Higher Radiation Doses Safe in NSCLC

TOPLINE:

Heterogeneous escalation of radiotherapy dose guided by imaging in locally advanced non–small cell lung cancer (NSCLC) does not increase early toxicity, a new trial found.

METHODOLOGY:

• Radiotherapy with concurrent chemotherapy is the standard of care for patients with locally advanced NSCLC, despite curatively intended treatment showing suboptimal locoregional control.
• Previous phase 3 trials comparing standard-dose vs high-dose concurrent chemoradiotherapy reported worse survival outcomes in the high-dose arm, attributed to increased treatment-related deaths.
• For the new trial, researchers recruited 350 patients from seven institutions in Scandinavia between January 2015 and March 2023, with participants randomly assigned to standard (66 Gray) or heterogeneously dose-escalated radiotherapy arms.
• Eligibility criteria encompassed patients aged at least 18 years with Eastern Cooperative Oncology Group performance status 0-1, histologically confirmed NSCLC stage IIB-IIIB, and feasibility of delivering 66 Gray/33 fraction treatment plan.
• The treatment plans for each patient were created before random assignment with matched mean lung dose and V20Gray, incorporating strict dose constraints for all normal tissues, while toxicity was evaluated weekly during radiotherapy and every 3 months after randomization.
• In this trial, the researchers used fluorodeoxyglucose PET to guide their escalation of radiotherapy doses.

TAKEAWAY:

• Analysis of 178 patients in the standard arm showed median gross tumor and planning target volumes of 54 and 321 cm³, respectively, and that of 172 patients in the dose-escalated arm showed volumes of 61 and 339 cm³, respectively.
• In the standard vs the dose-escalated arm, the rate of grade 2 esophagitis during radiotherapy was 28.1% vs 25.6%, grade 3 esophagitis was 7.3% vs 4.1%, grade 2 pneumonitis was 15.7% vs 20.3%, and grade 3 pneumonitis was 3.9% vs 5.8%.
• The maximum grade of early toxicity aggregated over all toxicities was 35% for grade 3 or greater and 1% for grade 5 in both arms, with four patients experiencing potential treatment-related mortality.
• Heterogeneous dose escalation achieved 88 Gray mean dose to primary tumor without increasing early toxicity compared with standard treatment.

IN PRACTICE:

“Patients with [locally advanced] NSCLC can have radiotherapy dose escalation safely performed using mid-treatment fluorodeoxyglucose positron emission tomography scans, intensity-modulated radiotherapy, and strict adherence to normal tissue dosimetry. This approach was piloted in the randomized phase 3 Scandinavian NARLAL2 trial that documented improved locoregional control…Whether this approach impacts overall survival now needs to be tested in patients who also receive consolidative immunotherapy,” the authors of the study wrote.

SOURCE:

This study was led by Tine Schytte, PhD, and Marianne M. Knap, PhD, from Odense University Hospital in Odense, Denmark. It was published online on April 18 in Journal of Clinical Oncology.

LIMITATIONS:

This study approach depends on additional mid-treatment PET scans and requires rapid planning turnaround, which may present logistical challenges in implementation. The authors noted that while previous studies showed no increased toxicity with fluorodeoxyglucose PET–driven adaptive dose escalation, those studies had relatively modest dose escalation levels compared with this trial.

DISCLOSURES:

Knap received travel accommodations and expenses from MSD Oncology. Rune S. Thing, PhD, disclosed research funding from Elekta and travel accommodations and expenses from RaySearch Laboratories. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.