2534 - High PD-L1 Expression is Associated with Adaptive Replanning in Patients with Locally Advanced (LA) Non-Small Cell Lung Carcinoma (NSCLC) Treated with Chemoradiotherapy (chemoRT)
Presenter(s)
J. Zagelbaum1,2, M. J. Khandekar1,3, A. J. Cooper4, H. Willers3, and F. K. Keane3; 1Harvard Medical School, Boston, MA, 2Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 3Department of Radiation Oncology, Mass General Brigham/ Massachusetts General Hospital, Boston, MA, 4Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY
Purpose/Objective(s): For patients with LA-NSCLC receiving definitive chemoRT, significant decreases in tumor volumes and other anatomical changes over the course of treatment can necessitate adaptive replanning. Adaptive replanning has been shown to spare surrounding organs at risk (OAR) and facilitate dose-escalation but can be resource intensive. There are limited data identifying which patients are most likely to require adaptive replanning. Increased PD-L1 expression is predictive of response to immune checkpoint inhibitors but its association with chemoRT response is not well understood. We hypothesized that PD-L1 expression would impact the likelihood of needing adaptive replanning during chemoRT.
Materials/Methods: We retrospectively analyzed the records of consecutive patients with LA-NSCLC treated with definitive RT to a dose of > or equal to 60 Gy with concurrent chemotherapy followed by consolidative durvalumab from 9/1/17 through 12/31/22. Patients were immobilized with a custom vac-lok bag, and 4D CT was performed. VMAT was used for all patients. Treatment was delivered using daily cone-beam CT guidance. Selection of patients for off-line adaptive replanning was at the discretion of the treating physician.
Results: We identified 73 consecutive patients treated with definitive chemoRT followed by durvalumab. Median age was 68 years (range 49-83). Median ECOG PS was 1 (range 0-2). 20 tumors (27.4%) had PD-L1 expression > or equal to 50%, 18 (24.7%) had PD-L1 expression 1-49%, 19 (26.0%) had PD-L1 expression <1%, and 16 (21.9%) had unknown expression. A total of 31 patients (42.5%) required adaptive replanning at a median of 23 days after start of RT (range 12 Ð 43), with a median decrease in ITV volume of 32.5% (range 8 Ð 57.7%). When stratified by PD-L1 expression, there was a significant increase in the likelihood of replanning for patients with PD-L1 > or equal to 50% compared with the rest of the study population (65% vs. 34%, p = 0.02 calculated by Chi-squared test). With a median follow-up of 52.4 months (range 4.9 Ð 90.1), there was a significant improvement in median OS in patients with PD-L1 > or equal to 50% compared with the rest of the cohort (NR vs. 34.3 months, p = 0.0035).
Conclusion: PD-L1 expression > or equal to 50% was associated with an increased likelihood of needing adaptive replanning during definitive chemoRT. These data support that PD-L1 expression can be used as a biomarker when determining which patients may benefit from online adaptive therapy. Future studies to investigate whether aggressive replanning of PD-L1 high patients allows for lymphocyte and lymph node sparing may be fruitful in increasing the efficacy of adjuvant immunotherapy after chemoRT.