Feasibility Study of Accelerated Preoperative Radiotherapy for Early Breast Cancer

Study Overview
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Brief Summary
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The standard treatment for women with a relatively small breast cancer without arguments for involvement of the axillary lymph nodes, is breast conserving surgery followed by radiotherapy of the whole breast, often with a complementary dose to the operated area (boost). A delay of 3-4 weeks after surgery is advisable for allowing wound healing before the start of radiotherapy. Historically, whole breast radiotherapy plus boost are delivered in 6-7 weeks. This treatment can be associated with temporary fatigue and decrease in quality of life. Randomized trials have shown that shorter schedules, delivering slightly more dose per day during 3 weeks, are equal to the long schedules. In an earlier clinical study, the investigators have tested such a short schedule and shown that it is equally safe and equally well tolerated as the conventional schemes. Other hospitals have examined (and still are examining) the safety and tolerance of even shorter schedules, delivering radiotherapy in 1 week. This clinical study involves delivering radiotherapy in 1 week and before the surgery in stead of following surgery. In the postoperative setting, it is often debatable which volume should be included in the boost. Often boost-volumes remain large because of uncertainties in delineation. Preoperative radiotherapy has the advantage that the tumor is visible on imaging. This can result in smaller boost volumes. The surgery will follow shortly after termination of the radiotherapy, resulting in a very short treatment period. This study is an open study investigating the effect on quality of life of a very short preoperative radiotherapy for early breast cancer.

Detailed Description
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Women with early breast cancer are treated with breast conserving surgery (BCS) followed by whole breast irradiation (WBI) and a complementary dose to the lumpectomy cavity (boost). A delay of 3-4 weeks after surgery is advisable for allowing wound healing before the start of radiotherapy. Historically, WBI plus boost are delivered in 6-7 weeks. This treatment is associated with fatigue and a decreased quality of life. Randomized trials have shown that shorter hypofractionated schedules, delivering radiotherapy in 3 weeks, are equal to the long schedules. The investigators have shown that a hypofractionated tomotherapy with a simultaneous integrated boost is oncologically safe, well tolerated and has less impact on quality of life than the conventional schemes. In the postoperative setting, it is often debatable which volume should be included in the boost. Surgical clips can help to decrease inter-observer variability, but often boost-volumes remain large because of uncertainties in delineation. Preoperative radiotherapy has the advantage that the gross tumor volume (GTV) is visible on imaging. This can result in smaller boost volumes. The aim of this study is to investigate the feasibility of a short preoperative tomotherapy. The potential benefits are a decrease in overall treatment time a positive effect on quality of life a more precise target delineation profitable health economics.

Official Title
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Feasibility Study of Accelerated Preoperative Radiotherapy for Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Tomotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Histological diagnosis of unifocal invasive breast carcinoma, no special type (ductal carcinoma) Tumor Staging: cT1-2N0M0 Luminal A or B Candidate for breast conserving surgery N0-status confirmed by lymph node cytology Exclusion Criteria: Multifocal/multicentric disease Prior thoracic radiotherapy Pregnancy SBR3 grading Triple negative status which benefit neoadjuvant chemotherapy

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: preoperative tomotherapy<br>This study is an open study investigating the effect on quality of life of a very short preoperative radiotherapy for early breast cancer, including approximately 24 women. Radiotherapy will be performed in 1 week and before the surgery in stead of following surgery.Preoperative radiotherapy has the advantage that the tumor is visible on imaging. This can result in smaller boost volumes. The surgery will follow shortly after termination of the radiotherapy, resulting in a very short treatment period. | Radiation: Tomotherapy<br>* Dose prescription: Whole breast irradiation: 25 Gy in 5 daily fractions of 5 Gy Boost: 30 Gy in 5 daily fractions of 6 Gy The boost will be delivered as a simultaneous integrated boost (SIB). Target volumes: Clinical target volume (CTV) breast: defined by the soft tissue of the breast down to the pectoralis fascia, but excluding the skin and the underlying muscle, ribs, lung and heart. Gross tumor volume (GTV) boost: includes all gross tumor volume, as visible on computer tomography, mammography and/or magnetic resonance imaging (MRI). MRI imaging is preferentially performed in treatment position. CTV boost: includes the primary tumor, with a margin of 1.0 cm in all directions to encompass potential microscopic disease extension. The CTV boost excludes the skin, pectoralis muscle, ribs, lung and heart. Planning target volume (PTV): CTV plus a margin of 5 mm in all directions, but limited at 5 mm below the skin surface.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the surgical procedure | Duration of the breast conserving surgery (lumpectomy + sentinel lymph node procedure) | from 2 to 8 days after the last radiotherapy session. | 
| Quantity of blood lost | Quantity of blood that has been lost during the breast conservation surgery, performed 2 to 8 days after the last radiotherapy session. | from 2 to 8 days after the last radiotherapy session. | 
| Dindo score | Post operative morbidity assessment according to Dindo, Demartines et al. | Week 6 after radiotherapy start | 
| Wound disruption (yes/no) | Presence of wound disruption defined as skin dehiscence from any cause including seroma or hematoma. | up to 30 days post operative | 
| Wound infection (yes/no) | Presence of wound infection, defined as: purulent drainage, cellulitis, abscess or wound requiring drainage, debriding, and antibiotics associated with a clinical diagnosis of infection. | up to 30 days post operative | 
| Number of adverse events | Acute radiation toxicity measure | up to three months after radiotherapy start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QLQ-C30 questionnaire | Assessment of the quality of life, according to the QLQC30 questionnaire | week 3 after radiotherapy start | 
| QLQ-C30 questionnaire | Assessment of the quality of life, according to the QLQC30 questionnaire | week 6 after radiotherapy start | 
| EORTC QLQ-BR23 questionnaire | Assessment of the quality of life, according to the EORTC BR23 questionnaire | week 3 after radiotherapy start | 
| EORTC QLQ-BR23 questionnaire | Assessment of the quality of life, according to the EORTC BR23 questionnaire | week 6 after radiotherapy start | 
| Number of adverse events | Late toxicity measure | from three months after radiotherapy start till end of study (up to 1 years) | 
| Local recurrence (yes/no) | Local control: presence of local cancer recurrence | up till the end of study (1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short preoperative tomotherapy, Radiotherapy