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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.

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Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.

Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered as a boost using the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. Upon the presence of additional risk factors, 37 participants subsequently received whole breast radiation therapy (WBRT); thus, these participants received an unplanned IORT boost and were removed from the primary analysis but will continue to be followed for the duration of the 10-year study. Cosmesis (Harvard Scale) was assessed in this subset of participants. The primary outcome for the main trial is recurrence of ipsilateral breast tumor at 5 years. Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Early Findings 37 boost participants received WBRT (up to 50 Gy) after IORT (36 received the prescribed 20 Gy dose; one received 14 Gy). Mean follow-up time was 430 days (range 13-1119). Mean age at IORT was 62 years (range 45-78). Boost participants had either DCIS (N=5) or invasive ductal carcinoma (N=32). The DCIS nuclear grade was high (N=3), intermediate (N=1), or low (N=1). Invasive cancers were Grade 1 (N=15), 2 (N=10), 3 (N=6), or unknown (N=1). 29 participants had T1, 3 had T2, and 5 had Tis lesions. Mean tumor size was 13.04 ± 10.26 mm. For the two participants who have reached 3-year follow-up, cosmesis was excellent (N=1) and fair (N=1). For the six participants who have reached 2-year follow-up, cosmesis was excellent (N=4), good (N=1), and fair (N=1). There was one serious adverse event with a Grade 3 for skin necrosis. The most frequent side effects were seroma (10%), edema (9%), pain (9%), erythema (6%), and induration (5%). There have been no deaths, recurrences, or new primary tumors among the boost participants to date. Conclusions Early results from this multi-center trial suggest that IORT as a tumor-bed boost using the Xoft Axxent eBx System at the time of breast conservation surgery is safe and has low morbidity. To date, the majority of participants receiving an unplanned IORT boost have had excellent to good cosmetic results and the majority of adverse events have been low-grade. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Citation Format: Syed AMN, Chang H, Schwartzberg B, Bremner A, Boylan S, Lopez-Penalver C, Vito C, Davis M, Dooley W, Chakravarthy AB, Coomer C, Proulx G, Golder S, Ivanov O, Fernandez K, Farha MJ, Gonzalez V, Wengler C, Bhatnagar A, Neuner GA, Kopkash K, Rahman S, Costa P. A multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer: Early results of unplanned boost participants [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-20.