SCIENCE@home

The current status of intraoperative radiation therapy in breast cancer: Challenges and promises

J. Bradley

Published 2018 in The Breast Journal

ABSTRACT

In 2017, the American Society for Radiation Oncology (ASTRO) updated and published the consensus guidelines for accelerated partial breast irradiation. For the use of intraoperative radiation therapy (IORT), these guidelines stated that, “Low-energy x-ray IORT for PBI [partial breast irradiation] should be used within the context of a prospective registry or clinical trial” and only for those patients whose characteristics meet the outlined “suitable” criteria. The recommendation rested largely on the ongoing controversy regarding the TARGIT-A trial. While the TARGIT-A study showed that IORT was not inferior to whole-breast irradiation (WBI) in the prepathology subgroup, a statistically significant difference in the 5-year ipsilateral breast tumor recurrence (IBTR) rate was seen among the entire cohort: 3.3% for IORT vs 1.3% for WBI (P = .42). In the study by Barrou et al, the criteria for adding WBI following IORT were more stringent than in the TARGIT-A trial, leading to almost half of the patients receiving WBI after IORT (45.7%). At present, a wide range of criteria help determine when WBI should be used after IORT with no standard approach. The more stringent criteria for the use of WBI in the Barrou study resulted in a low local recurrence rate (3/275 patients), with a crude rate of 2% with IORT alone vs 0% with IORT + WBI (P = .25). The length of time between IORT and WBI also has varied among and within studies, with a range of 19-227 days in the Barrou study. It has been reported that efficacy of WBI decreases when more than 20 weeks pass between breast conserving surgery and the start of WBI; therefore, what would be the optimal timing of IORT and WBI? Also of interest, laboratory data are emerging to suggest that IORT may influence the operative bed microenvironment through altered microRNA expression in the surgical wound fluid, thereby decreasing tumor regrowth promotors in the surgical wound fluid. A hypothesis-generating finding, further investigation is needed before any conclusions can be drawn. All of these factors—patient selection, criteria for use of WBI, timing between IORT and WBI, and radiobiology—will impact the clinical utility of IORT for patients with early-stage breast cancer, but currently none of the IORT studies have enough follow-up to evaluate long-term disease control. Regarding toxicity in the Barrou et al study, the breast fibrosis rate nearly doubled with the addition of WBI, from 12% with IORT alone to 21% with IORT + WBI (odds ratio = 0.5; P = .04). The question then arises, what is the rate of fibrosis with WBI alone? Barrou et al’s data do not address this. The authors compare their fibrosis rate to that of the EORTC boost trial, which is an older trial using a boost dose of 16 Gy, a higher dose compared to current standards for negative margins. They also note that recent studies report lower fibrosis rates for WBI alone (<10%). Other IORT series have also reported high rates of breast fibrosis with the combination of IORT and WBI, but not all. While cosmesis was not reported in this study, it is known that surgical technique can affect cosmesis. In an effort to minimize the positive margin rate, lumpectomies included resection “from the subcutaneous layer to the pectoral muscle” so that “only positive lateral margins requested re-excision and external RT.” This approach to breast-conserving surgery is atypical. The positive margin rate was 8.5%. While the definition of positive margin was not provided, if assumed as “no tumor on ink,” then this rate is higher than those reported in the literature and contributed to the number of patients undergoing WBI after IORT. The patient population in this study was favorable, with primarily small tumors, hormone receptor-positive disease, and older patient age. However, the median follow-up was only 2.5 years, and it has been well-established that IBTR continues well beyond 5 and even 10 years for early-stage, hormone receptor-positive breast cancer. It is possible that a statistically significant difference in IBTR may arise with additional follow-up. Such a difference has been seen in other early-stage trials, such as the CALGB C9343 trial that reported a 5-year IBTR rate of 1% with WBI and 4% with endocrine therapy alone, which increased to 2% and 10%, respectively, at 10 years. Despite an increase in recurrence over time, the local control rate remained at 90% in the CALGB study without radiotherapy, and neither overall survival nor distant metastases was impacted by radiotherapy. These data have contributed to some ongoing clinical trials that are exploring omission of radiation and reliance on surgery and endocrine therapy alone in luminal A patients, including younger patients. In the Barrou et al study, 86% of patients had luminal A breast cancer and, therefore, may have been eligible for other studies that further de-escalate treatment through radiotherapy omission. In another recent study of IORT, the authors note, “it seems clear that the local recurrence rate following IORT will be somewhat higher than that seen in patients treated with standard WBRT but lower than that observed in those treated with excision alone.” It is incumbent on us as physicians to guide our patients through these options to select the treatment that yields the optimal therapeutic ratio for each individual, while considering factors such as patient age and comorbidities, disease characteristics, and patient values. Continued study of IORT through clinical trials will guide these discussions, and further evidence development will allow decisions on IORT use to be based on clear, evidence-based criteria. Received: 2 May 2018 | Accepted: 2 May 2018 DOI: 10.1111/tbj.13071

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-27 of 27 references · Page 1 of 1

CITED BY