Circadian as a prognostic factor for radiation responses in patients with cervical cancer: A nested case‑control study

Irwan Ramli, Susworo Susworo, Laila Nuranna, Muchtaruddin Mansyur, Alida Roswita Harahap, Setiawan Soetopo, Nurjati Chairani Siregar, Septelia Inawati Wanandi

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The radiation response of cervical cancer is thought to be enhanced by the levels of melatonin due to its roles in the circadian cycle and cancer growth. In the present study, the roles of circadian rhythms and melatonin levels as prognostic factors for predicting the radiation response in patients with cervical cancer were examined. In this nested case‑control study, patients with good and poor responses to radiotherapy were assessed in terms of the time‑of‑day radiation treatment was administered and further influencing factors. The radiation time was determined, as the subjects were either irradiated in the morning (06.00‑10.00 am) or afternoon (04.00‑06.00 pm). Data on tumour size and other biological parameters were collected and analysed by binary logistic regression. Among the 56 patients examined, most subjects had good radiation responses. Most patients were <50 years old with an initial body weight of >50 kg, no pain prior to radiation, low erythrocyte sedimentation rates, normal intravenous urography results, moderate or good differentiation on pathology and histo‑pathologically non‑keratinised cells. According to the multivariate analysis, the irradiation time as a surrogate of the circadian cycle (morning vs. afternoon), the initial haemoglobin (Hb) level and the clinical tumour size were significant predictors of the radiation response. The circadian cycle, tumour size and Hb levels may affect the radiation response in patients with cervical cancer. In addition, the morning group had better 5‑year overall survival, but it was not significant, possibly due to the small cohort size. Further research is required to identify more relevant prognostic factors using different radiotherapy techniques [National Clinical Trial (NCT) no. NCT05511740, registration date, 08/20/2022].

Original languageEnglish
Article number199
JournalOncology Reports
Issue number5
Publication statusPublished - 1 Nov 2022


  • cervical cancer
  • circadian rhythms
  • melatonin
  • nested case‑control
  • prognosis
  • radiation response


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