Hypo Versus Conventional Fractionation in Reconstructed-Breast Cancer Mastectomy Patients

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Radiotherapy; Complications
• Intervention / Treatment: Radiation: Hypofractionation; Radiation: Conventional Fractionation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 622
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: In Ah Kim, MD. PhD.; Phone Number: +82 31-787-7651; Email: inah228@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionation; 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; Radiation regimen of 2.5-3.0Gy x 13-17 fractions +/- sequential boost 0-7 fractions
Active Comparator: Conventional Fractionation; 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; Radiation regimen of 1.8-2.0Gy x 23-28 fractions +/- sequential boost 0-5 fractions

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm Lymphedema [Optional]	In each follow-up time, arm circumference is measured at 10 cm above the ipsilateral and contralateral anterior cubital fossa. Lymphedema is considered to be occurred if a difference of ≥10% between two measures.	Up to 2 years after the completion of radiation therapy
Cosmetic Outcome [Optional]	Skin 3D reconstruction was performed based on the radiation therapy plan CT and breast CT at 24 months after radiotherapy. Using in-house software based on deep learning algorithm, cosmetic scores are produced and compared between groups.	Up to 2 years after the completion of radiation therapy

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Seoul National University Hospital
• Investigators: Principal Investigator: In Ah Kim, MD. PhD., Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): December 31, 2027
• Study Completion (Anticipated): December 31, 2032

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Reconstruction; Radiation therapy; Mastectomy; Complication; Hypofractionation; Conventional fractionation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: KROG 21-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No