In unresectable stage IIIA/IIIB NSCLC, does escalating definitive thoracic RT from 60 Gy to 74 Gy improve survival when given with concurrent chemotherapy? [RTOG 0617]
In unresectable stage IIIA/IIIB NSCLC, does escalating definitive thoracic RT from 60 Gy to 74 Gy improve survival when given with concurrent chemotherapy?
Absolute Effect
Median OS was 28.7 months with 60 Gy versus 20.3 months with 74 Gy; HR 1.38 (95% CI 1.09–1.76) for 74 vs 60 Gy. Five-year OS was 32.1% versus 23.0%.
Absolute effect: At 5 years, OS was 9.1 percentage points lower with 74 Gy (23.0% vs 32.1%). This is an absolute harm from dose escalation, not merely failure to demonstrate benefit.
NNT: not applicable. The high-dose strategy was inferior; a number-needed-to-treat-for-benefit is inappropriate.
NNH: 9, based on grade ≥3 esophagitis (17.4% vs 5.0%; absolute increase 12.4 percentage points).
Follow-up: Median follow-up 5.1 years in the long-term report.
Clinical results and treatment burden
- Intervention: Standard-dose arm: 60 Gy in 30 fractions with concurrent weekly carboplatin/paclitaxel followed by consolidation chemotherapy. High-dose arm: 74 Gy in 37 fractions with the same systemic backbone. The factorial cetuximab question is not the focus of this page.
- Principal toxicity: The principal clinically central toxicity was severe esophageal toxicity. Grade ≥3 dysphagia was 12.1% vs 3.2% and grade ≥3 esophagitis 17.4% vs 5.0% with 74 vs 60 Gy. Grade-5 adverse events were 9 vs 3.
- Other efficacy/recurrence findings: Grade ≥3 pulmonary toxicity was similar (19.3% vs 20.6%). Treatment-related toxicity and difficulty completing chemotherapy were greater with 74 Gy. No clinically meaningful survival subgroup overturned the main dose finding.
- Quality of life: Quality-of-life analyses supported the clinical relevance of increased esophageal toxicity; the survival disadvantage remained the dominant result.
Eligibility and clinical context
464 eligible patients with newly diagnosed unresectable stage IIIA/IIIB NSCLC; most had good performance status and modern PET-based staging.
Limitations and maturity: The trial used conventional 2-Gy fractionation and older-era concurrent chemotherapy/supportive care. The dose comparison cannot be extrapolated to modern proton/SABR strategies or altered fractionation. The factorial cetuximab question was separately negative.