Scalp cooling versus standard cold-cap in preventing chemotherapy-induced alopecia in patients with localized breast cancer: ICELAND protocol, a randomized controlled trial and economic evaluation.

BACKGROUND: Chemotherapy-induced alopecia (CIA) remains one of the most distressing adverse effects for patients with localized breast cancer receiving anthracycline and taxane-based chemotherapy regimens. Although automated scalp cooling systems and standard non-automated cold-cap devices have demonstrated efficacy in reducing CIA, controlled trials with direct randomization comparing these two modalities of scalp cooling are lacking. This study aims to compare clinical efficacy, patient-reported outcomes, and medico-economic impact of a scalp cooling system (PAXMAN® PSCS 2) versus standard cold-cap therapy in preventing CIA.

METHODS/DESIGN: ICELAND is a prospective, multicenter, open-label, randomized controlled phase III trial conducted in three French cancer centers. This study addresses female adult patients with histologically confirmed, non-metastatic breast cancer, scheduled to receive neoadjuvant or adjuvant chemotherapy with epirubicin-cyclophosphamide (3 or 4 cycles) followed by either docetaxel (3 cycles) or paclitaxel (9-12 weekly cycles) as per routine practice. A total of 196 patients will be 1:1 randomized to automated scalp cooling device (experimental arm) or standard non-automated cold-cap therapy (control arm), with stratification on chemotherapy regimen, menopausal status and centre. The primary endpoint is the proportion of patients experiencing no more than half hair loss (NCI-CTCAE v5.0 grade 0-1) from baseline to chemotherapy completion, as assessed by blinded central review of standardized photographs. Secondary endpoints include: degree of CIA before taxane initiation; hair regrowth 6 months after the end of chemotherapy; patient adherence and comfort for each scalp cooling modality; body image (BIS); quality of life (EORTC QLQ-C30/BR23); anxiety/depression (HADS); satisfaction with care (OUTPATSAT-35-CT); return to work; nursing time associated with device use; and cost-utility in QALYs.

DISCUSSION: This study will provide the first high-quality randomized evidence directly comparing scalp cooling and standard cold-cap use for CIA prevention in localized breast cancer. The results will inform both clinical practice and health policy by integrating clinical efficacy, patient-reported outcomes, and medico-economic considerations.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06011525.