The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer.

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.