3681 - Prognostic Value of the Time-of-Day Radiotherapy in Non-Small Cell Lung Cancer Patients Receiving Concurrent Chemotherapy and Radiotherapy Followed by Immunotherapy
Presenter(s)
H. Yu1,2, X. Liu3, J. Ma4, Y. Qin5, J. Lv6, J. Yuan7, F. Wang7, Y. Xu7, B. Tian7, and D. Chen7; 1Shandong University Cancer Center, Shandong University, Jinan, Shandong, China, 2Shandong Cancer Hospital and Institute, Jinan, Shandong, China, 3Shandong Second Medical University, weifang, China, 4Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 5Shandong University Cancer Center, Jinan, Shandong, China, 6Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 7Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
Purpose/Objective(s):
Circadian rhythms have far-reaching physiological effects and extend to influence clinical practice, as evidenced in the field of immunotherapy. Early time-of-day administration (ToDA) of immune checkpoint inhibitors (ICIs) has been shown to improve survival. However, the effects of circadian rhythms on radiotherapy (RT) remain unclear. This study aimed to investigate the impact of time-of-day RT on patients with unresectable stage III non-small cell lung cancer (NSCLC).Materials/Methods:
This retrospective study included unresectable stage III NSCLC patients from our institution in China between July 2020 and December 2023. Patients were divided into two cohorts based on the ToDA of the initial four ICI infusions (Cohort 1: =2 infusions before 11:30; Cohort 2: 0-1 infusion before 11:30). RT delivery time points were converted to decimal hours (e.g., 10:30 becomes 10.5). Kaplan-Meier and Cox models were used to evaluate the association between RT timing and survival outcomes across a range of cut-off times ranging from 10:30 to 13:30. To account for the circular nature of time, Cox models with periodic restricted cubic splines (RCS) were employed to assess the relationship between continuous RT timing and the risk of death or disease progression. The Akaike Information Criterion (AIC) guided the selection of knot numbers. The median RT time for each patient was used as a continuous variable in the periodic RCS models, adjusting for characteristics such as age and gender.Results:
A total of 177 patients were included (Cohort 1: n=67; Cohort 2: n=110). The cohort was predominantly male (n=164, 92.7%) and presented with squamous cell carcinoma (n=125, 70.6%). All patients received either anti-PD-1 (n=94, 53.1%) or anti-PD-L1 (n = 83, 46.9%) inhibitors as consolidation therapy. Notably, in Cohort 2, patients for whom the majority of cCRT sessions were delivered after 12:00 showed significantly improved progression-free survival (PFS) (HR=0.57 [95% CI, 0.33-0.98]) and higher post-RT absolute lymphocyte count (ALC) (p=0.02). This benefit of afternoon RT was further supported by a continuous analysis, which revealed a significant and gradual increase in the risk of death or progression for treatments administered in the morning, peaking around 7:00 AM (HR=1.18 [95% CI, 1.04-1.33]). This association between RT timing and survival was not observed in Cohort 1, where patients received the majority of their ICI infusions before 11:30.Conclusion:
This time-of-day RT study suggests that morning RT is associated with worse outcomes compared to afternoon RT. Administering RT after noon appears to protect lymphocytes, enhance the efficacy of immunotherapy, and improve patient survival. These findings are of significant importance for guiding the timing of clinical RT and warrant validation in prospective randomized trials to inform future clinical practice.