ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Restoration of Melatonin Rhythms Reduces Tumor-Promoting Inflammation in Esophageal Cancer Survivors: A prospective cohort study
Tinghui Xu
Ying Jiang
Wenyan Shao
Zhejing Zhou
Pengyi Guo
Department of Cardiothoracic Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China., Ning bo, China
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Abstract
Background: Blunted nocturnal melatonin amplitude is linked to tumour-promoting inflammation in oesophageal-cancer survivors, but it is unclear whether restoring endogenous rhythms improves clinical outcomes.. Methods: In an 18-month prospective cohort conducted in Class 3A hospitals in China and the China Urban Cancer Early Diagnosis and Treatment Project Cohort, 492 stage I–III oesophageal-cancer survivors underwent salivary melatonin profiling and measurement of hs-CRP, IL-6, TNF-α and the neutrophil-to-lymphocyte ratio. Survivors with a night-to-day melatonin ratio < 2.5 initiated a behavioural circadian-realignment programme; rhythm-intact peers received usual care. Linear mixed-effects and Cox models related rhythm restoration to change in composite inflammation burden—calculated as the standardised mean of the four markers—and to major adverse events, adjusting for demographic and clinical covariates. Results: Of 266 rhythm-blunted survivors, 202 (76 %) achieved amplitude ≥2.5 by 12 months. Their composite inflammation score fell by −0.30 ± 0.18 versus −0.03 ± 0.15 in observation participants (between-group difference −0.27, 95 % CI −0.30 to −0.24). Significant time × group interactions were seen for every marker (all p < 0.001). Over 18 months, circadian restoration was associated with a 62 % lower hazard of recurrence, cardiovascular events, second primaries or death (adjusted HR 0.38, 95 % CI 0.21–0.68). Pittsburgh Sleep Quality Index improved by −2.7 points relative to usual care. Conclusion: Behavioural realignment of endogenous melatonin rhythms was associated with sustained reductions in systemic inflammation and fewer adverse events in oesophageal-cancer survivors. Routine circadian-hygiene counselling combined with simple salivary monitoring may help support long-term oncologic and cardiometabolic health.
Summary
Keywords
cancer survivorship, Chronotherapy, circadian hygiene, Melatonin amplitude, Oesophageal cancer, systemic inflammation
Received
12 October 2025
Accepted
16 February 2026
Copyright
© 2026 Xu, Jiang, Shao, Zhou and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Pengyi Guo
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