Scalp Cooling as a Biopsychosocial Intervention in Patients Receiving Highly Alopecia-Inducing Chemotherapy: Prospective Single-Arm Study.

Background: Chemotherapy-induced alopecia is among the most psychologically distressing adverse effects of systemic cancer therapy. Although scalp cooling is increasingly used to mitigate hair loss, it is still largely perceived as a cosmetic intervention. Its broader psychological relevance and the biological basis of treatment success, particularly the preservation of follicular integrity under ongoing cytotoxic exposure, remain insufficiently explored. Objective: This study aimed to reconceptualize scalp cooling beyond visible hair preservation by examining its psychological impact on patients receiving highly alopecia-inducing chemotherapy, while integrating quantitative objective hair preservation metrics with structural and ultrastructural analyses of hair follicle damage to identify avenues for improving follicular integrity and scalp-cooling efficiency. Methods: A total of 82 patients undergoing highly alopecia-inducing chemotherapy consisting of a sequential anthracycline-taxane regimen (4 cycles of epirubicin and cyclophosphamide followed by 12 weekly paclitaxel applications) received standardized scalp cooling. Objective hair preservation was quantified using the hair mass index (HMI) as a standardized and reproducible measure of hair retention. Structural and ultrastructural follicular integrity was assessed using light microscopy as well as scanning and transmission electron microscopy. Objective hair preservation metrics were analyzed in relation to patient-reported quality-of-life outcomes (EORTC [European Organisation for Research and Treatment of Cancer]-based measures), subjective treatment burden, and cognitive appraisal of the scalp-cooling experience. Multivariable regression models were applied to identify determinants of posttherapeutic quality of life. Results: Visible chemotherapy-induced alopecia was successfully prevented in more than half of the treated patients. Scalp cooling resulted in substantial objective hair preservation as quantified by the HMI. However, HMI values showed only a limited association with posttherapeutic quality-of-life outcomes. In contrast, the cognitive appraisal of scalp cooling emerged as a central determinant of posttherapeutic quality of life, independent of the degree of objective hair retention. Structural and ultrastructural analyses demonstrated that the preservation of follicular integrity was closely associated with successful macroscopic hair retention under ongoing cytotoxic exposure, supporting a biological basis for the clinical effectiveness of scalp cooling. Conclusions: The clinical relevance of scalp cooling extends beyond objective and visible hair preservation and appears to reside predominantly in its psychological impact on patients undergoing highly alopecia-inducing chemotherapy. Importantly, the identification of structural and ultrastructural markers of follicular vulnerability provides a mechanistic foundation for the future optimization of scalp-cooling approaches and for the development of adjunct follicle-directed protective strategies to enhance follicular integrity and support patient well-being during cytotoxic therapy.