Evaluation of the Medical Benefit of Spa Therapy on Fibrosis After Postoperative Radiotherapy for Breast Cancer

Study Overview
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Brief Summary
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FIBROTHERME is a comparative, controlled, randomized, multicenter and simple blinded (investigator) trial. The aim of this study is to evaluate the medical benefit in terms of quality of life on the dermatological sequelae of fibrosis 6 months after a dermatologically oriented spa therapy in patients with severe late reactions affecting the skin and/or soft tissues at least 6 months after the end of postoperative radiotherapy for breast cancer.

Detailed Description
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Radiation-induced fibrosis is an equivalent of an orphan disease, in which oncologists have only recently shown interest, despite its prevalence. No study on the medical service provided by crenotherapy has been published in late radiation-induced fibrosis, which shares a common pathophysiology and medico-psycho-social sequelae with the sequelae of burns. Chronic progressive dermatoses are part of the 12 main therapeutic orientations of medical thermalism. In particular, burn scars are a very current indication. Crenotherapy allows the attenuation, or even the disappearance of: pruritus and dysesthesia, local inflammation, hypertrophy and sclerosis and favours the recovery of chronic superficial erosions. Fibrous scars, even old ones, respond favourably to thermal treatments. The thermal treatment combines baths which have a sedative, muscle-relaxing effect and which favour joint mobilisation, sprays which have a decongestant effect and above all thread-like showers which are carried out by jets of thermal water under high pressure for several minutes. The primary endpoint is the self-assessment by the patient of the dermatological quality of life by the DLQI score at 6 months after the end of the treatment compared between the intervention group (immediate treatment) and the control group (delayed treatment after 6 months).

Official Title
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Evaluation of the Medical Benefit of a Spa Therapy on the Evolutionary Genius of Late Sequelae Fibrosis After Postoperative Radiotherapy for Breast Cancer in Remission

Conditions
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Fibrosis, Breast Cancer

Intervention / Treatment
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* Other: Thermal cure with a primary dermatological indication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Age ≥ 18 years In situ or invasive breast cancer DLQI ≥ 6 (at least moderate effect on patient's life) General status WHO 0-1 Post-operative radiotherapy completed at least 6 months ago (with no maximum post radiotherapy delay) Unilateral breast radiotherapy Skin or soft tissue toxicity (- modules: Skin and subcutaneous tissue disorders / Musculoskeletal disorders / Reproductive organs and breast disorders) CTCAE v4.0 grade ≥ 2 No inflammatory or infectious flare at inclusion Female of childbearing potential: negative urine pregnancy test at inclusion Patient informed and signed consent Affiliation to a social security systeme or equivalent Exclusion Criteria: Progressive phase of cancer Metastatic disease Patient undergoing specific treatment for breast cancer (except adjuvant hormone therapy and/or adjuvant herceptin) Bilateral breast/parietal radiotherapy Breast prosthesis wearer Obvious skin ulceration in the treated breast Contraindication to spa treatment (acute inflammatory disease, active infections, heart failure with NYHA stage > 1, chronic respiratory failure, labile hypertension, bullous disease) Chronic progressive dermatological disease Women who are pregnant or likely to become pregnant within 6 months or who are breastfeeding Persons deprived of liberty or under guardianship

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 groups: Immediate spa therapy: the patient carries out the spa therapy soon after the enrolment in the study Late spa therapy: the patient carries out the spa therapy after the 6-month follow up visit
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate spa treatment<br>The spa treatment must be carried out within a maximum of 6 weeks after the inclusion visit. | Other: Thermal cure with a primary dermatological indication<br>* The thermal treatment combines baths which have a sedative, muscle-relaxing effect and encourage joint mobilisation, sprays which have a decongestant effect and, above all, thread-like showers which are carried out by jets of thermal water under high pressure for several minutes plus educational workshops (relaxation, sophrology, hygiene...)<br>|
| Sham Comparator: Late spa treatment<br>The spa treatment must be carried out after the 6-month visit. | Other: Thermal cure with a primary dermatological indication<br>* The thermal treatment combines baths which have a sedative, muscle-relaxing effect and encourage joint mobilisation, sprays which have a decongestant effect and, above all, thread-like showers which are carried out by jets of thermal water under high pressure for several minutes plus educational workshops (relaxation, sophrology, hygiene...)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the medical benefit in terms of quality of life on the dermatological sequelae of fibrosis after a dermatologically oriented spa treatment. | Self-assessment by the patient of the dermatological quality of life by the DLQI (Dermatology Life Quality Index) score at 6 months after the end of the treatment compared between the intervention group (immediate treatment) and the control group (delayed treatment after 6 months). The DLQI score is between 0 and 30 where a high score indicates a significant impairment of quality of life. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Generic quality of life | Evaluation of the medical benefit on generic quality of life. Patient self-assessment of generic quality of life using the EQ5D-3L. EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ5D has 6 items intended to measure general health. The index score is between -0.53 and 1 where a high value indicates a good quality of life. The perceived health status is between 0 and 100 where a high value indicates good health. | 6 months | 
| Breast Cancer quality of life | Evaluation of the medical benefit on quality of life in patients with breast cancer. Patient self-assessment of quality of life using the EORTC (European Organisation for Research and Treatment of Cancer) QLQ C30 Score (Quality of Life of Cancer Patients). The EORTC QLQ-C30 has 15 domains. There is no total score. For each domain, the score is between 0 and 100 where a high score for overall health and functional dimensions represents a good quality of life; and a high score for symptomatic dimensions represents a high level of symptoms. | 6 months | 
| Senological quality of life | Evaluation of the medical benefit on the quality of senological life. Patient self-assessment of breast quality of life using the specific QLQ-BR23 module (breast cancer-specific quality of life questionnaire). The QLQ-BR23 has 8 domains. There is no total score. For each domain, the rank is between 1 and 5 where a high score represents the death. | 6 months | 
| Sequelae self assessment | Evaluation of the medical benefit on the self-assessment of the impact of radio induced sequelae. Self-assessment by the patient with an evaluation of the severity of the radiation-induced sequelae via the Pro-CTCAE self-questionnaire (item 25: skin dryness, item 28: itching, item 36: skin reaction to radiation, item 37: skin darkening, item 48: general pain, item 53: fatigue, item 54: anxiety, item 56: sadness, item 72: breast swelling and tenderness). | 6 months | 
| Lesions radiological assessment | Hetero-evaluation of the clinical and imaging efficacy of treatment on post-radiation lesions with CTCAE scale (Common Terminology Criteria for Adverse Events). For each domain, the score is between 0 and 100 where a high score for the functional dimensions represents a good quality of life; and a high score for the symptomatic dimensions represents a high level of symptoms. | 6 months | 
| Thickness radiological assessment | Hetero-evaluation of the clinical and imaging efficacy of treatment on post-radiation lesions of thickness. Imaging assessment with blinded measurement by an independent radiologist of comparative thickness by ultrasound: Dermal radiotoxicity can indeed be defined as the difference in dermal thickness between the 2 breasts (lesion area and mirror area of the contralateral breast) Dermal thickness is defined as the distance between the input ultrasound signal and the signal at the dermal-hypodermal interface at 6 months. | 6 months | 
| Volumetric aspect radiological assessment | Hetero-evaluation of the clinical and imaging efficacy of treatment on post-radiation lesions with HBCS (Harvard-Breast-Cosmesis-Scale). Evaluation of the cutaneous and volumetric aspect by an evaluation carried out by the practitioner with the Harvard-breast-cosmesis-scale (HBCS) score at 6 months. The HBCS score is assessed by a 4-point Likert scale where a high value indicates a high severity, 1 represents excellent breast shape or texture, 2 means good, 3 average and 4 poor with a severely deformed breast. | 6 months | 
| Consumption of treatment | Comparison of the type of treatment between the 2 groups. | 6 months | 
| Consumption of medical consultation | Comparison of the number of hospitalisations, consultations, physiotherapy, specific cosmetic consultations between the 2 groups. | 6 months | 
| Adverse events | Comparison of the adverse events in the 2 groups. Description of adverse events between the 2 groups. | 6 months | 
| Long-term cure quality of life benefice | Evaluation of the stability of the long-term effect for the immediate cure group. Evaluation of the maintenance of benefits at 12 months (stability of the long term effect) on the primary outcome and secondary outcomes. Self-assessment by the patient of the dermatological quality of life by the DLQI (Dermatology Life Quality Index). | 12 months | 
| Treatment effect size | Evaluation of the effect size of the treatment for the delayed treatment group. Confirmation of the size of the effect of the treatment on the primary and main secondary endpoints between 6 and 12 months. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrosis, breast cancer, radiotherapy, spa treatment