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Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients.

K Johnson1, J Chang-Claude2, A-M Critchley1

  • 1Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Clinical Oncology (Royal College of Radiologists (Great Britain))
|November 4, 2018
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Summary

Morning radiotherapy may increase late side effects in breast cancer patients, particularly those with specific circadian rhythm gene variants. Optimizing treatment timing based on genetic profiles could reduce toxicity.

Keywords:
Adverse reactionsbreast cancercircadian rhythmgenetics

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Area of Science:

  • Oncology
  • Genetics
  • Chronobiology

Background:

  • Radiotherapy is a cornerstone cancer treatment, but late side effects impact a subset of patients.
  • Emerging evidence implicates circadian rhythm disruption in the development of these radiotherapy-induced toxicities.

Purpose of the Study:

  • To investigate the impact of radiotherapy timing on acute and late side effects in breast cancer patients.
  • To explore the association between circadian rhythm gene variants and radiotherapy toxicity.

Main Methods:

  • Retrospective analysis of 535 breast cancer patients (LeND cohort) for late effects using LENT-SOMA.
  • Prospective assessment of 343 patients (REQUITE study) for acute effects using CTCAE v4.
  • Genotyping for candidate circadian rhythm variants.

Main Results:

  • Morning radiotherapy was linked to significantly increased late toxicity in the LeND cohort (P=0.01).
  • Increased acute effects were observed with morning treatment in the REQUITE group (univariate, P=0.03).
  • Specific genotypes (PER3 4/4 and NOCT rs131116075 AA) were associated with increased late effects from morning radiotherapy.

Conclusions:

  • Radiotherapy timing may influence treatment toxicity.
  • Identifying patients with specific circadian rhythm gene variants could allow for personalized radiotherapy scheduling to minimize side effects.