Radiation Therapy and the Evolving Definition of Low Risk in Ductal Carcinoma in Situ
Authors: Chirag Shah, Frank Vicini, Atif Khan, Douglas Arthur, David Wazer
Journal: Journal of Clinical Oncology (2016)

from their prospective ECOG-ACRIN E5194 study demonstrating a continued increase in the rate of ipsilateral breast events (IBE) with excision alone. At 12 years, the rates of IBE were 14.4% and 24.6% in the low-grade (grade 1/2, # 2.5 cm, margins $ 3 mm) and high-grade (grade 3, # 1c m, margins$ 3m m) cohorts, respectively. Importantly, no plateau in IBEs has emerged over time. Just as disconcerting, 50% of these recurrences represented invasive disease. 1 These findings confirm previous studies that have failed to identify a low-risk cohort of patients with ductal carcinoma in situ (DCIS) for whom radiation therapy can safely be omitted. Similarly, the 8-year update of the Dana-Farber prospective trial evaluating excision alone (predominantly low- or intermediate-grade DCIS, # 2.5 cm mammographically, margins$ 1cm)demonstrated a 10-year local recurrence rate of 15.6%, translating into 1.9% per year, despite widely negative margins. 2 The RTOG 9804 phase III trial, which did not accrue fully, demonstrated higher rates of local recurrence (6.7% v 0.9%) with excision alone compared with excision followed by radiation, despite, again, a low-risk cohort of patients with DCIS (, 2.5 cm, margins $ 3 mm, grade I-II). 3 It will be interesting to see how stable the rates of recurrence are in the 9804 trial with additional follow-up. It should be noted that the benefit of radiation in this trial was shown despite use of endocrine therapy (62% of patients). As compliance with endocrine therapy approaches 50% off-study, radiation therapy can reduce the risk of local recurrence in those patients who are not compliant with endocrine therapy. Despite several randomized trials, controversy regarding optimallocaltherapy for DCIShas persistedfordecades and has recently re-emerged in the context of overtreatment of low-grade DCIS. 4 However, the current study confirms not only the importance of treatment but the advisability of radiation therapy as part of breastconserving therapy for most women with DCIS to reduce the risk of local recurrence. With approximately 50% of recurrences being invasive, women with DCIS face the potential for IBEs that are not only locoregional but that can also potentially be distant and portend toxic systemic therapies as part of salvage therapy. Furthermore, the psychosocial impact of breast cancer recurrences, as well as the costs associated with managing them, must be factored into the treatment decision-making process. Although clinical studies continue to address the potential for overtreatment and identifying low-risk cohorts for whom treatment can be minimized, the current results demonstrate the potential pitfall of moving too fast. Whereas initial data from the ECOG study were promising and were used off protocol by many clinicians, the lack of plateau of IBEs represents a major concern because it signifies that we have not yet identified a low-risk cohort of patients with DCIS. Although tumor genetics may play a future role in identifying these patients, prospective studies are still required to validate the potential of such tests, particularly due to the costs associated with their use. 5,6 Until then, advances in radiation therapy allow for alternatives to traditional wholebreast irradiation. Hypofractionated whole-breast irradiation can be delivered in 3 weeks, as demonstrated in randomized trials showing equivalence with standard fractionation with invasive disease. 7,8 Another potential alternative is accelerated partialbreast irradiation, which allows for treatment in 1 week or less. Randomized trialsand prospective data have demonstrated excellent clinical outcomes and toxicity profiles with this approach in appropriately selected cases. 9,10 Although concerns have been raised about the toxicityof adjuvant radiation inwomenwith DCIS compared with the local control benefit, data continue to demonstrate low rates of acute and chronic toxicity with modern breast radiotherapy. At this time, adjuvant radiation therapy remains the standard of care for most women with DCIS following breast-conserving surgery. Although we continue to look for low-risk cohorts for whom adjuvant radiation or local treatment can be omitted all together, unfortunately, the data have not identified such a group. Whereas new models including tumor genetics have been developed, the commonly utilized ECOG criteria have not been validated with a continued increase in ipsilateral breast events noted with further follow-up. As such, new alternatives and techniques currently allow for a reduction in the burdens associated with adjuvant radiation (duration, toxicity) while providing the local control benefit associated with radiotherapy.