Accelerated Intensity Modulated Radiation Therapy (AIMRT) to the Breast After Segmental Mastectomy

Accelerated Intensity Modulated Radiation Therapy (AIMRT) to the Breast After Segmental Mastectomy: a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Accelerated intensity modulated radiation therapy (AIMRT)

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.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10003
      • NYU Langone Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated intensity modulated radiation therapy (AIMRT); All patients shall receive a total of 40.5 Gy to the entire breast in 2.7 Gy/fraction x 15 fractions, Monday to Friday for 3 weeks delivered prone in uniform daily doses through IMRT tangent fields. A concurrent boost to the original tumor bed of 0.50 Gy will be delivered.	Radiation: Accelerated intensity modulated radiation therapy (AIMRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Local Recurrence in Breast	Defined by the discovery of invasive disease or DCIS in the same region of the breast after segmental mastectomy and radiation, by clinical or radiographic means.	5 years
Number of Participants With Regional Recurrence	Defined by the discovery of invasive disease or DCIS regional recurrence in the lymph node after segmental mastectomy and radiation, by clinical or radiographic means.	5 years
Number of Participants With Contralateral Breast Cancer	Defined by the discovery of contra-lateral breast cancer after segmental mastectomy and radiation, by clinical or radio-graphic means.	5 years
Number of Participants With Distant Metastases	number of participants found to have distant metastases after segmental mastectomy and radiation, by clinical or radiographic means	5 years
Number of Participants With an Outcome of Death	Overall 5-Year cumulative rate of death based on Kaplan-Meier Analysis	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival		5 years
Maximum Grade Late Radiation Toxicity	Measure of treatment related late toxicities at or more than 6 months after completion of radiation therapy.	5 years
Patient Self-assessment of the Cosmetic Results		5 years

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Carmen Perez, MD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2005
• Primary Completion (Actual): June 2, 2016
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (Estimate): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: July 31, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 11105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No