Background: Chemotherapy-induced alopecia (CIA) is one of the most distressing adverse
effects for breast cancer patients, particularly when involving eyebrow and eyelash loss
(madarosis). While scalp cryotherapy has demonstrated efficacy in reducing CIA, no
standardized protocols exist for preventing madarosis. Preliminary studies suggest
localized cryotherapy may mitigate this effect but robust evidence is lacking.
Objectives: The primary objective is to evaluate the efficacy of supraorbital cryotherapy
in preventing anthracycline- or taxane-induced madarosis in breast cancer patients.
Secondary objectives include: (1) Quantifying chemotherapy-induced alopecia of eyebrows
(madarosis) and eyelashes (milphosis) in control groups, (2) developing a novel alopecia
classification scale for eyebrows and eyelashes (currently nonexistent), (3) assessing
quality-of-life impact using validated questionnaires "European Organisation for Research
and Treatment of Cancer Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23)" and, and
Eyelash Satisfaction Questionnaire (ESQ). (4) monitoring cryotherapy-related adverse
events (e.g., headache, localized pain).
Methodology: This non-randomized, quasi-experimental multicenter trial will be conducted
at hospitals in Salamanca and Santander. The study population will comprise 120 breast
cancer patients receiving anthracycline/taxane-based chemotherapy (sample size may be
adjusted based on recruitment). Inclusion criteria: women >18 years old with recent
diagnosis and no prior treatments. The intervention group will receive supraorbital
cryotherapy using temperature-controlled devices (-4°C to -7°C) applied 15 minutes before
chemotherapy infusion and maintained for 20 minutes post-infusion.
Outcome Measures: Primary outcomes will be assessed via:
Photogrammetric analysis (TIDOP Research Group) at four timepoints: baseline,
mid-treatment, end-of-treatment, and 1-month follow-up. Hair retention will be
quantified using automated AI algorithms (DAM-Net).
Patient-reported outcomes using the EORTC QLQ-BR23 and ESQ questionnaires.
Adverse event monitoring through ad hoc surveys. Statistical Analysis: Data will be
analyzed using ANOVA and Mann-Whitney tests for intergroup comparisons,
Pearson/Spearman correlations for continuous variables, and linear regression to
identify predictive factors.
Ethics: The study has been approved by the Ethics Committees of Salamanca Health Area
(Ref: 2023 09 1427) and Hospital Universitario Marqués de Valdecilla (Cantabria, Spain)"
(Ref: 2024.459). All participants will provide written informed consent in accordance
with the Helsinki Declaration and "General Data Protection Regulation (GDPR)".
Limitations: Current evidence on madarosis/milphosis is limited, and no validated scales
exist for grading eyebrow/eyelash alopecia.
Innovations: This study introduces: (1) the first classification scale for
chemotherapy-induced madarosis, (2) evidence for cryotherapy as a preventive
intervention, and (3) an objective AI-powered photogrammetry methodology.