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.

Outcomes After Accelerated Partial Breast Irradiation in Women With Triple Negative Subtype and Other "High Risk" Variables Categorized as Cautionary in The ASTRO Guidelines.

PURPOSE: To report a primary objective clinical outcome of ipsilateral breast recurrence following accelerated partial breast irradiation (APBI) in women with triple negative and other high risk breast cancer (as described in 2017 ASTRO guidelines) (i.e., age 40-49, size 2.1-3.0 cm, estrogen receptor negative and invasive lobular breast cancer). Secondary objectives of axillary and regional failure as well as overall survival are also reported. METHODS AND MATERIAL: Patients from two clinical trials (NCT01185145, NCT01185132) were treated with 38.5 Gy IMRT or 3D-CRT APBI w/3.85 Gy fraction/BID fractionation for 10 fractions. Triple negative and other high risk patients (n=269) were compared to a total of 478 low risk patients which ASTRO defined as "suitable" for APBI. High risk patients, for the purpose of this study, were defined as those who possess one or more high risk criteria: triple negative (n=30), tumor size >2 cm <3 cm (n=50), HER 2+ (n=54), age range 40-50 years (n=120), ER- (n=43), and ILC histology (n=52). RESULTS: Median follow up was 4.0 years for all patients. No significant difference was found for this high-risk cohort at 5 years for ipsilateral breast, or regional recurrences. Axillary recurrence was significantly adversely impacted by triple negative and ER- statuses (p=0.01, p=0.04). There were significant correlations between triple negative type and axillary recurrence on multivariate analysis (p=0.03). Overall survival for all patients was unaffected by any of the high-risk categories. CONCLUSION: The data from this study suggests that women possessing high risk features are at no more meaningful risk for recurrence than other patients considered to be acceptable for APBI treatment. However, the finding of axillary recurrence in patients with triple negative breast cancer does warrant a degree of caution in proceeding with accelerated partial breast irradiation technique in this patient group.

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.

Predictors for clinical outcomes after accelerated partial breast intensity-modulated radiotherapy.

PURPOSE: To correlate the treatment planning parameters with the clinical outcomes in patients treated with accelerated partial breast intensity-modulated radiotherapy. METHODS AND MATERIALS: A total of 105 patients with Stage I breast cancer were treated between February 2004 and March 2007 in a Phase II prospective trial and had detailed information available on the planning target volume (PTV), ipsilateral breast volume (IBV), PTV/IBV ratio, lung volume, chest wall volume, surgery to radiotherapy interval, follow-up interval, breast pain, and cosmesis. The first 7 of these patients were treated to 34 Gy, and the remaining 98 were treated to 38.5 Gy. All patients were treated twice daily for 5 consecutive days. Univariate and multivariate analyses were performed. RESULTS: The median follow-up was 13 months. No recurrences or deaths were observed. Of the 105 patients, 30 reported mild or moderate breast pain in their most recently recorded follow-up visit. The irradiated lung volume (p < 0.05) and chest wall volume receiving >35 Gy (p < 0.01) were associated with pain. The PTV, but not the PTV/IBV ratio, also correlated with pain (p < 0.01 and p = 0.42, respectively). A total of 72 patients reported excellent, 32 reported good, and 1 reported poor cosmesis. Physician-rated cosmesis reported 90 excellent and 15 good. None of the tested variables correlated with the cosmetic outcomes. CONCLUSION: Radiotherapy to the chest wall (chest wall volume receiving >35 Gy) and to lung correlated with reports of mild pain after accelerated partial breast intensity-modulated radiotherapy. Also, the PTV, but not the PTV/IBV ratio, was predictive of post-treatment reports of pain.