ESTRO 2024 - Abstract Book

S1606

Clinical - Lung

ESTRO 2024

Standard treatment for locally advanced NSCLC (LA-NSCLC) involves treating primary pulmonary tumors and involved lymph nodes with a uniform radiotherapy dose of approximately 60 Gy[1]. Recent trials have demonstrated that radiotherapy dose escalation may not improve outcomes[2,3] and that LA-NSCLC patients are at risk for cardiopulmonary toxicity following thoracic radiotherapy[4-6].

We previously performed a single-arm trial testing a personalized, risk-adapted, and de-intensified RT strategy[7]. We now report findings from a randomized trial testing this novel approach.

Material/Methods:

Patients with a new diagnosis of LA-NSCLC and ECOG performance status 0-2 were eligible for this trial (NCT03481114). LA-NSCLC was defined as unresectable stage II disease, stage III disease, or oligometastatic disease for which metastases were treated radically, and concurrent chemoradiotherapy to address the thoracic disease was planned. On each participant’s staging FDG -PET, a semiautomatic gradient-based contouring tool was utilized to delineate the primary tumor and involved regional lymph nodes and calculate metabolic tumor volume (MTV) for each hypermetabolic lesion. Participants were stratified by performance status and primary tumor size and randomized 1:1 to receive standard RT (60 Gy in 30 daily fractions delivered to pulmonary tumor and involved lymph node target volumes) versus dose-painted RT (55 Gy delivered to tumors and lymph nodes with metabolic volume exceeding 20 cm3 and 44-48 Gy to other lesions, all in 20 daily fractions). Standard dosimetric constraints were utilized in both study arms. Concurrent chemotherapy (weekly carboplatin and paclitaxel) was given in both arms, and standard adjuvant systemic therapy was permitted. The primary study objective was to characterize patient-reported outcomes (PROs) utilizing PRO-CTCAE. Secondary objectives included characterizing physician-scored adverse events, establishing associations between RT metrics and PROs, and comparing outcomes between study arms. Fifty participants were enrolled between 2017 and 2023. Twelve patients (24%) had ECOG performance status 0, 25 (50%) patients had performance status of 1, and thirteen patients (26%) had performance status of 2. Forty-seven patients (94%) completed the planned radiotherapy course, and 38 patients (76%) received adjuvant systemic therapy, with 36 receiving durvalumab and two receiving osimertinib for adenocarcinoma with EGFR mutation. The most common grade 3 patient-reported adverse events observed within 90 days of RT completion were dysphagia (38%), fatigue (38%), cough (32%), and wheezing (28%). Using CTCAE v 5.0, rates of physician-scored grade 3 esophagitis, fatigue, and pneumonitis were only 8%, 0%, and 4%, respectively. After adjusting for disease burden, treatment on the dose-painting arm was associated with lower mean RT dose received by the esophagus (-4.0 Gy, p=0.044). Normal tissue complication probability modeling demonstrated strong associations between the extent of normal tissue irradiation and PROs. For example, a mean esophageal dose of 10 Gy yields a 28% risk of grade 3 patient-reported dysphagia, while a mean dose of 30 Gy increases that risk to 57%. Grade 3-4 lymphopenia was significantly less frequent in the dose-painted RT arm than in the control arm (48% v. 81%, chi-square p=0.012). Results:

With a median follow-up duration of 36 months after study entry, the median progression-free survival (PFS) duration is 18 months, and the median overall survival (OS) duration is 42 months. PFS and OS rates were similar