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

• ClinicalTrials.gov Identifier: NCT03422003
• Recruitment Status: Active, not recruiting
• First Posted: February 5, 2018
• Last Update Posted: November 22, 2023
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Patient-Centered Outcomes Research Institute
• Information provided by (Responsible Party): Rinaa Punglia, MD, MPH, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: January 19, 2018
• First Posted Date: February 5, 2018
• Last Update Posted Date: November 22, 2023
• Actual Study Start Date: April 1, 2018
• Actual Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2018)

Patient reported outcomes using the FACT-B [ Time Frame: 6 months ]

The primary outcome is the change at 6 months from baseline in patient-reported outcomes on the Physical Well Being sub-domain of the FACT-B.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 2, 2018)

• Oncologic and clinical outcomes assessed using medical record abstractions. [ Time Frame: 10 years ]
  Clinical and oncologic outcomes (rare radiation side effects, recurrence, infections, additional surgeries) will be assessed over a period of 10 years through annual medical record abstractions.
• Cosmetic outcomes assessed using photographic evaluations. [ Time Frame: 18 months ]
  Cosmetic outcomes (quality of reconstructive surgery throughout and after radiation therapy) will be assessed from baseline to 18 months by trained physicians using a standardized rating scale.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Breast Cancer

Intervention

Radiation: Radiation Therapy

For the conventional fractionation arm: Each fraction will consist of 200 cGy per day. Total dose = 5000 cGy to the chest wall and 4600-5000 cGy to the lymph nodes.

For the hypofractionation arm: Each fraction consists of 266 cGy per day. Total dose = 4256 cGy to the chest wall and 3990 cGy to the lymph nodes.

Study Arms

• Experimental: Arm 1: Hypofractionation
  16 fractions of radiation therapy (daily, Monday through Friday) to the chest wall with or without internal mammary nodes, and 15 fractions to the supraclavicular (with or without axillary) lymph nodes.
  Intervention: Radiation: Radiation Therapy
• Active Comparator: Arm 2: Conventional Radiation Therapy
  25 fractions of radiation therapy (daily, Monday through Friday) to the chest wall with or without internal mammary nodes, and 23-25 fractions to the supraclavicular (with or without axillary) lymph nodes.
  Intervention: Radiation: Radiation Therapy

Publications *

• 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. Erratum In: Lancet. 2014 Nov 22;384(9957):1848.
• Duxbury PJ, Gandhi A, Kirwan CC, Jain Y, Harvey JR. Current attitudes to breast reconstruction surgery for women at risk of post-mastectomy radiotherapy: A survey of UK breast surgeons. Breast. 2015 Aug;24(4):502-12. doi: 10.1016/j.breast.2015.05.002. Epub 2015 May 26.
• START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008 Apr;9(4):331-41. doi: 10.1016/S1470-2045(08)70077-9. Epub 2008 Mar 19.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 2, 2018): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 1, 2030
• Actual Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03422003
• Other Study ID Numbers: 16-304
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rinaa Punglia, MD, MPH, Dana-Farber Cancer Institute
• Original Responsible Party: Rinaa Punglia, MD MPH, Dana-Farber Cancer Institute, Prinicipal Investigator
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Patient-Centered Outcomes Research Institute

Investigators

• Study Chair: Rinaa Punglia, MD MPH; Dana-Farber Cancer Institute
• Study Chair: Julia Wong, MD; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: November 2023