ESTRO 2024 - Abstract Book

S1611

Clinical - Lung

ESTRO 2024

III(N2) non-small cell lung cancer (NSCLC). We report on the RT quality assurance (RTQA) and interim safety of RT within the study.

Material/Methods:

In this non-comparative randomized phase II trial, patients with resectable stage IIIA-B(N2) NSCLC receive three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 followed by a single-dose of durvalumab (1500 mg) and one of three randomized RT regimens: 20 x 2 Gy (arm A), 5 x 5 Gy (arm B), or 3 x 8 Gy (arm C; delivered inhomogeneously with prescription to the 65% - 80% isodose). Patients then undergo resection, followed by adjuvant durvalumab (1500 mg q4w) for one year. The primary endpoint is 12-month event-free survival (EFS) for the entire cohort, with exploratory (including translational) analyses studying potential differences between the RT regimens. Immune-modulatory RT is delivered to the primary tumor only, with strict constraints for organs at risk (OAR) and metastatic lymph nodes (LN) in the mediastinum. For the purpose of safety and immune-stimulation, these constraints have priority over planning target volume (PTV) coverage. RTQA procedures included a pre-trial dummy run, and plan review of each center’s first patient per arm. A planned interim safety analysis was conducted after 25 patients had undergone surgery. Sixty patients, with a median age of 64 years (range, 40-75), were enrolled at 14 participating centers between July 2020 and October 2023. The pre-trial dummy run procedure was completed successfully by all centers, with major deviations observed in 2 (6%) out of 36 test plans. Thirty-three clinical plans have been reviewed at the time of submission (10 in arm A, 10 in arm B, and 13 in arm C). The median gross tumor volume (GTV) and PTV measured 11.2 cc (range, 0.5-250.6) and 37.3 cc (range, 5.1-402.5), respectively. Incidental dose delivered to mediastinal (N2) LN was a median of 3.5 Gy (Dmean; range, 0.0-6.1), and mean lung doses were 2.9 Gy (range, 0.7-11.9) and 1.8 Gy (range, 0.4-6.0) for the ipsilateral and total lung, respectively. Central thoracic OARs were spared as intended, with median doses of 5.2 Gy (D1cc; range, 0.7-19.1) for the esophagus, 10.8 Gy (D0.1cc; range 0.1-40.0) for proximal bronchial tree, and 0.3 Gy (Dmean; range, 0.1-12.3) for the heart. Two major protocol violations were observed: one chest wall constraint, and one in-PTV hot-spot, both deemed non-critical. Results of the planned interim safety analysis were presented previously (ASCO 2023). Out of 31 patients included, 81% underwent resection (96% R0). There were no treatment-related cancellations or delays in surgery, and 30-day postoperative mortality was 0%. RT-related adverse events (AEs) accounted for 4% of total AEs, with 4 G1, 7 G2 and 1 G4 (postoperative empyema) AEs that were at least possibly related to RT. There was no difference in safety between the arms. Results:

Conclusion:

Immune-modulatory RT was introduced in a multicenter trial for resectable stage III(N2) NSCLC. The RTQA program verified compliance with strict planning constraints, and there were no early safety signals. The SAKK 16/18 study continues enrollment with a target accrual of 90 patients.