Hypo Versus Conventional Fractionation in Reconstructed-Breast Cancer Mastectomy Patients

Study Overview
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Brief Summary
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This randomized Phase III study aims to show major complication rate of hypofractionation radiation therapy is not inferior, compared to conventional fractionation radiation therapy in breast cancer patients undergoing mastectomy and reconstruction surgery.

Detailed Description
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This study is a multicenter, randomized, phase 3 clinical trial. For breast cancer patients who underwent breast reconstruction after mastectomy, the hypofractionation radiotherapy group (experimental group) and the conventional fractionation radiotherapy group (control group) were divided 1:1 and compared to reveal the non-inferiority with hypofractionation in terms of major complication rate. I. Primary Objective To show the non-inferiority of major complication rate in reconstructed-breast between the hypofractionation radiotherapy group (experimental group) and the conventional fractionation radiotherapy group (control group) at 2 years after radiation therapy. The main complications are defined at those requiring hospitalization or surgery among complications. II. Secondary Objective: Comparison of other side effects between the two groups. Comparison of complication rate stratified by reconstruction timing and type of reconstruction Immediate implant-based reconstruction Immediate autologous reconstruction Delayed-immediate implant reconstruction (2-stage) Comparison of quality of life between the two groups. Comparison of local and regional control rates between the two groups. III. Tertiary Objective: Comparison of cosmetic evaluations between the two groups. Dosimetry analysis for correlation between the occurrence of complications and the dose profile.

Official Title
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A Randomized Phase III Trial of Hypofractionated Versus Conventionally Fractionated Radiotherapy in Breast Cancer Patients With Reconstruction After Mastectomy

Conditions
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Breast Cancer, Radiotherapy; Complications

Intervention / Treatment
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* Radiation: Hypofractionation
* Radiation: Conventional Fractionation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patient who underwent mastectomy for invasive breast cancer Patients who have undergone breast reconstruction after mastectomy or who have inserted a tissue expander (y)p patients with stage IIIA or lower (excluding T4 and N3 patients) who need adjuvant radiation therapy Eastern Cooperative Oncology Group Performance ≤ 2 Age ≥ 19 years Patients who agreed to participate in the study Exclusion Criteria: Patients who already had implants at the time of diagnosis of breast cancer or who have already undergone reconstructive surgery Patients who underwent reconstruction after partial resection or breast conserving surgery rather than mastectomy Patients who are using or planning to use an air expander Patients receiving radiation therapy for salvage or palliative purposes Patients with distant metastases at the time of diagnosis Patients who are scheduled to undergo concurrent chemoradiation therapy Patients with bilateral breast cancer Male breast cancer patients Patients who have previously received radiation therapy for the ipsilateral breast or supraclavicular area Patients with history of cancers other than thyroid cancer, intraepithelial cancer of the cervix, or skin cancer Patients diagnosed with ductal breast carcinoma in situ, lobular carcinoma in situ, phyllodes, metaplastic cancer, or other benign tumors based on histological diagnosis

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypofractionation<br>For the cumulative total dose of 39-45.9 Gy to the chest wall, a daily dose of 2.5-3.0 Gy is administered 13-17 fractions. Should be started within 3 months of completion of mastectomy or chemotherapy. Clinical target volume (CTV) may include regional lymph nodes. If a tissue expander or implant is present at the time of radiotherapy planning, CTV contouring should be performed according to the ESTRO ACROP implant-based target delineation guidelines. | Radiation: Hypofractionation<br>* Radiation regimen of 2.5-3.0Gy x 13-17 fractions +/- sequential boost 0-7 fractions<br>|
| Active Comparator: Conventional Fractionation<br>For the cumulative total dose of 45-50.4 Gy to the chest wall, a daily dose of 1.8-2.0 Gy is administered 23-28 fractions. Should be started within 3 months of completion of mastectomy or chemotherapy. Clinical target volume (CTV) may include regional lymph nodes. If a tissue expander or implant is present at the time of radiotherapy planning, CTV contouring should be performed according to the ESTRO ACROP implant-based target delineation guidelines. | Radiation: Conventional Fractionation<br>* Radiation regimen of 1.8-2.0Gy x 23-28 fractions +/- sequential boost 0-5 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Complication Rate | Unplanned re-hospitalization or re-operation for intervention Implant removal due to infection, autologous flap total failure (reconstruction failure) | Up to 2 years after the completion of radiation therapy | 
| Capsular Contracture (If implant-based recontruction is performed) | • Baker Scale G1: the breast is normally soft and appears natural in size and shape G2: the breast is a little firm, but appears normal G3: the breast is firm and appears abnormal G4: the breast is hard, painful to the touch, and appears abnormal | Up to 2 years after the completion of radiation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematoma | NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE) Ver.5.0 G1: Mild symptoms; intervention not indicated G2: Minimally invasive evacuation or aspiration indicated G3: Transfusion; invasive intervention indicated G4: Life-threatening consequences; urgent intervention indicated G5: Death | Up to 2 years after the completion of radiation therapy | 
| Wound infection | NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE) Ver.5.0 G1: Localized, local intervention indicate G2: Oral intervention indicated (e.g., antibiotic, antifungal, or antiviral) G3: IV antibiotic, antifungal, or antiviral intervention indicated; invasive intervention indicated G4: Life-threatening consequences; urgent intervention indicated G5: Death | Up to 2 years after the completion of radiation therapy | 
| Wound Dehiscence | NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE) Ver.5.0 G1: Incisional separation, intervention not indicated G2: Incisional separation, local care (e.g., suturing) or medical intervention indicated (e.g., analgesic) G3: Fascial disruption or dehiscence without evisceration; revision by operative intervention indicated G4: Life-threatening consequences; symptomatic hernia with evidence of strangulation; fascial disruption with evisceration; major reconstruction flap, grafting, resection, or amputation indicated G5: Death | Up to 2 years after the completion of radiation therapy | 
| Seroma | NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE) Ver.5.0 G1: Asymptomatic; clinical or diagnostic observations only; intervention not indicated G2: Symptomatic; simple aspiration indicated G3: Symptomatic, elective invasive intervention indicated | Up to 2 years after the completion of radiation therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mastectomy, Reconstruction, Radiation therapy, Conventional fractionation, Hypofractionation, Complication