LOYOL A UNIVERSITY HEAL TH SYSTEM Oncology Program · • Infrastructure work was completed on the...

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oncology Program 2013 annual report

2013 Oncology Program Annual Report • 1

Table of contents

IntroductionChairman’s message . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Membership ListOncology committee members and specialty . . . . . . . . . . . . . . . . . . . . 3

Oncology ServicesServices available . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Primary site tableStatistical breakdown of 2013 cases . . . . . . . . . . . . . . . . . . . . . . . 5

Data analysisNarrative results of 2013 cases . . . . . . . . . . . . . . . . . . . . . . . . 6

Cancer incidenceCancer incidence by sex and site comparison with national and state . . . . . . . . . . . . 8

Brain tumors study with survival comparisonA long term patient care evaluation of malignant brain tumors . . . . . . . . . . . . . 10

Pancreatic cancer study with survival comparison patient care evaluation of pancreatic cancer . . . . . . . . . . . . . . . . . . . 23

Glossary Definitions and references . . . . . . . . . . . . . . . . . . . . . . . . . 32

The Cardinal Bernardin Cancer Center is located on the east side of the campus and faces First Avenue. Parking is available in a parking lot in front of the building and valet parking is available at the entrance. A coffee bar is located just inside the building on the first floor. Named in honor of the late Archbishop of Chicago Joseph Cardinal Bernardin, the cancer center was the first free-standing facility in Illinois dedicated to cancer research, diagnosis, treatment and prevention. Loyola’s cancer center contains all outpatient cancer care along with extensive research laboratories, offices and educational space. Many of the multidisciplinary clinics within the cancer center provide a one-visit, one-team approach, providing patients with a diagnosis and treatment plan in the same day. Patients can see their physician, have lab work done, undergo chemotherapy and have cancer care-related prescriptions filled, among many other services in the building

Mission Statement

Trinity Health Mission StatementWe serve in Trinity Health, in the spirit of the Gospel, to heal body, mind and spirit to improve the health of our communities, and to steward the resources entrusted to us.

Loyola University Health System is committed to excellence in patient care and the education of health professionals . We believe that our Catholic heritage and Jesuit traditions of ethical behavior, academic distinction and scientific research lead to new knowledge and advance our healing mission in the communities we serve . We believe that thoughtful stewardship, learning and constant reflection on experience improve all we do as we strive to provide the highest-quality health care .

We believe in God’s presence in all our work . Through our care, concern, respect and cooperation, we demonstrate this belief to our patients and families, our students and each other . To fulfill our mission, we foster an environment that encourages innovations, embraces diversity, respects life and values human dignity . We are committed to going beyond the treatment of disease . We also treat the human spirit .

Brand promiseThe people of Loyola promise patients that we go beyond the illness to treat the whole person .

2 • Loyola University Health System 2013 Oncology Program Annual Report • 3

MEMBER

Constantine Godellas, MD Oncology Program Committee Chairman

Gerard Abood, MD Oncology Program Cancer Liaison Physician

Caarol Bier-Laning, MD

Davide Bova, MD

Lauren Bowling, MS, GC

Krista Curley, RHIA

Violeta Dimovic, CTR

Kathleen Fujiu, RN, BA, BSN, MBA, OCN

Megan Giblin

Maria Giron-Carrillo

Sister Fran Glowinski

Kathy Grego, RHIT, CTR

Ewa Jaraczewska

Kelli Hutchens, MD

Margaret Liotta-David, D.O.

Tess McCoo

Edward Melian, M.D.

Laura Michaelis, M.D

Stephanie Mills, RHIT

Laura Morrell

Patricia Mumby, PhD

Janet Palutsis, RN

Gayle, Payonk

Ceil Petrowsky, RN MSN CCRC

Mark Speyer, MD

Sheryl Svoboda

Peter Tortorice

SPECIALTY

Surgical Oncology

Surgical Oncology

Otolaryngology

Diagnostic Radiology

Cancer Genetic Counselor

Director, HIM, LUMC

Manager, Oncology Data Management

Nurse Manager, 6 West, Coordinator

ACS Nurse Navigator

Oncology Data Management

Associate Chaplain, Pastoral Care

Oncology Data Management, Coordinator

Manager, Orthopaedic Surgery & Rehabilitation

Pathology

Assistant Professor OB/Gyne Cancer Center

Radiation Therapy

Radiation Therapy

Hematology/Oncology, Co-Chairman

Oncology Data Management

Social Work, Cancer Center, Coordinator

Professor, Psycho-Oncology

Assistant Manager Clinic A Cancer Center

Cancer Service Line, Oncology Support Executive Director

Manager Cancer Clinical Trials Office

Palliative Care

Dietician, Cancer Center

Manager, Pharmacy Oncology

Prepared by: V. Dimovic, CTR

In June 2013, Loyola renovated the Bone Marrow Transplant Unit . The bone marrow transplant unit is part of a patient care initiative to redesign and renovate a complete Oncology Acute Care Center on the sixth floor of Loyola University Medical Center . One of the center’s four wings is devoted to bone marrow transplant patients and their families . Patients typically stay on the wing for three to four weeks . Highlights include:

• 16,605-SF multi-phase in-hospital renovation of 6th floor bone marrow transplant suite

• 20 patient rooms and multiple family spaces

• I nfrastructure work was completed on the 5th and 7th floors, penthouse and lower level that included offsetting of the main plumbing risers, offsetting main fire protection standpipes, a new fiber backbone from the basement and a new transformer and main panel for the building replacing the existing

• New custom 27,500 CFM rooftop air handling unit with fan wall technology on the roof and fan filtered HEPA diffusers in every room

• Replacement of all exterior glazing at the 6th Floor (North and East wings)

• Unique features include circadian lighting and Lutron control system which will gradually change the light in the AM/PM to simulate the Circadian Rhythm cycle to ease the bone marrow patients

In September 8, 2013, the 25th Annual BMT Celebration of Survivorship was held and money was raised to assist our patients with transplant related costs . E-learning on Safe Handling was developed and required of all registered nurses . Hospital wide training of nurses on disposal of hazardous drugs was implemented and oncology policies on chemotherapy administration, chemotherapy extravasation and safe handling were reviewed and updated .

Innovation and change brought growth to colon and rectal surgery division . The division introduced a number of initiatives and innovations that include:

• A multidisciplinary clinic to treat women with pelvic floor disorders in conjunction with Urogynecology, Urology, Gastroenterology and Physical Medicine and Rehabilitation

• A screening program using high-resolution anoscopy for patients at high risk for anal cancer

• A quadrupling of the number of colectomies performed laparoscopically – 51 percent of colon resections at LUMC are now performed using minimally invasive techniques

• Digital images of tissue vascularity to assess blood flow in the colon in the OR

• Innovative strategies to treat fecal incontinence, including sacral nerve stimulation and injectable agents

• Clinical services offered at Gottlieb, Homer Glen and Oakbrook Terrace

• A new rotation in advanced surgery, focusing on advanced colon and rectal surgery, for fourth-year medical students

• Advances within colon and rectal surgery, with presentations accepted at the Southeastern Surgical Congress, and scientific meetings of the Society of Gastrointestinal Endoscopic Surgeons, the American Society of Colon and Rectal surgeons and the American College of Surgeons .

For the 11th time in 13 years, Loyola University Medical Center has been named one of the nation’s Most Wired Hospitals and Health Systems . Hospitals are recognized based on their progress in adoption, implementation and use of information technology in infrastructure, business and administrative management, clinical quality and safety and clinical integration .

Loyola University Chicago broke ground August 16, 2013 on a $137 million medical research and education building that will support nearly 500 scientists and staff working together to improve human health . Center for Translational Research and Education is scheduled to open in April 2016 on the university’s Health Sciences Campus in Maywood . The center will include open laboratory and support space for 72 principal investigators plus space for 40 lead scientists engaged in desktop research such as public health, health services, nursing, bioinformatics, and epidemiology . A 250-seat auditorium will provide a link with the local community, serving primarily as a showcase for health-related programming .

Message from the chairman

The year 2013 brought combined improvements to the wide array of cancer services available to patients of Loyola University Medical Center, American College of Surgeons Accredited Oncology Program . It is with great pleasure to offer my congratulations to the entire cancer team from administration to all clinical and volunteer staff in this institution to providing high quality cancer care to our patients, meeting and exceeding the standards set by our Cancer Program .

This report provides an overview of the Program’s organization of services and highlights a statistical summary in a narrative, tabular and graphic form of all cancer cases diagnosed and treated at Loyola University Medical Center .

Through our commitment and determination the accomplishments of the Oncology program is wholly dependent upon the tireless efforts of a team of caring professionals, without whom we could not strive to reach our goal in providing oncology service of highest caliber .

Membership list

The Cancer Committee membership is multidisciplinary, representing physicians from the diagnostic and treatment specialties and non-physicians from administrative and supportive services . The following list of Committee members in 2013 reflects the multidisciplinary nature of the Cancer Committee:


Medical Services

All patients at the Cardinal Bernardin Cancer Center begin with a visit to one of the center’s specialty or multidisciplinary clinics . There, the patient and family meet with the cancer specialist responsible for establishing an individual treatment plan and coordinating care . Within our unique multidisciplinary setting, a patient will meet with a team of cancer experts that may include surgeons, medical oncologists, radiation oncologists, radiologists, pathologists and plastic surgeons . These specialists work together to evaluate a patient’s condition . During the same visit, patients might also meet with a nutritionist, nurse, social worker or other supportive staff .

Programs and ServicesBelow is a list of our programs and services for cancer care: LoyolaMedicine.org/Cancer

Table: 1

Art therapy

Bone marrow transplantation

Breast cancer

Breast care

Breast Oncology Center

CAN-HELP Cancer information service

Cancer Genetics Evaluation Program

Cancer risk assessment & prevention

Cancer-Pediatric Hematology & Oncology

Through our membership in the Children’s Oncology Group, we participate in clinical trials and studies for pediatric conditions such as: (Leukemia, Lymphoma, Brain Tumors, Neuroblastoma, Wilm’s Tumor, Rhabdomyosarcoma & Other Soft Tissue Sarcoma, Bone Malignancies)

Cancer Survivorship Program

Caregivers class for bone marrow transplant patients

Centers for Fitness

Chaplain services

Chemotherapy classes

Clinical research

Coleman Foundation Image Renewal Center

Gastroenterology services

Gastrointestinal Oncology Center

Gynecologic oncology services

Head & neck oncology clinic

Hematology clinic

Hematology/oncology services

Home care & hospice

Image Renewal Center

Melanoma Clinic

Neuro-Oncology Clinic

Nutrition services

Psychology support services

Radiation oncology services

Screening and early detection - cancer

Skin Cancer and Mohs Micrographic Surgery Center

Speech therapy

Surgical oncology

Thoracic & Lung Oncology Program

Urologic Oncology Clinic

Analytic: A cases first diagnosed and / or receiving first course treatment at the facility, or diagnosed at autopsy.

Non-Analytic: Any case diagnosed at another facility and receiving all first course treatment at that facility, then seen at Loyola University medical Center for subsequent treatment.

Primary site table / Year 2013

The following table summarizes the primary sites by gender for 2013 . The top five most frequent occurring cancers at Loyola University Medical Center in 2013 were: breast, lung, prostate, thyroid and colorectal .

Primary Site Male Female Analytic Non-analytic Total

All sites 1454 1533 2618 369 2987

Oral cavity 116 59 150 25 175Lip 1 1 2 0 2

Tongue 37 22 50 9 59

Oropharynx 5 2 4 3 7

Hypopharynx 2 2 3 1 4

Other 71 32 91 12 103

Digestive system 303 227 467 63 530

Esophagus 19 6 24 1 25

Stomach 35 15 42 8 50

Colon 61 49 92 18 110

Rectum 43 29 64 8 72

Anus/anal canal 2 7 7 2 9

Liver 70 30 87 13 100

Pancreas 53 49 95 7 102

Other 20 42 56 6 62

Respiratory system 150 111 226 35 261Nasal /Sinus 7 2 8 1 9

Larynx 36 11 35 12 47

Lung/bronchus 106 97 182 21 203

Other 1 1 1 1 2

Blood and Bone marrow 127 108 190 45 235

Leukemia 77 53 110 20 130

Multiple myeloma 25 32 41 16 57

Other 25 23 39 9 48

Bone 2 1 3 0 3

Connect/soft tissue 13 13 21 5 26Skin 103 64 147 20 167

Melanoma 92 58 131 19 150

Other 11 6 16 1 17

Breast 2 338 327 13 340

Female Genital 0 229 229 20 249Cervix uteri 0 31 30 1 31

Corpus uteri 0 139 132 7 139

Ovary 0 50 44 6 50

Vulva 0 18 14 4 18

Other 0 11 9 2 11

Male Genital 197 0 197 26 224Prostate 182 0 182 22 204

Testis 13 0 13 3 16

Other 2 0 2 1 3

Urinary system 182 71 211 42 253

Bladder 89 26 89 26 115

Kidney/renal 79 43 108 14 122

Other 14 2 14 2 16

Brain and CNS 63 65 110 18 128Brain (benign) 3 3 6 0 6

Brain (malignant) 16 17 30 3 33

Other 44 45 74 15 89

Endocrine 74 133 188 19 207Thyroid 53 121 162 12 174

Other 21 12 26 7 33

Lymphatic system 71 66 106 31 137Hodgkin’s Disease 9 6 13 2 15

Non-Hodgkin’s 62 60 93 29 122

Unknown primary 21 17 32 6 38

Other/Ill-defined 4 11 13 1 15

*click on bolded programs and services to view website page.

Annual Report 2011 • 7Oncology Program 20126 • Loyola University Health System

Graph 1: Incidence per yearData shows that the number of cases diagnosed and treated at Loyola University Medical Center in 2013.

3000

2500

2000

1500

1000

500

0

# of cases

# of

cas

es

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

For all analytical cases, the most frequent site is Breast 33% (327). Next in frequency is the Lung 18% (182); Prostate with 18% (182), Thyroid with 16% (162) and finally Colorectal with 15% (156) (See Graph 2)

Graph 2: Five major sites

Male

Female

ColorectalThyroidProstateLungBreast

350

300

250

200

150

100

50

02

92

324

90

0

182

114

48

# o

f C

ase

s

Breast Lung Prostate ColorectalThyroid

64

92

Data analysis Data analysis

In most of the 2013 cases (2,987), a total of 49% (1431), patients received their initial diagnosis at LUMC (Class 1); 37% (1119) of patients were diagnosed elsewhere, but came in our facility to be treated; (Class 0) 2% (68) of patients were diagnosed at our facility and all their first course of therapy was done elsewhere; (Class 0) and 12% (367) of the patients came here for treatment of recurrent disease (Class 3) (See Figure 1)

Figure 1: Class of case

Class 0

Class 1

Class 2

Class 3

37%

12% 2%

49%

Most of the 2013 cases, 54% (1,588) of the patients were seen from Cook county, followed by 19% (560) from DuPage, 8% (253) from Will, 5% (156) from Kane. Out-of-state cases accounted for 3% (96) and the remaining others accounted for 11% (332).

Figure 2: Cases by diagnosis county

Cook

DuPage

Will

Kane

Out of State

Other

11%

3%

5%

19%

8%

54 %

For new analytic cases 53% (1380) were female and 47% (1236) male. Graph 3 below shows that the diagnosis of cancer was most found in the 60 – 69 year range for males and females.

Graph 3: Age by sex

Male

Female

8 9 1011

3323

61

38

94

148

386

294

125

318

10

268

150

18

400

350

300

250

200

150

100

50

0

# o

f C

ase

s

Age of Patients

00-09 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99

245

364

For all analytic combined staged cases: (121) were stage 0; (818) Stage I; (432) Stage II; (383) Stage III; (422) Stage IV, (73) Unknown Stage and (367) accounted for non-applicable cases for staging.

Graph 4: AJCC stage by sex

0

100

200

300

400

500

600

# o

f C

ase

s

AJCC Stage

0 I II III IV UNK N/A

52

508

69

310

219213195188

174

247

4134

174193

Male

Female

Table 2: Age by sex

Age range Male Female

0-9 8 9

10-19 11 10

20-29 23 33

30-39 38 61

40-49 94 148

50-59 245 318

60-69 388 365

70-79 294 268

80-89 125 150

90+ 10 18

Total (2,548) 1236 1380


Cancer incidence by sex and site with the state and national

Table 3: Males

Table 4: Females

Site LUMC % (1,236) Year 2013

ILLINOIS % (32,713) Year 2011

NATIONAL % (854,790) Year 2013

Prostate 15 .0 25 .8 27 .9

Lung 7 .4 14 .7 13 .8

Colorectal 7 .4 10 .0 8 .6

Skin 6 .2 4 .1 5 .3

Kidney 5 .7 4 .5 4 .7

Bladder 5 .4 6 .5 6 .4

Leukemia 5 .1 3 .0 3 .3

Liver 4 .9 1 .9 2 .7

Pancreas 4 .0 2 .7 2 .7

Thyroid 3 .9 1 .4 1 .7

Site LUMC % (n=1,380) Year 2013

ILLINOIS % (n=32,596) Year 2011

NATIONAL% (n=805,500) Year – 2013

Breast 23 .5 29 .4 28 .8

Corpus Uteri 9 .6 6 .6 6 .2

Thyroid 8 .3 4 .3 5 .6

Lung 6 .5 13 .3 13 .7

Colorectal 4 .6 9 .4 8 .6

Melanoma 3 .9 3 .2 3 .9

Non-Hodgkin’s 3 .6 3 .8 4 .0

Leukemia 3 .4 2 .4 2 .6

Pancreas 3 .3 2 .7 2 .8

Ovary 3 .2 2 .6 2 .8

Comparison of Survival between Loyola University Medical Center and National Cancer Data base is shown below (Table 5) for the five major sites . Survival rate measures the percentage of patients with a specific type of cancer who are still alive after a certain period of time . In this case, time frame used from LUMC was from year 2003 through 2006 and time frame used from NCDB was also from 2003 – 2006 . Categories for our survival comparison will include the five major sites; breast, lung, prostate, thyroid and colorectal . For most cancers, the survival rate, measured as five-year survival, is best when the cancer is found in an early stage . Early diagnosis, followed by the best treatment that stage, can increase the chances for survival and can decrease post-treatment problems . Survival is usually lower when cancer is found at a later stage .

Cancer observed survival rates below indicate how many patients were still alive five years after diagnosis but are not adjusted for many factors which affect survival . The survival rates depicted in the table below illustrates for all deaths, regardless of cause . Patients may have been diagnosed somewhere else and treated here or diagnosed here and treated somewhere else .

The comparison data are from the Commission on Cancer American College of Surgeons, © 2013 NCDB Benchmark Reports .

Notice: When comparing survival rates between our cancer program and all other CoC-accredited cancer programs: if the confidence intervals of stage-specific or overall survival rates overlap after five years, then there is no statistical difference between survival rate of patients at or facility with that of other CoC-accredited cancer programs

The American Cancer Society national estimates for site and sex distribution for all races were used to compare the estimates with Loyola University Medical Center data and the State of Illinois Cancer Statistics . The numbers reported are percentages of the total cases by sex . For the male population as compared to both the state and the nation, we observed quite a high incidence of leukemia, skin (melanoma), pancreas, stomach and bladder but a lower level of prostate, lung, and lymphoma .

For the female population as compared to the state and nation, we observed quite a high incidence of Corpus Uteri, skin, pancreas and ovary, but a lower level of breast, lung and colorectal .

Table 5: Five-year survival comparison, LUMC vs NCDB

Site/AJCC Stage LUMC (%) NCDB (%)

Breast

0 99 .1 95 .6

1 93 .2 92 .2

2 87 .0 85 .4

3 70 .4 66 .7

4 19 .4 21 .1

Lung (excludes small cell Ca)

1 56 .7 46 .8

2 N/A 27 .6

3 17 .0 11 .2

4 5 .7 2 .7

Prostate

1 N/A 83 .0

2 93 .3 90 .8

3 94 .3 91 .1

4 56 .8 37 .6

Thyroid

1 100 .0 98 .1

2 N/A 95 .7

3 92 .8 92 .7

4 N/A 59 .8

Colorectal

0 87 .6 81 .5

1 80 .4 77 .8

2 67 .0 66 .1

3 59 .4 56 .0

4 16 .2 10 .1

2013 Oncology Program Annual Report • 11

Overview of primary malignant brain tumors Pathologic classification, epidemiology, molecular biology and prognostic markers 2009 – 2013

10 • Loyola University Health System Oncology Program

Gerard Abood, MD Cancer Liaison Physician, Cancer Committee Surgical Oncology

Violeta Dimovic, CTR Manager, Oncology Data Cancer Program

An estimated 69,720 new cases of primary brain tumors are expected to be diagnosed in 2013 and includes both malignant (24,620) and non-malignant (45,100) brain tumors . These estimates are based on an application of age-sex-race-specific incidence rates from the 2013 CBTRUS Statistical Report using SEER and NPCR data to project 2013 US population estimates for the respective age-sex-race groups .

There are different types of brain and spinal cord tumors . Brain and spinal cord tumors are named based on the type of cell they formed in and where the tumor first formed in the CNS . The grade of a tumor may be used to tell the difference between slow-growing and fast-growing types of the tumor . The World Health Organization (WHO) tumor grades are based on how abnormal the cancer cells look under a microscopic and how quickly the tumor is likely to grow and spread .

The brain is made up of many specialized areas that work together:

• The cortex is the outermost layer of brain cells . Thinking and voluntary movements begin in the cortex .

• The brain stem is between the spinal cord and the rest of the brain . Basic functions like breathing and sleep are controlled here .

• The basal ganglia are a cluster of structures in the center of the brain . The basal ganglia coordinate messages between multiple other brain areas .

• The cerebellum is at the base and the back of the brain . The cerebellum is responsible for coordination and balance

The brain is also divided into several lobes:

• The frontal lobes are responsible for problem solving and judgment and motor function .

• The parietal lobes manage sensation, handwriting, and body position .

• The temporal lobes are involved with memory and hearing .

• The occipital lobes contain the brain’s visual processing system .

Brain cancers are first classified by the type of brain cell and the level of maturity of the brain cell from which the cancer originated:

• Neuroblastomas arise from neuronal precursor cells .

• Neuromas arise from neurons .

• Glioblastomas arise from glial cell precursors .

• Gliomas arise from glial cells, liomas can further be segregated by the type of glial cell from which the cancer originated .

• Astrocytomas arise from astrocytes .

• Ependymomas arise from ependymal glial cells .

• Oligodendrogliomas arise from oligodendroglial cells .

Contemporary neuropathology plays a key role in the multidisciplinary management of brain tumor patients, in part due to increased supplementation of histopathological assessments by molecular diagnostic tests involving brain tumor tissue . Several molecular tests have become routine for clinical practice, and not only contribute to a refinement of tumor classification, but also aid in improved prediction of prognosis and in development of a tailored approach to therapy . Diagnosis and classification of brain tumors are sometimes grounded on some tools, the most important of which are: histology, cytology, immunohistochemistry, molecular and genetics studies, biochemistry, DNA cytofluorometry and neuroimaging .

The purpose of this study is to provide an overview of classification and grading of brain tumors, review the treatment of patients with malignant brain tumors at LUMC and compare the treatment of similar patients throughout the nation . For this reason we have chosen patients treated in our institution from 2009 through 2013 . This comparison will hopefully give us information as how our treatment can be modified to improve the quality and duration of life for our patients . This analysis addresses diagnostic evaluation, treatment modalities, prognostic factors, and survival data and compares the LUMC data with National Cancer Data Base (NCDB) benchmarks . Evaluating the individual components of the cancer experience ensures that quality care is available and provided to all cancer patients diagnosed and or treated at Loyola University Medical Center .

According to the American Cancer Society, primary brain tumors in adults are rare and constitute fewer than 2% of all malignant neoplasms . In children, however, they form the second most common type of tumor, after leukemias . Of all intracranial tumors, neuroepithelial tumors are the most common neoplasms, representing more than 60% of central nervous system (CNS)–derived lesions .

FPO


Table 2: Gender by Tumor Group

Male Female

C70 (Cerebral Meninges) 1 0

C71 (Brain) 90 68

C72 (Cranial Nerve) 3 3

C75 (Pituitary Tumors) 3 4

Total 97 75

The reported cases were predominantly in the Non-Hispanic whites accounting for 78% (135), 11% (19) for Hispanics, 8% (14) for Black and the Asian, Chinese and one Unknown race accounted for 2% (4) .

People with malignant glioma can suffer from a range of symptoms and impairments . Some symptoms may be general and others may be specific to the area of brain where the tumor is located . General symptoms included in these cases were headache, anorexia, nausea, vomiting, seizures, drowsiness, personality changes, and cognitive slowing . In general, more focal (specific) symptoms could include difficulties with hearing, speech, ambulation, dexterity, visual difficulties, and mood disturbances . These symptoms can have a profound effect on the quality of life of the patient as well as their ability to work and to care for themselves .

The physician usually will test how well a patient is able to function and carry out everyday activities by using a functional assessment scale, such as the Karnofsky Performance Scale (KPS), outlined below . A higher score indicates a better functional status . Typically, someone who is better able to walk and care for themselves has a better prognosis .

Table 1 below shows the cross-tabulation of age by topography seen at LUMC between 2008 through 2013 year .

Table 1: Age by topography

Age 00–19 20–29 30–39 40–49 50–59 60–69 70–79 80–89 Total

Frontal 3 5 4 10 9 10 2 2 45

Temp 0 2 4 4 4 11 6 2 33

Brain, NOS 2 2 4 0 4 3 1 3 19

Parietal 1 0 1 2 3 4 5 1 17

Overlapping Lesion 2 1 0 1 2 1 3 1 11

Occipital 2 0 0 1 2 2 2 1 10

Brain Stem 5 0 0 0 1 0 1 0 7

Ventricle 1 1 0 0 2 1 1 0 6

Spinal Cord 2 0 2 0 0 1 0 0 5

Cerebellum 3 0 0 1 0 0 1 0 5

Cerebrum 2 2 0 0 0 1 0 0 5

Pineal Gld 2 0 0 1 0 1 0 0 4

Piituitary gld 2 0 0 0 0 0 0 0 2

Nervous Sys 1 0 0 0 0 0 0 0 1

Parathyroid Gld 0 0 1 0 0 0 0 0 1

Cerbral Meningis 0 0 0 1 0 0 0 0 1

Other 0 0 0 0 0 0 0 0 0

Total 28 13 16 21 27 35 22 10 172

The highest incidence occurred in the 60 – 69 age groups and tumor identified to be located for all ages at the frontal lobe .

The facts and statistics here include malignant brain and central nervous system tumors, including spinal cord, pituitary and pineal gland tumors . Statistics by ICD-O-3 primary sites are grouped in the following manner for Brain, C71: the frontal lobe (C71 .1); temporal lobe (C71 .2); parietal lobe (C71 .3); and occipital lobe (C71 .4) are grouped together . Cerebrum (C71 .0), ventricle (C71 .5), cerebellum (C71 .6), and brain stem (C71 .7) are each grouped independently . For purposes of analysis, the category other brain is used to refer to ICD-O codes C71 .8-C71 .9, which are defined as overlapping regions of the brain and brain, not otherwise specified respectively as listed under C71 . The Spinal Cord, Cranial Nerves, and Other Parts of the

Central Nervous System are listed under C72 . The cranial nerve category (C72 .2-C72 .5) includes the olfactory nerve, optic nerve, acoustic nerve, and other cranial nerves . The spinal cord (C72 .0) and cauda equina (C72 .1) are grouped together . The category other central nervous system is used to refer to ICD-O codes C72 .8-C72 .9, which includes overlapping regions of the brain and central nervous system, and central nervous system, not otherwise specified in C72 . The meninges C70 include the cerebral meninges and spinal meninges (C70 .0-C70 .9) . Pituitary tumors (C75 .1-C75 .2) include tumors located in the pituitary gland and craniopharyngeal duct . Pineal tumors (C75 .3) include tumors located in the pineal gland . In this report, tumors located in the nasal cavity (C30 .0) are olfactory tumors (defined by ICD-O-3 histology codes 9522 and 9523) .


Table 3: Karnofsky Performance Status

Initial questions Follow-up questions Symptom characterization KPS Comments %

Is the patient able to carry on with his/hernormal work or activity? Does the patient

have symptoms?(pain, loss or gain of weight, reduced energy)

No symptoms 100 Normal, no complaints, noevidence of disease

Mild symptoms 90 Able to carry on normal activity, minor signs or symptoms of disease

Moderate symptoms 80 Normal activity with effort, some signs or symptoms of disease

Is the patientbedridden for morethan half a day?

Does the patientneed assistance?(grooming, food intake, dressing, other dailyactivities)

No assistance 70 Cares for self, unable to carry on normal activity or to do active work

Occasional assistance 60 Requires occasional assistance,but is able to care for most of his needs

-

Considerable assistance 50 Requires considerable assistanceand frequent medical care

-

What is thepatient’s degree ofdisability in terms of bed confinement?

Bedridden in more than 50% of the time

40 Disabled, requires specialcare and assistance

Almost completely bedridden

30 Severely disabled, hospitalization is indicated althoughdeath not imminent

-

Completely bedridden anddependent upon extensivenursing care by professionals and/or family

20 Hospitalization necessary, very sick active support treatment necessary

Completely bedridden and comatose or barely arousable

10 Moribund, fatal processes progressively rapidly

Dead 0 Dead

YES

YES

NO

NO

The KPS allows for the classification and stratification of patients whose clinical conditions are often highly complex . Along with the ECOG (Eastern Cooperative Oncology Group) (ZUBROD) Performance Scale, it is the only method for stratifying patients in a vast and mixed arena of heterogeneous diseases and disabilities .

We reviewed all glioblastoma cases to review if physicians documented the KPS scores .

A total of 85 cases were reviewed for documentation . Six cases were excluded due to patients refusing any treatment .

Patients with low KPS scores need to be evaluated prospectively to identify the extent to which different therapies will improve outcomes .

Results of documentation of score performance on 79 cases:

KPS=27 ECOG=10 No documentation=42

Methods to accurately collect and report performance scores may vary across cancer centers . In general, it appears best if the performance score is and should be documented in a systematic fashion at the time of assessment by the clinicians in way that is readily available to the data professionals that performs audit analysis . Although the KPS is very commonly used, we observed that some clinicians preferred to collect the ECOG performance scores to decide which patients are physically suitable for treatment and/or entry into clinical trials

Accurate and systematic fashion collection and reporting of the performance score is very important and should be included in the routine auditing of data . Our data showed that 42 (53%) had no documentation of performance scores . Treatment plans for brain tumors is/should be tailored to each individual patient with particular attention paid to performance status and goals of care .

The goal is to increase the use of the KPS in a standard way for quick assessment of general functioning and survival and also to use the performance status as a flag for likehood of need for services and timing therapeutic interventions . We will continue to monitor the documentation of charting and retrospectively conduct future audits to assess compliance concordance with the National Comprehensive Cancer Network guidelines .

One-hundred sixty-five (95%) of the cases were histologically confirmed and only nine (5%) cases were diagnosed by radiography . The different histolgies represented among the cases showed (70%) a favorable prognostic subtype of glioblastoma and mixed glioma .

Table 4: Histology distribution

Histology # of Cases

Carcinoma 1

Epithelioid sarcoma 1

Germinoma 2

Germ cell tumor 1

Teratocarcinoma 1

Hemangiopericytoma malignant 1

Pineoblastoma 2

Chordoma 1

Glioma malignant 17

Gliomatosis cerebri 2

Mixed glioma 16

Choroid plexus 1

Ependymoma NOS 6

Ependymoma anaplastic 6

Astrcytoma 10

Fibillary astrocytoma 6

Pilocytic astrocytoma 6

Pleomorphic xanthoastrocytoma 1

Glioblastoma 60

Giant cell glioblastoma 1

Gliosarcoma 6

Oligodendroglioma 13

Medullablastoma 2

Desmoplastic medullablastoma 1

Anaplastic medullablastoma, Large Cell 1

Neuroblastoma 3

Ganglioglioma 2

Atypical Teratoid/Rhabdoid tumor 1

Langerhans cell histocytosis 1

Total 172


Neuroradiology evaluation of patients with brain tumors have advanced remarkably . Neuroimaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI) were used as the initial evaluation . Obtaining these images is useful for preoperative planning and to avoid missing the diagnosis of a neoplastic disease (improving sensitivity) and avoid performing diagnostic surgery in non-neoplastic disease (improving specificity) . Goal of these imagings are usually to utilize the techniques to predict the type of cancer in non-invasively and treat patients without histologic confirmation to acquire 100% specificity .

When dealing with patients with a brain tumor, standard X-rays and CT scan is initially used in the diagnostic process . MRI was generally used for the cases reviewed . According to the ACR (American College of Radiology) MRI’s are more useful because it provides detailed information about the tumor type, position and size, tumor anatomy, treatment and monitoring of the disease . It is recommended that MRI scan should always be obtained both with and without contrast material .

Basically the most important goals of conventional MRI in the diagnosis of brain tumors are:

• Discover the lesion and define its nature (blood, ischemia, tumor) .

• Localize the lesion (intra- or extra-axial, above or under the tentorium) and define its limits and relations with the surrounding structures, with the use of gadolinium .

• Evaluate mass effect (compression, dislocations, cerebral herniation) .

• Evaluate the characteristics (necrosis, calcifications, surrounding edema, hemorrhage, rupture of blood-brain barrier) .

• Give indications about the most probable histological nature and grade of malignancy of the tumor .

• Define the vascularization and the relations with the closest cerebral vessels (very important in meningioma, where it is necessary to evaluate the feeding arteries, in order to consider the possibility of a preoperative endovascular embolization, and the possible infiltration of dural sinus or cerebral vessels) .

A staging system is used for most other types of cancer to describe where a tumor is located, if or where it has spread, and whether it is affecting other parts of the body . However, there is no recommended systemic staging system for adult brain tumors because most primary tumors do not usually spread beyond the central nervous system .

This classification is based on the World Health Organization (WHO) classification of central nervous system (CNS) tumors . The WHO approach incorporates and interrelates morphology, cytogenetic, molecular genetics, and immunologic markers in an attempt to construct a cellular classification that is universally applicable and prognostically valid .

The histologic grades are as follows:

WHO grade I includes lesions with low proliferative potential, a frequently discrete nature, and the possibility of cure following surgical resection alone .

WHO grade II includes lesions that are generally infiltrating and low in mitotic activity but recur more frequently than grade I malignant tumors after local therapy . Some tumor types tend to progress to higher grades of malignancy .

WHO grade III includes lesions with histologic evidence of malignancy, including nuclear atypia and increased mitotic activity . These lesions have anaplastic histology and infiltrative capacity . They are usually treated with aggressive adjuvant therapy .

WHO grade IV includes lesions that are mitotically active, necrosis-prone, and generally associated with a rapid preoperative and postoperative progression and fatal outcomes . The lesions are usually treated with aggressive adjuvant therapy .

Brain tumor grading system:

(World Health Organization grading system)

Grade I tumor

• Benign = non-cancerous

• Slow growing

• Cells look almost normal under a microscope

• Usually associated with long-term survival

• Rare in adults

Grade II tumor

• Relatively slow growing

• Sometimes spreads to nearby normal tissue and comes back (recurs)

• Cells look slightly abnormal under a microscope

• Sometimes comes back as a higher grade tumor

Grade III tumor

• Malignant = cancerous

• Actively reproduces abnormal cells

• Tumor spreads into nearby normal parts of the brain

• Cells look abnormal under a microscope

• Tends to come back, often as a higher grade tumor

Grade IV tumor

• Most malignant

• Grows fast

• Easily spreads into nearby normal parts of the brain

• Actively reproduces abnormal cells

• Cells look very abnormal under a microscope

• Tumor forms new blood vessels to maintain rapid growth

• Tumors have areas of dead cells in their center (called necrosis)


Table 5: WHO Grading of CNS Tumors (AJCC, Cancer Staging Manual, 7th Edition)

To decide on the best treatment for a brain tumor, both the type and grade must be determined . Certain factors that help physicians determine the appropriate treatment plan and determine prognosis are tumor histology which includes the type and the grade, age of patient, extent of tumor residual, tumor location, functional neurologic status, metastatic spread, and biogenetic markers . As it has for pathological diagnoses for other organ systems, immunohistochemistry has had a major impact on operative pathology of the nervous system . This technique is employed to recognize antigens on or within neoplastic cells by immunofluorescence or, more commonly, by the immunoperoxidase method, which can be used on paraffin-embedded material . S-100 is a soluble protein found within the cytoplasm and nuclei of cells of the central and peripheral nervous system . It is expressed strongly in Schwann cells and is useful in establishing this cellular origin for acoustic and spinal schwannomas . The strong S-100 staining of melanocytes is also helpful in identifying amelanotic metastatic malignant melanomas . Other applications of immunohistochemistry include the characterization of germ cell neoplasms in the pineal region, characterization of the hormones produced by pituitary adenomas, and differentiation in medulloblastomas . There is also increasing interest in the chromosomal abnormalities of human neoplasms because of the possibility that such changes are related etiologically to the neoplasms by means of certain oncogenes and tumor suppressor genes . The estimate of a neoplasm’s proliferative potential is done inferentially by study of the cytological characteristics of the cells

or more directly by determination of a mitotic index . A monoclonal antibody, MIB-1, recognizes the same antigen as Ki-67 but retains strong reactivity in paraffin sections .

These molecular diagnostic tests are performed routinely on certain glioma specimens because the results are useful either for prognostic purposes or to predict a response to chemotherapy . State–of-the-art molecular testing is performed in the evaluation of central nervous system neoplasms and includes 1p/19q loss of heterozygosity in gliomas, EGFR amplifications, p53 mutational analysis and MGMT testing for brain tumors .

These include:

1p 19q deletions — Allelic loss of chromosome 1p and 19q is a powerful predictor of chemotherapeutic response and longer progression-free and overall survival following chemotherapy in patients with oligodendroglial tumors . Those tumors with 1p and 19q loss in the setting of polysomy of chromosomes 1 and 19 have intermediate prognoses . Testing for 1p and 19q status is performed on all tumors with oligodendroglial differentiation because the results might be used to influence therapeutic decisions and enrollment in clinical trials .

MGMT methylation — O6-Methylguanine-DNA-methyltransferase (MGMT) is an enzyme that is responsible for DNA-repair following alkylating agent chemotherapy . In the course of tumor development, the MGMT gene may be silenced by methylation of its promoter, thereby preventing repair of DNA damage and increasing the potential effectiveness of chemotherapy . MGMT promoter methylation is associated

with improved survival in patients with glioblastoma and may also suggest a greater risk of pseudo progression in a patient with glioblastoma following initial chemoradiation .

IDH1/IDH2 mutations — Mutations in isocitrate dehydrogenase 1 (IDH1) and, less commonly, IDH2, are associated with significantly improved survival in patients with diffuse gliomas across a range of histologic grades, independent of other prognostic factors . Immunohistochemical staining for the most common mutant form of IDH1 (R132) can be performed on diffuse gliomas both for diagnostic purposes, to help distinguish infiltrating astrocytoma cells in a small biopsy specimen from reactive gliosis and for prognostic purposes .

Others include loss of heterozygosity (LOH): LOH on chromosome arm 10q is the most frequent gene alteration for both primary and secondary glioblastomas . The mutations in p53, a tumor suppressor gene, were among the first genetic alterations identified in astrocytic brain tumors . The p53 gene appears to be deleted or altered in approximately 25-40% of all glioblastoma multiforme, more commonly in secondary glioblastoma multiforme . The p53 immunoreactivity also appears to be associated with tumors that arise in younger patients . The EGFR gene is involved in the control of cell proliferation . Multiple genetic mutations are apparent, including both overexpression of the receptor as well as rearrangements that result in truncated isoforms . Overexpression or activation mutations in this gene are more common in primary glioblastoma .

WHO Grades of CNS Tumors I II III IV

Astrocytic tumors

Subependymal giant cell astrocytoma X

Pilocytic astrocytoma X

Pilomyxoid astrocytoma X

Diffuse astrocytoma X

Pleomorphic xanthoastrocytoma X

Anaplastic astrocytoma X

Glioblastoma X

Giant cell glioblastoma X

Gliosarcoma X

Oligondendroglial tumors

Oligodendroglioma X

Anaplastic oligodendroglioma X

Oligoastrocytic tumors

Oligoastrocytoma X

Anaplastic oligoastrocytoma X

Ependymal tumors

Subependymoma X

Myxopapillary ependymoma X

Ependymoma X

Anaplastic ependymoma X

Choroid plexus tumors

Choroid plexus papilloma X

Atypical choroid plexus papilloma X

Choroid plexus carcinoma X

Other neuroepithelial tumors

Angiocentric glioma X

Chordoid glioma of the third ventricle X

Neuronal and mixed neuronal-glial tumors

Gangliocytoma X

Ganglioglioma X

Anaplastic ganglioma X

Desmoplastic infantile astrocytoma and ganglioglioma X

Dysembryoplastic neuroepithelial tumor X

Central neurocytoma X

Extraventricular neurocytoma X

Cerebellar liponeurocytoma X

Paraganglioma of the spinal cord X

Papillary glioneuronal tumor X

Rosette-forming glioneural tumor of the fourth ventricle X

Pineal tumors

Pineocytoma X

Pineal parenchymal tumor of intermediate differentiation X X

Pineoblastoma X

Papillary tumor of the pineal region X X

Embryonal tumors

Medulloblastoma X

CNS primitive neuroectodermal tumor (PNET) X

Atypical teratoid/rhabdoid tumor X

Tumors of the cranial and paraspinal nerves

Schwannoma X

Neurofibroma X

Perineurioma X X X

Malignant peripheral nerve sheath tumor (MPNST) X X X

Meningeal tumors

Meningioma X

Atypical meningioma X

Anaplastic/malignant meningioma X

Hemangiopericytoma X

Anaplastic hemangiopericytoma X

Hemangioblastoma X

Tumors of the sellar region

Craniopharyngioma X

Granular cell tumor of the neurohypophysis X

Pituicytoma X

Spindle cell oncocytoma of the adenohypophysis X


Tumor histology and malignancy grade guide treatment decisions while taking into account clinical parameters such as age, Karnofsky performance status and extent of tumor resection, are all important prognostic factors . Identification of molecular prognostic markers will be crucial for the design of future trials . However, many markers may just reflect a different natural history and not necessarily contribute to decisions for individual patient management . Nevertheless, molecular markers may greatly improve diagnostic precision and characterize tumor entities with distinct biological behavior .

A glioblastoma multiforme before and after surgical resection demonstrates what is referred to as a “gross total resection .” Depending on the tumor histology, grade, and patient’s functional level Karnofsky Performance Status (KPS), (see Table 3) patients are usually treated after surgery, either

biopsy or resection, with external beam radiotherapy or chemotherapy . Radiation therapy typically is administered over a 6-week period with limited-field exposure (i .e ., not the whole brain) . Patients receive approximately 6000 cGy in 30 fractions (200 cGy per fraction) . Oligodendrogliomas are usually more chemosensitive than astrocytomas, and hence radiotherapy is often delayed for these tumors . Historically, oligodendrogliomas and anaplastic astrocytomas have been treated with procarbazine-lomustine-vincristine (PCV) .

Treatment for brain tumors is based on many factors, such as age, overall health, medical history, type, location, size of the tumor, whether the tumor has spread or is a recurrence and the patient’s tolerance for specific medications, procedures, or therapies .

Surgery is the standard treatment for this disease and is necessary to remove not only the tumor but also some normal tissue around it in order to minimize the chances of metastases . It is often the preferred treatment when a tumor can be removed without any unnecessary risk of neurological damage .

The standard approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation therapy (also called radiotherapy), or chemotherapy . Such treatments are used alone or, more commonly, in combination with one another .

As can be seen in Table 6, 33% LUMC patients were treated with surgery alone .

The survival rates in people with brain tumors depend on many different variables:

• Type of tumor (such as astrocytoma, oligodendroglioma, or ependymoma)

• Location and size of tumor (these factors affect whether or not the tumor can be surgically removed)

• Tumor grade

• Patient’s age

• Patient’s ability to function

• How far the tumor has spread

According to the American Cancer Society, patients with some types of tumors have relatively good survival rates . Five-year relative survival rates for patients with ependymoma and oligodendroglioma are, respectively, 86% and 82% for people ages

20–44, and 69% and 48% for patients ages 55–64 . Glioblastoma multiforme has the worst prognosis with 5-year survival rates of only 14% for people ages 20–44, and 1% for patients age 55–64 . Survival rates tend to be highest for younger patients and decrease with age .

Tables and Graphs below illustrate the comparison calculations of the observed 5-year survival rate by the Actuarial, Life Table Method (calculates the proportion surviving to each point in time that death occurs) from Loyola University Medical Center to the National Cancer Database combined data .

Table-7 LUMC (Kaplan-Meier ) survival rates (%) Cases diagnosed in 2003–2006 (147 cases identified )

Years Total 0-Year 1-Year 2-Year 3-Year 4-Year 5-Year

Overall 147 100 61 .9 44 .2 39 .3 34 .2 30 .3

The 5 year relative survival rate following diagnosis for LUMC of a primary malignant brain tumor (excluding lymphoma) is 30 .3% vs 21 .8% . On an institutional level, LUMC patients have an excellent outcome .

Table-8 NCDB (Kaplan-Meier ) survival rates (%) NCDB observed survival rates (%) for malignant brain tumorscases diagnosed in 2003–2006 (48,459 cases identified)data from 1,421 national programs (ACoS)

Years Total 0-Year 1-Year 2-Year 3-Year 4-Year 5-Year

Overall 48,459 100 50 .6 33 .4 27 .3 24 .1 21 .8

Table 6: Treatment combination for (all cases combined [LUMC])

Treatment type # of cases

Surgery 57 (33 .1%)

Surgery /Chemotherapy/ Radiation 31 (18%)

Surgery / Radiation 26 (15 .1%)

None 12 (6 .9%)

Chemotherapy/Radiation 8 (4 .6%)

Radiation 6 (3 .4%)

Surgery/Chemotherapy/Radiation/Hormone 6 (3 .4%)

Surgery/Hormone 5

Radiation/Hormone 4

Hormone 4

Chemotherapy 4

Surgery/Chemotherapy 4

Surgery/Radiation/Hormone 2

Chemotherapy/Hormone 1

Surgery/Chemotherapy/Radiation/Immunotherapy 1

Total Cases 172

Annual Report 2013• 23Oncology Program

Pancreatic Malignancies: Survival and Mortality of the Whipple Procedure 2009–2013

22 • Loyola University Health System

As data collection is improved, it will become possible for individual institutions to evaluate themselves in the context of national cross sections of nearly identified patients . In order for to perform such analysis, especially with malignant brain tumors, it will be extremely important for panels of experts to reassess data collection parameters and standardize them such that the critical factors for each disease setting are recorded .

Graph 1: LUMC vs NCDB survival rates (Year: 2003–2006)

20

40

60

80

100

NCDBLUMC

In conclusion, brain tumors come in many varieties, with varying prognoses and management options . In this review we have tried to provide an overview of the different pathology that is included under the term of brain tumors . Histologic classification and grading remains a powerful and cost-effective tool for providing prognostically meaningful diagnosis for glial neoplasms . This is an area of much research and hopefully further developments will provide improved outcomes for patients and new techniques to improve morbidity and mortality from even the most aggressive tumors . We remain optimistic that significant progress toward further understanding of the pathophysiology, the clinical behavior, and the optimal management of these tumors will continue to be made in the coming years .

Notice: When comparing survival rates between your cancer program and all other CoC-accredited cancer programs: if the confidence intervals of stage-specific or overall survival rates overlap after five years, then there is no statistical difference between survival rate of patients at your facility with that of other CoC-accredited cancer programs

Gerard Abood, MD Cancer Liaison Physician, Cancer Committee Surgical Oncology

Violeta Dimovic, CTR Manager, Oncology Data Cancer Program

Pancreatic cancer is the 10th most common cancer diagnosis among men and the 9th most common among women in the US . In 2013, an estimated 45,220 new cases of pancreatic cancer are to be diagnosed nationwide . Pancreatic cancer accounts for about 7% of all cancer deaths and ranks fourth as a cause of cancer death among both men and women in the US . In 2013, approximately 38,460 people are expected to die from pancreatic cancer nationwide .

The pancreas is an organ in the upper abdomen located beneath the stomach and adjacent to the first portion of the small intestine, called the duodenum . The pancreas is composed of glands that are responsible for a wide variety of tasks . The glandular functions of the pancreas can be divided into the following two categories:

• Exocrine: The exocrine glands secrete enzymes into ducts that eventually empty into the duodenum . These enzymes then help in the digestion of food as it moves through the intestines .

• Endocrine: The endocrine glands secrete hormones, including insulin, into the bloodstream . Insulin is carried by the blood throughout the rest of the body to assist in the process of using sugar as an energy source . Insulin

also controls the levels of sugar in the blood .

The pancreas can be divided into the following four anatomical sections:

• Head – The rightmost portion that lies adjacent to the duodenum

• Uncinate process – An extension of the head of the pancreas

• Body – The middle portion of the pancreas

• Tail – The leftmost portion of the pancreas that lies adjacent to the spleen

• FPO


Intraductal papillary mucinous neoplasia (IPMN) is a type of pancreatic cancer that is beginning to be recognized more frequently . This pancreatic cancer has a better prognosis than other types of pancreatic cancer . Intraductal papillary mucinous neoplasia is usually diagnosed endoscopically The most common type of pancreatic cancer arises from the exocrine glands and is called adenocarcinoma of the pancreas . The endocrine glands of the pancreas can give rise to a completely different type of cancer, referred to as pancreatic neuroendocrine carcinoma or islet cell tumor . These two types of cancer have different clinical courses, different diagnostic procedures, different treatment patterns and different molecular underpinnings .

Pancreatic endocrine tumors are rare cancers which account for 1% to 2% of all pancreatic malignancies with approximately 1,000 new cases per year in the US . These tumors have an indolent behavior and long-term survival is common . TNM staging of these tumors had started to be performed using the AJCC Staging 7th Edition with cases diagnosed on or after 2010 year . Classification of these tumors is based upon mitotic rate and tumor proliferative index as assessed by Ki-67 immunoreactivity . These tumors are classified by degree of differentiation, with well differentiation tumors (grade 1 and 2) generally considered low grade and poorly differentiated considered high grade, for which management may differ . Table 1 below shows the WHO classification of the pancreatic neuroendocrine tumors as should be classified according to the CAP (American College of Pathology) .

Table1: WHO classification of pancreatic neuroendocrine tumors

Classification WHO grade Features

Well-differentiated neuroendocrine tumor, grade 1

G1<2 mitoses per 10 HPF; Ki-67 labeling index ≤2%

Well-differentiated neuroendocrine tumor, grade 2G2

2 to 20 mitoses per 10 HPF; Ki-67 labeling index 3%–20%

Poorly differentiated neuroendocrine carcinoma (small cell carcinoma or large cell endocrine carcinoma), grade 3#

G3>20 mitoses per 10 HPF; Ki-67 labeling index >20%

Current treatment options, according to ASCO guidelines for pancreatic neuroendocrine tumors are limited: Surgery is the most common treatment and currently the only curative option . The doctor may take out the tumor and most or part of the pancreas . Sometimes the stomach is partially removed (gastrectomy) because of ulcers . Lymph nodes in the area may also be removed . Combination chemotherapy may provide effective palliation (treat partially, but not cure completely) as well as increased survival in selected patients . Hormone therapy uses hormones (somatostatin analogues) to relieve symptoms caused by the tumor by blocking activity of hormones . Hepatic arterial occlusion or embolization uses drugs or other agents to reduce or block the flow of blood to parts of the liver in order to specifically deliver local chemotherapy to treat metastases in the liver . With the exception of pain relief from bone metastases, radiation therapy has a limited role in this disease . Two targeted therapies are approved for the treatment of advanced pancreatic NET, and have the potential to change the treatment paradigm for the disease after years of limited therapeutic options .

359 of the cases were histologically classified as distinct types of pancreatic cancer . 69 were diagnosed by cytology, and six were diagnosed by radiography . The different histologies represented among the cases showed a favorable prognostic subtype adenocarcinoma, which accounted for about 78% (337) of all the cases and 9% (41) accounted for the neuroendocrine pancreatic tumors .

Table 2: Histology distribution by AJCC stage

0 I IA IB II IIA IIB III IV Unknown Non-applicable

TOTAL

Neoplasm malignant 2 2 4

Carcinoma in situ NOS 4 4

Carcinoma, NOS 1 2 1 4 1 9

Carcinoma anaplastic NOS 1 1

Pleomorphic carcinoma 1 1

Small cell Ca 2 1 3

Squamous cell Ca 1

Adenocarcinoma

In Situ 1 1

Adenocarcinoma, NOS 9 11 1 37 99 55 123 2 337

Neuroendocrine tumor, Grade 1 5 3 2 2 3 3 18

Neuroendocrine carcinoma 1 4 3 5 5 5 23

Adenocarcinoma w/mixed subtypes

1 1

Papillary adenocarcinoma 1 1

Clear cell adenocarcinoma 1 1

Solid pseudopapillary carcinoma 2 2

Intraductal papillary-mucinous carcinoma non-invasive

3 3

Mucinous adenocarcinoma 1 2 1 4 8

Mucin-producing adenocarcinoma 1 1 1 1 4

Poorly cohesive carcinoma, signet-ring carcinoma

1 1

Infiltating duct ca 2 1 3

Acinar cell ca 1 1

Adenosquamous Ca 1 1 2 4

Adenocarcinoma w/squamous metaplasia

1 1

Carcinoma w/neuroendocrine differentiation

1 1

Paraganglioma malignant 1 1

Overall total 8 1 19 21 1 46 114 64 148 3 9 434


A staging system is a standard way for doctors to sum up how far a cancer has spread . The main system used stage cancers of the pancreas is the American Joint Committee on Cancer (AJCC) TNM system . The TNM system is based on 3 key pieces of information:

• T describes the size of the main (primary) tumor and whether it has grown outside the pancreas and into nearby organs .

• N describes the spread to nearby (regional) lymph nodes .

• M indicates whether the cancer has metastasized (spread) to other organs of the body . (The most common sites of pancreatic cancer spread are the liver, lungs, and the peritoneum — the space around the digestive organs .)

Stage 0 (Tis, N0, M0): The tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues . It has not spread outside of the pancreas . These tumors are sometimes referred to as pancreatic carcinoma in situ or pancreatic intraepithelial neoplasia III (PanIn III) .

Stage IA (T1, N0, M0): The tumor is confined to the pancreas and is 2 cm across or smaller (T1) . It has not spread to nearby lymph nodes (N0) or distant sites (M0) .

Stage IB (T2, N0, M0): The tumor is confined to the pancreas and is larger than 2 cm across (T2) . It has not spread to nearby lymph nodes (N0) or distant sites (M0) .

Stage IIA (T3, N0, M0): The tumor is growing outside the pancreas but not into major blood vessels or nerves (T3) . It has not spread to nearby lymph nodes (N0) or distant sites (M0) .

Stage IIB (T1-3, N1, M0): The tumor is either confined to the pancreas or growing outside the pancreas but not into major blood vessels or nerves (T1-T3) . It has spread to nearby lymph nodes (N1) but not to distant sites (M0) .

Stage III (T4, Any N, M0): The tumor is growing outside the pancreas into nearby major blood vessels or nerves (T4) . It may or may not have spread to nearby lymph nodes (Any N) . It has not spread to distant sites (M0) .

Stage IV (Any T, Any N, M1): The cancer has spread to distant sites (M1) .

Extent of resection: For patients who have surgery, another important factor is the extent of the resection — whether or not all of the tumor is removed:

• R0: All visible and microscopic tumor was removed .

• R1: All visible tumor was removed, but lab tests of the removed specimen show that some small areas of cancer were probably left behind .

• R2: Some visible tumor could not be removed

Metastatic: If the cancer has spread to distant organs, it is called metastatic . These cancers can’t be removed completely . Surgery might still be done, but the goal would be to relieve symptoms, not to cure the cancer .

The stage distribution of the pancreatic cancer at LUMC was: 0 (2%); I (9%); II (37%); III (15%); IV (34%); Unknown stage or Non-Applicable for staging (2%)

Summary stage at diagnosis was: In-situ 8 (2%); Local 52 (12%); Regional 205 (47%) and Distant 165 (38%)

Table 3: AJCC stage by gender

Stage Male Female Total

0 2 6 8

I 18 23 41

II 78 83 161

III 27 37 64

IV 89 59 148

Unknown stage 2 1 3

Non-applicable for staging 6 3 9

Total 222 212 434

Electronic medical records were retrospectively reviewed for 434 patients with pancreatic malignancies . Patients diagnosed and treated elsewhere were excluded . Of the patients, 222 were male and 212 female . Nationally men are more commonly affected . Age group ranged from 19 to 90 . The highest incidence occurred in the 70-79 age group .

Table 4: Age by gender

Age range Male Female

00–19 0 1

20–29 0 0

30–39 3 1

40–49 14 11

50–59 44 43

60–69 43 57

70–79 75 68

80–89 18 28

90–99 5 3

Total 222 212

Patient initially presented with epigastric pain and often radiating to the back, jaundice, weight loss, nausea, constipation and diarrhea were other common manifestations .

The type of surgical operation for pancreatic tumors depend on the location of the tumor in the pancreas and on the type of the tumor . Aggressive surgical treatment is offered for patients with an adenocarcinoma of the pancreas since this tumor is associated with a poor outcome if not completely eradicated by surgery . For tumors located in the head of the pancreas, a Whipple procedure is indicated . For tumors in the body and tail of pancreas a radical distal pancreatectomy is performed, a procedure in which the spleen and the body and tail of the pancreas are removed . Because the Whipple procedure continues to be one of the most demanding and risky operations for surgeons and patients, the National Comprehensive Cancer Network panel recommends that it is best to have the procedure done at a hospital that performs at least 15–20 pancreas surgeries per year to ensure the best outcome


Figure 1: Pancreas

Of the 434 cases from 2009–2013 years, 97 patients (22%) underwent a Whipple resection .

1 : Head of pancreas 2 : Uncinate process of pancreas The uncinate process

is the formed prolongation of the angle of junction of the lower and left lateral borders in the head of the pancreas

3 : Pancreatic notch

4 : Body of pancreas

5 : Anterior surface of pancreas

6 : Inferior surface of pancreas

7 : Superior margin of pancreas

8 : Anterior margin of pancreas

9 : Inferior margin of pancreas

10 : Omental tuber

11 : Tail of pancreas

12 : Duodenum

Years TOTAL # 0-Year (%) 1-Year (%) 2-Year (%) 3-Year (%) 4-Year (%) 5-Year (%)

Stage 0 7 100 100 86 70 70 70

Stage I 25 100 92 80 70 70 63

Stage II 14 100 93 93 93 93 77

Stage III 25 100 88 77 77 58 58

Stage IV 110 100 81 76 75 71 64

Years TOTAL # 0-Year (%) 1-Year (%) 2-Year (%) 3-Year (%) 4-Year (%) 5-Year (%)

Stage 0 33 100 73 60 50 50 50

Stage I 200 100 91 77 72 62 54

Stage II 321 100 82 67 59 52 46

Stage III 670 100 77 63 56 49 45

Stage IV 2125 100 61 44 37 33 30

Stage IV 2125 100 61 44 37 33 30

Table 5 shows the breakdown of Whipple procedures per year .

Table 5: # of Whipple procedures per year

Year 2009 2010 2011 2012 2013

# of Cases 103 91 84 73 83

Whipple Procedures 21 22 16 17 21

Cross tabulation of topography by AJCC Stage Group is shown below in Table 6 .

Table 6: Site by AJCC stage

Stage 0 1 1A 1B 2 2A 2B 3 4 88 9 Total

Head of pancreas 4 1 10 8 0 33 99 38 73 2 1 269

Body of pancreas 1 0 1 4 1 6 3 17 34 2 0 69

Tail of pancreas 1 0 6 5 4 8 2 27 3 0 56

Other sites 1 0 0 1 0 2 0 0 2 0 0 6

Overlapping sites 0 0 1 3 0 1 4 4 7 1 1 22

Pancreas, Not otherwise specified 1 0 1 0 0 0 0 3 5 0 1 11

Islets of Langerhans 0 0 0 0 0 0 0 0 0 1 0 1

Total 8 1 19 21 1 46 114 64 148 9 3 434

88=Non-Applicable for Staging

9=Unknown Stage

• FPO


Treatment of stage I and stage II pancreatic cancer may include the following:

• Surgery

• Surgery followed by chemotherapy

• Surgery followed by chemoradiation

• A clinical trial of combination chemotherapy

• A clinical trial of chemotherapy and targeted therapy, with or without chemoradiation

• A clinical trial of chemotherapy and/or radiation therapy before surgery

Treatment of stage III pancreatic cancer may include the following:

• Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine

• Chemotherapy followed by chemoradiation

• Chemoradiation followed by chemotherapy

• Chemotherapy with or without targeted therapy

• A clinical trial of new anticancer therapies together with chemotherapy or chemoradiation

• A clinical trial of radiation therapy given during surgery or internal radiation therapy

Treatment of stage IV pancreatic cancer may include the following:

• Palliative treatments to relieve pain, such as nerve blocks, and other supportive care

• Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine

• Chemotherapy with or without targeted therapy

• Clinical trials of new anticancer agents with or without chemotherapy

Treatment options for pancreatic cancer are shown below in Table 3 .

Table 4: Treatment combination at LUMC (2009–2013)

Treatment Type # of cases

None 146

Surgery 104

Chemotherapy 102

Surgery/Chemotherapy 41

Surgery/Chemotherapy/Radiation 17

Chemotherapy/Radiation 16

Other 2

Radiation 2

Surgery/Other 1

Chemotherapy/Immunotherapy 1

Chemotherapy/Hormone 1

Immunotherapy 1

Total Cases 434

According to the national statistics, percentage rate of resection is 18% at LUMC vs 10% at NCDB

First course treatment of pancreas cancer diagnosed in 2000–2012 Loyola University Medical Center, Maywood, IIL. vs. all types hospitals in all states

All Diagnosed Cases – Data from 1578 Hospitals

# First Course Treatment My (N) Oth. (N) My (%) Oth. (%)

1 . Surgery Only 204 31709 17 .88% 9 .54%

2 . Surgery & Chemotherapy 62 13845 5 .43% 4 .17%

3 . Radiation & Chemotherapy 122 31247 10 .69% 9 .4%

4 . Chemotherapy Only 229 83598 20 .07% 25 .16%

5 . Surgery, Radiation & Chemotherapy 115 21189 10 .08% 6 .38%

6 . Other Specified Therapy 40 14606 3 .51% 4 .4%

7 . No 1st Course Treatment 369 136090 32 .34% 40 .96%

Col. TOTAL 1141 332284 100% 100%

Table 3: NCCN Options for Pancreatic Cancer

Stage Treatment Options

Stage I and Stage II pancreatic cancer

Surgery/ radical pancreatic resection including

Whipple procedure (pancreaticoduodenal resection)

Total pancreatectomy when necessary for adequate margins

Distal pancreatectomy for tumors of the body and tail of the pancreas

Postoperative therapy (chemotherapy with or without chemoradiation therapy)

Postoperative chemotherapy: Gemcitabine and capecitabine/Gemcitabine and erlotinib/Gemcitabine and erlotinib with or without 5-FU/capecitabine-based chemoradiation

Stage III pancreatic cancer Palliation Surgery

Chemoradiation therapy

Chemotherapy

Stage IV pancreatic cancer Palliative Therapy

Chemotherapy

Recurrent pancreatic cancer Palliative Therapy

Chemotherapy


The 30-day operative mortality in our 97 Whipple procedure cases was at 1% and nationally it is reported at 3 .3% .

Tables and Graphs below illustrate the comparison calculations of the observed 5-year survival rate by the Actuarial, Life Table Method (calculates the proportion surviving to each point in time that death occurs) from Loyola University Medical Center to the National combined data .

Note: Excludes 5 patients with unknown stage. Survival rate is not calculated for patients under a caseload of 50 cases or less for that particular Stage

LUMC (Kaplan-Meier ) Survival Rates (%) Cases diagnosed 2003–2006

Years # of cases 0-Year 1-Year 2-Year 3-Year 4-Year 5-Year

Stage 0 1

Stage I 24

Stage II 68 100 64 .7 33 .8 21 .7 21 .7 21 .7

Stage III 60 100 30 .0 6 .7 1 .7 1 .7 1 .7

Stage IV 100 100 16 .4 9 .2 9 .2 5 .8 4 .3

NCDB Observed Survival Rates (%)Cases diagnosed 2003–2006

Years # of cases 0-Year 1-Year 2-Year 3-Year 4-Year 5-Year

Stage 0 430 100 77 .2 72 .3 69 .5 64 .7 63 .0

Stage I 5,653 100 49 .9 32 .9 26 .0 22 .3 20 .0

Stage II 15,293 100 50 .3 25 .8 16 .5 12 .2 10 .0

Stage III 9,550 100 32 .9 10 .2 4 .9 3 .1 2 .5

Stage IV 36,019 100 13 .3 4 .8 2 .7 2 .0 1 .8

Adenocarcinoma of the pancreas remains a disease with generally dismal prognosis . Potentially curable lesions are typically confined to the head of the pancreas and present early with obstructive jaundice . Aggressive evaluation with appropriate staging should be performed . Surgical management with either resection for cure by pancreaticoduodenectomy or operative palliation should be performed by surgeons experienced in the management of the disease to minimize morbidity and mortality . Lymph node counts, according to NCCN guidelines, have recommended the minimum of 11–17 be examined for purposes of providing optimal staging and serving as an indicator . The other recommendation is the specimen orientation . Various margins need to be identified and reported by uniform nomenclature . Margins defined include the SMA; retroperitoneal/uncinated margin, posterior, PV groove, proximal and distal PV margins, pancreatic neck , transection, and the bile duct margin . Following resection,

postoperative adjuvant radiation and chemotherapy should be offered to most patients for improved long-term survival . Palliative efforts may also be directed to the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer . Optimal palliation of symptoms to maximize remaining quality of life is of primary importance to patients and their families .

Loyola University Medical Center’s expertise high volume directly translates into a safer procedure and longer survival . A clinical pathway is in place to ensure that patients receive best practice care from the moment they enter the hospital until discharge . The interdisciplinary team caring for patients with pancreatic cancer meet regularly to discuss, review and update a plan of care . Each member plays an important role and the complexity of this cancer requires all members working together to meet the patient’s needs . Interdisciplinary collaboration is the only effective way to facilitate positive patient outcomes after discharge for the patient living with this disease .

Expanded data elements should be implemented to include all information vital to this specific site and should be compiled and monitored for capturing future key outcomes in this complex and unique patient population . This includes re-admissions related to operative complications, disease progression, recurrences, pain management plans, psychosocial interventions, rehabilitation and ongoing nutritional assessments . Resources need to be identified, implemented, and evaluated to ensure positive outcomes . This will allow analysis to be conducted and interventions implemented . Close monitoring and attention to the clinical signs and symptoms if they arise, will surely assist the clinician to optimize the patient’s status and help prevent devastating complications . These are among the few challenges that exist in the area of quality assurance to develop more effective methods for defining and evaluating and ensuring the best quality of care for our patients .


Glossary of Terms:

Accession The addition of new cancer cases to the Oncology Registry . Each patient is assigned a separate and permanent number .

ACOS American College of Surgeons

ACS American Cancer Society

Class of Case The class of case divides cases recorded in the database of the facility into categories of analytic and non-analytic . Analytic data includes cases diagnosed at the accessioning facility and/or administration of any of the first course of treatment after the *registry’s reference date . Non-analytic cases are first diagnosed and receive all of first course of therapy at another institution, or are diagnosed at autopsy or by death certificate only . Non-analytic cases are not usually included in routine treatment or survival statistics . Based on category, the cancer program selects cases to be used by their facility or to be reported to the central registry, as well as the National Cancer Data Base (NCDB) .

Analytic: A case first diagnosed and/or receiving first course treatment at that facility, or diagnosed at autopsy .

Non-analytic: Any case diagnosed at another facility and receiving all of first course treatment at that facility, then seen at Loyola University Medical Center for subsequent treatment .

Class 0 Diagnosis at accessioning facility and the entire first course of treatment was performed elsewhere or the decision not to treat was made at another facility . > Patients who elect to be treated elsewhere . > Patients who are referred elsewhere for treatment for any reason . For example, lack of special equipment; proximity

of a patient’s residence; financial, social or rehabilitative considerations

Class 1 Diagnosis at the accessioning facility, and all or part of the first course of treatment was performed at the accessioning facility .

Patients diagnosed at the accessioning facility whose treatment plan is either not to treat or watchful waiting .

Patients diagnosed at the accessioning facility who refuse treatment .

Patients diagnosed at the accessioning facility who are not treatable or who were given palliative care only due to age, advanced disease, or other medical conditions .

Patients diagnosed at the accessioning facility for whom it is unknown whether treatment was recommended or administered .

Patients diagnosed at the accessioning facility for whom treatment was recommended, but it is unknown whether it was administered .

Patients diagnosed at a staff physician’s office who receive their first course of treatment at the accessioning facility . “Staff physician” refers to any medical staff with admitting privileges at the accessioning facility .

Patients diagnosed at the accessioning facility who received all or part of their first course of treatment in a staff physician’s office

Class 2 Diagnosis elsewhere, and all or part of the first course of treatment was performed at the accessioning facility .

Patient provided palliative care in lieu of first course treatment, or as part of the first course of treatment, at the accessioning facility .

Class 3 Diagnosis and all of first course treatment done elsewhere .

Patient treated or managed at the accessioning facility, but first course of treatment information is unknown .

Patient for whom the accessioning facility developed a treatment plan or provided “second opinion” services, but the diagnosis and treatment was provided elsewhere .

References

Illinois Cancer Facts and Figures American Cancer Society, Incidence 2013

AJCC Manual for Staging Sixth and Seventh Editions

National Cancer Data Base American College of Surgeons, Commission on Cancer

Electronic Registry Systems Cancer Data Management Database Systems 2013

College of American Pathologists CAP Cancer Protocols, www.cap.org

NCCN Guidelines in Oncology-v .2 .2014 National Comprehensive Cancer Network, 2014

NCDB The National Cancer Database

National Cancer Facts and Figures, ACS American Cancer Society, Inc ., Surveillance Research, CDC, 2013

Wikipedia Wikipedia, Free Encyclopedia

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