Effect of Cryotherapy in the Prevention of Madarosis Produced by Chemotherapy in Breast Cancer Patients

University of Salamanca

Status: Enrolling

Conditions: Eyebrow Diseases; Eyelash Diseases; Madarosis; Alopecia; Breast Neoplasms; Anthracyclines; Taxoids; Side Effects

Treatments: Device: cryotherapy for chemotherapy-induced madarosis

Study type: Interventional

Funder types: Other

Identifiers

NCT06955702

PC_TCUE23-24_033

Details and patient eligibility

About

Chemotherapy-induced alopecia (CIA) significantly compromises body image in breast cancer patients, particularly when involving eyebrow and eyelash loss (madarosis). While scalp cooling devices are routinely employed to prevent scalp alopecia, no standardized interventions exist for madarosis prevention. This quasi-experimental study assesses the efficacy of targeted eyebrow cryotherapy in reducing anthracycline- and taxane-induced madarosis.

The trial will enroll patients from two tertiary hospitals in Salamanca (intervention arm: cryotherapy) and a control cohort from Santander. Cryotherapy will be administered (-4°C to -7°C) 15 minutes pre-chemotherapy infusion and maintained for 20 minutes post-infusion. Primary outcomes include hair retention quantified through photogrammetric analysis (TIDOP Research Group) at four timepoints: baseline, mid-treatment, chemotherapy completion, and 1-month follow-up. Secondary endpoints evaluate quality of life (QLQ-C30 validated scales) and cryotherapy-related adverse events (CTCAE v5.0 criteria).

This investigation aims to establish the first evidence-based protocol for madarosis prevention and develop a novel alopecia classification scale, addressing a critical gap in supportive oncology care

Full description

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.

Enrollment: 120 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Female participants aged ≥18 years
• Newly diagnosed breast cancer (any stage)
• Scheduled to receive anthracycline- and/or taxane-based chemotherapy as first-line systemic treatment
• No prior history of antineoplastic treatment
• Willing and able to provide written informed consent

Exclusion criteria

• Patients with recurrent disease who have received prior hormone therapy, chemotherapy, and/or immunotherapy
• Presence of alopecia prior to the initiation of cancer treatment
• History of cerebral radiotherapy

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Cryotherapy on Eyebrows + Chemotherapy (Anthracyclines and Taxanes)

Experimental group

Description:

Cryotherapy is administered via thermally regulated cold eye masks (-10°C ± 2°C) positioned over the supraorbital region, with application commencing 15 minutes pre-chemotherapy and continuing through the infusion period plus 20 minutes post-administration. Chemotherapy includes anthracyclines (doxorubicin/epirubicin) and/or taxanes (paclitaxel/docetaxel) per standard protocols.

Treatment:

Device: cryotherapy for chemotherapy-induced madarosis

Standard chemotherapy (no cryotherapy)

No Intervention group

Description:

Patients receive anthracycline/taxane-based chemotherapy per institutional protocols without application of cold eye masks or any cryotherapy intervention. All other supportive care measures match the experimental group.