Clinical Benefit of Spa Care on Severe Radiation-induced Fibrosis After Postoperative Radiotherapy for Breast Cancer

Study Overview
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Brief Summary
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This study evaluates the dermatological life quality six months after spa cares in patients with severe late toxicity involving the skin and / or soft tissues after postoperative radiotherapy for breast cancer. Half of the patients will be treated with a combination of pentoxifylline (PTX) and alpha-tocopherol (Vit E) when Half of the patients will receive skin-oriented spa cares in addition.

Detailed Description
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The combination of PTX and vit E appears as the standard treatment of radiation induced fibrosis. Synergism between PTX and Vit E is likely, as treatment with each drug alone is ineffective. This combination was also positively evaluated in the treatment of osteoradionecrosis, radiation-induced pelvic neuropathies, pneumoniae as well as bowel pathologies. Spa cares are part of the standard treatment of burn scars. Two spa treatments per year enable the mitigation or disappearance (after several treatments) of pruritus, dysesthesia, local inflammation, hypertrophy and sclerosis. They promote the healing of chronic superficial erosions. The spa treatment combines baths, sprays and especially filiform showers with thermal water jets under high pressure for a few minutes.

Official Title
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Evaluation of the Clinical Benefit of a Spa Care on the Evolution of Late Fibrosis After Postoperative Radiotherapy for Breast Cancer in Remission

Conditions
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Breast Carcinoma, Fibrosis

Intervention / Treatment
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* Other: skin-oriented spa care
* Drug: Pentoxifylline
* Drug: Tocopherol acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women age ≥ 18 and <80 years old invasive or in situ breast carcinoma non-metastatic disease. postoperative radiotherapy completed since at least 6 months unilateral breast radiotherapy grade > 2 dermal and/or soft tissue toxicity (CTCAE v4.0) no inflammatory ou infectious flare on the breast at the time of inclusion ability to provide an informed written consent form affiliation to a social security system Exclusion Criteria: age <18 or ≥ 80 years old evolutive cancer Metastatic Disease Patient undergoing specific treatment for breast cancer (except adjuvant endocrine therapy and / or adjuvant Herceptin) at the time of inclusion bilateral Breast/chest wall Radiotherapy breast prosthesis bearer Body Mass Index > 40 or <18.5 chronic skin ulceration within the treated breast at the time of inclusion contraindications to spa care : inflammatory disease in flare at the time of inclusion active infections heart failure (NYHA class> 1) chronic respiratory failure labile blood pressure bullous dermatitis evolutive chronic skin disease hypersensitivity to pentoxifylline or any of the excipients acute myocardial infarction ongoing hemorrhage or major bleeding risk use of oral anticoagulants pregnant or likely to be in 6 months or breastfeeding patients deprived of liberty or under supervision

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination tocopherol/pentoxifylline + spa care<br>pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months AND skin-oriented spa care (18 days) | Other: skin-oriented spa care<br>* standardized procedure : 72 care sessions over 18 days of treatment +/- Additional care according to the specificity of each spa<br>Drug: Pentoxifylline<br>* 400 mg bid during at least 6 months<br>Drug: Tocopherol acetate<br>* 500 mg bid during at least 6 months<br>|
| Active Comparator: combination tocopherol/pentoxifylline<br>pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months | Drug: Pentoxifylline<br>* 400 mg bid during at least 6 months<br>Drug: Tocopherol acetate<br>* 500 mg bid during at least 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Quality of life at 6 months | Self-reported dermatology quality of life using the standardized Dermatology Life Quality Index (DLQI) ; This score assess the functional impact of fibrosis: eg. intensity of pain, itching... (10 items). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | 6 months after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Quality of life at 12 months | Self-reported dermatology quality of life using the standardized Dermatology Life Quality Index (DLQI) ; This score assess the functional impact of fibrosis: eg. intensity of pain, itching... (10 items). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | 12 months after the end of treatment | 
| Overall quality of life | quality of life questionnaire (EORTC QLQ C30 score) | 6 months | 
| Breast-oriented quality of life | EORTC QLQ-BR23 score | 6 months | 
| late radiation toxicity | Evaluation of late toxicity performed independently and in blind by another radiation oncologist from the same center, using the CTCAE v4.0 scale modules: Skin and subcutaneous tissue disorders / Musculoskeletal skeletal / Reproductive organs and breast | 6 months | 
| Skin thickness | The skin thickness will be assessed in blind by an independently radiologist using a standardized Ultrasound scan procedure (Yoshida EJ, et al; Int J Radiat Oncol Biol Phys. 2012) Skin thickness is measured as the distance between the entry ultrasound echo signal to the border between the dermis and hypodermis . Measurements are acquired from ten locations: five on the treated (irradiated) breast (12:00, 3:00, 6:00, 9:00, and tumor bed), and five corresponding locations on the untreated (contralateral) breast - serving as controls to account for patient baseline variation | 6 months | 
| Cosmetic appearance | The cosmetic appearance will be evaluated by the investigator with the Harvard-breast-cosmesis-scale (HBCS). HBCS classifies the overall aesthetic results in four categories from excellent, good, fair to poor; comparing the treated breast to the control breast | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spa care, randomised controlled trial, pentoxifylline/tocopherol combination, late sequelae, radiotherapy