Association of the time of day of chemoradiotherapy and durvalumab with tumor control in lung cancer

Abstract

Background/purpose: The circadian clock governs the expression of genes related to immunity and DNA repair. We investigated whether the time of day of radiotherapy and/or systemic therapy infusions (chemotherapy or anti-PD-L1) are associated with disease control and survival in locally advanced non-small cell lung cancer (LA-NSCLC).

Materials/methods: 178 consecutive patients with inoperable LA-NSCLC who received definitive chemoradiotherapy followed by durvalumab between 5/2017-8/2022 were reviewed. Outcomes evaluated included progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional control (LRC), and overall survival (OS).

Results: At a median follow up of 48.0 mo from durvalumab initiation, median PFS and OS were 26.2 mo and 50.0 mo, respectively. Median LRC and DMFS were not reached and 41.0 mo, respectively. Receiving > 50 % (N = 23) versus ≤ 50 % (N = 155) of radiotherapy treatments within 3 h of sunset was associated with younger age; otherwise, there were no other differences between cohorts. There were no significant differences in characteristics between patients who received > 50 % (N = 23) versus ≤ 50 % (N = 155) of durvalumab infusions within 3 h of sunset. On multivariable analysis, receiving > 50 % of radiotherapy treatments within 3 h of sunset was independently associated with reduced risk for progression (HR 0.39, p = 0.017) and distant metastasis (HR 0.27, p = 0.007); conversely, receiving > 50 % of durvalumab infusions within 3 h of sunset was independently associated with increased risk for distant metastasis (HR 2.13, p = 0.025). The timing of chemotherapy was not associated with disease outcomes.

Conclusion: The time of day of radiotherapy and durvalumab infusion may be associated with disease control in LA-NSCLC, and the optimal time of treatment depends on the treatment modality.

Keywords: Chronotherapy; Circadian clock; Durvalumab; Non-small cell lung cancer; Radiotherapy.