lung cancer

Question 1

etiology and patho

Answer 1

acquire molecular lesions (tobacco smoke, environmental respiratory carcinogens, inherited genetic risk factors)–> inhibition of tumor suppressor genes ,production of autocrine growth factors, immune system evasion, activation of proto-oncogenes –> malignant transformation

Question 2

common metastatic sites for NCLC and SCLC

Answer 2

contralateral lung
lymp nodes
liver
adrenal glands
bone
CNS

Question 2

clinical presentation

Answer 2

pulmonary symptoms: cough, dyspnea, chest pain or discomfort, with or without hemoptysis
extra-pulmonary symptoms: fatigue, weight loss, anorexia
SVC syndrome- tumor blocks blood flow–> swelling in face + neck
Paraneoplastic syndromes- hypercalcemia and SIADH (most common in SCLC)

Question 2

SCLC

Answer 2

faster growing, worse prognosis, sensitive to chemo and radiation

Question 3

risk factors

Answer 3

smoking
secondhand smoke
asbestos exposure
metal exposure
radiation
air pollution

Question 4

pack years

Answer 4

pack years= years of smoking * number of packs/day smoked

Question 5

screening (who)

Answer 5

adults age 50-80 yrs
current or former smoker who quit within the last 15 years AND
20 pack-year smoking history or longer

Question 6

screening (what)

Answer 6

yearly low dose CT
advantages:
20% lower risk of dying from lung cancer
7% overall mortality decrease
disadvantages:
false positives, unnecessary stress/biopsies
will not find all lung cancer
cost
radiation exposure

Question 7

Diagnosis

Answer 7

Step 1: radiologic evaluation
-computed tomography (CT) scan of chest and upper abdomen
Step 2: Lung tissue biopsy
-confirms presence of active malignancy
-determines specific tumor type
-provides sample for molecular analysis (PD-L1 expression, genetic mutations)

Question 8

SCLC limited stage

Answer 8

spread: confined to one lung
lymph node involvement: same side of chest

Question 9

SCLC extensive stage

Answer 9

spread: involves both lungs
lymph node involvement: both sides of chest
extrapulmonary metastases

Question 10

NSCLC treatment goals

Answer 10

Stage I-III: cure
stage IV: prolong survival

Question 11

SCLC treatment goals

Answer 11

limited stage: cure
extensive stage: prolongation of survival

Question 12

NSCLC stage 1

Answer 12

surgical resection
unresectable- RT alone

Question 13

NSCLC stage 2

Answer 13

surgical resection +/- neoadjuvant therapy, adjuvant therapy

unresectable- concurrent ChemoRT

Question 14

NSCLC stage 3

Answer 14

surgical resection, neoadjuvant therapy, adjuvant therapy. +/- RT

unresectable- concurrent ChemoRT, durvalumab maintenance

Question 15

perioperative therapy

Answer 15

treatment before, after or both surgical intervention

Question 16

neoadjuvant regimens

Answer 16

nivolumab + platinum-based: chemotherapy for 3 cycles
pembrolizumab + cisplatin-based chemotherapy for 4 cycles - continue pembrolizumab adjuvant therapy
platinum based chemotherapy for 4 cycles (if not a candidate for immune checkpoint inhibitor)

Question 17

adjuvant regimens

Answer 17

osimertinib daily for up to 3 years- must be EGFR +
atezolizumab for up to 1 year
pembrolizumab for up to 1 year
platinum based chemo for 4 cycles (if not candidate for immune checkpoint inhibitor)

Question 18

calvert equation

Answer 18

total dose= target AUC x (CrCl +25)
*CrCl used should not exceed 125 ml/min

Question 19

taxanes- paclitaxel, docetaxel

Answer 19

MOA: inhibits mitosis through disruption of microtubule depolymerization
PK: CYP3A4 substrate and CYP2C8 (paclitaxel only)
ADEs: myelosuppression, alopecia, peripheral neuropathy, hypersensitivity reaction (solvent related)- pre med w dexamethasone, famotidine, diphenhydramine, peripheral edema (docetaxel)- pre med with dexamethasone day before, of and after infusion

Question 20

pemetrexed

Answer 20

*non squamous histology only
MOA: inhibits dihydrofolate reductase and thymidylate synthase, thereby depleting DNA building blocks
PK: primarily renal elimination
ADEs: myelosuppression, erythematous/pruritic skin rash
-folic acid and vitamin B12 supplement proph
-dexamethasone day before, or and after for skin rash

Question 21

advanced NSCLC targetable genetic mutation

Answer 21

Mutation in EGFR, ALK, ROSI, BRAF, NTRK, RET, MET
-kinase inhibitor targeted to mutation

Question 22

advanced NSCLC PD-LI positive: >1%

Answer 22

PD-I/PD-LI +/- chemotherapy

Question 23

advanced NSCLC PD-L1 <1%

Answer 23

PD-I/PD-LI inhibitor + chemotherapy

Question 24

EGFR inhibitors

Answer 24

most prevalent in adenocarcinomas and nonsmokers 1st gen: erlotinib, gefitinib, afatinib 2nd gen: dacomitinib 2nd gen>>1st 3rd gen: osimertinib (first line) significantly improved PFD and OS improved CNS activity compared to other EGFR targeting agents better tolerability

Question 25

EGFR inhibitor rash management

Answer 25

prevention -SPF 25 -gentle skin care: loose fitting clothing, pH neutral baths/bath oil, avoidance of hot showers, avoidance of OTC acne products, hydrophilic creams treatment -topical or systemic steroids -topical or systemic antibiotics

Question 26

ALK inhibitors

Answer 26

superior to chemo 1st gen: crizotinib, ceritinib 2nd: alectinib, brigatinib 3rd: lorlatinib 2nd and 3rd preferred alectinib improvement in overall survival lorlatinib improved potency + penetration of the BBB

Question 27

KRAS inhibitor

Answer 27

more commonly associated with cigarette smoking confers poor disease prognosis indicated for advanced or metastatic NSCLC and KRAS G12C mutation after receipt of one prior therapy *sotorasib- avoid coadministration with PPIs and H2RAs *adagrasib- pH independent absorption

Question 28

immunotherapy single agent

Answer 28

pembrolizumab, atezolizumab, cemiplimab

Question 29

immunotherapy + chemo (squamous)

Answer 29

carboplatin + paclitaxel (or albumin bound paclitaxel) + pembrolizumab cisplatin or carboplatin + placlitaxel + cemiplimab

Question 30

immunotherapy + chemo (non-squamous)

Answer 30

cisplatin or carboplatin + pemetrexed + pembrolizumab cisplatin or carboplatin + pemetrexed + cemiplimab

Question 31

NSCLC 2nd line no previous checkpoint inhibitors

Answer 31

pembrolizumab nivolumab atezolizumab

Question 32

NSCLC 2nd line previous checkpoint inhibitor

Answer 32

docetaxel + ramucirumab (preferred over single agent) docetaxel gemcitabine albumin-bound paclitaxel pemetrexed (nonsquamous)

Question 33

VEGF inhibitors

Answer 33

NSCLC specific agents: bevacizumab, ramucirumab avoid in pts with squamous histology (bev), recent hemoptysis, on therapeutic anticoagulation for new onset VTE, recent surgical procedure (hold 28 days)

Question 34

SCLC

Answer 34

treatment of choice is chemotherapy +/- radiation disease recurrence usually occurs within 6-8 months after complete response

Question 35

1st line SCLC limited stage treatment

Answer 35

carboplatin (or cisplatin)+ etoposide + concurrent RT

Question 36

1st line SCLC extensive stage treatment

Answer 36

carboplatin + etoposide + atezolizumab ( extensive-stage only) carboplatin + etoposide + durvalumab (extensive-stage only) cisplatin + etoposide + durvalumab (extensive stage only)

Question 37

2nd line SCLC treatment

Answer 37

topotecan (oral or IV) lurbinectedin clinical trials

Question 38

etoposide

Answer 38

MOA: topoisomerase II inhibitor--> leads to double stranded DNA breaks AE; myelosuppression, N/V, stomatitis, alopecia

Question 39

topotecan

Answer 39

MOA: topoisomerase I inhibitor--> leads to single stranded DNA breaks reduce dose by 50% if CrCl 20-39 mL/min and avoid if CrCl < 20 mL/min AE; myelosuppression (neutropenia), diarrhea, nausea, vomiting fatigue, alopecia

Question 40

lurbinectedin

Answer 40

MOA: alkylates DNA residues that ultimately result in DNA damage and cell death PK: substrate of CYP3A4 AE: fatigue, hepatic enzyme elevations, extravasation, nausea, myelosuppression, increase in SCr, musculoskeletal pain pretreatment with dexamethasone ( decreased hepatic enzyme elevations) and 5-HT3 antagonist for antiemetic purposes