A prospective Phase III trial evaluating patient self-reported pain and cosmesis in accelerated partial breast irradiation utilizing 3-D versus intensity-modulated radiotherapy.

PURPOSE/OBJECTIVE: The primary objective is to examine patient self-assessment of breast pain and cosmesis between three-dimensional (3D-CRT) versus intensity-modulated radiotherapy (IMRT). The secondary objective is to evaluate any relationship of treatment planning conformality of both cohorts to patient-assessed pain. Assessments were performed at interim 12, 24, 36, and 48 months with a final 5-year assessment. MATERIALS/METHODS: In total, 656 patients (3D-CRT n = 328; IMRT n = 328) were randomly assigned to either IMRT or 3D-CRT accelerated partial breast radiotherapy to 38.5 Gy in 10 BID 3.85 Gy fractions. RESULTS: Median follow-up was 3 years. Multivariate analysis showed that pain severity significantly decreased from baseline to the 12-month follow-up visit (<0.001 for both 3D-CRT and IMRT) in each cohort. There was significantly less pain at 2 (p = 0.002) and 3 years (0.045) in the IMRT arm versus the 3D-CRT arm when compared to the baseline pain level. There was no difference in patient-assessed cosmesis at any follow-up point; however, although MD-assessed cosmesis showed no difference from years 1 to 4, there was significantly better cosmesis for 3D-CRT versus IMRT (p = 0.047) at 5 years. There was a significant correlation between a maximum pain score and an increase in the CI100 (indicating less conformity) in the IMRT cohort (p < 0.01) and in the IMRT subgroup when the CI100 was ≤0.37 cohort arm (p = 0.01). CONCLUSION: In the analysis of our primary objective we found that at 2 years, IMRT resulted in more interval improvement in breast pain after baseline when compared to patients treated with 3D-CRT planning. As seen in our secondary analysis, this may be due to the ability of IMRT to achieve higher conformality (as evidenced by lower CI values) resulting in less fibrosis. There were no differences in patient-assessed cosmesis or MD-assessed cosmesis for years 1-4; however, physician-assessed 5-year cosmesis was better with 3D-CRT.

A Comparison of Predicted Ipsilateral Tumor Recurrence Risks in Patients With Ductal Carcinoma in Situ of the Breast After Breast-Conserving Surgery by Breast Radiation Oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center DCIS Nomogram, and the 12-Gene DCIS Score Assay.

PURPOSE: To compare ipsilateral breast event (IBE) risks in patients with ductal carcinoma in situ of the breast (DCIS) post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center (MSKCC) DCIS nomogram, and the 12-gene Oncotype DX DCIS score assay. METHODS AND MATERIALS: Consecutive DCIS cases treated with lumpectomy from November 2011 to August 2014 with available DCIS score results were identified. Three radiation oncologists independently estimated the 10-year IBE risk. The Van Nuys Prognostic Index and MSKCC nomogram 10-year IBE risk estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated. RESULTS: Ninety-one patients were identified for inclusion. Forty-eight percent would have been ineligible for the E5194 study. The mean risk of IBE from the DCIS score assay was 12.4%, compared with a range of 18.9% to 26.8% from other sources. The mean IBE risk from the DCIS score assay was lower regardless of E5194 eligibility. The MSKCC nomogram and DCIS score assay risk estimates were weakly correlated with each other (P = .23) and were each moderately correlated with the other risk estimates (P = .41-.56). When applying the radiation oncologists' treatment recommendations based on their proposed risk cutoffs, evaluating risk according to the DCIS score assay led to the highest proportion of patients recommended excision alone. CONCLUSIONS: IBE risk estimates for this general community cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual radiation oncologist estimates. Surgical margins and tumor size continue to factor prominently in radiation oncologist decision algorithms. The differences found between the IBE risk estimate methods suggests that they are not interchangeable and the methods that rely on clinicopathologic features may tend to overestimate risk.

The impact of genomic testing on the recommendation for radiation therapy in patients with ductal carcinoma in situ: A prospective clinical utility assessment of the 12-gene DCIS score™ result.

BACKGROUND AND OBJECTIVES: Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% having a local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX(®) 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians' recommendations for radiation. METHODS: Ten sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known. RESULTS: In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8 mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%CI: 49.6-68.2%) post-assay (P= 0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment. CONCLUSIONS: The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%CI: 23.0-40.6%) of the time--a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.

External beam accelerated partial breast irradiation yields favorable outcomes in patients with prior breast augmentation.

PURPOSE: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT. MATERIALS AND METHODS: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria. RESULTS: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2-58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm(3). The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%. CONCLUSION: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted.

Four-year clinical update from a prospective trial of accelerated partial breast intensity-modulated radiotherapy (APBIMRT).

This prospective Phase II single-arm study gathered data on the use of intensity-modulated radiotherapy (IMRT) to deliver accelerated partial breast irradiation (APBI). Four-year efficacy, cosmesis, and toxicity results are presented. Between February 2004 and September 2007, 136 consecutive patients with Stage 0/I breast cancer and negative margins ≥0.2 cm were treated on protocol. Patients received 38.5 Gy in 10 equal fractions delivered twice daily. Breast pain and cosmesis were rated by patient, and cosmesis was additionally evaluated by physician per Radiation Therapy Oncology Group (RTOG) criteria. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0) was used to grade toxicities. 136 patients (140 breasts) with median follow-up of 53.1 months (range, 8.9-83.2) were evaluated. Population characteristics included median age of 61.9 years and Tis (13.6 %), T1a (18.6 %), T1b (36.4 %), and T1c (31.4 %). Kaplan-Meier estimates at 4 years: ipsilateral breast tumor recurrence 0.7 %; contralateral breast failure 0 %; distant failure 0.9 %; overall survival 96.8 %; and cancer-specific survival 100 %. At last follow-up, patients and physicians rated cosmesis as excellent/good in 88.2 and 90.5 %, respectively; patients rated breast pain as none/mild in 97.0 %. Other observations included edema (1.4 %), telangiectasia (3.6 %), five cases of grade 1 radiation recall (3.6 %), and two cases of rib fractures (1.4 %). This analysis represents the largest cohort and longest follow-up of APBI utilizing IMRT reported to date. Four-year results continue to demonstrate excellent local control, survival, cosmetic results, and toxicity profile.