In an analysis from the Scandinavian phase III NARLAL2 trial, reported in the Journal of Clinical Oncology, Schytte et al found that fluorodeoxyglucose (FDG)-PET–guided heterogeneously dose-escalated radiotherapy was not associated with greater 6-month toxicity vs standard radiotherapy in definitive chemoradiation therapy for patients with locally advanced non–small cell lung cancer (NSCLC).
Study Details
Between January 2015 and March 2023, 350 patients from 7 Scandinavian sites were randomly assigned to receive standard radiotherapy at 66 Gy in 33 fractions (n = 178) or heterogenous radiotherapy dose escalation (n = 172). Heterogeneous dose escalation was driven by FDG-PET–avid regions, with strict normal tissue dose constraints. Concurrent chemotherapy was cisplatin/carboplatin and vinorelbine. The primary outcome measure was toxicity within 6 months of random assignment. The mean tumor radiotherapy dose in the dose-escalation group was 88 Gy.
Key Findings
At 6 months, there were no significant differences in toxicity between the standard group and dose-escalation group. Grade 2 esophagitis during radiotherapy occurred in 28.1% vs 25.6%, and grade 3 esophagitis was reported in 7.3% vs 4.1%. Grade 2 pneumonitis occurred in 15.7% vs 20.3%, and grade 3 pneumonitis was reported in 3.9% vs 5.8%. Grade 4 toxicity was observed in four patients, all in the standard radiotherapy group (dyspnea, infection, thromboembolic event, and osteomyelitis).
Grade ≥ 3 serious adverse events in the standard vs dose-escalation groups included febrile neutropenia (8 vs 5 patients), lung infection (10 vs 8 patients), pulmonary embolism (5 vs 3 patients), hemoptysis (1 vs 1 patient), and heart toxicity (2 vs 2 patients). Among all patients, 35% had grade ≥ 3 toxicity, and 1% had grade 5 toxicity. Death from potential treatment-related toxicity occurred in four patients, including three in the standard group (from pneumonitis, hemoptysis, and sudden death) and one in the dose-escalation group (from hemoptysis).
The investigators concluded: “Heterogeneous dose escalation did not increase early toxicity despite delivery of 88 Gy mean dose to the primary tumor, demonstrating this as an attractive strategy for [locally advanced] NSCLC radiotherapy dose escalation.”
Tine Schytte, PhD, of the Department of Oncology, Odense University Hospital, Odense, Denmark, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Danish Research Center for Lung Cancer. For full disclosures of the study authors, visit ascopubs.org.
