Randomized Evaluation of the PET-Adjusted IMRT for NSCLC Trial (REPAINT)

Area of Science:

• Radiation Oncology
• Medical Physics
• Clinical Trial Design

Background:

• Standard radiation therapy (RT) for locally advanced nonsmall cell lung cancer (LA-NSCLC) uses a uniform dose of ~60 Gy.
• Recent trials suggest RT dose escalation may not improve outcomes and can increase toxicity.
• A prior single-arm trial explored a personalized, risk-adapted, deintensified RT strategy.

Purpose of the Study:

• To report findings from a randomized trial testing a novel, personalized, risk-adapted, and deintensified RT strategy for LA-NSCLC.
• To compare patient-reported outcomes between standard RT and dose-painted RT.
• To evaluate the impact of RT de-escalation on progression-free survival (PFS) and overall survival (OS).

Main Methods:

• Patients with LA-NSCLC (ECOG 0-2) were randomized 1:1 to standard RT (60 Gy/30 fractions) or dose-painted RT (55 Gy/20 fractions to high-metabolic-volume areas, 44-48 Gy/20 fractions to others).
• Metabolic tumor volume was assessed using fludeoxyglucose PET to guide dose painting.
• Concurrent chemotherapy and adjuvant therapy were administered in both arms; patient-reported outcomes were the primary endpoint.

Main Results:

• Fifty patients were enrolled; common grade 3 toxicities included dysphagia, fatigue, cough, and wheezing.
• Median PFS was 18 months and median OS was 42 months, with no significant difference between arms (P=.562 and P=.765, respectively).
• Dose-painted RT significantly reduced grade 3-4 lymphopenia (48% vs 81%, P=.012).

Conclusions:

• High-grade patient-reported toxicity is common with concurrent chemoradiotherapy for LA-NSCLC.
• Risk-adapted RT de-escalation did not compromise clinical outcomes (PFS, OS) in this trial.
• Further studies are warranted to confirm the improved safety profile of this de-escalation approach in LA-NSCLC treatment.