Objectives: To describe observations of one-year follow-up of subjects treated on a multi-center, non-randomized study with a single fraction of intra-operative radiation therapy (IORT) using the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection of early stage breast cancer. Methods: Two-hundred forty three (243) subjects were treated at seventeen (17) US hospitals. Upon meeting the inclusion/exclusion criteria, patients underwent partial mastectomy, placement of a balloon applicator suitable to the surgical bed in the lumpectomy cavity and inflated with saline (30 – 75 cc). The skin was temporarily closed over the balloon and ultrasound examination performed to confirm that the balloon surface-to-skin distance was > 1.0 cm. A single fraction of intra-operative radiation therapy was delivered to the lumpectomy cavity using the Xoft System. The prescribed dose was 20 Gy at the balloon applicator surface, and the mean treatment time was 10.2 minutes. After treatment, the balloon was deflated and removed, and skin sutured. Results: Two-hundred forty two (242) subjects received the prescribed dose of 20 Gy; one subject received 21 Gy. Eighteen (18) subjects were removed from the primary analysis post-IORT due to positive surgical margins (N=2), positive sentinel lymph nodes (N=13), or balloon surface-to-skin distance < 1 cm (N=3). However, these eighteen subjects will continue to be followed for the duration of this 10-year study. The mean follow-up for the two-hundred twenty five evaluable subjects is 494 days (range 300-465 days). The mean patient age was 65 years (41-89). Forty-nine subjects (21.8%) had ductal carcinoma in situ, one-hundred seventy one (76%) had invasive ductal carcinoma, and five (2.2%) had unknown histology. The DCIS nuclear grade was evenly distributed between high (N=18) and low/intermediate (N=23); 5 were unknown. Invasive cancer was Grade 1-2 in 142/171 cases. Two-hundred twelve subjects (94.2%) had T1 lesions, eight (3.6%) had T2 lesions, and five (2.2%) were unknown. The mean tumor size was 10.6 mm ± 6.4 mm. At the time of the last subject visit, 49/318 reported adverse events were Grade 2 or higher, and only 1/100 had serious side effects, i.e. infection. One patient died of aortic aneurism and two developed secondary malignancies, i.e. ovarian cancer and chronic lymphocytic leukemia. The most frequent side effects were seroma (12.5%), erythema (9.1%), and induration (7.5%). Cosmesis was excellent to good in 95% of cases. Conclusions: IORT using the Xoft System as part of the conservative treatment of breast cancer is safe, with low morbidity. Early results from this multi-center trial demonstrate this short, convenient course of radiation therapy for select patients with early stage breast cancer has excellent-to-good cosmetic results and a low rate of low-grade adverse events. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremner AK, Lopez-Penalver C, Coomer C, Boylan S, Chakravarthy A, Vito CA, Bhatnagar A, Proulx GM, Dooley WC, Davis M, Golder SL, Ivanov O, Fernandez K, Rahman S. One-year follow-up results of a multi-center trial of intra-operative radiation therapy using electronic brachytherapy at the time of breast conservation surgery for early stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-11.

Purpose/Objective(s): Hypofractionated whole breast radiotherapy (HF-WBRT) is being increasingly used in the treatment of breast cancer. The most widely used hypofractionated regimens are delivered over three to four weeks, with an optional tumor bed boost over one or more weeks. We conducted a Phase 2 trial of HF-WBRT completed in three weeks inclusive of a sequential boost. Previous report on an initial cohort at short-term follow-up showed excellent rates of tumor control, toxicity, and cosmesis. In this planned expansion cohort, we sought to evaluate longer-term cosmesis and outcomes in a larger number of patients. Materials/Methods: Women with Stage 0-IIIA breast cancer were enrolled on a prospective, Phase 2 trial of HF-WBRT with boost after lumpectomy. Patients with DCIS through T2N2a invasive cancers were eligible. We delivered a whole breast dose of 36.63 Gy in 11 daily fractions of 3.33 Gy (EQD2 Z 45 Gy) followed by a tumor bed boost of 13.32 Gy in 4 daily fractions of 3.33 Gy over a total of 15 treatment days (Total EQD2 Z 61 Gy). When indicated, regional nodal irradiation (RNI) was delivered in 11 fractions of 3.33 Gy to 36.63 Gy. Primary endpoints were locoregional control and acute and late toxicity. Cosmesis was scored using the Harvard Cosmesis Scale. Results: Between 2009 and 2017 we enrolled 150 patients, of whom 146 received the protocol treatment and were included in the analysis. Median age was 54 years (range 33-82), with 48 patients (33%) 50 years old. Median follow-up was 47 months, with 69 patients (47%) having at least five years of follow-up. Receptor status was ER+ (79%), PR+ (75%), HER2+ (10%), and ER-/PR-/HER2-(11%). Sixteen patients (11%) received RNI, 17 patients (12%) received neoadjuvant chemotherapy, and 35 patients (24%) received adjuvant chemotherapy. Cosmesis was good or excellent in 97% of evaluable patients, remaining at 94% in patients with at least two years of follow-up. Acute grade 2 and 3 toxicities were observed in 30% and 1% of patients, respectively. Late grade 2 and 3 toxicities were observed in 9% and 3% of patients, respectively. There were no Grade 4 or 5 toxicities. Five-year freedom from locoregional failure was 97.1% (95% confidence interval [CI]: 91.1%-99.1%). Five-year freedom from distant failure was 97.4% (95% CI: 92.1%-99.2%). Fiveyear breast cancer-specific and overall survival were 98.9% (95% CI: 92.8%-99.9%) and 97.8% (95% CI: 91.6%-99.5%), respectively. Conclusion: Our phase 2 trial offers one of the shortest courses of HF-WBRT, delivered in 15 fractions inclusive of a standardized sequential boost. The study cohort is representative of a broad spectrum of conservatively-treated breast cancer patients including a high percentage of young women and women requiring chemotherapy and/or RNI. With extended follow-up there continues to be excellent locoregional control and low toxicity with good to excellent cosmetic outcomes.

To describe early follow-up results of a trial of single-fraction, intra-operative radiation therapy (IORT) delivered with an electronic brachytherapy system immediately following surgical resection for treatment of early-stage breast cancer. Materials/Methods: To date, 1,028 participants have been enrolled in this open label, single-arm, prospective, non-randomized trial at 28 hospitals in the USA ( 27) and Portugal (1). 1,023 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by IORT to the lumpectomy cavity. A presterilized lead shield was placed on the chest wall and a balloon applicator suitable to the surgical bed was placed in the lumpectomy cavity and inflated with saline (30-75 cc). Balloon surface-to-skin distance of ! 1.0 cm was confirmed by ultrasound. Single-fraction IORT (20 Gy) was delivered at the balloon applicator surface with a mean radiation treatment time of 11.3 minutes. Following IORT, balloon was deflated and removed along with lead shielding, and surgical site was sutured. The prespecified primary outcome of this 10-year follow-up study is ipsilateral breast tumor recurrence at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Results: Median follow-up time was 1.2 years with 320, 102, and 10 participants completing 2-, 3-, and 4-year follow-up, respectively. Mean age at enrollment was 66 years (range 41-93). 246 participants had DCIS and 777 had invasive ductal carcinoma. DCIS nuclear grades were high (82), intermediate ( 119), or low (45) with three identified as bilateral. Invasive cancers were Grade 1 (318) including two bilateral cases, Grade 2 (340) with one bilateral case, Grade 3 (105) with two bilateral cases, or no Grade (14). Mean tumor size was 12.01 AE 10.8 mm. Cosmesis was excellent in 100% of participants at 4-year followup and excellent to good in 94% and 91% of participants at 2-and 3year follow-up, respectively. The number of reported adverse events (AEs) that were Grade 2 or higher was 169 (9%). Seroma, breast induration, erythema, breast fibrosis, and breast pain were the most frequent AEs. There were ten deaths, none of which were breast cancer related. There were six ipsilateral breast recurrences and three new contralateral breast cancers. Conclusion: Single-fraction IORT using an electronic brachytherapy system following breast conservation surgery may be a promising treatment option for select early-stage breast cancer patients. Early findings from this multicenter trial suggest that the short and convenient course of radiation therapy has low morbidity, excellent to good cosmetic results, and a low rate of high-grade adverse events and recurrences.

Breast radiation therapy is associated with misconceptions and fears among patients. Although the efficacy and toxicity of breast radiation has been extensively studied, little is known regarding patient's perspective on their treatment experience. Materials/Methods: Patients treated with radiation therapy (RT) from 2012-2016 who were without recurrence and had 6 months of follow-up were surveyed. The survey evaluated original fears, and how short-and long-term toxicities compared to initial expectations by asking if the actual experience was as expected, worse, or better than expected. Patients were also asked about how their pre-treatment beliefs about RT compared to the actual experience. Results: The response rate was 65% (327/502). The median age was 59 years and the stage distribution was 18% stage 0, 38% stage I, 34% stage II, and 9% stage III. Eighty-two percent of patients underwent breast conservation therapy, 13% underwent axillary dissection, 37% received chemotherapy, and 70% received adjuvant endocrine therapy. Radiation treatments were as follows: 42% standard whole-breast RT, 28% hypofractionated whole-breast RT, 22% regional nodal RT, 6% partial breast RT and 2% chest wall RT. The most feared treatment at time of diagnosis was: 55% chemotherapy, 36% surgery, 7% RT and 5% endocrine therapy. Sixty-eight percent of patients endorsed that they initially had little to no knowledge about RT; however, 47% reported that they had heard or read frightening stories about RT. The most commonly ranked top fear about RT was damage to internal organs (40%), skin burning (24%), and being radioactive (7%). Regarding shortterm side effects, 75%, 61%, and 78% reported pain, skin changes, and fatigue, respectively, to be less than or as expected. Eighty-three percent of the patients reported overall short-term side effects to be better than or as expected. Regarding long-term effects, 85% reported appearance changes to be better than or as expected. Seventy-nine percent, 73%, and 70% of patients found long-term breast pain, breast size changes, and breast textural changes, respectively, to be less than or as expected. Eighty-four percent reported overall long-term side effects to be better than or as expected. Very few patients agreed that the negative stories they initially heard (2%) and read (3%) about RT were actually true. Ninety percent of respondents agreed that their RT experience was less scary than expected. 89% agreed with the statement that RT is not as "bad as they say it is" and 90% agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Conclusion: There is significant misinformation and fear about breast radiation therapy. However, patients' experiences are overwhelmingly superior to initial expectations, and the majority of patients agree that their initial negative impressions about breast RT were unfounded. These data can play a critical role in counseling future patients and providers on breast radiation therapy.