Toxicity and Outcome of Whole Breast Hypofractionated Radiotherapy: a Single Institution Experience

Study Overview
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Brief Summary
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This is a homogeneous, single institution, observational, non-interventional, prospective study of 500 patients who will be treated according to the standard protocol of adjuvant hypofractionated radiotherapy after breast conserving surgery, at a total dose of 40 Gy/ 15 fr (5 fr/ week, 3 consecutive weeks). In addition to the regular follow up, the patients will respond to the quality-of-life questionnaires (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC), general, QLQ- C30, and specific for breast (BR), QLQ- BR23, at the first visit, at the end of radiotherapy and at the subsequent follow-up visits from 6 months up to 5 and a half years, to evaluate the quality of life during and after the treatment. The study also has a retrospective arm of approximately 1300 patients, treated from January 2009, for whom disease control and toxicity will be evaluated.

Detailed Description
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The study is observational, homogeneous (performed in a single institution), non-interventional, and composed of two parts: one retrospective and one prospective (for which we request the registration in the register of clinical trials). The patients with breast cancer treated with adjuvant hypofractionated radiotherapy at the Department of Radiotherapy of San Raffaele Scientific Institute (IRCCSSRaffaele) from January 2009 will be identified and their clinical and dosimetric data retrieved and analyzed. The objectives of the retrospective arm of the study are the analysis, with a follow up of 5 years, of acute and late toxicity, and clinical outcomes, such as local and regional control, overall survival, disease free survival and cancer-specific survival. A secondary objective is the identification of prognostic factors for toxicity and disease progression. The objective of the prospective arm of the study, for a cohort of 500 consecutive patients who agree to participate in the study, is to assess the quality of life of the patients treated with hypofractionated short course (3 weeks) radiotherapy. The quality-of-life questionnaires (QLQ) of the European organization for research and treatment of cancer (EORTC): QLQ-C30 (general) and QLQ-BR23 (specific for the breast), will be distributed before radiation treatment, at the time of patient enrollment, at the end of therapy and during the follow up visits, for a duration of 5 years after the first follow up, scheduled first at 6 months and then annually. Given the non-interventional, observational nature of the study, the follow up program of the patients with breast cancer, treated according to the standard departmental protocol, will not be modified. The patients will be identified from the patient data base from medical records retrieved from the radiotherapy archive, and the images monitoring local evolution from the photo archive. The data will be extracted from medical records. In addition, the dosimetric data of the treatments will be recovered from the physical dosimetric archives and the extrapolated data will be correlated with clinical and toxicity outcomes. For the patients of the prospective observational arm, the dosimetric data and quality of life questionnaires, as well as the follow up visit results, will be prospectively collected, registered in a data base, and subsequently analyzed. The toxicity registered during the visits carried out during the treatment will be determined using the Radiation Therapy Oncology Group (RTOG) scale; the Scoring system of late effects of radiation on normal tissues (SOMA-LENT scale) will be used for toxicity registered during the follow up visits. The clinical points analyzed will include: quality of life, overall survival, disease free- and cancer specific-survival, local and regional control, distant metastasis free survival, acute and late toxicity, physical dosimetry and aesthetic results. The correlation between detected parameters will be evaluated for the identification of prognostic factors. Statistical analyses will be performed with SPSS software version 17.0 (SPSS Inc. Released 2008; SPSS Statistic for Windows, Version 17.0. Chicago, USA: SPSS Inc.) and MedCalc v.12.1.4.0 (MedCalc Software, Ostend, Belgium) and any updated version. Statistical tests to be used will include: uni- and multi-variate logistic regression to define predictors of incidence and prevalence of toxicity and local/ distant relapses; Cox model ( proportionally-hazard regression) uni- and multi-variate for actuarial analysis of predictors of toxicity and local/ distant relapses; Wilcoxon matched -pair test for the quality of life index variations; Spearman test for the correlation between continuous variables, ANOVA test for the effect of treatment variables on changes in QoL scores over time. *Enrollment in the quality-of-life study was suspended in November 2021 due to patients' refusal to participate during the Sars-Cov2 pandemic, the adoption of shorter schedule protocols to minimize patient hospital visits, the adoption of a simultaneous integrated boost for patients with high risk of local relapse(TNBC, HER2+) requiring a change in the technique utilized.

Official Title
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Toxicity and Outcome of Whole Breast Hypofractionated Radiotherapy Without Boost: Results of a Homogeneous Single Institution Experience

Conditions
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Breast Cancer, Quality of Life, Radiotherapy; Adverse Effect, Dermatitis or Eczema

Intervention / Treatment
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* Other: Quality of life measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer patients with TNM Classification of Malignant Tumours pathological stage T1-T2, N0-N1a (pathologically node negative - up to three positive lymph-nodes), treated with conservative surgery and whole breast hypofractionated radiotherapy without boost Exclusion Criteria: male breast cancer patients breast cancer patients treated with conservative surgery and partial breast irradiation, relapsed, and treated with adjuvant whole breast radiotherapy after salvage conservative surgery breast cancer patients treated with mastectomy patients with TNM pathologic stage N1a treated with whole breast radiotherapy and supraclavicular fossa +/- axillary radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Quality of life<br>Quality of life of breast cancer patients treated with conservative surgery (quadrantectomy) and adjuvant hypofractionated whole breast radiotherapy according to the institutional standard regimen, to a total dose of 40 Gy in 15 fraction over 3 weeks will be measured with EORTC quality of life questionnaires QLQ-C30 and QLQ-BR23, before the start of the radiotherapy, at the end of the radiotherapy and subsequently at every follow-up visit (the first at 6 months after the end of the treatment, then annually for 5 consecutive years after the first follow up visit). | Other: Quality of life measurement<br>* The quality of life of breast cancer patients treated with conservative surgery and adjuvant whole breast hypofractionated radiotherapy, without boost, will be evaluated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life after hypofractionated adjuvant radiotherapy | degree of general quality of life worsening of patients treated with hypofractionated adjuvant radiotherapy after breast conserving surgery assessed with EORTC quality of life questionnaires QLQ C30 | up to 66 months | 
| breast specific quality of life after hypofractionated adjuvant radiotherapy | degree of specific quality of life worsening of patients treated with hypofractionated adjuvant radiotherapy after breast conserving surgery assessed with EORTC quality of life questionnaire QLQ BR23 | up to 66 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local control | percentage of patients without local relapse at five years | up to 66 months | 
| regional control | percentage of patients without regional (axillary, supraclavicular) relapse at five years | up to 66 months | 
| distant metastases free survival | percentage of patients without distant metastases at five years | up to 66 months | 
| disease free survival | percentage of patients without local and/or distant progression at five years | up to 66 months | 
| cancer specific survival | percentage of patients who have not died from breast cancer at five years | up to 66 months | 
| overall survival | percentage of patients alive at five years | up to 66 months | 
| acute toxicity | acute toxicity after hypofractionated whole breast adjuvant radiotherapy evaluated with Radiation Therapy Oncology Group (RTOG) scale at 5 years | up to 66 months | 
| late toxicity | late toxicity after hypofractionated whole breast adjuvant radiotherapy evaluated with Scoring systems of late effects of radiations on normal tissues SOMA-LENT scale at 5 years | up to 66 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypofractionated whole breast radiotherapy, breast cancer, conservative treatment, quality of life