June 29, 2018

Spotlight Trial: A New Trial is Comparing Hypofractionated Radiotherapy to Conventional Radiotherapy in Women Who Have Undergone Mastectomy and Implant-Based Reconstruction

A new randomized multicenter trial led by Rinaa S. Punglia, MD, MPH (DFCI) and Julia S. Wong, MD is comparing clinical and cosmetic outcomes in women with breast cancer who have undergone mastectomy and immediate implant-based reconstruction. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI), which funds comparative clinical effectiveness research that engages patients and caregivers.

Patient-centered, patient-informed study design

Drs. Punglia and Wong selected the primary outcome for the study after conducting a patient survey asking what outcome was most important to their quality of life (QoL). The inclusion of patient stakeholders in the design is a unique aspect of this study. Moreover, the principal investigators solicited input from patient advocates and stakeholders to shape educational materials and accrual planning.

The study, entitled FABREC (Radiation Fractionation on Outcomes After Breast REConstruction), plans to enroll 400 patients over the next 2 to 2.5 years from academic and community sites in Massachusetts, Rhode Island, Maine, and across the country. Radiation oncologists at DFCI/BWH and satellite centers, with colleagues from Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Johns Hopkins Medical Center and satellites, Yale, Stanford, UCSF, and University of Washington will assist in patient accrual for the study. 

The central question in post-mastectomy radiotherapy after reconstruction

Mastectomy is utilized in over one-third of women with early-stage breast cancer and over half with late-stage breast cancer. Breast reconstruction after mastectomy provides significant psychosocial and QoL benefits, while radiotherapy after mastectomy improves locoregional control and survival outcomes. However, post-mastectomy radiotherapy is also associated with inferior cosmetic outcomes after breast reconstruction, as well as complications such as reconstruction loss, scar tissue around implant, and additional surgical revisions, thereby increasing treatment burden.

The beneficial survival effect, weighed against the increased complications risk and poor cosmetic outcomes, is a critical predicament for patients and oncologists alike. The FABREC trial hopes to provide a resolution to this difficult choice.

Conventional versus hypofractionated radiotherapy

In conventional irradiation, daily fraction sizes of 1.8 to 2 Gy per fraction, delivered for 5 to 6 weeks, are commonly used. Hypofractionation utilizes shorter regimens at higher doses, >2.2 Gy per fraction, delivered for 3 to 4 weeks. The shorter course is more convenient for patients and reduces treatment burden. Hypofractionation may reduce acute radiation therapy side-effects, decrease fatigue, and improve cosmesis. Hypofractionated radiotherapy after mastectomy is in routine clinical use in the UK. The FABREC study, along with other ongoing studies, could provide the key randomized trial data to help transform clinical practice in the United States.

“Although there are established data on outcomes with hypofractionation in the breast-conservation setting, hypofractionation has not been studied as rigorously in the post-mastectomy post-reconstruction setting,” said Punglia.

Study Design

Study participants will be randomized 1:1 to receive either the short-course (3-week) radiation therapy or long-course (5-week) conventional radiation therapy after mastectomy and breast reconstruction with a tissue expander or implant. All patients will be asked to fill out surveys and will be assessed for highly relevant QoL outcomes, cosmetic and reconstruction outcomes, and lymphedema at 6, 12 and 18 months after radiation initiation. Data collection will be continued during annual medical record review for 10 years.

Three categories of outcomes will be evaluated – experience of survivorship, benefit or change in likelihood of surgical complications and clinician-reported cosmetic results, and oncologic outcomes of recurrence and survival. The primary outcome, selected with patient input, is the change in physical well-being (PWB) on the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument.

Clinical Impact

Over 300,000 new cases of invasive and in situ breast cancer diagnoses are estimated in women in the US in 2018. Mastectomy and reconstruction will be utilized for thousands of women with breast cancer. Given existing data for hypofractionation superiority in the breast-conserving setting, the study investigators expect the shorter course to improve clinical, psychosocial, and cosmetic outcomes in the mastectomy-reconstruction setting as well.

“I think it is a really important study and we are excited to be able to offer it to patients,” said Dr. Wong, “the study is of nationwide interest and it is timely, addressing a current question in breast cancer radiation oncology.”  

FABREC Trial Details

Title: Study of Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) for Invasive Breast Carcinoma

Principal Investigators: Rinaa S. Punglia, MD, MPH (DFCI) and Julia S. Wong, MD

NIH/ClinicalTrials.gov Identifier: NCT03422003

DF/HCC Protocol Number: 16-304

The trial is actively recruiting patients. Find more information at ClinicalTrials.gov.

–       Krithika Subramanian