Background

Question 1

What are the estimated annual # of new lung cancer cases diagnosed in the United States and the # of deaths from lung cancers?

Answer 1

In 2017, the American Cancer Society estimates there will be 222,500 new cases of lung cancer and 155,870 deaths. This accounts for more deaths than all colon, breast, and prostate cancers combined, although it is the 2nd most common cancer (prostate cancer is more common in men, while breast cancer is more common in women).

Question 2

What is the lifetime risk of developing lung cancer—in men and women? Is there a difference by race?

Answer 2

The risk of a man developing lung cancer is currently 1 in 14, and the risk of a woman developing lung cancer is currently 1 in 17; however, the rate in men has decreased more rapidly than the rate in women, most likely in response to later adoption of smoking. Black men have a 20% higher incidence of lung cancer than white men, while black women have a 10% lower incidence than white women.

Question 3

Overall, what is the 5-yr survival rate for lung cancer pts by stage?

Answer 3

The overall 5-yr survival rate for NSCLC is: stage IA 49%, stage IB 45%, stage IIA 30%, stage IIB 31%, stage IIIA 14%, stage IIIB 5%.

Question 4

How many lobes are there in the lung? How many segments are there per lobe?

Answer 4

There are 5 lobes in the lung—3 on the right and 2 on the left: RUL, RML, RLL, LUL, and LLL. Lingula is the anatomic equivalent of LML and is part of the LUL. There are 5 segments per lobe, except for the RUL and RML, which are divided in 3 and 2 segments, respectively, supplied by tertiary bronchi.

Question 5

Name the 9 N2 nodal stations.

Answer 5

N2 nodal stations:

Station 1: highest mediastinal

Station 2: upper paratracheal

Station 3: prevascular (3A) and retrotracheal/prevertebral (3P)

Station 4: lower paratracheal

Station 5: subaortic (AP window)

Station 6: P-A

Station 7: subcarinal

Station 8: paraesophageal

Station 9: pulmonary ligament

Question 6

Where are the intrapulmonary and hilar nodes located?

Answer 6

Intrapulmonary nodes are nodes along the secondary bronchi, whereas hilar nodes are those along the main stem bronchi. These are all considered N1 nodes.

Question 7

Name the 5 N1 nodal stations.

Answer 7

N1 nodal stations (Note: N1 nodes are all double digits):

Station 10: hilar

Station 11: interlobar

Station 12: lobar

Station 13: segmental

Station 14: subsegmental

Question 8

What are the 3 histologic subtypes of NSCLC in decreasing order of frequency?

Answer 8

Histologic subtypes of NSCLC are: adenocarcinoma (50%) > SCC (35%) > large cell (15%)

Question 9

In addition to tobacco smoke, what are 3 other environmental exposure risk factors for developing lung cancers?

Answer 9

Environmental exposure risk factors for lung cancer:

1. Radon
2. Asbestos (Note: Smoking and asbestos exposures are synergistic in early reports, but more recent studies suggest less than a multiplicative effect.)
3. Occupational exposure (arsenic, bis-chloromethyl ether, hexavalent chromium, mustard gas, nickel, polycyclic aromatic hydrocarbon)

Question 10

What is the estimated RR for lung cancer in heavy smokers vs. nonsmokers?

Answer 10

Heavy smokers have a 20-fold excess of lung cancer (ACS cohort study). There is also a 2%–3% per yr risk of tobacco-induced 2nd primary cancer.

Question 11

What is the risk of lung cancer in former smokers compared to current smokers?

Answer 11

The risk of developing lung cancer in former smokers is around half (9 times vs. 20 times) that of current smokers. (ACS cohort study)

Question 12

What is the risk of lung cancer from passive smoke exposure?

Answer 12

There is a RR of 1.24 for developing lung cancer from passive smoke exposure. (NCCN 2018)

Question 13

Appx what % of smokers develop lung cancer?

Answer 13

<20% of smokers actually develop lung cancer (in the Carotene and Retinol Efficacy Trial, 10-yr cancer risk was 1%–15%).

Question 14

What histology subtype of NSCLC is least associated with smoking?

Answer 14

Adenocarcinoma is the histologic subtype that is least associated with smoking.

Question 15

Name 3 histologic variants of adenocarcinoma of the lung.

Answer 15

Adenocarcinoma in situ (previously bronchoalveolar), acinar, and papillary

Question 16

Discuss the natural Hx and Tx response of adenocarcinoma in situ (formerly bronchoalveolar) carcinoma.

Answer 16

Adenocarcinoma in situ is typically not associated with smoking. It can present as a solitary nodule or multifocally. The pneumonitic form may spread along alveoli without basement membrane invasion. These tumors may have a good response to TKIs.

Question 17

Name 2 variants of large cell cancer of the lung.

Answer 17

Giant cell and clear cell

Question 18

What is the most common stage at initial presentation?

Answer 18

The most common stage of presentation for lung cancer is stage IV (30%).

Question 19

What are the most common sites of DMs for lung cancer?

Answer 19

Bone, adrenals, and brain

Question 20

What are the paraneoplastic syndromes associated with lung cancers?

Answer 20

Hypercalcemia of malignancy d/t PTHrP, SIADH → ↓ Na, Cushing (d/t ↑ ACTH), Lambert–Eaton syndrome, other neurologic disorders, hypercoagulability (adenocarcinoma), gynecomastia (large cell), carcinoid (including vasoactive intestinal peptide → diarrhea), and hypertrophic osteoarthropathy (adenocarcinoma).

Question 21

What is the cause of Lambert–Eaton syndrome? Clinically, how can Lambert–Eaton is distinguished from myasthenia gravis?

Answer 21

Lambert–Eaton syndrome is caused by circulating autoantibodies against presynaptic P/Q calcium channel. Lambert–Eaton strength improves with serial effort but not myasthenia gravis.

Question 22

Which histologic subtypes of lung cancer are associated with peripheral and central locations?

Answer 22

Peripheral: adenocarcinoma, large cell

Central: SCC

Question 23

With which histologic subtypes of lung cancer is Thyroid Transcription Factor-1 (TTF-1) staining associated?

Answer 23

Adenocarcinoma, nonmucinous bronchioalveolar carcinoma (adenocarcinoma in situ), and neuroendocrine tumors (i.e., small cell lung cancer, carcinoid). TTF-1 is rare in SCC. A thyroid cancer primary must be excluded.

Question 24

In NSCLC, what is the role of CXR or CT screening for high-risk pts?

Answer 24

CXR is NOT recommended for screening. The USPSTF recommends annual screening with LDCT in people b/t the ages of 55 and 80 with a greater than 30 pack-yr smoking Hx in current smokers or former smokers who quit <15 yrs ago.

Question 25

What RCT have reported on low-dose CT screening for lung cancer among high-risk groups?

Answer 25

The National Lung Cancer Screening Trial (NLST, N Engl J Med 2011) was a prospective, RCT of lung ca screening comparing LDCT vs. annual CXR for 3 yrs in pts at high risk for lung cancer. Results suggested that LDCT decreased the RR of lung cancer death by 20%. To prevent 1 death from lung cancer, 320 high-risk individuals needed to be screened with LDCT.

Question 26

What factors define the high-risk group for lung cancer according to the NCCN guidelines?

Answer 26

Per NCCN 2018: Age 55–74 yrs and ≥30 pack-yr smoking Hx and smoking cessation <15 yrs (category 1) OR age ≥50 and ≥20 pack-yr Hx of smoking and additional risk factors that increase the risk of lung cancer to ≥1.3% using the Tammem↑gi lung cancer risk calculator (Tammem↑gi MC et al., PLOS Med 2014). Additional risk factors used in the risk calculation include Hx of COPD/emphysema/bronchitis, cancer Hx, family Hx of lung cancer, and ethnicity. Exposure to 2nd-hand smoking is not an independent risk factor.

Question 27

What is lead-time bias and how could it affect the results of a screening trial?

Answer 27

The lead time in Dx is the length of time b/t detecting the cancer from screening and when the Dx would have otherwise have occurred (i.e., through Sx or imaging studies). This could lead to an apparent increase in survival.

Question 28

What is length-time bias and how could it affect the results of a screening trial?

Answer 28

Length-time bias occurs when a screening test detects cancers that take longer to become symptomatic (i.e., d/t the detection of slower-growing or indolent cancers). This too could lead to an apparent increase in survival.

Question 29

What is the single most clinically significant acquired genetic abnormality in NSCLC?

Answer 29

EGFR mutation in exon 19 (45% of EGFR mutants, an in-frame deletion of 4 amino acid, LREA [leucine, arginine, glutamate, alanine]) and exon 21 (40%, L858R point mutation); results in a constitutively active receptor. Others include exon 21 (L861Q) and exon 18 (G719X).

Question 30

Among pts with NSCLC, in what particular groups are the EGFR mutations common, and for what do these mutations predict?

Answer 30

In the overall lung cancer population, EGFR mutations are seen in only ∼10%, but this occurs at high rates (30%–70%) in nonsmokers, adenocarcinomas, and Asians. These mutations predict for a high response rate of >80% to TKIs; gefitinib, erlotinib, afatinib, and most recently, osimertinib based on the phase 3 FLAURA trial compared to erlotinib or gefitinib. (Ramalingam SS, ESMO 2017)

Question 31

Is EGFR overexpression more common in SCC or adenocarcinoma?

Answer 31

EGFR may be overexpressed in 80%–90% of SCCs vs. 30% of adenocarcinomas.

Question 32

What are some common mechanisms associated with TKI resistance?

Answer 32

T790M is the point mutation in the exon 20 of the EGFR gene that occurs in 60% of primary TKI resistance. Most pts develop T790M mutation after about 9–13 mos of therapy with oral TKIs (erlotinib, gefitinib, or afatinib). Other resistance mechanisms include KRAS mutation, ALK or ROS1 gene rearrangements, exon 20 insertion mutations, small cell transformation, and epithelial–mesenchymal transition phenotype.