Abstract
To the editor,
We read with great interest the recently published article by Sadeghi Yazdankhah et al 1 titled “Efficacy of Melatonin in Alleviating Radiotherapy-Induced Fatigue, Anxiety, and Depression in Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled Trial.” The authors provide us with a well-conducted randomized, triple-blind, placebo-controlled trial investigating the efficacy of daily 20 mg oral melatonin in alleviating radiotherapy-induced fatigue, anxiety, and depression in breast cancer patients undergoing adjuvant radiotherapy. They conclude that melatonin administration during radiotherapy significantly improved symptoms of fatigue, anxiety, and depression, with consistent benefits observed across different disease stages. We commend the authors for their valuable contribution to this field but further considerations to enhance the accuracy of future studies would be valuable. I hope the authors will consider the following suggestions.
Firstly, the control for confounding factors appears insufficient. While randomization ensures balance in known variables, other unmeasured variables—including psychosocial support, diet, and exercise habits—that might influence fatigue and emotional states were not accounted for. Crucially, the protocol for concomitant medications, such as endocrine therapy, 2 was not explicitly detailed, leaving uncertainty about whether these treatments were uniformly administered across the study groups.
Secondly, while the authors performed subgroup analyses by cancer stage, more granular analyses—such as stratifying by specific adjuvant treatments (eg, type and duration of endocrine therapy)—could have been insightful. Such analyses might reveal whether melatonin’s efficacy is modified by different therapeutic contexts.
Furthermore, the exclusion of patients with comorbidities like diabetes and hypertension, while methodologically sound, may limit the generalizability of the findings to the broader population of breast cancer patients, who often present with such conditions, and might have selected for a cohort with overall healthier profiles.
Finally, while the use of validated subjective tools such as the Multidimensional Fatigue Inventory and Beck’s inventories is commendable, the study’s findings would have been further strengthened if complemented by objective biomarkers. Incorporating physiological measures, such as cortisol 3 and thyrotropin-releasing hormone levels, 4 could have provided a more robust and pathophysiologically grounded assessment of the outcomes.
