Lung Cancer Review: Epidemiology, Pathology, Staging, Diagnosis, and Treatment (English Flashcards)

A curated set of flashcards covering the major topics from the lecture notes on lung cancer, including epidemiology, histology, staging, diagnostics, and treatment (surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy) for NSCLC and SCLC.

What percentage of bronchopulmonary cancer (CBP) is non-small cell lung cancer (NSCLC)?

Approximately 85% of CBP are NSCLC.

What percentage of CBP is small cell lung cancer (SCLC)?

About 15% of CBP are SCLC.

Among NSCLC, what are the two most frequent histological subtypes and their approximate proportions?

Adenocarcinoma ~50–60%; Squamous cell carcinoma ~20–25%.

What is the approximate proportion of neuroendocrine lung tumors and what subset do they include?

Neuroendocrine lung tumors account for about 20% of CBP; around 14% are small cell lung carcinoma (SCLC).

Which mutations are common in NSCLC and SCLC respectively: p53, KRAS, ALK, ROS1?

p53 mutation occurs in about 50% of NSCLC and nearly all SCLC. KRAS most common in NSCLC (especially adenocarcinoma). ALK mutations are common in never/scant smokers (often adenocarcinoma). ROS1 rearrangements are associated with non-squamous NSCLC.

What is the five-year survival for CBP overall (NSCLC+SCLC) and for NSCLC specifically?

Overall CBP 5-year survival ~19%; NSCLC 5-year survival ~25%.

What is the average age at diagnosis for SCLC?

Approximately 70 years.

What proportion of CBP is linked to cigarette smoking, and how much greater is the risk for smokers compared with never-smokers?

Smoking accounts for about 85–90% of CBP; smokers have roughly a 30-fold higher risk than never-smokers.

What is the impact of passive smoking on CBP risk?

Passive smoking doubles the risk of CBP.

Name some carcinogens associated with tobacco smoking that contribute to CBP.

Nitrosamines, benzo[a]pyrene diol epoxide, polycyclic aromatic hydrocarbons.

What is the role of radon exposure in CBP?

Radon is associated with up to about 6% of CBP cases.

What is the impact of quitting smoking on CBP risk for those with a history of smoking?

Risk declines after quitting; for some with ≤20 pack-years, risk approaches that of never-smokers after about 15 years of abstinence.

What is the current stance on vitamin A and beta-carotene for lung cancer prevention?

Informing risk; supplements with vitamin A and beta-carotene have not demonstrated benefits.

Is low-dose CT screening effective for reducing CBP mortality, and what are the high-risk screening criteria?

Low-dose CT screening appears to improve 5-year survival in high-risk individuals; high-risk criteria: age 55–74, ≥30 pack-years, current smoker or quit within ≤15 years, good health.

Why is SCLC screening generally not feasible in at-risk populations?

Screening for SCLC is not feasible because the disease is aggressive and can develop between annual scans.

Where do SCLC tumors tend to arise and how often are they central vs peripheral?

SCLC are central/hilar in about 95% of cases, more often central than peripheral.

What is the typical metastatic pattern at presentation for SCLC?

Approximately 66% present with M1 disease, commonly involving the contralateral lung, liver, brain, bone, bone marrow, and pleura.

What are common paraneoplastic syndromes associated with SCLC?

Lambert-Eaton syndrome, encephalomyelitis, sensory neuropathy, SIADH, ectopic ACTH/Cushing syndrome, hypertrophic osteoarthropathy, anemia of chronic disease, thromboembolism (Trousseau), etc.

What is the typical behavior of NSCLC in terms of metastasis and nodal involvement relative to histology?

Adenocarcinoma tends to be peripheral and often presents with nodal/metastatic spread; squamous cell is more central with potential local recurrence; large cell histology spreads hematogenously.

What immunohistochemical profile distinguishes squamous cell carcinoma from adenocarcinoma?

Squamous: p40 or p63 positive; TTF-1 negative. Adenocarcinoma: TTF-1 positive and napsin A positive in >80%.

Which markers help differentiate common lung cancer primary sites (thyroid, breast, kidney, GI, etc.)?

• Adenocarcinoma of thyroid: thyroglobulin, PAX8; breast: ER, PR, mammaglobin, GATA-3; renal: PAX8; GI (colorectal): CDX2; prostate: NKX3.1; carcinoids: chromogranin, synaptophysin; mesothelioma: WT-1, calretinin; SCLC: TTF-1, chromogranin, synaptophysin, NSE, CD56; and negative for p63.

What are the characteristic histology and markers for SCLC?

SCLC is a neuroendocrine carcinoma: TTF-1 positive, chromogranin positive, synaptophysin positive, NSE positive, CD56 positive; typically Ki-67 very high; p63 negative.

What is the TNM-based staging framework for NSCLC?

Localized disease: Stages I–IIa/b; Locally advanced: Stages IIIa–IIIb; Advanced/metastatic: Stage IV (with distant metastases, including pleural/pericardial involvement).

What is the staging framework for SCLC?

Limited disease (restricted to one hemithorax that can be encompassed in a single radiation field, typically I–III TNM with certain exclusions) and extensive disease (beyond ipsilateral hemithorax, including pleural/pericardial involvement or hematogenous metastases).

What is the role of mediastinoscopy and EBUS in NSCLC staging?

Mediastinoscopy or EBUS-FNA is used for mediastinal staging before surgery, especially with suspicious or enlarged nodes; can replace more invasive procedures in many cases.

What imaging modalities are commonly used for NSCLC staging and what is PET-CT mainly used for?

CT for anatomical extent; PET-CT for distant/metastatic assessment and restaging; MRI (brain/spine) for suspected CNS involvement or epidural metastases.

What is the standard surgical approach for early-stage NSCLC and what is preferred when feasible?

Lobectomy with systematic mediastinal lymph node dissection is preferred when feasible; VATS lobectomy offers less morbidity; segmentectomy/sub-lobar resection for selected small peripheral tumors.

What is the standard adjuvant chemotherapy for non-squamous NSCLC after surgical resection?

Cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 every 21 days for 4 cycles (with B12 and folate supplementation).

What adjuvant regimens are used for squamous NSCLC or when cisplatin is not tolerated?

Cisplatin + docetaxel or cisplatin + gemcitabine; if cisplatin not tolerated, alternatives include carboplatin-based regimens (carboplatin + paclitaxel, carboplatin + gemcitabine, etc.).

What is Durvalumab consolidation and after which therapy is it given in NSCLC?

Durvalumab consolidation after chemoradiation for stage II–III NSCLC (Cohort from PACIFIC): 10 mg/kg every 2 weeks (or 1500 mg every 4 weeks) up to 12 months; given only if disease did not progress after definitive chemoradiation.

What is the recommended radiation dose range for definitive radiotherapy in NSCLC and why is 74 Gy not routine?

Definitive RT is typically 60–70 Gy in 2 Gy fractions over 6–7 weeks; 74 Gy is not routinely recommended due to toxicity without clear additional benefit; aim to limit dose to organs at risk.

What is the role of SBRT (stereotactic body radiotherapy) in NSCLC?

SBRT is used for early-stage, medically inoperable tumors (stages I–IIA) to achieve local control with high precision and minimal normal tissue exposure.

Which targeted therapy is preferred for ALK-rearranged metastatic NSCLC in first line?

Alectinib is a preferred first-line ALK inhibitor; other options include Brigatinib and Lorlatinib; Crizotinib is used if others are not available or after progression.

What are the approved drugs for ROS1 rearrangements in NSCLC and typical sequencing after progression?

Entrectinib is preferred; Crizotinib is another option; after progression, Lorlatinib may be used.

What are the treatment options for NTRK gene fusions in NSCLC?

Larotrectinib or Entrectinib are preferred options for NTRK fusions.

What are the approved therapies for MET exon 14 skipping mutations in NSCLC?

Capmatinib or Tepotinib are preferred MET inhibitors; Crizotinib can be considered in some circumstances.

What RET inhibitors are approved for RET alterations in NSCLC?

Selpercatinib or Pralsetinib are approved RET inhibitors.

What is the KRAS G12C targeted therapy and its clinical context?

Sotorasib is a KRAS G12C inhibitor; KRAS mutations are associated with poorer prognosis and lack of response to EGFR inhibitors; limited activity with some checkpoint inhibitors.

What is the role of PD-L1 expression in selecting immunotherapy for NSCLC?

High PD-L1 expression (e.g., ≥50%) supports pembrolizumab monotherapy in first line for NSCLC without EGFR/ALK alterations; other combos include pembrolizumab with platinum-based chemotherapy or other PD-1/PD-L1 inhibitors depending on histology.

What are common first-line immunotherapy options for metastatic NSCLC with non-squamous histology?

Pembrolizumab monotherapy for high PD-L1 expression; or pembrolizumab + pemetrexed + platinum for non-squamous disease; other combinations include nivolumab + ipilimumab with chemo in certain contexts.

What is the standard first-line treatment for metastatic NSCLC with PD-L1 negative or unknown status?

Chemotherapy-based regimens, often platinum-based (e.g., cisplatin/carboplatin) with pemetrexed (non-squamous) or with other agents depending on histology.

What is the typical treatment approach for limited-stage SCLC?

Chemoradiation with platinum-based chemotherapy (etoposide + cisplatin or carboplatin) given concurrently with thoracic radiotherapy; formulate MDT plan.

What is the standard first-line therapy for extensive-stage SCLC (ES-SCLC) in combination with immunotherapy as described in the notes?

Etoposide + platinum (cisplatin or carboplatin) with atezolizumab (EP + Atezolizumab) as first-line regimen; immunotherapy continuation may occur as maintenance.

What is the role of prophylactic cranial irradiation (PCI) in SCLC and what is the typical dose?

PCI reduces brain metastases risk in SCLC, especially after response to therapy; typical dose is 25 Gy in 10 fractions; not recommended for ECOG 3–4 or significant cognitive impairment.

What are common second-line or later-line therapies for relapsed SCLC?

Topotecan (IV or oral), Irinotecan, Paclitaxel, Docetaxel, Temozolomide; immunotherapy options include Nivolumab +/- Ipilimumab or Pembrolizumab; Vinorelbine, Etoposide, Gemcitabine, Ramucirumab+Docetaxel, etc.

What are the main goals and general approaches of radiotherapy in NSCLC?

Definitive RT for local control in locally advanced disease; palliative RT for symptom control; stereotactic radiotherapy (SBRT/SABR) for oligometastatic or early-stage inoperable tumors; IMRT/VMAT/proton therapy to reduce normal tissue toxicity.

What is the recommended approach for follow-up after NSCLC treatment (stages I–II) treated with surgery ± chemo?

Regular physical exams and CT scans (low-dose CT when ongoing surveillance) at defined intervals (e.g., every 3–6 months in the first years, then yearly). Monitoring for new nodules that could be new primaries or metastases.

What systemic therapy considerations are there after NSCLC surgery for stage II–III where adjuvant therapy is indicated?

Adjuvant chemotherapy or chemoradiotherapy as indicated by stage; targeted therapy (e.g., osimertinib) can be used for EGFR-mutant disease in specific adjuvant settings; radiotherapy decisions depend on margins and nodal status.

What is the recommended maintenance approach after first-line treatment for metastatic NSCLC with PD-L1 expression?

Maintenance strategies include PD-(L)1 inhibitors or pemetrexed, depending on histology and prior treatments; switch maintenance options are listed (e.g., pemetrexed, gemcitabine) based on histology and response.

What are common toxicities and supportive care measures relevant to NSCLC treatment?

Toxicities include neutropenia, neuropathy, mucositis, esophagitis, pneumonitis, anorexia; supportive care includes G-CSF prophylaxis for high-risk regimens, antiemetics for high-emetogenic regimens, hydration and nutrition support, and symptom management.

What is the concept of oligometastatic NSCLC and its management implication?

Oligometastatic disease (few metastases) may benefit from metastasis-directed local therapy (RT or surgery) in addition to systemic therapy to potentially improve survival.

What is the role of Ki-67 in distinguishing SCLC from carcinoid tumors?

Ki-67 is very high in SCLC, helping differentiate it from less proliferative carcinoid tumors.

What are the typical paraneoplastic features associated with squamous NSCLC?

Hypercalcemia due to ectopic PTHrP production, osteoarthropathy, neutrophilia, arthralgias, hypercoagulability.

What is the role of p53 mutation in CBP prognosis and treatment considerations?

p53 mutation occurs in about half of NSCLC and almost all SCLC; it is a common prognostic marker and may influence responses to therapy in some contexts.

What is the typical pattern of brain metastases in NSCLC versus SCLC?

SCLC commonly metastasizes to the brain and prophylactic cranial irradiation is often considered; brain metastases are frequent in NSCLC as well, but PCI is more standard in SCLC.

What are common actionable mutations with approved targeted therapies in NSCLC?

EGFR (exon 19 deletion, L858R; exon 20 insertions with Amivantamab or other agents), ALK (Alectinib, Brigatinib, Lorlatinib), ROS1 (Entrectinib, Crizotinib), NTRK fusions (Larotrectinib, Entrectinib), MET exon 14 skipping (Capmatinib, Tepotinib), RET fusions (Selpercatinib, Pralsetinib), KRAS G12C (Sotorasib) and BRAF V600E (Dabrafenib+Trametinib).

What is the significance of PD-L1 expression in selecting Pembrolizumab for NSCLC?

PD-L1 expression helps identify patients who may benefit from pembrolizumab monotherapy in first-line NSCLC when PD-L1 is high (e.g., ≥50%); PD-L1 status guides combination strategies as well.

What is the typical first-line systemic therapy for limited-stage SCLC if not using immunotherapy?

Etposide + a platinum agent (cisplatin or carboplatin) with concurrent thoracic radiotherapy.

What is the typical prophylactic cranial irradiation dose for SCLC and when is it considered?

25 Gy in 10 fractions; recommended for limited-stage disease responders to therapy and considered in some extensive-stage cases, not recommended for poor performance status (ECOG 3–4) or cognitive impairment.

What is amivantamab-vjmw and in what context is it used?

Amivantamab-vmjw is a humanized bispecific antibody against EGFR and MET used for EGFR exon 20 insertion mutations in NSCLC after progression on prior therapy.

What is the role of pralsetinib and selpercatinib in NSCLC?

Pralsetinib and Selpercatinib are RET inhibitors used for RET fusions in NSCLC.

What are the two main NSCLC treatment approaches in stage III disease after neoadjuvant therapy?

Postoperative radiotherapy (RT) may be added if margins are positive or nodes are involved; chemoradiation can be used depending on nodal status and response.

What is the relationship between adjuvant therapy and radiotherapy in Stage II NSCLC?

Adjuvant chemotherapy improves survival; adjuvant radiotherapy may be used in select high-risk cases or after chemoradiation in specific contexts.

What are common regimens for adjuvant therapy in NSCLC (non-squamous and squamous), including dosing concepts?

Non-squamous: Cisplatin 75 mg/m2 + Pemextrexed 500 mg/m2 q21d x4; Squamous: Cisplatin 75 mg/m2 + Docetaxel or Gemcitabine; Carboplatin-based regimens are alternatives for comorbidity.

What are key considerations for post-therapy follow-up imaging in NSCLC?

Regular clinical visits with CT imaging per stage and treatment; include brain imaging if clinically indicated; consider MRI for CNS symptoms.

How is PD-L1 status relevant for treatment choices in NSCLC?

High PD-L1 expression informs use of pembrolizumab monotherapy in first line for eligible NSCLC with no driver mutation; PD-L1 status influences combination immunotherapy decisions as well.

What is the management approach if NSCLC recurs after a complete response to first-line therapy?

If relapse occurs within 3 months, consider re-challenge or alternative regimens; if relapse after 6 months, reinitiate the same line of therapy; prior exposure to immunotherapy influences subsequent choices.

What is the general approach to controlling symptoms and maintaining quality of life in stage IV NSCLC?

Early integration of palliative care, symptom-directed RT for local issues, maintenance therapy decisions based on tolerability, and social/supportive care to improve QoL.

What is the general approach to treating brain metastases in NSCLC vs SCLC?

In NSCLC, brain imaging and metastasis-directed RT may be used; in SCLC, PCI is commonly considered due to high CNS involvement risk, with careful attention to cognitive outcomes.

Which tumors are commonly biopsied via EBUS and why?

Mediastinal lymph nodes in NSCLC; EBUS allows minimally invasive sampling to stage disease and guide management, often replacing more invasive mediastinoscopy.

What is the role of PET-CT in NSCLC and SCLC staging?

PET-CT is used to assess distant disease and nodal involvement; helpful for restaging and detecting occult metastases; may be used in conjunction with CT/MRI.

What advance in radiotherapy has reduced treatment-related pneumonitis in NSCLC?

Intensity-modulated radiotherapy (IMRT) and advanced techniques (VMAT, proton therapy) reduce exposure to normal lung tissue and lower pneumonitis risk.

What is the standard management for patients with NSCLC and driver mutations who have progressed on TKIs?

Switch to alternative targeted agents when possible (e.g., different TKIs for specific mutations) or switch to immunotherapy/chemotherapy depending on mutation status and prior therapies.