Clinical trial NCT02606708: Accelerated Intensity Modulated Radiation Therapy (AIMRT) to the Breast After Segmental Mastectomy
Official title: Accelerated Intensity Modulated Radiation Therapy (AIMRT) to the Breast After Segmental Mastectomy: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2015-11-17
Enrollment: 314
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the feasibility and tolerability of a regimen of accelerated (hypofractionated) Intensity Modulated Radiation Therapy (AIMRT) to the whole breast as part of breast preservation. In addition, the investigators want to prospectively collect blood specimens to: assess TGF-β polymorphisms to identify potential carriers at higher risk for post-treatment fibrosis; generate a blood specimen repository for future studies of other relevant polymorphisms. The study investigators also want to prospectively follow each treated woman yearly to assess long-term radiation sequelae of the current regimen by using the LENT/SOMA scores.

Detailed description: Despite level I evidence of comparable efficacy to that of mastectomy, breast conserving therapy (BCT) remains underutilized in the United States. In 1990, the National Institutes of Health (NIH) Consensus Development Conference concluded that BCT was the appropriate method of treatment for the majority of women with early stage I and II breast cancer. However, this subsequently only translated in a moderate increase in the utilization of BCT, shifting from 34% to 60% for stage I breast cancer and from 19% to 39% for stage II breast cancer.

There appear to be multiple causes for underutilization. The demands of the standard radiation schedule probably play the main role. Generally, post-lumpectomy radiation therapy consists of 4 to 5 weeks of whole breast radiation of a total dose 45 to 50 Gy in 23-25 fractions, usually followed by a boost of 10 to 16 Gy in 5-8 fractions to the tumor bed area. The total length of treatment is 5-7 weeks, commonly six weeks. Practically, women who choose BCT automatically commit to a regimen of approximately six weeks of daily radiation visits (Monday to Friday) to complete the local management of their breast cancer. For many women, concerns about this commitment are likely to influence the choice for mastectomy instead of breast preservation since only 40-60% of women who meet criteria for BCT actually undergo the procedure. In addition to possible biases of the primary health care provider affecting these choices, it is known that distance from RT treatment facilities also plays an important role in women's choice for mastectomy instead of BCT. Unfortunately, 15-30% of patients who have actually selected BCT, in particularly older patients and those with 2 or more co-morbid conditions, do not receive postoperative RT. These facts warrant a critical assessment of standard radiation therapy in this clinical setting.

The actual standard approach to post-segmental mastectomy adjuvant radiation at our institution consists of surgical excision followed by 6 weeks of breast irradiation for a total of 30 fractions of 2 Gy each, 23 (46 Gy) to the whole breast while 7 to the original tumor bed (14 Gy). Instead, the women in this study will only receive 15 larger radiation fractions (2.7 Gy) to the entire breast with a concomitant boost to the tumor bed (2.7 Gy + .5 Gy, total 3.2 Gy per fraction). All women will be treated prone to best apply IMRT techniques while avoiding the rest of the body.

Treatment with fewer fractions over a shorter duration of time offers several advantages, provided it is as effective as the conventional treatment regimens and without added morbidity. The potential advantages include: 1) less time away from homes, families and jobs; 2) less cost associated with travel and time away from work; 3) ease the demand on radiation treatment resources and produce savings to the health-care system. Moreover, treatment prone assures that only minimal dose of radiation is delivered to the lung, heart and to the controlateral breast.

Patients will have completed all breast surgical procedures prior to accrual into this protocol in order to establish eligibility criteria. All patients will then be treated prone with 2.7 Gy/fraction delivered in 15 fractions over a 3-week period for a total dose of 40.5 Gy.

All patients will be followed 1, 3, 6, 12 months after treatment course, then yearly thereafter.

Eligibility criteria: Inclusion Criteria:

* Pre- or post-menopausal women with Stage I and II breast cancer
* Biopsy-proven invasive breast cancer, excised with negative margins of at least 1 mm
* Status post segmental mastectomy. and after sentinel node biopsy and/or axillary node dissection
* At least 2 weeks from last chemotherapy
* Tumors \< 5 mm do not require nodal assessment

Exclusion Criteria:

* Previous radiation therapy to the ipsilateral breast.
* More than 3 involved nodes identified at axillary staging, requiring adjuvant axillary radiation.
* Active connective tissue disorders, such as lupus or scleroderma.
* Prior or concurrent malignancy other than basal or squamous cell skin cancer or carcinoma in-situ of the cervix, unless disease-free \> 5 years.
* Pregnant or lactating women.

Primary outcomes:
measure: Number of Participants With Local Recurrence in Breast
timeFrame: 5 years
measure: Number of Participants With Regional Recurrence
timeFrame: 5 years
measure: Number of Participants With Contralateral Breast Cancer
timeFrame: 5 years
measure: Number of Participants With Distant Metastases
timeFrame: 5 years
measure: Number of Participants With an Outcome of Death
timeFrame: 5 years
Secondary outcomes:
measure: Maximum Grade Late Radiation Toxicity
timeFrame: 5 years
measure: Patient Self-assessment of the Cosmetic Results
timeFrame: 5 years
measure: Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
Study officials:
affiliation: NYU Langone Medical Center
name: Carmen Perez, MD
role: PRINCIPAL_INVESTIGATOR
References: