Restoration of melatonin rhythms reduces tumour-promoting inflammation in oesophageal cancer survivors: a prospective cohort study.

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.