treatment Update: Lung Cancer cancerCare® connect Booklet SerieS Lung Cancer treatment Update:
Lung Cancer Update
Transcript of Lung Cancer Update
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Lung Cancer Update
David M. Jackman, MD
Senior Physician, Lowe Center for Thoracic Oncology,
Dana-Farber Cancer Institute
Medical Director of Clinical Pathways, Dana-Farber Cancer Institute
Assistant Professor, Harvard Medical School
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Titles: • Senior Physician, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute
• Medical Director of Clinical Pathways, Dana-Farber Cancer Institute
• Assistant Professor, Harvard Medical School
Education and Training:• MD: Brown Medical School
• Residency, Internal Medicine: Beth Israel Deaconess Medical Center, Boston, MA
• Fellowship, Medical Oncology: Dana-Farber/Massachusetts General Hospital, Boston, MA
Specialty: • Thoracic Oncology
• Clinical Pathways and Care Delivery
David Jackman, MD
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• I have no financial disclosures.
Disclosures
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• Epidemiology
• Clinical Presentation, Diagnosis, Staging
• Screening
• Overview of Lung Cancer Therapy
• Sample Questions
Agenda
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Epidemiology
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Practice Question 1
Which of the following statements is true about cancer?
A. Breast cancer is the most common cause of cancer death in women.
B. For former smokers, it takes ~ 10 years for the risk of lung cancer to decrease to that of a nonsmoker.
C. More than half of new lung cancers are already metastatic at the time of diagnosis.
D. Tumor grade (level of differentiation under the microscope) is a more important predictor than tumor stage (extent of disease on scans)
E. Small cell lung cancer is both more aggressive and more common than non-small cell lung cancer.
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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Lung Cancer is the leading cause of cancer death
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
Death
s p
er
year
131,880
52,98048,220 44,130
LUNG
CANCER
COLON
CANCER
PANCREATIC
CANCER
BREAST
CANCERData from Cancer statistics, 2021.
Siegel et al, Ca Cancer J Clin
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Smoking is the leading risk factor for lung cancer
Cum
ula
tive r
isk (
%)
2
4
6
8
10
12
14
5545 65 75
Continuing cigarette smokersStopped age 60Stopped age 50Stopped age 40Stopped age 30Lifelong non-smokers
Peto et al, BMJ 2000; 321 (7257): 323-9
Age
• Risk is proportional to the
amount and duration of
tobacco smoking
• Cessation lowers risk, but
it never returns to that of a
lifelong non-smoker
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Non-smokers account for 10-20% of lung cancer cases in the United States
Causes of lung cancer in non-smokersAdapted from American Cancer Society Facts & Figures 2006. Special
section Environmental Pollutants.
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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Stage is the most important prognostic factor
Stage
Goldstraw et al, JTO 2016
Stage at
Diagnosis*
15
22
55
*Stage unknown
in 8%
SEER 2000
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Impact of Lung Cancer Histology
15%
21%
34%
9%
17%
4%
Small Cell
Non-Small Cell
Squamous
Adenocarcinoma
Large
Cell
Other
NOS Small Cell Squamous Adenocarcinoma
Most Common
LocationCentral Central
Central or
Peripheral
Found in non-
smokers?Exceedingly Rare Rare Yes
Targetable
genomic
alterations
Extremely unlikely Unlikely
Possible,
especially in
nonsmokers
Classic
Paraneoplastic
Syndrome(s)
SIADH,
Cushings,
Lambert-Eaton
Hypercalcemia -
Adapted from Targeted Oncology, 11/20/17
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
Non-Small Cell
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Practice Question 1
Which of the following statements is true about cancer?
A. Breast cancer is the most common cause of cancer death in women.
B. For former smokers, it takes ~ 10 years for the risk of lung cancer to decrease to that of a nonsmoker.
C. More than half of new lung cancers are already metastatic at the time of diagnosis.
D. Tumor grade (level of differentiation under the microscope) is a more important predictor than tumor stage (extent of disease on scans)
E. Small cell lung cancer is both more aggressive and more common than non-small cell lung cancer.
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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Lung Cancer Screening
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According to current USPSTF Guidelines, low-dose CT screening for lung cancer is currently recommended for which of the following asymptomatic patients?
A. A 42 year-old nonsmoking former naval midshipmen with a history of asbestos
exposure
B. A 56 year-old non-smoker whose father had died of lung cancer at age 64.
C. A 76 year-old who had smoked 1 pack per day for 30 years (from age 16-46).
D. A 70 year-old who had smoked 1 pack per day for 30 years (from age 35-65).
E. A frail 84 year-old with Class III CHF who has continued to smoke 2 packs per day
since age 14.
Practice Question 2
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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ABCs of Lung Cancer Screening
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
BenefitAudience Calendar
• Asymptomatic adults, and
• Aged 55 to 80 years, and
• Heavy and recent
smoking history:
• > 20 pack-years, and
• Currently smoke or
quit smoking within
the past 15 years.
• Annual Low-Dose Chest
CT
• Screening should be
discontinued once a person
has not smoked for 15
years or develops a health
problem that substantially
limits life expectancy or the
ability or willingness to have
curative lung surgery.
NLST (NEJM 2011. 365: 395-409):
• 20% decrease in lung cancer
mortality
• 6.7% decrease in all cause
mortality
NELSON (de Koning et al, WCLC
2018):
• 26% decrease in lung cancer
mortality
USPSTF: Grade B
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Follow-up of Radiographic Findings
Setting Guidelines
Screening of an asymptomatic patient LUNG-RADS1
Incidental finding on a scan performed for another
reason
Fleishner Guidelines2
Radiographic study performed as part of evaluation
of a symptomatic patient
Aggressive follow-up
1. LUNG-RADS: American College of Radiology. https://www.acr.org/-/media/ACR/Files/RADS/Lung-
RADS/LungRADSAssessmentCategoriesv1-1.pdf
2. Fleishner Guidelines: MacMahon et al, Radiology 2017.
https://pubs.rsna.org/doi/10.1148/radiol.2017161659
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Screening Follow-up: LUNG-RADS
Category Definition
Risk of
Malignancy
Estimated
Population
Prevalence Recommended Follow-Up
Category 0 (incomplete)
• prior CT studies were performed, but are not available for comparison
• Part or all of lungs cannot be evaluated
N/A 1%
Comparison with prior studies
before assignment of Lung-
RADS classification
Category 1: Negative
• no lung nodules
• lung nodule(s) with specific findings favoring benign nodule(s): complete, central,
and/or popcorn calcification; calcification in concentric rings; fat-containing nodules
<1%
90%
Continue annual screening with
LDCT
Category 2: Benign appearance or behavior
• solid nodule(s)
• <6 mm at baseline
• new nodule <4 mm
• subsolid nodule(s)
• <6 mm on baseline screening
• ground glass nodule(s)
• <30 mm (Version 1.1 change previously 20 mm)
• ≥30 mm and unchanged or slowly growing (Version 1.1 change previously 20
mm)
• category 3 or 4 nodules that are unchanged for ≥3 months
< 1%
Continue annual screening with
LDCT
From 2019 LUNG-RADS from ACR
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Category DefinitionRisk of
Malignancy
Estimated
Population
Prevalance
Recommended
Follow-Up
Category 3: Probably Benign
• Solid nodule(s)
• ≥6 mm to <8 mm at baseline, OR
• new nodule 4 mm to <6 mm
• Part solid nodule(s)
• ≥6 mm total diameter with solid component <6 mm, OR
• new <6 mm total diameter
• Non-solid nodule(s)
• (GGN) ≥30 mm on baseline CT or new
1-2% 5%
6-month follow-up
with LDCT
Category 4A: Suspicious
• Solid nodule(s)
• ≥8 mm to <15 mm at baseline, OR
• growing nodule(s) <8 mm, OR
• new nodule 6 mm to <8 mm
• Part solid nodule(s)
• ≥6 mm total diameter with solid component ≥6 mm to <8 mm, OR
• With a new or growing <4 mm solid component
• Endobronchial nodule
5-15% 2%
• 3-month follow-up
with LDCT
• PET/CT may be
used if there is a
≥8 mm solid
component
Screening Follow-up: LUNG-RADS From 2019 LUNG-RADS from ACR
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Category DefinitionRisk of
Malignancy
Estimated
Population
Prevalence
Recommended Follow-Up
Category 4B, Very Suspicious
• Solid nodule(s)
• ≥ 15 mm at baseline, OR
• new or growing, and ≥8 mm
• subsolid nodule(s)
• solid component ≥8 mm, OR
• new or growing ≥4 mm solid component
>15% 2%
For 4B and 4X:
• Chest CT with or without
contrast, as appropriate
• PET-CT and/or tissue
sampling depending on
the probability of
malignancy and
comorbidities (PET-CT if
solid component ≥8 mm)
• For new large nodules that
develop on an annual
repeat screening CT, a 1
month LDCT may be
recommended to address
potentially infectious or
inflammatory conditions.
Category 4X, Very Suspicious
• category 3 or 4 nodules with additional features or imaging findings that increase
the suspicion of malignancy
• includes:
• spiculation
• ground glass nodule(s) that double in size in 1 year
• enlarged regional lymph nodes
>15% 2%
Category S: Other - Modifier may add on to category 0‐4 coding
• Clinically Significant or Potentially Clinically Significant Findings (non lung cancer)N/A 10%
• As appropriate to the
specific finding
Screening Follow-up: LUNG-RADSFrom 2019 LUNG-RADS from ACR
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According to current USPSTF Guidelines, low-dose CT screening for lung cancer is currently recommended for which of the following asymptomatic patients?
A. A 42 year-old nonsmoking former naval midshipmen with a history of asbestos
exposure
B. A 56 year-old non-smoker whose father had died of lung cancer at age 64.
C. A 76 year-old who had smoked 1 pack per day for 30 years (from age 16-46).
D. A 70 year-old who had smoked 1 pack per day for 30 years (from age 35-65).
E. A frail 84 year-old with Class III CHF who has continued to smoke 2 packs per day
since age 14.
Practice Question 2
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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Clinical Presentation,
Diagnosis,
and Staging
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A 68 year-old man with ongoing tobacco use (1ppd x 50 years) presents with worsening shortness of breath over 2 months time, along with hoarseness. CT angiogram is negative for pulmonary embolus, but it does show a large left hilar mass, along with subcarinal and left supraclavicular adenopathy and concerns for lesions in the liver and left adrenal. Serum chemistries are notable for a sodium of 124.
What is the most likely cause of hyponatremia?
Practice Question 3
A. DehydrationB. Psychogenic polydipsiaC. Syndrome of inappropriate andidiuretic hormone (SIADH)D. Laboratory error
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Clinical Presentation of Lung Cancer:
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
Lungs
Brain
Liver
Adrenals
Bones
Lymph Nodes
Generalized Symptoms
Symptoms related to local destruction, obstruction, or replacement
Paraneoplastic Syndromes
• Fatigue
• Weight loss
• Night sweats
• Cough
• Shortness of breath
• Hemoptysis
• SVC Syndrome
• Focal bone pain
• Fracture
• Cord Compression
• Focal CNS symptoms
• Seizure
• Altered Mental Status
• SIADH
• Paraneoplastic Cushings
• Hypercalcemia
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CT chest with IV contrast
Lung Cancer Staging:
Mediastinal Nodes
• Mediastinal staging:
• For potentially resectable
patients
• For patients with locally
advanced disease
• How:
• Mediastinoscopy
• Bronchoscopy/EBUS
• Lymph node dissection at
the time of surgery
Lungs
Lymph Nodes
Brain MRI with gad (preferred), or
CT head with IV contrast
PET/CT (preferred), or
Bone scanBones
Liver
Adrenals
Brain
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Lung Cancer Diagnosis:
ENDS
❑ Safe, timely, accurate diagnosis
❑ Obtain sufficient tissue for subsequent
biomarker studies, clinical trial eligibility
❑ Confirm spread (when applicable)
MEANS
❑ CT-guided biopsy
❑ Bronchoscopy/EBUS
❑ Mediastinoscopy
❑ Thoracentesis, other drainage
❑ Surgical procedure
❑ Other
Additional Information:
❑ Bone biopsies are usually inadequate for biomarker studies, trial eligibility. The
decalcification process that bone biopsies undergo denatures DNA.
❑ If there appears to be only a single site of spread, it should be biopsied to confirm or rule
out metastasis.
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Paraneoplastic SyndromesDisease Paraneoplastic Syndrome Mechanism
Squamous NSCLC Hypercalcemia PTHrP
Small cell lung cancer Syndrome of inappropriate antidiuretic
hormone (SIADH)
Anti-diuretic hormone
(aka arginine vasopressin)
Cushing syndrome Ectopic ACTH
Lambert-Eaton Ab against voltage-gated calcium
channels
Thymoma Myasthenia gravis Ab against nicotinic acetylcholine
receptors
Pure red cell aplasia Suspect IgG against erythroblasts,
epo
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A 68 year-old man with ongoing tobacco use (1ppd x 50 years) presents with worsening shortness of breath over 2 months time, along with hoarseness. CT angiogram is negative for pulmonary embolus, but it does show a large left hilar mass, along with subcarinal and left supraclavicular adenopathy and concerns for lesions in the liver and left adrenal. Serum chemistries are notable for a sodium of 124.
What is the most likely cause of hyponatremia?
Practice Question 3
A. DehydrationB. Psychogenic polydipsiaC. Syndrome of inappropriate andidiuretic hormone (SIADH)D. Laboratory error
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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Overview of Therapy
For Lung Cancer
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A 66 year-old woman currently on therapy for her stage IV non-small cell lung cancer presents to her local ED with several days of worsening shortness of breath, dry cough, and low-grade fevers. CT chest is concerning for pneumonitis. Which of the following could be an explanation for these findings?
Practice Question 4
A. Alectinib (ALK inhibitor)-related pneumonitisB. Docetaxel-related pneumonitisC. Pembrolizumab (immunotherapy)-related pneumonitisD. SARS CoV2 infectionE. All of the above
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Overview of Therapy for Lung Cancer
NSCLC
SCLC
Stage I
Stage II
Stage III
Stage IV
Limited
Extensive
Stage Stage Description Therapy
Limited to one lung +/- regional nodes,
in a feasible radiation portChemoradiotherapy
Anything beyond limited stage Palliative systemic therapy
Contralateral/distant spread and/or
malignant effusionPalliative systemic therapy
Even larger lung mass, and/or
mediastinum or supraclavicular nodesMultidisciplinary Therapy
Larger lung mass, and/or local/hilar
nodes
Resection +/- adjuvant
systemic therapy
Small lung mass, no spread Resection
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Overview of Therapy for Lung Cancer
NSCLC
SCLC
Stage I
Stage II
Stage III
Stage IV
Limited
Extensive
Stage Stage Description Therapy
Limited to one lung +/- regional nodes,
in a feasible radiation portChemoradiotherapy
Anything beyond limited stage Palliative systemic therapy
Contralateral/distant spread and/or
malignant effusionPalliative systemic therapy
Even larger lung mass, and/or
mediastinum or supraclavicular nodesMultidisciplinary Therapy
Larger lung mass, and/or local/hilar
nodes
Resection +/- adjuvant
systemic therapy
Small lung mass, no spread Resection
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
Genomically
Targeted Therapy
Chemotherapy +
Immunotherapy
Immunotherapy +
Immunotherapy
Chemotherapy
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Role of Radiation in Lung Cancer
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
The Role of Radiation in Lung CancerCurative
• Early-stage: alternative to
surgery in poor operative
candidates
• Locally advanced: with
chemotherapy as a
neoadjuvant (pre-operative)
or definitive strategy
Palliative
• To address an urgent
symptom. e.g.: cord
compression, SVC
syndrome, airway or
esophageal obstruction
• To palliate: e.g., bone
metastasis
• Brain metastases
Other
• Prophylactic cranial
irradiation (small cell)
• Consolidative chest radiation
(small cell)
• Oligo-progressive disease,
particularly for patients on
targeted tx or immunotherapy
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FDA Approvals for Lung Cancer
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
Landmark Approvals:
• 2004: The first targeted agents (gefitinib, erlotinib) are
approved for non-small cell lung cancer
• 2015: The first immunotherapy agent (nivolumab,
pembrolizumab) approved in non-small cell lung cancer
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FDA Approvals for Lung Cancer
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
Genomic alterations in lung cancer associated with an
FDA-approved targeted therapy
Mutations EGFR
BRAF V600E
KRAS G12C
MET exon 14
Fusions/Rearrangements ALK
ROS1
NTRK
RET
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Toxicities with Targeted Therapies
PresentationScreening Lung Cancer Therapy Other Thoracic TumorsEpidemiology
Gene Agent CYP3A4?1 Selected Common Side Effects2 Selected Serious Side Effects2
EGFR 1st gen:
• erlotinib
• gefitinib
2nd gen:
• afatinib
• dacomitinib
3rd gen:
• osimertinib
Y
Y
N
Y
Y
Rash, skin dryness, diarrhea Pneumonitis/Interstitial lung disease,
hepatotoxicity, nephrotoxicity, severe
rash/mucositis, severe diarrhea.
Osimertinib: Cardiotoxicity
ALK 1st gen:
• crizotinib
2nd gen
• alectinib
• brigatinib
• ceritinib
3rd gen:
• lorlatinib
Y
Y
Y
Y
Y
Fatigue, diarrhea, nausea, visual
changes.
Crizotinib: hypogonadism
Pneumonitis, hepatotoxicity
Lorlatinib: CNS / cognitive changes
ROS1 crizotinib Y Fatigue, diarrhea, nausea, visual
changes. Hypogonadism
Pneumonitis, hepatotoxicity
BRAF Dabrafenib+trametinib Y Fever, nausea. Hepatotoxicity, cardiotoxicity. Basal cell CA
NTRK entrectonib
larotrectinib
Y
Y
Hepatotoxicity, fatigue, nausea -
MET capmatinib Y Edema, nausea, nephrotoxicity Interstitial lung disease, hepatotoxicity
RET selpercatinib Y Dry mouth, diarrhea, hepatotoxicity Hepatotoxicity, hypertension
1. Collated from www.drugs.com. 2. This is not a comprehensive list of toxicities. For more information, see prescribing info for each agent.
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• Side effects can occur at any point in treatment course
• Can get immune-mediated toxicity of essentially any system
• Some severe but rare side effects include: pneumonitis,
hepatotoxicity, CNS toxicity, cardiotoxicity, SJS
• For severe toxicity: consult, hospitalization, steroids,
immunomodulators
Considerations with immunotherapy
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A 66 year-old woman currently on therapy for her stage IV non-small cell lung cancer presents to her local ED with several days of worsening shortness of breath, dry cough, and low-grade fevers. CT chest is concerning for pneumonitis. Which of the following could be an explanation for these findings?
Practice Question 4
A. Alectinib (ALK inhibitor)-related pneumonitisB. Docetaxel-related pneumonitisC. Pembrolizumab (immunotherapy)-related pneumonitisD. SARS CoV2 infectionE. All of the above
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Cancer statistics, 2020.
Siegel et al, Ca Cancer
J Clin
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• Stage is the most important predictor of outcome
• Small cell lung cancer is the most likely to be associated
with smoking and with paraneoplastic syndromes (esp
SIADH)
• Lung cancer screening: in smokers heavy (> 20 pk-yrs)
and recent (quit within the last 15 years)
• Staging: Chest CT w/ contrast, PET/CT, Brain MRI
Take Home Points, Test Prep version
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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• Staging: Brain imaging needs IV contrast
• The importance of adequate tissue for diagnosis and
testing (core > FNA, non-bone > bone)
• Many targeted therapies – metabolized via CYP3A4 –
drug interactions
• Lung Cancer Screening
Take Home Points, Clinical Practice Version
PresentationScreening Lung Cancer Therapy SummaryEpidemiology
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• Cancer statistics, 2020. Siegel et al, Ca Cancer J Clin
• www.drugs.com
• LUNG-RADS: American College of Radiology.
https://www.acr.org/-/media/ACR/Files/RADS/Lung-
RADS/LungRADSAssessmentCategoriesv1-1.pdf
• Fleishner Guidelines: MacMahon et al, Radiology 2017.
https://pubs.rsna.org/doi/10.1148/radiol.2017161659
References