Eduovisual
Respiratory
Non-small cell lung cancer: staging and treatment overview
— Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers; includes adenocarcinoma (most common, peripheral, non-smokers and smokers), squamous cell carcinoma (central, cavitating, hypercalcemia from PTHrP), and large cell carcinoma (peripheral, poorly differentiated)
— Leading cause of cancer death in both sexes in the US; ~50% present with metastatic disease at diagnosis
— Tobacco smoking (strongest; pack-year burden matters); secondhand smoke
— Radon exposure (basement dwellings, mining), asbestos (synergistic with smoking, especially squamous), arsenic, nickel, chromium, diesel exhaust
— Pulmonary fibrosis, COPD, prior chest radiation, family history, HIV
— Adenocarcinoma in never-smokers: younger patients, women, East Asian ancestry, EGFR/ALK drivers
— New or changed cough >3 weeks, hemoptysis, unexplained weight loss, recurrent pneumonia in same lobe, post-obstructive atelectasis
— Incidental pulmonary nodule on imaging, especially solid >8 mm, spiculated, upper lobe, in a smoker
— Paraneoplastic clues: hypercalcemia (squamous, PTHrP), SIADH (more often SCLC but can occur), hypertrophic osteoarthropathy/clubbing, dermatomyositis, migratory thrombophlebitis
— Local invasion syndromes: Pancoast tumor (shoulder/arm pain, Horner syndrome, T1 wasting), SVC syndrome, hoarseness (recurrent laryngeal nerve), phrenic palsy
— Annual low-dose chest CT for adults 50–80 with ≥20 pack-year history who currently smoke or quit within 15 years
— Stop screening if 15 years since cessation, life expectancy limited, or unwilling/unable to undergo curative therapy
Board pearl: A smoker presenting with a new lobar pneumonia that fails to resolve on repeat imaging at 6–8 weeks demands bronchoscopy or CT to exclude endobronchial obstructing tumor — do not just re-treat with antibiotics.
— Persistent cough (most common), dyspnea, hemoptysis (small-volume streaking typical), chest wall pain if pleural/rib invasion
— Post-obstructive pneumonia, wheeze localized to one lung field, hoarseness (left recurrent laryngeal nerve compression by AP window nodes)
— Pleural effusion → often malignant; cytology-positive effusion makes the tumor M1a (stage IVA)
— Pancoast (superior sulcus) tumor: shoulder pain radiating down ulnar arm, Horner syndrome (ptosis, miosis, anhidrosis), atrophy of intrinsic hand muscles — usually squamous or adeno
— SVC syndrome: facial/neck swelling, distended neck veins, headache worse leaning forward, cyanosis; right-sided upper lobe tumors classic
— Cardiac/pericardial invasion → tamponade physiology
— Brain (headache, seizure, focal deficit), bone (back pain, pathologic fracture, hypercalcemia), liver (RUQ pain, LFT abnormalities), adrenal (often asymptomatic, found on staging CT)
— Adenocarcinoma has higher propensity for brain mets at diagnosis
— Squamous: hypercalcemia (PTHrP) — polyuria, constipation, confusion
— Adenocarcinoma: hypertrophic pulmonary osteoarthropathy (clubbing + painful periostitis of long bones), migratory thrombophlebitis (Trousseau)
— Dermatomyositis (heliotrope rash, Gottron papules) → workup for occult malignancy including lung
— Smoking pack-years and cessation date; occupational/environmental exposures; family history of lung cancer
— Performance status (ECOG 0–4) — drives treatment eligibility more than age
— Weight loss >5% in 6 months, anorexia → cachexia, worse prognosis
Step 3 management: Always document ECOG performance status at diagnosis — ECOG ≥3 generally excludes patients from cytotoxic chemotherapy and shifts management toward palliation or single-agent targeted therapy if a driver mutation is present.
— Cachexia, temporal wasting, sarcopenia → poor prognosis and chemo tolerance
— Clubbing with or without hypertrophic pulmonary osteoarthropathy (tender wrists/ankles, periosteal new bone on x-ray)
— Tobacco stigmata: nicotine staining, tar-stained fingers, accelerated facial aging
— Horner syndrome (ptosis, miosis, ipsilateral anhidrosis) → Pancoast tumor invading sympathetic chain
— Supraclavicular lymphadenopathy (Virchow node on left, scalene nodes) → palpable node = N3 disease; easy biopsy target
— Hoarseness with normal vocal cord exam on direct visualization but unilateral vocal cord paralysis → recurrent laryngeal nerve involvement
— Facial plethora, periorbital edema, dilated neck/chest veins, Pemberton sign (facial flushing with arms raised) → SVC syndrome
— Localized monophonic wheeze = fixed obstruction (tumor); distinguishes from polyphonic asthma wheeze
— Dullness to percussion + decreased breath sounds + decreased fremitus → pleural effusion
— Bronchial breath sounds over consolidation from post-obstructive pneumonia
— Hepatomegaly, nodular liver edge → hepatic metastases
— Focal bony tenderness over spine, ribs, or pelvis → bone mets; check for cord compression signs (saddle anesthesia, hyperreflexia, bowel/bladder dysfunction)
— Focal deficits, cranial nerve findings, papilledema → brain metastases
— Proximal muscle weakness improving with use → Lambert-Eaton (more SCLC, but can occur in NSCLC)
— 0: fully active; 1: ambulatory, light work; 2: ambulatory >50% of waking hours, no work; 3: limited self-care, in bed/chair >50%; 4: completely disabled
Key distinction: A palpable supraclavicular node in a suspected lung cancer patient is gold — it is N3 disease by definition and provides the easiest tissue diagnosis; biopsy this before bronchoscopy when present.
— Chest x-ray is often the first study: mass, hilar fullness, mediastinal widening, pleural effusion, lobar collapse, elevated hemidiaphragm (phrenic palsy)
— Contrast-enhanced CT chest/upper abdomen through adrenals and liver is the cornerstone — characterizes primary tumor (T), mediastinal/hilar nodes (N), and common metastatic sites
— Solid nodule features favoring malignancy: size >8 mm, spiculated margins, upper lobe location, growth on serial imaging, doubling time 1 month to 2 years (faster = infection, slower = benign)
— Use patient risk (smoking, age) + nodule size and character
— Solid <6 mm low-risk: no follow-up; high-risk: optional 12-month CT
— Solid 6–8 mm: CT at 6–12 months
— Solid >8 mm: PET/CT, biopsy, or CT in 3 months based on probability
— Subsolid/part-solid nodules have different, longer surveillance (adenocarcinoma in situ behavior)
— CBC (anemia of chronic disease, marrow involvement), CMP (calcium for PTHrP, LFTs for liver mets, creatinine for cisplatin eligibility)
— LDH (tumor burden surrogate), albumin (nutrition/prognosis)
— Sodium (SIADH), coags if planning biopsy
— Smoking history quantification and cessation counseling documented
— Required before surgical resection: FEV1 and DLCO
— Predicted postoperative FEV1 >40% and DLCO >40% generally needed for lobectomy
— Below thresholds → cardiopulmonary exercise testing (VO2 max <10 mL/kg/min = prohibitive risk)
— ECG and RCRI-based perioperative risk assessment for surgical candidates; address coronary disease before thoracotomy
Board pearl: Never order tumor markers like CEA to diagnose lung cancer — they are neither sensitive nor specific; diagnosis requires tissue. Image-driven biopsy planning is the Step 3 move.
— Peripheral lung lesion: CT-guided transthoracic core needle biopsy
— Central lesion or endobronchial: bronchoscopy with biopsy/brushings
— Mediastinal nodes: endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration — preferred for mediastinal staging
— Pleural effusion: thoracentesis with cytology; if negative and suspicion remains, medical thoracoscopy/VATS
— Palpable supraclavicular node or distant met: biopsy that site (establishes diagnosis and stage simultaneously)
— Indicated for staging of clinical stage I–III disease; identifies occult nodal and distant metastases
— Hypermetabolic mediastinal nodes still require tissue confirmation (EBUS) — PET false positives from infection/inflammation common
— Not for routine surveillance after curative therapy
— MRI brain with contrast for all patients with clinical stage II–IV, or stage I with neurologic symptoms
— Adenocarcinoma has high CNS met rate — low threshold
— EGFR mutation (exon 19 del, L858R) — osimertinib
— ALK rearrangement — alectinib/lorlatinib
— ROS1, BRAF V600E, MET exon 14, RET, NTRK, KRAS G12C, HER2 — each with targeted agents
— PD-L1 expression by IHC (tumor proportion score) — guides immunotherapy
— Liquid biopsy (plasma ctDNA) acceptable when tissue insufficient
— T by size and invasion; N0 none, N1 ipsilateral hilar, N2 ipsilateral mediastinal, N3 contralateral or supraclavicular; M1a contralateral lung/pleura, M1b single extrathoracic, M1c multiple
Step 3 management: In a newly diagnosed non-squamous NSCLC, send the full molecular panel and PD-L1 at the time of initial biopsy — do not start chemotherapy before results return unless clinically urgent; first-line targeted therapy dramatically outperforms chemo if a driver is present.
— Lobectomy with mediastinal lymph node dissection/sampling is standard of care for medically operable patients
— Sublobar resection (segmentectomy) acceptable for tumors ≤2 cm with adequate margins (recent JCOG0802/CALGB140503 data)
— Medically inoperable: stereotactic body radiation therapy (SBRT) — excellent local control
— Adjuvant therapy generally not given for stage IA; consider for IB with high-risk features
— Surgery + adjuvant platinum-based chemotherapy (cisplatin-based doublet, typically cisplatin/vinorelbine or carboplatin/paclitaxel)
— Adjuvant osimertinib for 3 years if EGFR-mutant (ADAURA trial)
— Adjuvant atezolizumab if PD-L1 ≥1% and EGFR/ALK negative
— Heterogeneous; multidisciplinary tumor board essential
— Resectable IIIA: neoadjuvant chemoimmunotherapy (e.g., nivolumab + platinum doublet, CheckMate-816) → surgery
— Unresectable III: concurrent chemoradiation followed by consolidation durvalumab for 1 year (PACIFIC regimen)
— EGFR+: osimertinib first-line
— ALK+: alectinib or lorlatinib
— ROS1+: entrectinib or crizotinib
— No driver, PD-L1 ≥50%: single-agent pembrolizumab
— No driver, PD-L1 <50%: chemo + pembrolizumab (non-squamous: platinum/pemetrexed/pembrolizumab; squamous: platinum/paclitaxel/pembrolizumab)
— Aggressive local therapy (SBRT or surgery) to all sites + systemic therapy improves outcomes
Board pearl: The single biggest Step 3 stem trap: starting chemo before molecular results. In stage IV non-squamous NSCLC, wait for biomarkers (5–10 days) unless the patient is crashing — first-line osimertinib for EGFR-mutant disease is vastly superior to chemo.
— Osimertinib (EGFR): rash, diarrhea, QT prolongation, rare pneumonitis, cardiomyopathy — monitor EF
— Alectinib/lorlatinib (ALK): lorlatinib causes hyperlipidemia, CNS effects (mood, cognition); alectinib causes myalgia, edema, photosensitivity
— Entrectinib/crizotinib (ROS1): visual disturbance, edema, hepatotoxicity
— Sotorasib/adagrasib (KRAS G12C): hepatotoxicity, GI toxicity
— Pre-treatment: baseline ECG, LFTs, ophthalmology if indicated, pregnancy test
— Pembrolizumab, nivolumab, atezolizumab, durvalumab, cemiplimab
— Anti-PD-1/PD-L1 blockade; given IV every 3–6 weeks
— Immune-related adverse events (irAEs): pneumonitis (lung cancer patients high risk!), colitis, hepatitis, thyroiditis (hypo > hyper), hypophysitis, adrenalitis, dermatitis, myocarditis, nephritis
— Management: hold drug, prednisone 1–2 mg/kg/day for grade 2–3 irAE; permanent discontinuation for grade 4 or recurrent grade 3
— Endocrinopathies (hypothyroidism, adrenal insufficiency) → replace hormone, do not necessarily stop ICI
— Cisplatin or carboplatin + pemetrexed (non-squamous) or paclitaxel/gemcitabine (squamous)
— Cisplatin: nephrotoxicity (hydrate, magnesium), ototoxicity, neuropathy, severe emesis (need aprepitant + 5-HT3 + dex)
— Carboplatin: thrombocytopenia dose-limiting; dosed by Calvert formula (AUC × [GFR + 25])
— Pemetrexed: requires folic acid and B12 supplementation to reduce myelosuppression and mucositis; contraindicated in squamous histology
— Bevacizumab added to chemo in non-squamous; avoid in squamous (hemoptysis risk) and untreated brain mets, recent hemoptysis, or therapeutic anticoagulation considerations
CCS pearl: When ordering ICI therapy, always order baseline TSH, cortisol/ACTH, LFTs, and creatinine, and repeat TSH every cycle — the most common irAE you will catch on outpatient surveillance is thyroiditis.
— Lobectomy with systematic mediastinal lymph node dissection or sampling is standard for stage I–II and selected IIIA
— Pneumonectomy when tumor crosses fissure or involves main bronchus — higher morbidity, reserved for centralized disease
— Sleeve resection preserves lung parenchyma in central tumors involving main/lobar bronchus; preferred over pneumonectomy when feasible
— VATS or robotic approach preferred over open thoracotomy when oncologically equivalent — less pain, faster recovery
— PFTs: predicted postop FEV1 and DLCO each >40% (some centers >30% with exercise testing)
— Cardiopulmonary exercise test (CPET): VO2 max >20 mL/kg/min good, 10–20 borderline, <10 prohibitive
— Cardiac risk stratification (RCRI), smoking cessation ≥4 weeks preop ideally
— Mediastinal staging with EBUS prior to resection for tumors >3 cm or central location
— SBRT (stereotactic body radiation therapy): 3–5 fractions, ablative doses, for medically inoperable stage I — local control >90%
— Conventional fractionated RT: 60–66 Gy over 6 weeks, concurrent with chemo for unresectable stage III
— Palliative RT: bone mets, brain mets (whole brain or SRS), bronchial obstruction, SVC syndrome, hemoptysis
— Rigid bronchoscopy with debulking, stent placement, laser/electrocautery for obstructing central tumors causing post-obstructive pneumonia or dyspnea
— Photodynamic therapy and brachytherapy for select cases
— Pathologic upstaging (e.g., N2 found at surgery) → adjuvant chemo, possibly radiation
— Positive margins → re-resection if feasible, otherwise RT
Step 3 management: A stage I patient with borderline PFTs (predicted postop FEV1 35%) is not automatically inoperable — order CPET and discuss SBRT as an alternative; do not default to "no curative therapy."
— Age alone is not a contraindication to curative therapy — performance status, comorbidity, and geriatric assessment drive decisions
— Comprehensive geriatric assessment (CGA): functional status (ADLs/IADLs), cognition (Mini-Cog), nutrition (weight loss, albumin), polypharmacy, social support
— Surgical outcomes: lobectomy reasonable in fit septuagenarians/octogenarians; SBRT excellent alternative for stage I
— Chemo: carboplatin generally preferred over cisplatin in elderly due to better tolerability (less neuropathy, less nephrotoxicity, less emesis)
— Single-agent chemo or dose-reduced doublets for ECOG 2 or frail patients
— Immunotherapy generally well tolerated; monitor for irAEs which may be subtler in elderly
— Cisplatin contraindicated when CrCl <60 mL/min; switch to carboplatin (dose by Calvert AUC formula using measured GFR)
— Pemetrexed contraindicated if CrCl <45 mL/min
— Bevacizumab: monitor for proteinuria (hold for >2 g/24h), worsening hypertension
— Most targeted agents (osimertinib, alectinib) do not require renal dose adjustment but data limited in severe CKD
— ICIs: no dose adjustment, but watch for immune-related nephritis (rising Cr, sterile pyuria) — biopsy if unclear
— Many TKIs metabolized by CYP3A4 — osimertinib, alectinib, crizotinib require dose reduction or caution in Child-Pugh B/C
— Avoid pemetrexed if bilirubin >1.5× ULN
— Paclitaxel/docetaxel dose reduction with elevated bilirubin
— ICIs: hold for grade 2+ hepatitis (AST/ALT >3× ULN); rule out viral hepatitis, autoimmune hepatitis, drug-induced before attributing to irAE
— Prehabilitation (exercise, nutrition, smoking cessation) before surgery
— Address sarcopenia with protein supplementation, resistance training
Key distinction: ECOG performance status trumps chronological age in NSCLC treatment selection — a fit 80-year-old with ECOG 0 may receive standard concurrent chemoradiation, while a 60-year-old with ECOG 3 may not.
— Rare but increasing as childbearing age rises; adenocarcinoma in never-smoking young women, often EGFR/ALK driven
— Diagnostic imaging: ultrasound and MRI without gadolinium preferred; shielded chest CT acceptable when needed (fetal dose low)
— Avoid PET-CT during pregnancy (FDG crosses placenta)
— Treatment: surgery reasonable in 2nd trimester; platinum chemotherapy can be given after first trimester with acceptable fetal outcomes
— Targeted therapies and ICIs: limited safety data; avoid in pregnancy when possible; effective contraception required during and after therapy
— Multidisciplinary team (oncology, MFM, neonatology) and shared decision-making about timing of delivery
— ~15% of US lung cancer; higher proportion globally, especially East Asian women
— Disproportionately adenocarcinoma with actionable driver mutations (EGFR ~50%, ALK ~10%, ROS1, RET, HER2)
— Always send comprehensive molecular panel — never-smoker status is a major clue to a targetable driver
— Consider radon exposure, secondhand smoke, occupational exposures, family history
— Lung cancer extremely rare under 40; when present, more likely adenocarcinoma with driver mutations
— Carcinoid tumors (neuroendocrine, not NSCLC per se) more common in young patients with endobronchial lesions — different management (resection usually curative)
— Increased risk of lung cancer even on ART; treat with standard regimens
— Drug-drug interactions between ART and TKIs (especially CYP3A4 inducers) — coordinate with ID pharmacy
— ICIs generally safe in well-controlled HIV (CD4 >200)
— Relative caution with ICIs — risk of disease flare
— Mild/stable autoimmunity (e.g., controlled psoriasis, Hashimoto) is not an absolute contraindication; active organ-threatening disease (lupus nephritis, IBD on biologics) is
Board pearl: A 45-year-old never-smoking woman with a lung mass — assume adenocarcinoma with a driver mutation until proven otherwise, and ensure EGFR/ALK/ROS1 testing is done before any systemic therapy decision.
— Malignant pleural effusion: dyspnea; manage with therapeutic thoracentesis, then indwelling pleural catheter (PleurX) or pleurodesis for recurrence
— Malignant pericardial effusion/tamponade: pulsus paradoxus, JVD, hypotension — pericardiocentesis ± pericardial window
— SVC syndrome: elevate head, diuretics symptomatic only; definitive treatment is endovascular stenting for rapid relief, followed by RT/chemo based on histology
— Hemoptysis: small streaking common; massive (>200 mL/24h) → bronchial artery embolization, rigid bronchoscopy
— Spinal cord compression: emergent dexamethasone 10 mg IV, MRI whole spine, neurosurgery and rad-onc consult within hours
— Brain metastases: seizures (start AED if seizure occurred, not prophylactically), edema (dexamethasone), SRS vs WBRT vs resection
— Hypercalcemia of malignancy (PTHrP) — IV fluids, zoledronic acid or denosumab, calcitonin for rapid effect
— SIADH — fluid restriction, salt tabs, tolvaptan if refractory
— Hypertrophic pulmonary osteoarthropathy — treat underlying tumor; NSAIDs symptomatic
— Chemotherapy: neutropenic fever (admit, broad-spectrum IV antibiotics within 1 hour, piperacillin-tazobactam or cefepime), anemia, thrombocytopenia, neuropathy
— Radiation pneumonitis: cough, dyspnea, low-grade fever 4–12 weeks post-RT; ground-glass in radiation field; treat with prednisone 1 mg/kg
— Radiation esophagitis: dysphagia during chest RT; viscous lidocaine, PPI, nutritional support
— Surgical: prolonged air leak, bronchopleural fistula, atrial fibrillation post-thoracotomy (common, treat with rate control)
— irAEs: pneumonitis (must distinguish from progression, infection, RT pneumonitis), colitis, endocrinopathies
— Lung cancer is highly thrombogenic; new VTE → therapeutic DOAC (apixaban or rivaroxaban) or LMWH; lifelong anticoagulation while cancer active
CCS pearl: New dyspnea in a patient on pembrolizumab — order CT chest, hold ICI, start empiric prednisone if no clear alternative, and consult pulmonology; immune pneumonitis can be fatal if missed.
— Spinal cord compression: emergent dexamethasone, MRI, neurosurgery/rad-onc — admit, definitive treatment within 24 hours
— SVC syndrome with airway/cerebral edema: airway compromise → ICU; otherwise IR for stenting
— Massive hemoptysis (>200 mL/24h or hemodynamic instability): ICU, position bleeding side down, intubation often with double-lumen tube, IR/thoracic surgery
— Tumor lysis syndrome: rare in NSCLC but possible with bulky disease starting therapy — IVF, allopurinol, rasburicase if uric acid high
— Neutropenic fever: admit, blood cultures ×2, empiric cefepime or pip-tazo within 1 hour; add vancomycin for hemodynamic instability or line infection
— Tamponade: ICU, pericardiocentesis
— Hypercalcemic crisis (Ca >14 or symptomatic): admit, aggressive IVF, calcitonin + bisphosphonate
— Thoracic surgery: any potentially resectable disease; biopsy of accessible nodes
— Interventional pulmonology: EBUS for staging, endobronchial palliation, stent placement
— Radiation oncology: stage III, palliation, brain mets, cord compression
— Medical oncology: all systemic therapy decisions and survivorship
— Palliative care: early integration improves quality of life and survival (Temel et al., NEJM 2010) — refer at diagnosis of stage IV
— Genetic counseling if family history suggests germline syndrome (rare)
— Outpatient workup typically appropriate for stable patients with incidental nodule or stable symptoms
— Admit for hemoptysis requiring monitoring, hypoxia, post-obstructive pneumonia with sepsis, oncologic emergencies, intractable pain, malignant effusion with respiratory compromise
— Coordinate biopsy results, molecular testing, and tumor board scheduling before discharge
— Ensure follow-up appointment with oncology within 1–2 weeks of new diagnosis
Step 3 management: A patient with new back pain and lower extremity weakness on a known NSCLC — do not discharge from ED. Immediate dexamethasone 10 mg IV + MRI total spine + neurosurgery/rad-onc consult; time to treatment determines neurologic recovery.
— ~15% of lung cancers; strong smoking association; central, rapidly growing
— Neuroendocrine origin; paraneoplastic syndromes more common: SIADH, ectopic ACTH (Cushing), Lambert-Eaton, paraneoplastic encephalomyelitis
— Staged simply as limited (one radiation field) vs extensive; TNM also used now
— Treatment: platinum/etoposide + atezolizumab or durvalumab (extensive stage); concurrent chemoradiation for limited; prophylactic cranial irradiation in responders
— Highly chemo/radiation sensitive but relapses early and often
— Key distinction: Surgery rarely used (only very early T1N0); contrast with NSCLC where surgery is mainstay for early stages
— Typical (low-grade) and atypical (intermediate-grade); endobronchial, often in younger patients
— Hemoptysis, recurrent pneumonia, wheeze; rare carcinoid syndrome with liver mets
— Treatment: surgical resection usually curative; somatostatin analogs (octreotide/lanreotide) for advanced
— High-grade neuroendocrine; aggressive, treated more like SCLC
— Primary very rare; secondary (systemic NHL with lung involvement) more common
— Imaging: nodules, masses, consolidations, lymphadenopathy; biopsy needed
— Asbestos exposure latency 20–40 years; pleural-based not parenchymal
— Pleural thickening, effusion, chest pain; CT shows rind-like pleural disease
— Histology by VATS biopsy; immunohistochemistry distinguishes from adenocarcinoma (calretinin, WT-1 positive in mesothelioma)
— Treatment: cisplatin/pemetrexed + bevacizumab or nivolumab/ipilimumab; surgery selectively
— Anterior mediastinal mass; associations with myasthenia gravis (30–50%), pure red cell aplasia, hypogammaglobulinemia
— Surgical resection mainstay
Board pearl: A central mass with rapid growth and SIADH in a heavy smoker → think SCLC, not NSCLC; treatment paradigm is entirely different — get tissue urgently and start platinum/etoposide once confirmed.
— Pulmonary tuberculosis: cavitating upper lobe lesion, weight loss, hemoptysis, night sweats — can mimic squamous cell exactly; check sputum AFB ×3, IGRA, consider HIV
— Endemic fungi: histoplasmosis (Ohio/Mississippi River valleys), coccidioidomycosis (Southwest), blastomycosis — can produce nodules, masses, calcified granulomas; urine antigens, serology
— Lung abscess: cavitary lesion with air-fluid level, foul sputum, aspiration risk factors — anaerobic coverage
— Septic emboli: multiple peripheral nodules, often cavitating, in IVDU or endocarditis
— Sarcoidosis: bilateral hilar lymphadenopathy, parenchymal nodules, often asymptomatic — biopsy shows non-caseating granulomas; mimics N2 disease on PET
— Granulomatosis with polyangiitis (GPA): cavitating nodules, sinusitis, hematuria, c-ANCA/PR3+
— Rheumatoid nodules: in seropositive RA, peripheral nodules
— Hamartoma: well-circumscribed, popcorn calcification, contains fat on CT (diagnostic); no treatment needed
— Granuloma (old TB or fungal): central, laminated, or popcorn calcification = benign
— Pulmonary infarct: peripheral wedge-shaped opacity (Hampton hump) from PE
— Round atelectasis: associated with pleural thickening, "comet tail" sign
— Migratory consolidations, cough — responds to steroids, mimics malignancy on imaging
— Always biopsy or follow if unclear
— Benign calcification patterns: central, diffuse, laminated, popcorn → benign
— Malignant patterns: eccentric or absent calcification, spiculated margins, growth on serial imaging
— Doubling time: <1 month = infection/inflammation; 1 month–2 years = malignant; >2 years = benign
Key distinction: A solitary pulmonary nodule with popcorn calcification and intralesional fat on CT is a hamartoma — no biopsy, no follow-up imaging required. Don't be fooled into biopsy on a benign-appearing nodule.
— Continued smoking after diagnosis worsens survival, increases recurrence, reduces treatment efficacy, and raises risk of second primary
— Varenicline is most effective pharmacotherapy; bupropion, nicotine replacement (combination patch + short-acting) all evidence-based
— Behavioral counseling + pharmacotherapy doubles cessation rates; 5 A's framework (Ask, Advise, Assess, Assist, Arrange)
— Document cessation status at every visit
— Statin and antihypertensive optimization; cancer survivors die more often of cardiovascular disease than recurrence in some early-stage cohorts
— Diabetes control; screen for depression (common in lung cancer survivors)
— Annual influenza, COVID-19 boosters, pneumococcal (PCV20 or PCV15 + PPSV23), RSV if ≥60, zoster (Shingrix) — avoid live vaccines on active immunotherapy/chemo
— Pre-chemo: ideally vaccinate 2 weeks before initiation
— Lung cancer survivors have ~2%/year risk of second lung primary
— Surveillance CT chest after curative-intent treatment: every 6 months for 2–3 years, then annually for life
— Per NCCN: low-dose CT continues even beyond 5 years
— Oral targeted therapies require adherence counseling and drug-drug interaction review (CYP3A4 inhibitors/inducers — avoid grapefruit, strong inhibitors like ketoconazole)
— Pain management with WHO ladder; opioid stewardship
— Bone health: bisphosphonates or denosumab for bone mets; DEXA in long-term aromatase inhibitor users (not applicable here but check overall regimen)
— Pulmonary rehab after lobectomy improves QoL and exercise capacity
— Cancer-related fatigue: exercise is the most evidence-based intervention
— Refer to survivorship clinic for late-effects monitoring
Step 3 management: At every NSCLC follow-up visit, you should explicitly (1) ask about tobacco use and offer cessation pharmacotherapy, (2) verify vaccination status, and (3) screen for depression — these recur on Step 3 stems as the "next best step" in survivorship visits.
— History, physical, low-dose CT chest every 3–6 months for years 1–2, every 6 months for years 3–5, then annually for life
— Brain MRI not routine; obtain if symptoms develop
— PET-CT not used for routine surveillance — too many false positives, no survival benefit
— Tumor markers (CEA, CYFRA): not standard for surveillance
— Chemo cycles: CBC weekly during cycle, CMP, response imaging every 2–3 cycles (6–9 weeks)
— TKIs: ECG (QTc), LFTs every 4 weeks for first 3 months then every 8 weeks; lipid panel for lorlatinib; echo for osimertinib if cardiac symptoms
— ICIs: TSH/free T4 every cycle, CMP, CBC; cortisol/ACTH if fatigue or hypotension; troponin if cardiac symptoms (myocarditis); CT every 9–12 weeks
— Response assessment by RECIST 1.1 criteria (complete, partial, stable, progressive disease based on sum of longest diameters of target lesions)
— Pseudoprogression on immunotherapy: apparent growth followed by response — confirm with repeat imaging in 4–8 weeks if patient clinically stable
— Smoking status and cessation support
— Symptom review: new neuro symptoms (brain mets), bone pain (skeletal mets), dyspnea (effusion, pneumonitis, progression), weight loss
— Medication adherence and side effects
— Goals of care, advance directive status — revisit at progression or major clinical change
— Indicated post-surgery, post-radiation, and in advanced disease with dyspnea
— Improves exercise capacity, QoL, dyspnea scores
— Screen for caregiver burnout; connect to support groups, social work, financial counseling
Board pearl: A patient 6 weeks into chemoradiation develops new dyspnea and a low-grade fever, with new ground-glass opacities limited to the radiation field — this is radiation pneumonitis, not progression or infection. Treat with prednisone 1 mg/kg and taper over 6–8 weeks.
— Disclose realistic prognosis, treatment goals (curative vs palliative), and toxicities before consent to systemic therapy
— Stage IV NSCLC has median survival 1–3+ years depending on molecular profile and PD-L1 — patients deserve honest, numerical discussions
— Document discussion of clinical trials when available — failing to mention trial options is an ethical lapse
— Early palliative care integration (at stage IV diagnosis) improves QoL and survival — this is a Step 3 favorite
— Address code status, advance directives, and surrogate decision-maker at diagnosis of advanced disease, not in the ICU
— Hospice eligibility when life expectancy ≤6 months and patient prefers comfort-focused care
— Document shared decision-making conversation before LDCT screening — required by CMS for reimbursement; discuss benefits (mortality reduction), harms (false positives, incidental findings, radiation, biopsy complications), and overdiagnosis
— Discontinue screening when 15 years since cessation, or when patient unwilling/unable to undergo treatment
— Pending biopsy results at discharge — must have documented plan for follow-up; failure to communicate molecular results is a major safety event
— Hand off oral oncolytic adherence monitoring; prescription delays cause progression
— Ensure specialty pharmacy coordination for high-cost oral agents and prior authorization
— Asbestos and occupational carcinogen exposures may trigger workers' compensation claims; document exposure history
— Lung cancer is generally not a reportable communicable condition, but active TB found during workup is reportable to public health
— Black patients have higher lung cancer mortality and are under-screened; ensure equitable screening referral
— Address insurance, transportation, and language barriers proactively
— Patients on opioids or with brain mets/seizures: counsel on driving restrictions; state laws vary on physician reporting requirements
Step 3 management: At new diagnosis of metastatic NSCLC, the single highest-yield next step beyond starting therapy is a palliative care referral and goals-of-care conversation — improves survival, quality of life, and matches care to patient values.
— Adenocarcinoma: peripheral, never-smokers, driver mutations, hypertrophic osteoarthropathy
— Squamous cell: central, cavitating, PTHrP/hypercalcemia, smoking
— Large cell: peripheral, undifferentiated, poor prognosis
— Bronchioloalveolar/lepidic: ground-glass, indolent, may be multifocal
— EGFR → osimertinib
— ALK → alectinib/lorlatinib
— ROS1 → entrectinib/crizotinib
— BRAF V600E → dabrafenib + trametinib
— KRAS G12C → sotorasib/adagrasib
— MET exon 14 → capmatinib/tepotinib
— RET → selpercatinib
— NTRK → larotrectinib/entrectinib
— HER2 → trastuzumab deruxtecan
— Squamous → hypercalcemia (PTHrP)
— Adenocarcinoma → hypertrophic pulmonary osteoarthropathy, migratory thrombophlebitis (Trousseau)
— SCLC > NSCLC → SIADH, Cushing (ectopic ACTH), Lambert-Eaton, paraneoplastic cerebellar degeneration
— Pancoast = superior sulcus tumor → Horner + brachial plexus + T1 wasting
— SVC syndrome = facial plethora, dilated chest veins
— Hoarseness = recurrent laryngeal nerve (left more common, around aortic arch)
— Phrenic palsy = elevated hemidiaphragm
— Malignant pleural effusion = M1a, stage IVA
— Stage I-II → surgery (+/- adjuvant chemo if II, + osimertinib if EGFR+)
— Stage III unresectable → concurrent chemoRT + consolidation durvalumab (PACIFIC)
— Stage III resectable → neoadjuvant chemoimmunotherapy then surgery (CheckMate-816)
— Stage IV → biomarker-driven (TKI if driver, immunotherapy ± chemo if no driver)
— LDCT annually, age 50–80, ≥20 pack-years, current smoker or quit ≤15 years (USPSTF 2021)
— Popcorn calcification + fat = hamartoma
— Central/laminated calcification = benign granuloma
— Doubling time 1 mo–2 yr = malignant range
Board pearl: If a stem mentions central tumor + hypercalcemia + smoker → squamous cell carcinoma with PTHrP. If it's peripheral + never-smoker + Asian woman → adenocarcinoma with EGFR mutation → osimertinib.
— Stem: heavy smoker, weight loss, 4-cm RUL mass on CXR
— Right answer: CT chest/upper abdomen with contrast, then tissue diagnosis (CT-guided biopsy or bronchoscopy depending on location)
— Wrong answers: empiric antibiotics, repeat CXR in 3 months, tumor markers
— Stem: 55-year-old never-smoker Asian woman, lung adenocarcinoma with multiple lesions, EGFR exon 19 deletion detected
— Right answer: osimertinib
— Wrong answers: carboplatin/pemetrexed, pembrolizumab monotherapy, chemo + bevacizumab
— Stem: clinical stage IIIA NSCLC, FDG-avid mediastinal lymph node on PET
— Right answer: EBUS-TBNA for tissue confirmation before treatment planning
— Wrong: proceed to surgery, start chemoRT empirically
— Stem: known NSCLC, new back pain with leg weakness and urinary retention
— Right answer: IV dexamethasone immediately + MRI total spine + neurosurgery/rad-onc
— Wrong: outpatient MRI, plain x-rays, opioids alone
— Stem: 65-year-old smoker, 1-cm solid nodule incidentally on CT
— Right answer: depends on size/risk — for 8 mm in smoker, PET-CT or biopsy or 3-month CT
— Wrong: do nothing; immediate lobectomy
— Stem: 6 weeks on pembrolizumab, new dyspnea, hypoxia, bilateral ground-glass
— Right answer: hold pembrolizumab, start high-dose corticosteroids (1–2 mg/kg prednisone), rule out infection
— Wrong: continue ICI, antibiotics alone
— Stem: stage IIA NSCLC, pathologic N1, fit patient
— Right answer: adjuvant cisplatin-based chemotherapy (+ atezolizumab if PD-L1 ≥1%, + osimertinib if EGFR+)
— Wrong: observation alone
— Stem: 60-year-old, 30 pack-year history, quit 10 years ago
— Right answer: annual LDCT screening (meets USPSTF criteria)
— Wrong: chest x-ray, sputum cytology, no screening
Key distinction: Stage III gets divided in Step 3 stems by resectability — resectable IIIA → neoadjuvant chemo-IO; unresectable IIIA/B → concurrent chemoRT + durvalumab consolidation. Knowing which pathway to choose wins the question.
NSCLC management is staging-driven: surgery for I–II, multimodality (chemoradiation + durvalumab or neoadjuvant chemo-immunotherapy) for III, and biomarker-driven systemic therapy (targeted therapy for driver mutations, immunotherapy ± chemo otherwise) for IV — with smoking cessation, palliative care, and LDCT screening woven throughout.
Board pearl: When in doubt on a Step 3 NSCLC stem, the answer almost always rewards multidisciplinary thinking — tissue first, molecular testing second, stage-appropriate multimodal therapy third, and palliative care plus smoking cessation always.