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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03422003
• Other study ID #: 16-304
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 1, 2018
• Est. completion date: April 1, 2030

Study information

• Verified date: November 2023
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: April 1, 2030
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Eastern Maine Medical Center	Brewer	Maine
United States	Massachusetts General Hospital/North Shore Center for Outpatient Care	Danvers	Massachusetts
United States	Vail Health	Edwards	Colorado
United States	Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) at Milford Regional Medical Center	Milford	Massachusetts
United States	Yale Cancer Center	New Haven	Connecticut
United States	Lifespan/Rhode Island Hospital	Providence	Rhode Island
United States	University of California, San Francisco	San Francisco	California
United States	Maine Medical Center	Scarborough	Maine
United States	University of Washington	Seattle	Washington
United States	Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital	South Weymouth	Massachusetts
United States	Stanford University Medical Center	Stanford	California
United States	Johns Hopkins Medicine	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View 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. Erratum In: Lancet. 2014 Nov 22;384(9957):1848. — View 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. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient reported outcomes using the FACT-B	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.	6 months
Secondary	Oncologic and clinical outcomes assessed using medical record abstractions.	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.	10 years
Secondary	Cosmetic outcomes assessed using photographic evaluations.	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.	18 months