Thoracic Malignancies - Board Review Summary

PART I - EPIDEMIOLOGY, SCREENING, AJCC v9

Screening - NLST and NELSON

Trial	Population	Intervention	Result
NLST (NEJM 2011)	53,454 pts, age 55-74, ≥30 pack-yr, current or quit <15 yr	Annual LDCT x3 vs CXR	20% relative reduction in lung cancer mortality; 6.7% reduction in all-cause mortality
NELSON (NEJM 2020)	13,195 men, 2,594 women; age 50-74, ≥15 cig/day for ≥25 yr or ≥10/day for ≥30 yr	LDCT at 0, 1, 3, 5.5 yr vs no screening	10-yr lung cancer mortality reduced 24% in men, 33% in women

USPSTF 2021 criteria: ages 50-80, ≥20 pack-yr, currently smoking or quit within 15 yr. Using strict NLST criteria would only capture about 27% of incident lung cancers; broader eligibility improves yield.

AJCC v9 - Key Changes (memorize)

Category	Subdivision in v9	Rationale
N2 - ipsilateral mediastinal/subcarinal	N2a = single station; N2b = multiple stations	Single-station N2 has better prognosis in surgical series (Int-0139: HR 0.72)
M1c - distant mets	M1c1 = multiple extrathoracic mets, single organ system; M1c2 = multiple organ systems	Reflects the growing distinction between limited-burden and more disseminated metastatic disease

T and M1a/M1b are otherwise unchanged from v8. M1a: contralateral lung nodule, pleural/pericardial nodules, malignant pleural/pericardial effusion. M1b: single extrathoracic metastasis in a single organ.

Thoracic Workup / Staging: Board Checklist

Question	Board-style answer	Why it matters
What imaging before definitive therapy?	Diagnostic chest CT + PET/CT for potentially curable NSCLC; brain MRI for stage II-III, neurologic symptoms, SCLC, and most stage IV presentations	Stage migration is common; brain disease changes curative-intent plans
How to biopsy?	Choose the biopsy that gives diagnosis and highest-stage confirmation when feasible; EBUS/EUS is central for suspicious mediastinum	Do not biopsy the easiest lesion if it misses the staging question
What defines operability?	Thoracic surgery assessment, PFTs, predicted postop function, cardiac risk, frailty, and patient preference	SBRT vs surgery depends on true surgical fitness, not age alone
When to do molecular testing?	At minimum for nonsquamous advanced disease and unresectable stage III; EGFR status is now essential before choosing post-CRT systemic therapy	LAURA made EGFR testing practice-shaping in unresectable stage III
When to involve palliative care?	Early for stage IV or high-symptom thoracic disease, alongside disease-directed therapy	Symptom control and goals alignment improve care without replacing treatment

PART II - EARLY-STAGE NSCLC

Operability & PFT Cutoffs (ACCP Guidelines)

Metric	Safe / Standard Risk	High Risk / Inoperable
Absolute FEV1	> 1.5 L (Lobectomy) > 2.0 L (Pneumonectomy)	If lower, must calculate % predicted and ppo values.
Pre-op % Predicted	FEV1 and DLCO > 80%	If < 80%, calculate Predicted Postoperative (ppo) values.
ppoFEV1 & ppoDLCO	> 40%	30-40%: High risk → requires CPET (VO2 max). < 30%: Medically inoperable → SBRT candidate.
VO2 Max (CPET)	> 15 mL/kg/min	< 10-15 mL/kg/min: Medically inoperable.

Calculation: ppoFEV1 = Pre-op FEV1 × (1 - [functional segments removed / total functional segments]). The lung is typically divided into 19 segments. SBRT is the standard of care when patients fall into the medically inoperable categories.

Management Paradigm + Dose Anchors

Clinical setting	Preferred paradigm	Dose / anchor
Operable peripheral stage I	Surgery with mediastinal nodal evaluation remains reference standard; segmentectomy is reasonable for selected small peripheral tumors	SBRT considered after careful shared decision-making or if patient refuses surgery
Medically inoperable stage I	SBRT	Peripheral: 18 Gy x 3, 12 Gy x 4-5, or similar high-BED regimen
Chest-wall-adjacent peripheral lesion	Use more fractions if needed for ribs/chest wall	Common fallback: 50-60 Gy / 5 fx
Central lesion	SBRT with caution; avoid 3-fraction regimens	Common: 50 Gy / 5 to 60 Gy / 5; RTOG 0813 identified 12 Gy x 5 as MTD
Ultra-central lesion	More protracted SBRT / hypofractionation; prioritize airway, esophagus, and great-vessel constraints	SUNSET-style: 60 Gy / 8 fx with controlled hot spot
No safe biopsy	Empiric SBRT acceptable only after multidisciplinary review when malignancy probability is very high	Common threshold: pretest probability >85%
ILD / fibrotic lung disease	Major caution or alternate strategy	PFTs alone do not reliably predict fatal pneumonitis risk

Targeted Therapy Post-Surgery: For EGFR-mutated disease, the ADAURA trial established adjuvant osimertinib for resected stage IB-IIIA. However, this is not yet a routine standard of care after definitive SBRT for medically inoperable stage I disease.

SBRT vs Surgery: STARS / ROSEL Pooled

The STARS / ROSEL pooled analysis included 58 operable pts T1-T2a N0 NSCLC from two closed phase III trials. STARS: CyberKnife 18 Gy x 3 peripheral, 12.5 Gy x 4 central. ROSEL: linac SBRT 18 Gy x 3 or 12 Gy x 5, peripheral only. 3y OS 95% SBRT vs 79% lobectomy. The revised STARS analysis was favorable but still not a definitive randomized surgery comparison.

Operable T1-T2 NSCLC: STABLE-MATES / VALOR ongoing

Phase III comparisons are still pending. For clearly operable early-stage disease, the reference standard remains resection with mediastinal nodal evaluation. JCOG 0802 strengthened the case for segmentectomy in selected peripheral tumors up to 2 cm, but this does not make SBRT and surgery interchangeable.

Biopsy Before SBRT?

ASTRO guideline logic: biopsy whenever possible to confirm histologic diagnosis. If pretest probability >85% on a validated model such as Mayo or Brock, empiric SBRT can be acceptable after multidisciplinary review. Large no-biopsy cohorts have shown similar local, regional, and distant outcomes, but tissue is still preferred when safe.

Does Dose Matter? The sBED Concept

"Size-adjusted BED" (sBED) = BED minus tumor diameter in mm. Achieving sBED >= 80 Gy correlates with about 90-95% local control. Examples: 10 Gy x 5 for a 2 cm tumor or 12 Gy x 5 for a 5 cm tumor. Single-fraction SBRT and multi-fraction high-BED regimens can produce comparable control when the effective dose is adequate.

Landmark SBRT Dose-Response Trials

Trial	Design	Result
RTOG 0236	T1-T2 peripheral, medically inoperable; 18 Gy x 3	3y primary tumor control 98%; 3y LC 91%; 3y OS 56%
RTOG 0618	T1-T2 peripheral, operable; 18 Gy x 3	4y LC 96%, OS 56%; confirms strong SBRT efficacy in operable pts, though not as a surgery-comparison trial
CHISEL	RCT: SBRT vs conventionally fractionated RT, T1-T2a peripheral inoperable	SBRT reduced LR and improved OS

Central / Ultra-central SBRT - High-Yield Spectrum

Trial	Target / Dose	Toxicity
Timmerman "No-Fly Zone"	Central tumors: 20-22 Gy x 3	G3-5 toxicity unacceptably high; 3-fx regimens should not be used near central airways
RTOG 0813	Central, within 2 cm of proximal bronchial tree OR PTV touching mediastinal/pericardial pleura. 10-12 Gy x 5	12 Gy x 5 = MTD with about 7% DLT risk at 1 yr
HILUS	Primary or metastatic lung tumor <5 cm within 1 cm of proximal bronchial tree. 7 Gy x 8 to 67% isodose, 4 fx/week	G5 toxicity, mostly hemoptysis: 21% near trachea/mainstem vs 8% near lobar/intermedius bronchi
Expanded HILUS analysis	7 Gy x 8 pts within 2 cm of PBT	Bronchus intermedius should be treated with the same caution as the mainstem bronchi
SUNSET	Ultra-central primary tumors <6 cm with PTV overlapping PBT, esophagus, pulmonary vein, or pulmonary artery. 7.5 Gy x 8	Modern 60/8 framework with controlled hotspot and lower fatal toxicity than historical HILUS-style experience

Practical SBRT framework:

Peripheral tumors: 18 Gy x 3. Switch to 12 Gy x 5 if chest wall constraints cannot be met.
Ultra-central: 7.5 Gy x 8 or another protracted, constraint-driven regimen.
Other central tumors: 10 Gy x 5 for smaller lesions or 12 Gy x 5 for larger lesions, while respecting 5-fraction constraints.
Aim for 120-130% hot spots when appropriate.
Central = within 2 cm of PBT OR PTV touching mediastinal/pericardial pleura.

SBRT Contraindications - ILD

Pretreatment PFTs do not reliably predict pneumonitis risk. Small fibrotic ILD series treated with 50 Gy / 5 have reported substantial grade 4-5 pulmonary toxicity. The board answer is not "never," but the bar for SBRT should be high and multidisciplinary.

SBRT + Immunotherapy for Early-Stage NSCLC

Phase II I-SABR suggested activity for SBRT + nivolumab. Phase III trials have not confirmed a routine role: SWOG 1914 and KEYNOTE 867 closed for futility, and PACIFIC-4 has completed accrual. At present, there is no phase III evidence supporting routine IO after SBRT for early-stage NSCLC.

PART III - LOCALLY ADVANCED NSCLC

Management Paradigm + Dose Anchors

Clinical setting	Preferred paradigm	Dose / systemic anchor
Unresectable stage III, fit, no driver-directed post-CRT strategy	Concurrent platinum-based CRT followed by durvalumab if no progression	60 Gy / 30 fx; durvalumab for up to 12 months
EGFR exon 19 del / L858R unresectable stage III	Definitive CRT followed by osimertinib, not routine durvalumab	Osimertinib 80 mg daily until progression or intolerance
CRT-ineligible / frail stage III	Sequential chemo then RT, RT alone, or clinical trial integrating IO without chemo	Common definitive anchor: 60 Gy / 30 fx; selected hypofractionated trials use 60 Gy / 15 fx
Potentially resectable N2	Multidisciplinary decision; perioperative chemo-IO is established for appropriate surgical candidates	If surgery is abandoned, revert to definitive CRT principles
Dose escalation	Do not escalate whole thorax routinely	RTOG 0617: 74 Gy was worse than 60 Gy
Plan quality	Target coverage plus cardiac/lung/esophageal sparing	Heart mean ALARA, heart V40 <50%, lung V20 <35% historically, esophagus max EQD2 caution above 100-110 Gy

Foundational Trials

Trial	Design	Result
RTOG 73-01	Dose-finding RT alone: 40 vs 50 vs 60 Gy	Trend favoring 60 Gy. Median OS about 1 yr in an unresectable, pre-modern-systemic-therapy era
Sequential CRT meta-analysis	11 trials, cisplatin-based, 50-65 Gy, mostly induction chemo	3% absolute OS benefit at 2y
Concurrent CRT meta-analysis	6 trials, 49-66 Gy; platinum-based	5% absolute OS benefit at 5y. Established concurrent CRT as SOC
JCOG 0301	Age >70, cisplatin-ineligible; 60 Gy +/- low-dose carbo	Concurrent low-dose carboplatin improved OS in fit elderly pts
CONCERT/TROG	Tumor ≥8 cm and/or PS ≥2 and/or weight loss >10%. Carbo+vinorelbine +/- RT 42 Gy / 15 fx	RT benefit was more modest in a frailer population

RTOG 0617 - The Seminal Negative Dose-Escalation Trial

RTOG 0617 used a 2x2 design: standard 60 Gy vs high-dose 74 Gy; +/- cetuximab. Carbo/taxol concurrent. The 74 Gy arm had worse OS. Cetuximab provided no benefit. Mean heart dose emerged as a major adverse predictor, cementing 60 Gy as the standard dose and making cardiac sparing central to plan quality.

Failed Attempts to Improve Concurrent CRT (all negative RCTs)

Consolidation chemotherapy (HOG, KCSG)
Maintenance targeted therapy (SWOG S0023 - gefitinib, inferior OS)
Prophylactic cranial RT (RTOG 0214)
Trimodality (INT 0139 - no OS benefit overall)
Dose escalation (RTOG 0617 - inferior OS)
Concurrent cetuximab (RTOG 0617)
New chemotherapy platforms (PROCLAIM - pem/cis)
Metformin (NRG-LU001)
PET-based dose escalation (RTOG 1106, PET-PLAN)

Modern Constraints for LA-NSCLC CRT

Lung: V20 <35% historically; composite EQD2 V20 <40%. Mean lung dose as low as feasible.
Esophagus: minimize composite EQD2 max dose above 100 Gy; avoid above 110 Gy; strongly discourage above 120 Gy.
Heart: mean heart dose ALARA; heart V40 <50%.

PACIFIC

PACIFIC randomized 713 pts with unresectable stage III NSCLC without progression after platinum-based CRT within 42 days of CRT completion to durvalumab x 12 months vs placebo. Median PFS 16.9 vs 5.6 mo. The 5-year update showed median OS 47.5 vs 29.1 mo and 5y OS 42.9% vs 33.4%.

PACIFIC caveats: do not use durvalumab for EGFR-mutant or ALK-rearranged tumors when a targeted post-CRT strategy exists; benefit in PD-L1 TPS 0% remains less certain; and roughly 20-25% of real-world CRT pts never reach consolidation because of toxicity or early progression.

Concurrent vs Adjuvant IO + CRT

Trial	Design	Result
PACIFIC-2	Concurrent + adjuvant durvalumab vs placebo, with CRT	Negative for PFS; no OS benefit
EA5181	Concurrent + consolidative durvalumab vs consolidative alone	Primary endpoint OS; pending

LAURA - EGFR-Mutant Unresectable Stage III

LAURA randomized 216 pts with EGFR-mutant (ex19del or L858R) unresectable stage III NSCLC without progression after definitive CRT to osimertinib 80 mg daily until progression vs placebo. Median PFS 39.1 vs 5.6 mo. Osimertinib is now SOC for EGFR+ unresectable stage III after CRT and should replace durvalumab in this subgroup.

RT + IO Without Chemo (for CRT-Ineligible)

Trial	IO / PD-L1 requirement	RT regimen
NRG-LU004	Durvalumab x 1y (started with RT); PD-L1 ≥50%	60 Gy / 30 fx or 60 Gy / 15 fx
SPRINT	Pembrolizumab q3wk x3 before RT, then x13 after; PD-L1 ≥50%	48/55 Gy / 20 fx PET-based dose-painted
DOLPHIN	Durvalumab x 1y (with RT); PD-L1 ≥1%	60 Gy / 30 fx
SWOG S1933	Atezolizumab x 1y (after RT); any PD-L1	60 Gy / 15 fx
DART	Durvalumab x 1y (with RT); any PD-L1	60 Gy / 30 fx
TRADE-hypo	Durvalumab x 1y (with RT); any PD-L1	60 Gy / 30 fx or 55 Gy / 20 fx (closed for toxicity)
AIRING	Nivolumab x 6 mo (with RT); any PD-L1	66 Gy / 24 fx

Surgery for LA-NSCLC - Key Negative Trials

Trial	Design	Result
INT 0139	Stage IIIA(N2) resectable: CRT 45 Gy + cis/etop -> resection vs definitive CRT 61 Gy	PFS benefit with surgery but no OS difference. Exploratory signal favored lobectomy, not pneumonectomy
EORTC 08941	Stage IIIA(N2) after chemo response: resection vs RT about 60 Gy	No OS or PFS difference; surgery carried higher treatment-related mortality

Perioperative Immunotherapy

CheckMate 816: neoadjuvant nivolumab + platinum-doublet chemo vs chemo alone improved pCR, MPR, and EFS.
NADIM II: neoadjuvant nivolumab + chemo improved pCR in resectable IIIA disease.
KEYNOTE-671 and AEGEAN: perioperative pembrolizumab and durvalumab, respectively, improved event-free outcomes in resectable stage II-IIIB disease.
Practical takeaway: if a patient receives induction chemo-IO but does not proceed to surgery, management usually reverts to a definitive CRT framework followed by the appropriate post-CRT systemic strategy.

PART IV - POSTOPERATIVE (PORT) NSCLC

Management Paradigm + Dose Anchors

Postoperative setting	Preferred paradigm	Dose / board anchor
R0 pN0-1	No PORT	Classic meta-analysis showed harm in older-technique pN0-1 patients
R0 pN2 after complete resection	No routine PORT after Lung ART; individualize for very high locoregional-risk features	If used selectively: often 50-54 Gy
Close / positive margin	Discuss PORT or postoperative CRT depending on margin, nodal risk, and systemic plan	Microscopic residual commonly 54-60 Gy
Gross residual disease	Definitive-style postoperative RT / CRT if safely deliverable	Gross residual commonly 60-66 Gy
After neoadjuvant or perioperative systemic therapy	Do not use PORT reflexively; base decision on final margins, residual nodal disease, and surgical quality	Coordinate timing so systemic therapy is not unnecessarily delayed

PORT Meta-Analysis

Adjuvant RT after complete resection for NSCLC produced a 7% absolute decrement in 2y OS in pN0/pN1. The apparent harm was driven largely by outdated techniques. Benefit in pN2 remained uncertain.

Lung ART - Modern PORT for pN2

Lung ART randomized 501 pts with completely resected pN2 NSCLC to PORT 54 Gy / 27-30 fx vs observation. 3y DFS 47% vs 44%, no OS benefit, and more cardiopulmonary toxicity in the PORT arm. Modern PORT did not improve DFS or OS.

Current takeaway: PORT for pN2 is no longer routine. Consider it selectively for unusually high-risk scenarios such as positive/close margins, extracapsular extension, incomplete nodal dissection, or concerning residual mediastinal findings.

PART V - SMALL CELL LUNG CANCER

Management Paradigm + Dose Anchors

Clinical setting	Preferred paradigm	Dose / systemic anchor
Very limited T1-2 N0 SCLC	Lobectomy + mediastinal staging in highly selected peripheral tumors; adjuvant platinum/etoposide	Add thoracic RT if nodal disease is found
Limited-stage, fit	Concurrent platinum/etoposide + thoracic RT, started early when feasible	Classic: 45 Gy BID; daily alternatives: 66 Gy / 33 or 70 Gy / 35
Limited-stage after CRT without progression	Adjuvant durvalumab	Durvalumab q4wk up to 24 months
LS-SCLC complete/near-complete response	PCI vs MRI surveillance based on age, cognition, response, and patient values	PCI standard dose: 25 Gy / 10 fx; consider HA-PCI + memantine
Extensive-stage first line	Platinum/etoposide + atezolizumab or durvalumab	Median OS improvement is modest but standard
ES-SCLC chemo/IO responder with residual thoracic burden	Selective consolidative thoracic RT	Classic Slotman regimen: 30 Gy / 10 fx
ES-SCLC brain prevention	MRI surveillance is commonly favored; PCI remains individualized	Takahashi makes routine ES-SCLC PCI hard to defend with high-quality MRI access

Classic BID RT: Intergroup 0096

Turrisi / Intergroup 0096 tested concurrent cis/etoposide + RT: 45 Gy BID (1.5 Gy x 30 fx over 3 wk) vs 45 Gy daily (1.8 Gy x 25 fx over 5 wk). 5y OS 26% vs 16% favoring BID. G3 esophagitis was higher with BID but the survival gain made BID the classic benchmark regimen.

Dose-Escalated Daily RT (Equivalent Options)

Trial	Arms	Result
CONVERT	66 Gy / 33 fx daily vs 45 Gy BID	Equivalent OS; similar G3+ esophagitis
CALGB 30610 / RTOG 0538	70 Gy / 35 fx daily vs 45 Gy BID	Equivalent OS; trend toward improved local control with 70 Gy, without a definitive survival advantage

Very Limited Stage SCLC (T1-2 N0)

Lobectomy with mediastinal staging is reasonable in carefully selected peripheral node-negative disease. Adjuvant chemotherapy is standard; thoracic RT is added if nodal disease is found. SBRT-only strategies remain investigational.

ADRIATIC - Practice Change for LS-SCLC

ADRIATIC randomized 730 pts with LS-SCLC without progression after concurrent CRT to durvalumab (+/- tremelimumab) x 24 mo vs placebo. Median OS 55.9 vs 33.4 mo; median PFS 16.6 vs 9.2 mo. Adjuvant durvalumab after CRT is now SOC.

NRG-LU005 - Concurrent Atezolizumab with CRT

NRG-LU005 randomized LS-SCLC pts to CRT + atezolizumab (concurrent + consolidation) vs CRT alone. Negative for both OS and PFS, echoing the broader pattern that adjuvant sequencing has outperformed concurrent IO in thoracic CRT settings.

Extensive-Stage SCLC (ES-SCLC)

IMpower133 and CASPIAN: platinum/etoposide + atezolizumab or durvalumab. Median OS about 12-13 mo.
Slotman thoracic RT: in chemo-responders, thoracic RT 30 Gy / 10 fx improved longer-term thoracic control and 2y OS on secondary analysis.
In the IO era, consolidative thoracic RT remains a selective tool for pts with persistent intrathoracic bulky or symptomatic disease.

Prophylactic Cranial Irradiation - The Evolving Story

Trial	Population	Finding
Auperin	LS-SCLC CR after CRT	About 5% absolute OS benefit at 3y; major reduction in brain metastases
Le Pechoux	720 LS-SCLC CR pts: 25 Gy / 10 fx vs 36 Gy	25 Gy remained standard; 36 Gy was not better and was associated with worse OS
Slotman EORTC	286 ES-SCLC responders: PCI vs observation. No baseline MRI required	1y symptomatic brain mets 15% vs 40%; 1y OS 27% vs 13%
Takahashi	224 ES-SCLC responders: PCI vs MRI surveillance with mandatory baseline and serial MRI	Negative for OS; brain mets developed in 48% (PCI) vs 69% (surveillance). This justifies surveillance + salvage SRS to spare toxicity.

Hippocampal Avoidance PCI (HA-PCI)

Trial	Design	Finding
PREMER / GOECP-SEOR	PCI 25 Gy +/- HA. Primary: FCSRT delayed free recall decline	Positive: cognitive decline reduced, without loss of intracranial control
NKI	PCI 25 Gy +/- HA. Primary: HVLT total recall decline	Negative; likely affected by contouring/QC limitations
NRG-CC003	HA-PCI vs PCI; about half received memantine	Primary HVLT-R delayed recall endpoint NS, but composite neurocognitive failure favored HA-PCI

HA-PCI summary: mixed phase III data, but enough signal to make HA-PCI reasonable when contouring is rigorous and memantine is used. Per NRG-CC003-style constraints, hippocampal D100% should remain <9 Gy and Dmax <16 Gy.

PART VI - ADDITIONAL THORACIC QUICK HITS

Thymic Epithelial Tumors and Mesothelioma

Disease	Management paradigm	Dose / board anchor
Thymoma, resected R0	Surgery is central; PORT is selective for stage II high-risk features and generally favored for stage III+	PORT commonly 45-50.4 Gy
Thymoma / thymic carcinoma, R1	PORT recommended more strongly, especially thymic carcinoma or invasive stage	Microscopic positive margin: about 50-54 Gy
Thymic gross residual / unresectable	Definitive RT or CRT depending histology, resectability, and systemic plan	Gross disease: about 60-70 Gy
Malignant pleural mesothelioma, unresectable	Systemic therapy is the backbone; nivolumab/ipilimumab is a key first-line option	RT is usually palliative or highly selected hemithoracic therapy at expert centers
Mesothelioma palliation	Treat focal pain, chest-wall invasion, obstruction, or symptomatic metastases	8 Gy x 1, 20 Gy / 5, or 30 Gy / 10
Mesothelioma surgery caution	MARS 2 challenged extended pleurectomy/decortication by showing worse survival and more serious AEs versus chemotherapy alone	Radical surgery should be expert-center, carefully selected, and not reflexive

Thymoma Board Trap: Paraneoplastic syndromes (e.g., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia) occur in 30-50% of patients with thymomas, but they are rarely seen in patients with thymic carcinomas.

Post-EPP Hemithoracic RT: Strict constraints to the intact contralateral lung are mandatory to prevent fatal pneumonitis in mesothelioma patients after extrapleural pneumonectomy. The board anchor is contralateral lung V20 <7% and Mean Lung Dose <8-8.5 Gy.

PART VII - CROSS-CUTTING HIGH-YIELD POINTS

Thoracic workup: biopsy the site that confirms diagnosis and stage; PET/CT, brain MRI when indicated, EBUS/EUS, PFTs, and surgical assessment prevent avoidable undertreatment.
AJCC v9: N2 now splits into N2a (single station) and N2b (multiple stations); M1c splits by single-organ-system vs multi-organ-system dissemination.
Screening: NLST showed a 20% lung cancer mortality reduction; NELSON confirmed major benefit in a European cohort. USPSTF 2021 uses ages 50-80, ≥20 pack-yr, quit <15 yr.
SBRT dose/fractionation: peripheral 18 Gy x 3; central 12 Gy x 5; ultra-central 7.5 Gy x 8. Avoid 3-fx regimens near central airways.
HILUS matters: 7 Gy x 8 near trachea/mainstem carried very high fatal hemoptysis risk.
sBED >= 80 Gy correlates with excellent local control in peripheral SBRT.
Biopsy before SBRT is preferred unless the malignancy probability is convincingly high and tissue cannot be safely obtained.
RTOG 0617 established that 74 Gy is worse than 60 Gy and highlighted the importance of heart dose.
EGFR targeted therapy: Osimertinib is the modern standard (LAURA for unresectable stage III; ADAURA for resected IB-IIIA). Afatinib (an irreversible pan-ErbB blocker) is also an acceptable first-line agent for advanced EGFR+ (Exon 19 del / L858R) disease.
PACIFIC remains the standard post-CRT strategy for unresectable wild-type stage III NSCLC.
LAURA is the new standard for EGFR+ unresectable stage III disease after CRT.
Concurrent IO + CRT has not outperformed the adjuvant/consolidation approach in either NSCLC or LS-SCLC.
Lung ART means PORT is no longer routine after complete resection of pN2 NSCLC.
Turrisi BID 45 Gy remains a classic LS-SCLC standard; CONVERT and CALGB 30610 support daily alternatives.
ADRIATIC made adjuvant durvalumab standard after LS-SCLC CRT.
ES-SCLC PCI is now optional in the MRI-surveillance era because Takahashi failed to confirm the earlier EORTC survival benefit. The substantial risk of brain metastases justifies strict MRI surveillance + salvage SRS to spare ~50% of patients from whole-brain toxicity.
HA-PCI is reasonable with strong QA and memantine, but the randomized data are mixed.
Trimodality in stage IIIA(N2) is not a routine OS-improving strategy; lobectomy-only subgroups remain hypothesis-generating.
Perioperative IO is now established in resectable NSCLC, but if surgery does not happen, management generally falls back to definitive CRT principles.
Thymic tumors: dose escalates by residual disease: R0 about 45-50.4 Gy, R1 about 50-54 Gy, gross disease about 60-70 Gy.
Mesothelioma: systemic therapy dominates; RT is most often palliative, while hemithoracic RT is specialized and toxicity-sensitive.

CONSOLIDATED DOSE TABLE

Setting	Dose / regimen	Why it matters
Peripheral early NSCLC SBRT	18 Gy x 3	RTOG 0236 / 0618-style high-BED anchor
Peripheral near chest wall	50-60 Gy / 5 fx	More fractions can help meet chest wall / rib constraints
Central NSCLC SBRT	50-60 Gy / 5 fx	RTOG 0813 framework; avoid 3-fx central regimens
Ultra-central NSCLC	60 Gy / 8 fx	SUNSET-style safer ultracentral approach
Definitive LA-NSCLC CRT	60 Gy / 30 fx	Standard after RTOG 0617
Poor-prognosis LA-NSCLC hypofractionation	42 Gy / 15 fx	CONCERT/TROG-style shorter course
Postoperative NSCLC, selective R0 pN2	50-54 Gy	If PORT is chosen despite Lung ART
Postoperative NSCLC, microscopic residual	54-60 Gy	Close / positive margin range
Postoperative NSCLC, gross residual	60-66 Gy	Definitive-style residual-disease dose
LS-SCLC classic thoracic RT	45 Gy BID	Turrisi benchmark
LS-SCLC daily thoracic RT	66 Gy / 33 or 70 Gy / 35	CONVERT / CALGB 30610 daily alternatives
ES-SCLC consolidative thoracic RT	30 Gy / 10	Slotman regimen for selected responders
SCLC PCI	25 Gy / 10	Standard PCI dose; avoid 36 Gy
Thymic PORT, R0	45-50.4 Gy	Microscopic-risk postoperative dose
Thymic PORT, R1	50-54 Gy	Positive-margin dose
Thymic gross residual / unresectable	60-70 Gy	Gross disease range
Mesothelioma palliation	8 Gy x 1, 20 Gy / 5, 30 Gy / 10	Symptom-focused RT

KEY LANDMARK TRIALS (memorize)

Trial	Disease	One-line takeaway
NLST	Lung screening	LDCT reduced lung cancer mortality by 20%
NELSON	Lung screening	Confirmed a major mortality benefit, especially in women
STARS/ROSEL pooled	Operable T1-T2 N0 NSCLC	Suggestive SBRT survival signal, but underpowered and not definitive
RTOG 0236	Inoperable peripheral T1-T2 NSCLC	Established high local control with 18 Gy x 3
RTOG 0618	Operable peripheral T1-T2 NSCLC	Confirmed SBRT efficacy in operable pts
CHISEL	Peripheral inoperable T1-T2a	SBRT outperformed conventional RT
RTOG 0813	Central T1-T2 NSCLC	12 Gy x 5 identified as the MTD
HILUS	Ultra-central lung tumors	Highlighted major fatal bleeding risk with unsafe 8-fx schedules
SUNSET	Ultra-central NSCLC	7.5 Gy x 8 supports a safer modern approach
RTOG 73-01	LA-NSCLC RT alone	Helped establish 60 Gy as the classic RT-alone benchmark
Concurrent CRT meta-analysis	LA-NSCLC	Concurrent CRT improved OS over sequential therapy
RTOG 0617	LA-NSCLC	74 Gy was worse than 60 Gy; heart dose matters
PACIFIC	Unresectable stage III NSCLC	Durvalumab after CRT improved PFS and OS
PACIFIC-2	Unresectable stage III NSCLC	Concurrent durvalumab strategy was negative
LAURA	EGFR+ unresectable stage III NSCLC	Osimertinib after CRT transformed outcomes
INT 0139	Stage IIIA(N2) resectable	No OS benefit for routine trimodality; pneumonectomy problematic
EORTC 08941	Stage IIIA(N2) responders	Surgery was not superior to RT after induction chemotherapy
CheckMate 816	Resectable NSCLC	Neoadjuvant nivo + chemo dramatically improved pCR
KEYNOTE-671, AEGEAN	Resectable NSCLC	Perioperative IO improved event-free outcomes
Lung ART	Completely resected pN2 NSCLC	Modern PORT did not improve DFS or OS
Intergroup 0096 / Turrisi	LS-SCLC	45 Gy BID improved survival vs daily 45 Gy
CONVERT	LS-SCLC	66/33 daily was equivalent to BID treatment
CALGB 30610	LS-SCLC	70/35 daily also performed similarly to BID
ADRIATIC	LS-SCLC after CRT	Adjuvant durvalumab became the new standard
NRG-LU005	LS-SCLC	Concurrent atezolizumab + CRT was negative
Slotman thoracic RT	ES-SCLC responders	Supported selective consolidative thoracic RT
Auperin	LS-SCLC CR	PCI improved survival by about 5%
Le Pechoux	LS-SCLC PCI dose	25 Gy remained the PCI standard
Slotman EORTC	ES-SCLC responders	PCI improved brain control and OS before routine MRI surveillance
Takahashi	ES-SCLC with MRI surveillance	PCI did not improve OS in the MRI era; 48% brain mets with PCI vs 69% with surveillance.
GOECP-SEOR / PREMER	HA-PCI	Positive randomized signal for cognitive preservation
NRG-CC003	HA-PCI	Mixed result, but composite neurocognitive outcomes favored HA-PCI
CheckMate 743	Unresectable pleural mesothelioma	Nivolumab/ipilimumab improved OS versus platinum/pemetrexed chemotherapy
MARS 2	Resectable pleural mesothelioma	Extended pleurectomy/decortication worsened survival and serious AEs versus chemotherapy alone