Clinical trial NCT03422003: Study of Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) for Invasive Breast Carcinoma
Official title: Study of Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) for Invasive Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Breast Cancer
Radiation
Hypofractionation
Randomization
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2018-02-05
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study is a randomized trial of hypofractionation (short-course) radiation therapy versus conventional radiation therapy in women who have undergone mastectomy and immediate breast reconstruction. The investigators will assess cosmetic and reconstruction outcomes, lymphedema, cancer status, side effects, and oncologic outcomes.

Detailed description: Over 180,000 diagnoses of invasive breast cancer are made in the US each year. Over one-third of women with early stage and over half with late-stage breast cancer are treated with mastectomy (removal of the entire breast) due to tumor size, multiple cancers within the breast, genetic cancer predisposition, and/or patient preference. Following treatment with mastectomy, women who receive breast reconstructive surgery may experience better quality of life as they do not have to leave surgery with a bare chest wall. However, large randomized trials of post-mastectomy radiation therapy reveal a survival benefit with the addition of radiation after mastectomy in women who have cancer present in the axillary lymph nodes (6). The delivery of radiation therapy in the presence of a breast reconstruction is challenging and often leads to undesirable consequences including reconstruction loss, need for major surgical revision, or poor cosmetic outcomes. Therefore, oncologists and patients are forced to decide between the potential for improved oncologic outcomes with radiation therapy versus increased likelihood of complications and suboptimal cosmetic results. Because of this, some patients may be foregoing reconstruction if radiation therapy after mastectomy is needed; or foregoing radiation therapy if they have had breast reconstructive surgery (28).

Hypofractionation enhances patient convenience and decreases treatment burden. This regimen has been shown in randomized trials largely in the breast-conservation setting to reduce acute radiation therapy side-effects, decrease fatigue at six months and improve cosmetic results (21, 22). Despite these results, adoption of hypofractionation has been slow among women with breast cancer treated with breast-conserving surgery (24, 25) likely due to familiarity and experience of conventional long-course radiation therapy.

While hypofractionation is used commonly in the UK for patients with mastectomy, there are no randomized studies particularly studying outcomes following shorter course radiation therapy in women who undergo mastectomy with breast reconstruction. Therefore, there is an even greater barrier to the use of hypofractionation in this setting in the US. With improved cosmetic results found with hypofractionation, this shorter regimen may have the potential to improve reconstruction success rates which are unfortunately modest overall, for patients who require post-mastectomy radiation. Especially in contrast to financial disincentives to reduce number of radiation treatments, Level I randomized evidence is needed in this population to change practice patterns regarding radiation regimen.

Our study of radiation fractionation regimens has the potential to increase use of hypofractionation among women treated with mastectomy, thereby decreasing treatment burden. Our team of patient stakeholders ensures that our outcomes measures encompass all domains of survivorship after breast cancer (physical and mental health as well as satisfaction with the decision-making process). Despite the large numbers of breast cancer survivors who undergo mastectomy, reconstruction and radiation therapy, little is known about which domains of quality of life are affected and their importance to these patients. This study uses previously validated tools for measuring patient outcomes, and have added questions for areas which are important to patients that may not have been captured adequately by previous tools. In concert with the increasing awareness of the importance of survivorship care to cancer care, identifying a comprehensive set of outcomes measurement tools following treatment with radiation therapy, mastectomy, and reconstruction is an important asset for future treatment evaluation in these women.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed with clinical or pathologic stage I-III invasive breast cancer with TX-T3 tumor
2. Has been treated with mastectomy
3. Has undergone immediate reconstructive surgery with placement of a tissue expander or permanent implant at time of mastectomy
4. Is a candidate for unilateral post-mastectomy radiation therapy as per National Comprehensive Cancer Network (NCCN) guidelines (post-mastectomy radiation therapy is indicated for most patients with positive lymph nodes at time of surgery and infrequently for selected node-negative patients)
5. Use of bolus is permitted, but not required
6. Age ≥18

Exclusion Criteria:

1. T4 cancer
2. Recurrent breast cancer or history of prior breast radiation therapy
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, and/or mental health illness that the consenting investigator feels would affect patient's ability to participate in this study
4. Pregnant or nursing
5. History of a different malignancy except for the following circumstances:

   * Disease-free for at least five years and deemed by the investigator to be at low risk for recurrence of that malignancy (\<5 %).
   * Cervical cancer in situ and basal cell or squamous cell carcinoma of the skin
6. Breast cancer requiring bilateral breast/chest wall radiation therapy.

Primary outcomes:
measure: Patient Reported Outcomes Using the FACT-B
timeFrame: 6 months
Secondary outcomes:
measure: Oncologic and Clinical Outcomes Assessed Using Medical Record Abstractions.
timeFrame: 10 years
measure: Cosmetic Outcomes Assessed Using Photographic Evaluations.
timeFrame: 18 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Edwards
country: United States
facility: Vail Health
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Johns Hopkins Medicine
state: District of Columbia
city: Brewer
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Danvers
country: United States
facility: Massachusetts General Hospital/North Shore Center for Outpatient Care
state: Massachusetts
city: Milford
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) at Milford Regional Medical Center
state: Massachusetts
city: South Weymouth
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital
state: Massachusetts
city: Providence
country: United States
facility: Lifespan/Rhode Island Hospital
state: Rhode Island
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Rinaa Punglia, MD MPH
role: STUDY_CHAIR
affiliation: Dana-Farber Cancer Institute
name: Julia Wong, MD
role: STUDY_CHAIR
References:
citation: EBCTCG (Early Breast Cancer Trialists' Collaborative Group); McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, Gray R, Mannu G, Peto R, Whelan T, Wang Y, Wang Z, Darby S. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014 Jun 21;383(9935):2127-35. doi: 10.1016/S0140-6736(14)60488-8. Epub 2014 Mar 19.
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citation: Shaitelman SF, Schlembach PJ, Arzu I, Ballo M, Bloom ES, Buchholz D, Chronowski GM, Dvorak T, Grade E, Hoffman KE, Kelly P, Ludwig M, Perkins GH, Reed V, Shah S, Stauder MC, Strom EA, Tereffe W, Woodward WA, Ensor J, Baumann D, Thompson AM, Amaya D, Davis T, Guerra W, Hamblin L, Hortobagyi G, Hunt KK, Buchholz TA, Smith BD. Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial. JAMA Oncol. 2015 Oct;1(7):931-41. doi: 10.1001/jamaoncol.2015.2666.
citation: Bekelman JE, Sylwestrzak G, Barron J, Liu J, Epstein AJ, Freedman G, Malin J, Emanuel EJ. Uptake and costs of hypofractionated vs conventional whole breast irradiation after breast conserving surgery in the United States, 2008-2013. JAMA. 2014 Dec 17;312(23):2542-50. doi: 10.1001/jama.2014.16616.
citation: Jagsi R, Falchook AD, Hendrix LH, Curry H, Chen RC. Adoption of hypofractionated radiation therapy for breast cancer after publication of randomized trials. Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1001-9. doi: 10.1016/j.ijrobp.2014.09.032.