Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study

ABSTRACT

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

KEYWORDS:

• Nasopharyngeal carcinoma
• radiotherapy
• chronotherapy
• survival outcome
• toxicity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

JL, XTL and RZ contributed equally to this work. All authors have made significant contributions to the conception, supervision, and final approval of the manuscript.

Data availability statement

Data are available upon reasonable request to the corresponding author.

Ethics approval and consent to participate

The experiments involving human participants were reviewed and approved by internal review and the ethics boards of the Affiliated Cancer Hospital and Institute of Guangzhou MedicalUniversity(GYZL-ZN-2023(002)), Fujian Medical University UnionHospital(2023KY022), and The First Affiliated Hospital of Hainan MedicalUniversity(2023-KYL-021) and conducted in accordance with the Declaration ofHelsinki.

List of abbreviations

Nasopharyngeal carcinoma (NPC); radiotherapy (RT); intensity-modulated radiotherapy (IMRT);period circadian regulator 2 (PER2); overall survival (OS); progression-free survival (PFS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS); morning (DAY); night (NIGHT); darker half of the year (WINTER);  tumor – node – metastasis(TNM); Karnofsky performance status (KPS); hazard ratios (HRs); confidence intervals (CIs).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/07420528.2024.2337887.

Additional information

Funding

This study was financially supported by National Natural Science Foundation of China under [Grant 82102974, 82373516 and 82173452], the Guangzhou Science and Technology Program of China under [Grant 202201011048], National Natural Science Foundation of Fujian Province of China under [Grant 2020J011014], Fujian Provincial Health Technology under [Grant 2021CXA011], Natural Science Foundation of Guangdong Province of China under [Grant 2023A1515011670], the Medical Science and Technology Foundation of Guangdong Province under [Grant A2022287], Medjaden Academy & Research Foundation for Young Scientists under [Grant MJA202306035], Beijing Science And Technology Innovation Medical Development Foundation under [Grant KC2023-JX-0186-BQ081].