyond the lung (see General Principles of Pathologic Evaluation and Treatment on page 27 for further information regarding radiation therapy and chemotherapy, respectively).

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010Some cancer cells can be left behind even when the surgeon removes all the cancer that was visible at the time of the operation. A negative surgical margin (no cancer is found at the edges of the surgical specimen) is usually a sign that no cancer was left behind near where it was removed. A negative surgical margin does not guarantee a cure, however, because cancer cells may have spread to other areas of the body before surgery.

The following recommendations are based on the results of surgery and examination of the surgical specimen under the microscope. They are subdivided according to whether cancer was present at the edge of the tumor specimen.

When the Surgical Margins Are Negative After surgery, observation is recommended only for T1, N0 and many T2, N0 tumors that have been completely removed with no cancer found at the margin. Chemotherapy is also a consideration for T2 tumors that are called high risk because those tumors are more apt to have already spread beyond the lung. High-risk factors are based on what the pathologist sees under the microscope and include a very abnormal appearance of the individual cancer cells, tumor cells involving nearby blood vessels, or very narrow surgical margins. Chemotherapy is also recommended for patients when the lymph nodes contain tumor cells.

Radiation is generally not recommended when the surgical margins are negative, since that suggests that all the cancer has been removed during surgery. There is one exception, though. If the cancer is staged at T1-T2, N1 (a tumor with involvement of lymph nodes near the lung), then the addition of radiation depends on the presence of certain adverse, or unfavorable, factors, such as:

• the lymph nodes in the mediastinum cannot be evaluated as needed;

• the cancer has grown outside of the lymph nodes;

• there are many lymph nodes involved with cancer; or

• the margins may be very close to the edge of the cancer.

If no adverse factors are present and the surgical margins are negative, then only chemotherapy is recommended. If adverse factors are present, there is a higher risk that the surgery did not remove the entire tumor. In this case, chemotherapy alone or chemoradiation followed by additional chemotherapy may be recommended. If the cancer has spread to the lymph nodes between the lungs or near the main bronchus, radiation therapy may be added to the chemotherapy.

When the Surgical Margins Are Positive Additional therapy is recommended when tumor cells are found at the margin of the surgical specimen. Additional surgery is one option, which may be combined with chemotherapy when the original tumor is larger (stage IB, IIA). For smaller tumors (stage IA), radiation alone is an option. As the tumor gets larger, or the lymph nodes are involved and the risk for spread beyond the lungs increases, radiation is given sequentially, followed by chemotherapy alone.

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Stage IIB and IIIA Pretreatment Evaluation (based on page 16)This section is for patients with tumors that invade the chest wall, either in the superior sulcus, which is the upper part of the lung, or elsewhere; or tumors that invade the main bronchus near the trachea. Lymph nodes near the tumor may or may not show cancer spread (N0 or N1). Be-cause these cancers are larger than those discussed above, an extensive evaluation is needed before treatment can be started to ensure that the cancer hasn’t spread to the mediastinal lymph nodes or distant sites in the body and to determine if the tumor can be removed with surgery.

Bronchoscopy is done to check for more tumors in other areas of the lungs. Mediastinoscopy is recommended to find out if cancer has spread to the mediastinal lymph nodes. MRI of the brain and, for superior sulcus tumors, the spine, is done to look for spread to these tissues. A PET/CT scan is also done to look for spread. Finally, if not already done, pulmonary function tests are recommended.

This treatment pathway refers to other pages with more specific details depending on the findings of the previously discussed tests. If distant spread is found, the cancer is reclassified as M1 (for further information see page 23).

Stages IIB and IIIA Treatment (based on page 17)Tumors in the superior sulcus (very top part of the lung) often invade nerves and other tissues in that area. If the surgeon thinks the tumor can be completely removed (it is resectable), the recommendation is first to give concurrent chemoradiation to shrink the tumor, followed by surgery and more chemotherapy. If the tumor cannot be removed with surgery (it is unresectable), then chemotherapy together with a full dose of radiation therapy is recommended. In cases where the removal of the tumor is uncertain, chemoradiation is given followed by surgery and then more chemotherapy if the tumor becomes resectable. If the tumor remains unresectable, then radiation therapy is recommended as the primary thera-py, followed by chemotherapy.

Tumors growing into the chest wall, the main breathing tubes near the trachea, or the mediastinum may be treated with surgery first, which is the preferred treatment. Other options include chemotherapy alone or concurrent chemoradiation, both of which are followed by surgery.

If, after surgery, the margins are free of cancer, additional chemotherapy is recommended if it has not already been given. If the edges of the specimen contain cancer, the options include either: 1) additional surgery followed by chemotherapy (if not already given), or 2) chemoradiation followed by chemotherapy alone (if not given initially).

Stages IIIA Pretreatment Evaluation (based on page 18)This treatment pathway discusses the evaluation of patients with stage IIIA cancers that appear to have spread to the mediastinal lymph nodes (N2), as well as those with minimal lymph node spread (N0-N1), or a separate smaller nodule in another part of the lung. Patients should have bronchoscopy and biopsy of mediastinal lymph nodes, either by mediastinoscopy or fine-needle aspiration. A PET/CT scan and MRI of the brain are done to look for distant spread. If not previously done, pulmonary function tests are also recommended. These tests will determine if the tumor can be removed with surgery and whether or not chemotherapy and radiation are needed. Further treatment depends on the results of these tests.

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Stage IIIA Treatment (based on page 19)Three different stages are described on page 19. The first stage is T1–T3 with no cancer found in the biopsy of the mediastinal lymph nodes. Surgery with removal of the mediastinal nodes is recommended. If the cancer is completely removable and the mediastinal lymph nodes do not contain cancer (N0–1), then further treatment is described on pages 15 or 16, respectively. If cancer is found in mediastinal lymph nodes (N2) and the surgical margins do not contain cancer, chemotherapy may be given with radiation therapy. If the margins do contain cancer, chemoradiation with additional chemotherapy is recommended. If the original tumor cannot be completely removed, the tumor should be treated according to the stage as described on page 15.

The next 2 groups include patients whose tumors have spread to the mediastinal lymph nodes on the same side as the tumor (N2). The first group contains patients with smaller tumors (T1–T2) and larger tumors (T3) that have not spread to adjacent structures. If the brain MRI and PET/CT scan do not show cancer spread, there are 2 options: chemotherapy together with a full dose of radiation therapy, or a short course of chemotherapy with or without radiation can be given to determine if surgery is possible. If there is no disease progression during this treatment, surgery with or without chemotherapy and with or without radiation (if not given before) is an option. If there is tumor growth, then surgery is not an option, and radiation therapy with the option of chemotherapy is recommended. If there is no distant spread, radiation can be given (if not given already) with or without chemotherapy.

The second patient group is those with T3 tumors that have spread into adjacent structures, such as the diaphragm or lining of the heart or lungs. Surgery is not an option for these patients. If the MRI and PET/CT scans show no evidence of distant spread, patients can be initially treated with chemotherapy together with a full course of radiation therapy.

Treatment of Separate Nodules, Stage IV, IIIA (T4, N0-1) (based on page 20)The upper 2 pathways on page 20 describe the the treatment options when there is an additional site of cancer in either the same or opposite lung. The smaller tumors, called satellite tumors, are a result of tumor spread within the lung. Whenever possible, the surgeon tries to remove the tumor and any satellite tumors. If this is successful and the margins of the surgical specimen are negative, then chemotherapy is recommended after the surgery. If the margins are positive, chemoradiation is recommended.

If the satellite tumor is located in the other lung, surgery is still recommended, and the tumors can be treated as 2 distinct primary tumors (see evaluation for these tumors on page 12).

The bottom pathway describes treatment when the surgeon concludes that complete removal of the tumor is not possible and there is no fluid in the chest; concurrent chemoradiation is recommended, followed by additional chemotherapy.

Stage IIIB Pretreatment Evaluation and Initial Treatment (based on page 21)This treatment pathway describes the workup and treatment for patients who appear to have cancer that has spread to lymph nodes on the opposite side of the mediastinum or above the collar bone (N3); N3 disease must be confirmed through a biopsy of any suspicious lymph nodes. A variety of techniques may be used, based on the location of the suspicious nodes. A mediastinoscopy or mediastinotomy can be performed to

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010evaluate the mediastinal nodes. A thoracoscopy is done to look for cancer cells in the space between the lungs and chest wall, and lymph nodes or any suspicious looking area can be biopsied at this time.

A fine-needle aspiration can also be performed using an imaging test to guide the needle placement. An ultrasound device, placed in either the bronchus or esophagus can be used to guide a biopsy. PET/CT scan, brain MRI, and pulmonary function tests may also be performed. If all these tests are normal, meaning the enlarged lymph nodes do not contain cancer cells and there is no distant spread, and the patient had ad-equate lung function, then the cancer is treatable with surgery (see page 13). If the biopsies do show cancer but there is no distant spread, then chemoradiation is recommended, which may be followed by more chemotherapy. If the tests show distant spread, then treatment for widespread disease should be considered, as outlined on page 23.

Stage IIIB, Stage IV, M1a: Pretreatment Evaluation and Initial Treatment (based on page 22)Two different types of T4 tumors are discussed in this treatment pathway. T4 staging means that the cancer has spread to other structures in the chest or it is producing fluid that surrounds the lung (pleural effusion) or heart (pericardial effusion).

If a T4 tumor with wide spread to lymph nodes is suspected (N2 or N3), then these nodes should be biopsied using mediastinoscopy or with fine-needle aspiration, or the biopsy should be guided by ultrasound. Examining the chest using thoracoscopy will give information regarding how far the cancer has grown. Tests to look for spread outside the chest (brain MRI and PET/CT scan) should also be performed.

If the lymph nodes do not contain cancer, the cancer is classified as T4, N0-N1 and may be treated with surgery or as recommended on page 18. If the lymph nodes on the same or opposite side of the chest do contain cancer (N2-N3), then concurrent chemoradiation, followed by ad-ditional chemotherapy is recommended. Finally, if the tests show that cancer has spread outside the chest to distant sites, treatment should be as shown on page 23.

If there is fluid around the lungs or heart (stage IV, M1a), a sample of the fluid can be removed by placing a needle between the ribs and into the area surrounding the heart or lungs. The fluid is then checked under a microscope to see if cancer cells are present. If cancer can’t be diagnosed from cells in the fluid, it may be necessary to perform a thoracoscopy to make sure that the fluid is not related to cancer spread to the lining of the chest. If there are no cancer cells in the fluid, then the cancer should be treated according to its T and N stage as discussed on page 13. If cancer cells are present in the fluid, surgery is not an option. The fluid should be drained with a catheter (a tube used to withdraw fluids), and a small piece of the sac around the heart may need to be removed to prevent the build-up of pressure. Treatment should then be given as for stage IV disease (see page 23).

Stage IV Pretreatment Evaluation and Initial Treatment for Multiple Lung Primaries (based on page 23)Sometimes there is only 1 tumor nodule in 1 site of distant disease spread. This can only be determined after a complete evaluation with mediastinoscopy, bronchoscopy, brain MRI, and PET/CT scan. Treatment options depend on the site of metastasis.

If the cancer has spread only to the brain and there is only 1 tumor, surgery followed by radiation therapy is an available option. Two different types of radiation therapy may be recommended. Radiation therapy to the entire brain (whole-brain radiation therapy) is one option.

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Whole-brain radiation therapy is used to treat very small tumor spread that cannot be detected on brain MRI or PET/CT scan. Stereotactic radiosurgery is the second option for radiation therapy and can be focused specifically at the site where the metastasis was removed. Whole-brain radiation therapy may be followed by stereotactic radiosurgery. As another option, stereotactic radiosurgery can be the first treatment instead of surgery, followed by whole-brain radiation therapy. After treatment of the brain metastases, surgical removal of the lung tumor depends on its stage, as noted in the treatment pathway.

If the cancer has only spread to 1 adrenal gland (located in the abdomen), and this is confirmed through biopsy and is staged T1–T2, N0–N1 or T3, N0 (which means it can be completely removed by surgery), then both the adrenal gland tumors and the lung cancer can be removed or treatment for stage IV cancer (see page 25) can be given. Additional treatment depends on the disease stage. Radiation therapy is also an option for treating cancer in the adrenal gland.

Sometimes there is a separate cancer in another lobe of the lung or in the other lung. Both tumors should be removed if there is no lymph node involvement or distant spread of cancer. If there are multiple sites of spread, then surgery is not recommended. For further treatment recommendations, see page 25.

Follow-Up, Recurrence, and Widespread Disease (based on page 24)After initial treatment with surgery, chemotherapy, and/or radiation therapy, the guidelines recommend regular follow-up tests and exams (physical exam and chest CT scan) to check for recurrence. Tumors may recur locally (in the lung), regionally (near the lungs), or distantly (in distant organs).

If the tumor recurs in or near the lung, treatment depends on exactly where it is located and what symptoms it may be causing. Recurrent tumors may occur in the airways and block breathing passages. Treatment options include vaporizing the tumor with a laser; placing a stent inside the airway to keep it open; radiation therapy, with either brachytherapy (placing a small radioactive pellet inside the airway) or external-beam radiation therapy; and photodynamic therapy. Photodynamic therapy is the use of drugs that collect inside cancer cells and are activated by shining a special light on the tumor (see Palliative and Supportive Care, page 51).

Surgery to remove the recurrence may be an option in some cases, as is radiation therapy. If the tumor is located in the mediastinal lymph nodes, chemoradiation is recommended, but only if radiation therapy has not been previously given.

If the cancer is pressing on the large vein leading to the heart (the superior vena cava), a stent can be placed inside the vein to prevent it from collapsing. Radiation therapy is another option for shrinking tumors pressing on this vein. When cancer presses on or collapses this vein, blood flow from the head and arms is reduced, possibly resulting in uncomfortable severe swelling in both the face and arms.

If the tumor is causing bleeding into the airways, treatment options are similar to when the airway is blocked, but bleeding can also be controlled by blocking off the blood supply to the tumor, called embolization.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010If the lung cancer comes back at only 1 distant site, treatment options depend on the number and location of these recurrent tumors. If only 1 tumor is found, surgery to remove it may be an option (see page 23).

If there is spread to distant organs or more than one brain metastasis, external-beam radiation therapy is used to relieve symptoms. If cancer has spread to the bones and is causing pain, external-beam radiation therapy can also be used to help relieve the pain. If the disease has weakened the bone enough that a fracture may occur, doctors may recommend surgery to strengthen it. This can help relieve pain and may allow the patient to resume usual activities. Drug therapy may also be used to strengthen bones weakened by the tumor.

Although these treatments are described in the section on follow-up and recurrence, they also apply to patients who have distant metastases found at first diagnosis. Doctors may also recommend systemic therapy (usually chemotherapy; see page 25).

Stage IV and Treatment of Recurrence (based on pages 25 and 26)This treatment pathway focuses on the role of chemotherapy and how long the treatments should continue. Because chemotherapy can cause severe side effects, it is recommended only for patients in relatively good health. In patients in very poor health, chemotherapy may cause serious or life-threatening complications.

In deciding which patients should receive chemotherapy, NCCN doctors use precise definitions of good health or poor health based on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (see page 32 for more information).

NCCN recommends chemotherapy for patients with widespread disease who are in good health (performance status of 0–1). A variety of different chemotherapy options are available, which can be combined with a different type of systemic therapy called targeted therapy.

Chemotherapy is not designed to distinguish between normal cells and cancer cells, while targeted therapy is specifically designed to attack the cancer cells. Three different targeted therapies are used to treat lung cancer: bevacizumab, cetuximab, and erlotinib. Bevacizumab, which is combined with chemotherapy, is specifically designed to attack the blood vessels that feed the tumor. An increased risk of bleeding is a side effect of bevacizumab, so this drug cannot be used in patients who are using blood thinning drugs or who have any history of coughing up blood. In addition, the risk of bleeding is higher if the cancer has metastasized to the brain. Cetuximab is another targeted therapy that can be combined with chemotherapy. Erlotinib is the third targeted therapy and is a little bit different than bevacizumab or cetuximab since there is a test that can identify the specific tumors that will respond to this drug. The test is done on a piece of the tumor that was removed as part of surgery or with a biopsy. If this test is positive, patients are considered candidates for erlotinib, which is given by itself without additional chemotherapy.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010The same choices are generally recommended for patients in intermediate health (performance status of 2), though some chemotherapies may be favored over others. However, bevacizumab is not recommended for this group of patients.

Patients are usually evaluated after completing 2 cycles of therapy. If the cancer grows after the second cycle, the patient should be treated according to the guidelines for progressive disease (see page 26). If the cancer shrinks or at least doesn’t grow after 2 treatments, chemotherapy should be continued for 4 to 6 total cycles. Patients should have an evaluation after 6 cycles of chemotherapy. If the tumor has shrunk or does not spread and the patient is in good general health, the options are to continue getting the current treatment until the disease progresses, to get continuation maintenance therapy (meaning at least one of the drugs given as first-line therapy is continued) or switch maintenance therapy (meaning that patients are switched to a different maintenance therapy), or to get continuing evaluation but not treatment (observation).

Chemotherapy is not recommended for patients in poor health (performance status of 3 or 4). Erlotinib therapy is an option or supportive care can be considered. Supportive care is intended to relieve symptoms and to help keep patients as comfortable as possible; it is not intended to directly attack or cure the cancer.

Although participation in clinical trials is a good option for any patient with lung cancer, a study of a very new treatment in the early stages of testing (called a phase I or II clinical trial) may be a good option for patients whose disease progresses while on chemotherapy. Deciding on the right time to discontinue chemotherapy and focus on supportive care is never easy. Good communication with doctors, nurses, family, and clergy, as well as discussions with hospice staff, can help patients with cancer and their loved ones when facing this situation.

Stage IV with Disease Progression (based on page 26)Treatment after the cancer has begun to grow again is discussed in the treatment pathway on page 26. A different type of chemotherapy may be given for those in good health (performance status of 0–2). Docetaxol, pemetrexed, or erlotinib are treatment options at this point. One category of chemotherapy is called “platinum” chemotherapy (meaning it contains derivatives of the metal platinum); a combination of 2 of these drugs may be offered. If the tumor grows while the patient is taking any of these therapies, erlotinib can be given to patients who remain in good health (performance status 0-2), but only if the patient has not already received this drug. If the tumor grows while the patient is receiving erlotinib, treatment switches to supportive care. If the patient remains in good health, participation in a clinical trial is a consideration. Supportive care is recommended for patients in poor health (performance status 3–4).

Palliative and Supportive Care Most of these guidelines identify ways to cure some people with lung cancer or to help others live longer by removing or destroying lung cancer cells. If you are a person with lung cancer, however, it is also important to realize that controlling symptoms and helping you continue to do the things you want and need to do is another key goal. Do not hesitate to discuss your symptoms or how you are feeling with your cancer care team. There are effective and safe ways to treat pain, most symptoms of lung cancer, and most of the side effects caused by lung cancer treat-ment. Care to help relieve symptoms caused either by the lung cancer or side effects from its treatment is called palliative care or supportive care.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerDiscussion Version 2010Pain is a significant concern for patients with lung cancer. Pain can result from tumor growth around nerves or if cancer spreads to the bone. Mouth sores can also be a painful side effect of chemotherapy. One of the goals of your cancer care team is treatment of these side effects, so it is important to tell the cancer care team about any pain or other side effects. If you experience side effects between office visits be sure to keep track of your symptoms and concerns throughout your treatment to relay to your physician. Sometimes you will be getting routine blood tests at laboratories that are not part of your physician’s office, which may reduce direct contact with your cancer care team. This should not stop you from contacting your team whenever you have a problem, or letting the laboratory know of any problems; it is part of their responsibility to get in touch with your doctor.

In addition to the general supportive care measures for any type of advanced cancer, you may also benefit from specific measures that relieve some symptoms of lung cancer that are relatively rare with other cancers. For example, non-small cell lung cancer can produce a hormone that alters the level of calcium in your blood, which can lead to muscle weakness and other nervous system problems. Intravenous fluids and medications can help relieve some of these symptoms.

Sometimes patients may be given cancer treatment that is intended to reduce or prevent symptoms but is not expected to cure the cancer. This palliative care may include radiation or chemotherapy treatments that relieve symptoms by shrinking the tumor. Other palliative treatments for lung cancer include laser surgery and photodynamic therapy. Laser surgery can vaporize the part of a tumor that is blocking an airway and interfering with breathing, but it does not destroy all of the cancer. Photodynamic therapy uses a drug injected into a vein, which is selectively attracted to cancer cells. The drug is injected in an inactive form and is activated by shining light of a certain color on it. Beams of light can be aimed through a bronchoscope to help destroy the part of a tumor that is blocking an air passage by activating the drug there. Patients must avoid sunlight for a time to avoid side effects to the skin.

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NCCN Guidelines for Patients™: Non-Small Cell Lung CancerGlossary

AblationIn medicine, the removal or destruction of a body part or tissue or its function. Ablation may be performed by surgery, hormones, drugs, radiofrequency, heat, or other methods.

AdenocarcinomaCancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

Adjuvant therapy Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

Adrenal glands A small gland that makes steroid hormones, adrenaline, and noradrenaline. These hormones help control heart rate, blood pressure, and other important body functions. There are 2 adrenal glands, one on top of each kidney. Also called suprarenal gland.

AlveoliTiny air sacs located at the end of the bronchioles in the lungs where oxygen and carbon dioxide are exchanged.

AntitumorHaving to do with stopping abnormal cell growth.

Autofluorescence test A test that involves shining a special light through a bronchoscope which causes a cancer to glow. The light is similar to that used in photodynamic therapy but is used for diagnosis rather than treatment in this situation. See photodynamic therapy.

BevacizumabA drug used to treat several types of cancer, including certain types of colorectal, lung, breast, and kidney cancers and glioblastoma. It is also being studied in the treatment of other types of cancer. Bevacizumab binds to vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. It is a type of antiangiogenesis agent and a type of monoclonal antibody. Also called Avastin®.

BiopsyThe removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: 1) incisional biopsy, in which only a sample of tissue is removed; 2) excisional biopsy, in which an entire lump or suspicious area is removed; and 3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

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Blood chemistry Blood tests that evaluate the function of organs such as the liver and kidneys.

Blood vessel A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

Bone marrow The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

Bone scan A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner.

BrachytherapyA type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor. Also called implant radiation therapy, internal radiation therapy, and radiation brachytherapy.

BronchiThe large air passages that lead from the trachea (windpipe) to the lungs that carry air into and out of the lungs.

BronchoscopeA thin, tube-like instrument used to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs. A bronchoscope has a light and a lens for viewing and may have a tool to remove tissue.

BronchoscopyA procedure that uses a bronchoscope to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. The bronchoscope is inserted through the nose or mouth. Bronchoscopy may be used to detect cancer or to perform some treatment procedures.

BronchusThe singular form of bronchi.

CarboplatinA drug that is used to treat advanced ovarian cancer that has never been treated or symptoms of ovarian cancer that has come back after treatment with other anticancer drugs. It is also used with other drugs to treat advanced, metastatic, or recurrent non-small cell lung cancer and is being studied in the treatment of other types of cancer. Carboplatin is a form of the anticancer drug cisplatin and causes fewer side effects in patients. It attaches to DNA in cells and may kill cancer cells. It is a type of platinum compound. Also called Paraplatin®.

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CarcinomaCancer that begins in the skin or in tissues that line or cover internal organs.

Carcinoma in situ A group of abnormal cells that remain in the place where they first formed. They have not spread. These abnormal cells may become cancer and spread into nearby normal tissue. Also called stage 0 disease.

CAT scan See CT scan.

CBCSee complete blood count.

CetuximabA monoclonal antibody used to treat certain types of head and neck cancer and colorectal cancer that has spread to other parts of the body. It is also being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to cancer cells. Cetuximab binds to the epidermal growth factor receptor (EGFR), which is found on the surface of some types of cancer cells. Also called Erbitux®.

ChemoradiationTreatment that combines chemotherapy with radiation therapy. Usually the chemotherapy is given before the radiation therapy, but sometimes the radiation can be given first. If the chemotherapy and radiation are given together at the same time, the combination is described as concurrent chemoradiation.

ChemotherapyChemotherapy refers to drugs that are given by mouth (orally) or injected into a vein (intravenous, or IV). These enter the blood stream and travel throughout the body and can attack cancer cells wherever they may occur. Because of their widespread effects, chemotherapy is referred to as “systemic” therapy, which contrasts with “local” therapy which is only directed at the tumor itself. Chemotherapy is a treatment consideration whenever spread beyond the lung is suspected.

Chest wall The muscles, bones, and joints that make up the area of the body between the neck and the abdomen.

CisplatinA drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent. Also called Platinol®.

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Clinical trials A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease.

Combination chemotherapy Treatment using more than one anticancer drug.

Complete blood count A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called blood cell count and CBC.

Computed tomography scan See CT scan.

Concurrent chemoradiation Concurrent chemoradiation describes the simultaneous use of chemotherapy and radiation therapy.

Contrast material A dye or other substance that helps show abnormal areas inside the body. It is given by injection into a vein, by enema, or by mouth. Contrast material may be used with x-rays, CT scans, MRI, or other imaging tests.

CT scan A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computerized axial tomography scan, computerized tomography, and CT scan.

CycleChemotherapy, which may consist of a combination of drugs, is given according to a set schedule, called a cycle. The chemotherapy is interrupted after a cycle to allow the body to recover from the side effects, which often consist of low blood counts. Once the body has recovered, another cycle of chemotherapy can start again. An entire course of chemotherapy will consist of multiple cycles.

DiaphragmThe thin muscle below the lungs and heart that separates the chest from the abdomen.

Disseminate Scatter or distribute over a large area or range.

Distant recurrence A distant recurrence describes a tumor that comes back (i.e., recurs) outside the lung.

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DocetaxelA drug used together with other drugs to treat certain types of breast cancer, stomach cancer, prostate cancer, and certain types of head and neck cancer. It is also being studied in the treatment of other types of cancer. Docetaxel is a type of mitotic inhibitor. Also called Taxotere®.

Eastern Cooperative Oncology Group performance scale The Eastern Cooperative Oncology Group (ECOG) performance scale ranks the health of people with cancer on a scale of 0 to 4. A rank of 0 means that the patient is able to do the same things he or she could do before being diagnosed with cancer. At the other end of the scale, a rank of 4 means that the patient cannot do daily self-care activities (such as feeding, bathing, dressing, or going to the bathroom) and cannot get out of a chair or bed.

ECOG performance scale See Eastern Cooperative Oncology Group performance scale.

EGFRSee epidermal growth factor receptor.

EmbolizationThe blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor.

Epidermal growth factor receptor The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called EGFR, ErbB1, and HER1.

ErlotinibA drug used to treat certain types of non-small cell lung cancer. It is also used together with gemcitabine to treat pancreatic cancer and is being studied in the treatment of other types of cancer. Erlotinib is a type of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Also called Tarceva®.

EsophagusThe muscular tube through which food passes from the throat to the stomach.

EtoposideA drug used to treat testicular and small cell lung cancers. It is also being studied in the treatment of several other types of cancer. Etoposide blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of podophyllotoxin derivative and a type of topoisomerase inhibitor. Also called Toposar® and Vepesid®.

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External-beam radiation therapy This is the most common type of radiation therapy used in lung cancer. A type of radiation therapy that uses a machine to aim high-energy rays at the cancer from outside of the body. Also called external radiation therapy.

FatigueA condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.

Fine-needle aspiration biopsy This biopsy technique involves the use of a needle that is placed in the tumor. The removal of tissue or fluid with a thin needle for examination under a microscope. Typically an imaging test, such as CT scans or ultrasound, is used to guide the placement of the needle into the target.

First-line therapy Initial treatment used to reduce a cancer. First-line therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called induction therapy, primary therapy, and primary treatment.

GemcitabineThe active ingredient in a drug that is used to treat pancreatic cancer that is advanced or has spread. It is also used with other drugs to treat breast cancer that has spread, advanced ovarian cancer, and non-small cell lung cancer that is advanced or has spread. It is also being studied in the treatment of other types of cancer. Gemcitabine blocks the cell from making DNA and may kill cancer cells. It is a type of antimetabolite. Also called Gemzar®.

Growth factors A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.

Hematoporphyrin fluorescence Hematoporphyrin fluorescence uses a special chemical that accumulates in tumor cells and emits a light. This technique is used with bronchoscopy to identify very small tumors along the lining of the airway.

HospiceA program that provides special care for people who are near the end of life and for their families, either at home, in freestanding facilities, or within hospitals.

ImagingImaging is a general term to describe any test that takes pictures of areas inside the body. Imaging uses methods such as x-rays (high-energy radiation), ultrasound (high-energy sound waves), and radio waves.

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Induction therapy Initial treatment used to reduce a cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

Initial evaluation The initial evaluation describes the tests that are done at the time of cancer diagnosis to determine the location and spread of lung cancer. The initial work-up typically includes a thorough history and physical and various imaging tests.

Interventional radiologist An interventional radiologist is a physician who specializes in performing procedures, such as a biopsy, using an imaging technique for guidance (such as a CT scan).

IntravenousInto or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called IV.

IrinotecanThe active ingredient in a drug used alone or with other drugs to treat colon cancer or rectal cancer that has spread to other parts of the body or has come back after treatment with fluorouracil. It is also being studied in the treatment of other types of cancer. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of topoisomerase inhibitor and a type of camptothecin analog. Also called Camptosar®.

IVSee intravenous.

LaserA device that forms light into intense, narrow beams that may be used to cut or destroy tissue, such as cancer tissue. It may also be used to reduce lymphedema (swelling caused by a buildup of lymph fluid in tissue) after breast cancer surgery. Lasers are used in microsurgery, photodynamic therapy, and many other procedures to diagnose and treat disease.

Laser surgery A surgical procedure that uses the cutting power of a laser beam to make bloodless cuts in tissue or to remove a surface lesion such as a tumor.

LobectomyA surgical procedure where a section or lobe of the lung is removed.

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LobesSections of the lungs. The right lung has 3 lobes. The left lung has 2 lobes. It is smaller, because the heart takes up more room on that side of the body.

Local recurrence When cancer recurs in the lung.

Local therapy Treatment that affects cells in the tumor and the area close to it. Surgery and radiation therapy are examples of local therapy.

LymphThe clear fluid that travels through the lymphatic system and carries cells that help fight infections and other diseases. Also called lymphatic fluid.

Lymph fluid See lymph.

Lymph node A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels and help fight infections They are also called lymph glands.

Magnetic resonance imaging See MRI scan.

Maintenance therapy Treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time.

MarginThe edge or border of the tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed.

Mediastinal lymph nodes Lymph nodes that are located along the windpipe and major bronchial tube areas. Lung cancer frequently spreads to the mediastinal lymph nodes, and therefore there status is an important part of treatment planning for lung cancer.

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Mediastinoscopy A procedure in which a mediastinoscope is used to examine the organs in the area between the lungs and nearby lymph nodes. A mediastinoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. The mediastinoscope is inserted into the chest through an incision above the breastbone. This procedure is usually done to get a tissue sample from the lymph nodes on the right side of the chest.

MediastinotomyMediastinotomy is similar to mediastinoscopy, except instead of using a lighted tube, an incision is made and the surgeon can directly examine the mediastinum.

MediastinumThe area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the thymus, and lymph nodes but not the lungs.

Medical oncologist A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, biological therapy, and targeted therapy. A medical oncologist often is the main health care provider for someone who has cancer. A medical oncologist also gives supportive care and may coordinate treatment given by other specialists.

MetastasisThe spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases.

MetastasizeTo spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor.

MetastaticHaving to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

Monoclonal antibody A type of protein made in the laboratory that can bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

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MRI scan A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. Magnetic resonance imaging makes better images of organs and soft tissue than other scanning techniques, such as computed tomography (CT) or x-ray. Magnetic resonance imaging is especially useful for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. Also called MRI, NMRI, and nuclear magnetic resonance imaging.

Neoadjuvant therapy Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy. In lung cancer, neoadjuvant therapy describes chemotherapy or radiation therapy that is given before surgery in order to shrink the tumor.

NodeSee lymph node.

Non-small cell lung cancer A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer, accounting for approximately 85% of lung cancers.

NSCLCSee non-small cell lung cancer.

OncologistA doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation.

OpioidsA substance used to treat moderate to severe pain. Drugs such as morphine, codeine, oxycodone, and others that are effective in treating pain. Also called narcotics, these prescription medicines are the strongest pain relievers available.

Paclitaxel A drug used to treat breast cancer, ovarian cancer, and AIDS-related Kaposi sarcoma. It is also used together with another drug to treat non-small cell lung cancer. Paclitaxel is also being studied in the treatment of other types of cancer. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. Also called Taxol®.

Palliative care See supportive care.

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Paraneoplastic syndrome A group of symptoms that may develop when substances released by some cancer cells disrupt the normal function of surrounding cells and tissue.

PathologistThe pathologist is the physician who examines the surgical specimen under the microscope to determine whether cancer is present.

Pathology report The description of cells and tissues made by a pathologist based on microscopic evidence, and sometimes used to make a diagnosis of a disease.

Performance status A measure of how well a patient is able to perform ordinary tasks and carry out daily activities.

Pericardial effusion An unusual amount of fluid collected in the sac surrounding the heart.

PET/CT (positron emission tomography/computerized tomography) scan An imaging study using a radioactive material to look for cancer anywhere in the body. The PET scan involves the injection of glucose that is attached to radioactive material, which accumulates in the tumor cells. This radioactivity lights up when using a special camera. The CT component of the test is designed to show exactly where the radioactive material is located.

PET scan A procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body. Also called positron emission tomography scan.

PFTSee pulmonary function test.

Photodynamic therapy Treatment with drugs that become active when exposed to light. These activated drugs may kill cancer cells.

PlateletsA tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots.

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PleuraA thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity. It protects and cushions the lungs. This tissue secretes a small amount of fluid that acts as a lubricant, allowing the lungs to move smoothly in the chest cavity while breathing. There are two parts to the pleura. The visceral pleura attaches to the lung; the parietal pleura attaches to the chest wall. There is a potential space between them where fluid can accumulate.

Pleural effusion An unusual accumulation of fluid between the thin layers of tissue (pleura) lining the lung and the wall of the chest cavity. The accumulation of fluid may be due to cancer spread to the pleural membranes or may be caused by other benign conditions.

PneumonectomySurgery to remove all of one lung. In a partial pneumonectomy, one or more lobes of a lung are removed.

Positron emission tomography scan See PET scan.

PrognosisThe likely outcome or course of a disease; the chance of recovery or recurrence. For a patient with lung cancer, the prognosis depends, to a large extent, on the cancer’s stage and cell type.

Pulmonary function test A test used to measure how well the lungs work. It measures how much air the lungs can hold and how quickly air is moved into and out of the lungs. It also measures how much oxygen is used and how much carbon dioxide is given off during breathing. A pulmonary function test can be used to diagnose a lung disease and to see how well treatment for the disease is working. Also called lung function test and PFT.

PulmonologistA doctor who specializes in treating diseases of the lungs. Also called pulmonary specialist.

RadiationEnergy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

Radiation oncologist A physician who specializes in planning and delivering radiation therapy to treat cancer.

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Radiation therapy The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

RadiologistA doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy.

Randomized clinical trials A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient’s choice to be in a random-ized trial.

RecurTo come back or to return.

RecurrenceCancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Patients with lung cancer are always checked with various tests to detect any possible recurrence as quickly as possible.

Red blood cells A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.

RegimenA treatment plan that specifies the dosage, the schedule, and the duration of treatment. For example, a chemotherapy regimen may include multiple drugs that are given in combination over several cycles of therapy.

ResectableA resectable tumor is one that can be removed with surgery. Initial staging of lung cancer is designed to determine whether a tumor is resectable or not.

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Risk factor Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.

RTSee radiation therapy.

Satellite tumors Cancer that has spread within the lung, forming another tumor not more than 2 cm away.

Second-line therapy Treatment that is given when initial treatment (first-line therapy) doesn’t work or stops working.

Side effects A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores. Unwanted effects of treatment, such as hair loss caused by chemotherapy and fatigue caused by radiation therapy.

Social worker A professional trained to talk with people and their families about emotional or physical needs and to find them support services.

SputumMucus and other matter brought up from the lungs by coughing.

Sputum cytology The description of cells and tissues made by a pathologist based on microscopic evidence, and sometimes used to make a diagnosis of a disease.

Squamous cell carcinoma Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

SRSSee stereotactic radiosurgery.

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Stable disease Cancer that is neither decreasing nor increasing in extent or severity.

StageThe extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body. Determining the stage is essential for choosing the best treatment. The clinical stage describes the extent of disease present based on results of diagnostic tests and the physical examination. The pathological stage is determined after biopsy or surgery when the cancer cells have been looked at under a microscope.

StagingPerforming exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. The system most often used to describe the growth and spread of cancer is the TNM classification system, where T stands for tumor (size and how far it has spread to nearby organs), N stands for spread to lymph nodes, and M is for metastasis. Letters or numbers after the T, N, and M provide more details about each of these factors. These 3 categories are then grouped to come up with an overall stage numbered 0 to IV (using Roman numerals 0, I, II, III, IV). The higher the number, such as stage IV, the more serious the cancer.

StentA device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to keep the structure open.

Stereotactic radiosurgery A type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery. Stereotactic radiosurgery may be combined with whole-brain radiation therapy.

Superior sulcus The very uppermost part of the lung.

Superior vena cava The large vein in the right chest near the heart that returns the blood to the heart from the head, neck, arms, and chest. Some lung cancers can compress the superior vena cava causing symptoms.

Support group A group of people with similar disease who meet to discuss how better to cope with their disease and treatment.

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Supportive care Care given to improve the quality of life of patients who have a serious or life-threatening disease. The goal of supportive care is to prevent or treat as early as possible the symptoms of a disease, side effects caused by treatment of a disease, and psychological, social, and spiritual problems related to a disease or its treatment. Also called comfort care, palliative care, and symptom management.

Surgical margin See margin.

Surgical specimen The portion of lung that is removed at surgery which is sent to the pathologist to evaluate the location and extent of cancer.

SymptomsCough, chest pain, hoarseness, weight loss, or other problems that suggest a patient may have lung cancer, or new problems suggesting that the lung cancer has gotten worse, such as difficulty breathing, bone pain, back pain, swelling in both the face and arms.

Systemic therapy Treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body.

Targeted therapy Treatment that blocks the growth and spread of cancer by interfering with specific molecules involved in the process that makes normal cells become cancer cells and cause tumors to grow. The goal of targeted therapy is to specifically target and destroy cancer cells while causing little to no damage to normal, healthy cells. Targeted therapy may have fewer side effects than other types of cancer treatments.

TechnicianA person trained in the techniques (methods) and skills of a profession. For example, a mammogram technician is trained to perform mammograms.

ThoracentesisA procedure in which a needle is inserted between the ribs into the space next to the lungs. A sample of the fluid is removed and examined under the microscope to determine whether cancer cells are present.

Thoracic surgeon A surgeon who specializes in operating on organs inside the chest, including the heart and lungs.

ThoracoscopyExamination of the inside of the chest, using a thoracoscope. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease.

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TKISee tyrosine kinase inhibitor.

TMN staging system A system for describing the extent of cancer in a patient’s body. The staging system refers to tumor size (T), whether or not the lymph nodes are involved with tumor (N), and whether or not the cancer has metastasized (M), i.e., spread beyond the lung. TNM classification is an important part of cancer staging and is used to categorize treatment options for each grouping of T, N, and M.

TracheaThe airway that leads from the larynx (voice box) to the bronchi (large airways that lead to the lungs). Also called windpipe.

TumorAn abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Tyrosine kinase inhibitor A drug that interferes with cell communication and growth and may prevent tumor growth. Some tyrosine kinase inhibitors are used to treat cancer.

UltrasoundA procedure in which high-energy sound waves are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. Also called ultrasonography.

UndifferentiatedA term used to describe cells or tissues that do not have specialized (“mature”) structures or functions. Undifferentiated cancer cells often grow and spread quickly.

UnresectableA tumor that cannot be removed with surgery.

UpstagingIn cancer, changing the stage used to describe a patient’s cancer from a lower stage (less extensive) to a higher stage (more extensive). Upstaging is based on the results of additional staging tests. It is important to know the stage of the disease in order to plan the best treatment.

VeinA blood vessel that carries blood to the heart from tissues and organs in the body.

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VinblastineThe active ingredient in a drug used together with other drugs to treat several types of cancer, including advanced Hodgkin lymphoma and advanced testicular germinal-cell cancers. It is also being studied in the treatment of other types of cancer. Vinblastine comes from the periwinkle plant Vinca rosea Linn. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of vinca alkaloid and a type of antimitotic agent.

VinorelbineAn anticancer drug that belongs to the family of plant drugs called vinca alkaloids. Also known as Navelbine®.

Wedge resection Surgery to remove a triangle-shaped slice of tissue. It may be used to remove a tumor and a small amount of normal tissue around it.

White blood cells A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Physicians carefully monitor white blood cell counts; if they are too low, growth factors may be used to elevate the white count and lower the risk of infection.

WHOSee World Health Organization.

Whole-brain radiation therapy A type of external radiation therapy used to treat patients who have cancer in the brain. It is often used to treat patients whose cancer has spread to the brain, or who have more than one tumor or tumors that cannot be removed by surgery. Radiation is given to the whole brain over a period of many weeks. Also called WBRT and whole-brain radiotherapy.

WorkupThe testing used to evaluate a patient’s problem.

World Health Organization A part of the United Nations that deals with major health issues around the world. The WHO sets standards for disease control, health care, and medicines; conducts education and research programs; and publishes scientific papers and reports. A major goal is to improve access to health care for people in developing countries and in groups who do not get good health care. The headquarters are located in Geneva, Switzerland.

x-ray A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.

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NCCN Member InstitutionsCity of Hope Comprehensive Cancer CenterLos Angeles, California800.826.4673www.cityofhope.org

Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer CenterBoston, Massachusetts800.320.0022www.dfbwcc.org • www.massgeneral.org/cancer

Duke Comprehensive Cancer CenterDurham, North Carolina888.275.3853www.cancer.duke.edu

Fox Chase Cancer CenterPhiladelphia, Pennsylvania888.369.2427www.fccc.edu

Huntsman Cancer Institute at the University of UtahSalt Lake City, Utah877.585.0303www.huntsmancancer.org

Fred Hutchinson Cancer Research Center/Seattle Cancer Care AllianceSeattle, Washington206.288.7222 • www.seattlecca.org 206.667.5000 • www.fhcrc.org

The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland410.955.8964www.hopkinskimmelcancercenter.org

Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicago, Illinois866.587.4322www.cancer.northwestern.edu

Memorial Sloan-Kettering Cancer CenterNew York, New York800.525.2225www.mskcc.org

H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida800.456.3434 www.moffitt.org

The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research InstituteColumbus, Ohio800.293.5066www.jamesline.com

Roswell Park Cancer InstituteBuffalo, New York877.275.7724www.roswellpark.org

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineSt. Louis, Missouri800.600.3606www.siteman.wustl.edu

St. Jude Children’s Research Hospital/ University of Tennessee Cancer InstituteMemphis, Tennessee901.595.4055 • www.stjude.org 877.988.3627 • www.utcancer.org

Stanford Comprehensive Cancer CenterStanford, California877.668.7535www.cancer.stanfordhospital.com

University of Alabama at Birmingham Comprehensive Cancer CenterBirmingham, Alabama800.822.0933www.ccc.uab.edu

UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California800.888.8664http://cancer.ucsf.edu

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan800.865.1125www.mcancer.org

UNMC Eppley Cancer Center at The Nebraska Medical CenterOmaha, Nebraska800.999.5465www.unmc.edu/cancercenter

The University of Texas MD Anderson Cancer CenterHouston, Texas877.632.6789www.mdanderson.org

Vanderbilt-Ingram Cancer CenterNashville, Tennessee800.811.8480www.vicc.org

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Lung Cancer NCCN Guidelines 2010,

Documents

Transcript of Lung Cancer NCCN Guidelines 2010,