Clinical trial NCT06955702: Effect of Cryotherapy in the Prevention of Madarosis Produced by Chemotherapy in Breast Cancer Patients
Official title: Effect of Cryotherapy in the Prevention of Alopecia in Eyebrows and Eyelashes in Breast Cancer Patients Treated With Anthracyclines and Taxanes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Alopecia
Madarosis
Eyebrow Diseases
Eyelash Diseases
Anthracyclines
Taxoids
Side Effects
Keywords: Chemotherapy-induced alopecia
Madarosis
Eyebrow preservation
Taxane-induced alopecia
Anthracycline-induced alopecia
Cryotherapy
Supportive care in oncology
Quality of life
Scalp cooling
Patient-reported outcomes
Lead sponsor: University of Salamanca
Sponsor class: OTHER
First posted: 2025-05-02
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Quasi-experimental parallel design comparing cryotherapy vs. standard care in two separate patient groups.
Primary purpose: PREVENTION

Brief summary: 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Eyebrow hair preservation rate
timeFrame: From baseline to 1 month post-chemotherapy completion
Secondary outcomes:
measure: Eyelash hair preservation rate
timeFrame: From baseline to 1 month post-chemotherapy completion
measure: Control group madarosis incidence
timeFrame: From baseline to 1 month post-chemotherapy completion
measure: Change in Body Image Score Measured by EORTC QLQ-BR23
timeFrame: From baseline to 1 month post-chemotherapy completion
measure: Change in Eyelash Satisfaction measured by Eyelash Satisfaction Questionnaire (ESQ)
timeFrame: From baseline to 1 month post-chemotherapy completion
measure: Cryotherapy-related adverse events
timeFrame: From baseline through chemotherapy completion (approximately 20 to 24 weeks)
measure: Proposal of a new madarosis classification scale
timeFrame: Baseline, after cycles (anthracyclines:4; paclitaxel:8/12*; docetaxel:4/6*), 1mo post-treatment. *if n≥30. Duration: ~1 year
Other outcomes:
Locations:
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
Study officials:
affiliation: Universidad Salamanca
name: Marta González Fernández-Conde
role: PRINCIPAL_INVESTIGATOR
References: