Randomized Trial of Prone Accelerated Whole-Breast Radiation Therapy With a Daily Versus Weekly Boost to the Tumor Bed: Acute Toxicity and Associated Dosimetry

Abstract

Purpose/Objective(s): Currently, no biological molecular targets exist for women diagnosed with triple negative breast cancer (TNBC). In an in vitro murine breast cancer model, we have shown that radiation therapy (RT) combined with carboplatin potentiates immunogenic tumor cell death, thereby contributing to a pro-immunogenic milieu (Golden et al., Oncoimmunology 2014). Thus, we hypothesized that this regimen may not only radio-sensitize, but also trigger an adaptive anti-tumor immune response. We are conducting a phase I-II IRB-approved trial [clinicaltrials. gov NCT01289353] to test the feasibility and clinical efficacy of this combination in terms of rates of local control, distant recurrence, and overall survival. Materials/Methods: Women with Stage I e II (pT1-T2, pN0) TNBC are eligible after segmental mastectomy and axillary lymph node assessment. Weekly carboplatin (AUCZ2.0) is delivered x6 weeks with RT to the whole breast being delivered during weeks 2-4, via a 3D-CRT or IMRT technique in the prone position. The whole breast receives 40.5 Gy in 15 fractions (Monday-Friday). The tumor bed receives an additional 3 Gy boost, delivered on 2 consecutive Sundays (beginning of the 2 and 3weeks of RT). Consequently, a total of 46.5 Gy is delivered to the tumor bed in 17 fractions over 19 days. Adverse effects of treatment are assessed weekly during treatment, and once at 45-60 days, thereafter, using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results: A total of 33 patients have accrued so far. Acute toxicities are displayed below and never exceeded grade 3. Twenty patients received adjuvant chemotherapy. With a median follow-up of 25.9 months, 97% (32/33) of all women remain alive and without recurrent disease. One patient died with possible distant recurrence occurring at 5.6 months from beginning treatment. Conclusion: Adjuvant concurrent carboplatin and prone accelerated radiation therapy appears to be a safe and effective treatment for women diagnosed with early stage TNBC. Since approximately 50% of TNBC carriers recur within 2 years from treatment, it is encouraging that 97% of the patients in the trial have not experienced a recurrence.