Purpose/Objective(s) We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a cobalt stereotactic radiation system. Materials/Methods Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity graded (using the NCI version 5.0 and RTOG/EORTC late radiation scale). Results From March 2019 to October /2021, 74 patients were treated respectively. Of these, 38 were treated to 40 Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 36 months (mo), range (r) 3-58 mo. Median age was 63 years (r = 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. Fort-five of 46 invasive tumors were ER+. Sixty of 74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 225 acute grade 1 toxicities, and 30 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (12), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 103 Grade 1 late toxicities, 3 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis 1, and pain (2). Three patients developed grade 1 asymptomatic nonpalpable fat necrosis. The most common grade 1 late toxicities were breast pain (25), hyperpigmentation (11), fibrosis (11), and fatigue (5). Physicians scored cosmesis excellent or good 71/74 (95.9%), 59/61 (96.7%), 61/62 (98.3%), 33/33(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 63/72 (87.5%), 54/60 (90.0%), 57/64 (89.0%), 35/37 (94.6%). There have been no local regional or distant disease recurrences. Conclusion Results at 36-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Clinical trials.gov identifier is NCT03581136.

We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using the GammaPodTM stereotactic radiation system.Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity was graded using the NCI version 4.0 and RTOG/EORTC late radiation scale.From 3/2019-10/2021, 74 patients were treated respectively. Of these, 38 were treated to 40Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 24 months (mo), range (r) 3-39mo. Median age was 63 years (r 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. 45/46 invasive tumors were ER+. 60/74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 221 acute grade 1 toxicities, and 28 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (10), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 54 Grade 1 late toxicities, 4 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis (2), and pain (2). Two patients developed grade 1 asymptomatic nonpalpable fat necrosis both diagnosed at 12 months after radiation treatments. The most common grade 1 late toxicities were breast pain (14), hyperpigmentation (8), fibrosis (10), and fatigue (5). Physicians scored cosmesis excellent or good 70/73 (95.8%), 58/60 (96.7%), 36/36 (100%),17/17(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 62/71 (83.7%), 53/59 (89.8%), 33/36 (91.6%), 17/18 (94.4%). There have been no reports of disease recurrences.Results at 24-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Continued analysis of all cohorts is in progress.gov identifier is NCT03581136.

ABSTRACT PURPOSE: Several new commercial software packages have become available that can calculate the tumor and normal tissue dose distributions from post-treatment PET-CT scans for Y-90 microsphere treatments of liver lesions. This work seeks to validate the MIM SurePlan Liver Y90 software by comparing its results to a previously developed Monte Carlo derived voxel dose kernel calculation method. METHODS: We analyzed 10 patients who had treatments for metastatic liver cancer and created contours on post Y-90 treatment PET-CT images. We then performed dose calculations using three methods and compared the results. The first two methods calculated the dose using MIM SurePlan Liver Y90's LDM (Local Deposition Method) and the VSV (Voxel S Value) algorithms. The third method calculated the dose using a publicly available Fluka Monte Carlo-derived dose kernel (MCK) calculation (used as ground truth). We investigated 3D Gamma passing rates and several dosimetric parameters. RESULTS: A total of 3%/3 mm 3D gamma passing rates averaged 99.3% for the VSV and 78.9% for LDM. Compared to the MCK distribution, the differences for combined target GTV V 70Gy and normal liver and/or lobe mean doses were small. Larger differences were seen in GTV mean doses and D 95 , likely due to large dose gradients in the treated regions combined with differences in dose kernel, dose grid and finite volume effects. CONCLUSIONS: The MIM SurePlan Liver Y90 VSV algorithm agreed well with the MCK calculation for patients treated with Y-90 microspheres based on the gamma analysis and several dosimetric parameters. Larger dosimetric differences in lesion mean doses and D 95 suggests that these metrics are less robust to changes in calculation grid location and finite volume effects for small lesions. (c) 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose/Objective(s)With the increasing use of proton beam therapy (PBT) in treatment of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and other cancers involving the liver, there is a growing need to determine treatment-related toxicity, particularly when used as re-treatment. There is limited safety and efficacy data on re-treatment with PBT after Transarterial Radioembolization (TARE). This study evaluates safety of PBT use in patients who received PBT following previous TARE for liver-related cancer.Materials/MethodsA single center retrospective study identified 12 patients with liver-related cancers who received PBT after initial treatment with TARE between 2014 – 2020. Patient-related toxicity was assessed using Child-Turcott-Pugh (CTP) Scores and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary endpoints were overall survival (OS), progression-free survival (PFS), and Local control (LC).ResultsAll patients received microsphere-based 90Y TARE with a median dose of 150 Gy (range, 120 - 150 Gy) prescribed to the target lobe. Of the included patients, seven (58%) had hepatocellular carcinoma, three (25%) had metastatic disease, and two (17%) had intrahepatic cholangiocarcinoma. Prior to TARE median CTP score was A6 (range A5-B7). Median time to initial failure was 5.6 months (range 2.4 - 47.7 months) with seven (58%) local failures at site of TARE. Median CTV volume for PBT was 493ccs (range 104 – 1395ccs). Ten patients (83%) received 5805CGE in 15 fractions and two patients (17%) received 5000CGE in 5 fractions. No patients had a decline in CTP score greater than 1 point with a median CTP A6 (range A5 – B8). There were no CTCAE grade 3+ acute or late toxicities. Median follow-up after PBT was 12.7 months and median OS was 12.5 months (95% CI, 8.8 - 16.2 months) and PFS was 9.0 months (95% CI, 6.5 – 12.4 months). No patients had local failure, while two had liver failure, and eight had distant metastatic failure.ConclusionUse of PBT as re-treatment following 90Y TARE appears to be well-tolerated and safe in an early evaluation for patients with definitive doses. Larger, multi-institutional studies are needed to verify this evaluation.

Single-fraction stereotactic radiosurgery (SF-SRS) for the treatment of brain metastases can be delivered with either a frame-based platform (FB-SRS) or with a frameless linear accelerator (LA-SRS). These techniques vary based on patterns of prescribing, patient setup and radiation delivery but the effect of these differences on clinical outcomes is unknown. The purpose of this study is to compare local control and radiation necrosis outcomes between these two techniques at a single institution. Metastatic brain lesions treated with SF-SRS from 2014-2019 were retrospectively reviewed (n = 263). Lesions that received prior whole brain radiotherapy (WBRT) (n = 91), were located in the brainstem (n = 9) and/or without an MRI 30 days post-treatment were excluded (n = 35). Patient, tumor, and treatment-specific parameters were collected and analyzed. Covariates between groups were compared using a Chi-square analysis for dichotomous variables and t-test for continuous variables. Median follow up was calculated using the reverse Kaplan Meier (KM) method. Primary endpoints of local control (LC) and symptomatic radiation necrosis (RN) were estimated using the KM method with salvage WBRT used as a censoring event. Outcome estimates were compared using the log-rank test. Multivariate analysis (MVA) and Cox proportional hazards modeling were used for statistical analyses. Propensity score (PS) adjustments were used to reduce the effects confounding variables. One hundred and seventy-two lesions treated with FB-SRS (n = 79) or LA-SRS (n = 93) were included. Median overall follow up was 12 months (FB-SRS) and 6.7 months (LA-SRS) (p<0.001). Median SRS dose was 24Gy in both cohorts (range 12-24). Tumors were ≤ 2cm in 92% (n = 73) and 87% (n = 81) (p = 0.26) and adenocarcinoma histology in 73% (n = 58) and 69% (n = 64) (p = 0.22) of lesions treated with FB-SRS and LA-SRS, respectively. Concurrent systemic therapy was given for 41% (n = 32) and 12% (n = 11) of lesions treated with FB-SRS and LA-SRS, respectively (p <0.001). The rate of symptomatic RN was 1.4% (95% CI 0.1-6.6) (FB-SRS) and 9.9% (95% CI: 3.8-19.6) (LA-SRS) (p = 0.03). One-year LC was 95% (95% CI 87.1-98.7) (FB-SRS) and 81.9% (95% CI 57.6-96.6) (LA-SRS) (p = 0.07). Overall survival and distant brain failure rate at one year were 28.6% (95% CI 18.5-38.7) and 32.1% (95% CI 21.7-42.4) for the entire cohort. On MVA after PS adjustments, FB-SRS was the only covariate significant for LC (HR 0.07, 95% CI 0.01-.56: p = 0.01). In our retrospective cohort, we found a significantly lower incidence of symptomatic RN and a trend towards improved LC in patients treated with FB-SRS compared to LA-SRS. FB-SRS was the only covariate associated with improved local control on Cox regression analysis after PS adjustment. Further study with prospective cohorts is required to validate these observations.

Abstract Purpose: A breast specific radiosurgery device (BSRD) has recently been FDA cleared for treatment of accelerated partial breast irradiation. Using this device requires a vacuum assisted immobilization system to treat patients in the prone position. Alternatively, APBI delivery using intensity modulated proton therapy (IMPT) treats patients in the supine position at University of Maryland. This study aimed to compare dose distribution to targets and organs at risk (OARS), using BSRD plans versus IMPT plans for APBI. We hypothesized that despite the physical characteristics of IMPT the BSRD plans would be superior in conformality. Methods:An IRB approved retrospective review was performed for 13 patients who previously received a lumpectomy boost using the BSRD in prone position followed by whole breast irradiation in the supine position. APBI plans were created using dose a fractionation of 30Gy in 5 fractions. Previously contoured LPC volumes with a 1cm CTV expansion were created (modified at anatomic boundaries and within 5 mm of skin) followed by a 3 mm PTV expansion for BSRD plans, our standard for all BSRD plans, or CTV with beam specific PTV for IMPT plans. A single physicist created plans for BSRD with a different physicist for IMPT. Physicists were blinded to the results of the comparative plans. Plans were compared with respect to heart max, heart mean, ipsilateral lung V5, V20, normal breast D5, D20, D50 and D80, skin max, CTV coverage, conformality index (CI) and homogeneity index (HI). Paired t-test was used for statistical analysis. Results:Six out of thirteen patients had left sided breast cancer. The CTV volumes were comparable, with no difference in coverage of 95% of the CTV receiving the prescription dose (98% vs 97%). BSRD plans had superior CI (0.82 vs 0.63, p<0.0004), and HI (0.91 vs 0.65, p<0.0001) and improved Ipsilateral Lung V5 (2.3% vs 0.7%, p<0.055). IMPT plans had superior max heart dose (1.17Gy vs 4.13Gy, p<0.001), heart mean dose (0.05Gy vs 0.8Gy, p<0.0006), normal breast D5 (29 vs 31Gy p<0.003), D20 (13 vs 18Gy, p<0.04), D50 (0.79 vs 6.79, p<0.0001), D80 (0.07 vs 2.85, p<0.0001). There was no difference in max skin dose or ipsilateral lung V20. Conclusions: In conclusion, BSRD plans were associated with better dose conformity to the target and lower ipsilateral lung V5. When comparing dose to the heart and ipsilateral normal breast, both treatments plans delivered low doses below the acceptable limits, however plans were comparatively better with IMPT possibly due to target location. Additional patient evaluation is needed to further assess the impact of the breast immobilization device and target location on doses to OARs and the normal breast tissue. Overall, this comparison supports further evaluation of the BSRD technology Citation Format: Santanu Samanta, Elizabeth Nichols, Mark Zakhary, Mariana Guerrero, Baoshe Zhang, Ariel Pollock, Naru Lamichhane, Stewart Becker. Comparison between a breast specific radiosurgery device and intensity modulated proton therapy for accelerated partial breast irradiation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-14.

Yttrium-90 (Y90) radioembolization is often considered for local treatment in the setting of unresectable or chemoresistant hepatocellular carcinoma (HCC). For patients within Milan criteria, the goal of such therapy is to provide disease control until liver transplantation. Previous studies have assessed the dose response of radioembolization using radiographic criteria but, to our knowledge, none have assessed lesion-specific pathologic dose response of HCC with Y90 with dosimetric information. We performed an IRB-approved, single-institution retrospective analysis of patients with HCC who underwent Y90 microsphere radioembolization with post-treatment PET/CT and subsequent liver transplantation from 2016 to 2019. We contoured each treated lesion to determine lesion volume using pre-treatment magnetic resonance and computed tomography imaging and computed dosimetric coverage using post-treatment Y90 PET/CT. Lesion volume, delivered GBq, and mean/D70Gy dosimetric values were obtained and analyzed for complete pathologic response at the time of explant. Optimal cutoff values were generated for factors that demonstrated statistical significance for correlation using paired t-tests for complete pathological response. Sixteen lesions from ten patients met criteria for analysis. Fifteen of sixteen lesions were evaluated for complete pathologic response due to one patient undergoing transplant only 8 days after radioembolization. Lesions had a median volume of 3.3 cm3 (range: 0.9 to 74.5 cm3) and median largest dimension of 1.9 cm (range: 1.0 to 4.6 cm). The median prescription dose was 150 Gy (range: 120 to 150 Gy) which was prescribed to the target lobe volume, expecting much higher doses to individual lesions. Median interval between treatment and transplantation was 143 days (range: 34 to 410 days). Complete pathologic response was seen in ten lesions corresponding to four patients. Of the five lesions with partial response, two showed 80 to 95% necrosis while three showed 50 to 55% necrosis. Of the factors evaluated, only the PET/CT-derived mean dose received per lesion was found to be significantly associated with complete pathologic response (p<0.001). An optimal cut off value of mean dose >600 Gy was statistically significantly associated with higher complete pathologic response rates. Of those with lesions with a complete pathologic response, 10/10 (100%) had a mean dose >600 Gy. Of those lesions with viable tumor, 4/5 (80%) had a mean dose less than 600 Gy (p<0.001). There is limited data on the dosimetric factors associated with pathological complete response in radioembolization treatment for HCC. Here, we correlated increased mean delivered dose to pathological complete response. In this limited set of patients, a mean dose of >600 Gy delivered to the tumor was statistically significantly associated with complete pathologic response.

Stereotactic radiosurgery (SRS) is the preferred non-surgical treatment for patients (pts) with brain metastases (BMs). Pts often take immune checkpoint simultaneously (SRS+ICI) to manage their systemic disease. SRS+ICI may act synergistically to intensify the immune response. In pts with BMs, the combination of SRS and ICI (SRS+ICI) may improve outcomes but potentially at the expense of increased radionecrosis (RN). The objective of this study was to compare outcomes for pts undergoing SRS with and without ICI. We retrospectively reviewed pts treated for BMs with single or multi-fraction SRS at our primary academic institution and affiliated community practices. ICI included anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, ipilimumab), anti-programmed cell death protein receptor (PD-1, pembrolizumab, nivolumab) and anti-programmed cell death ligand (PD-L1, durvalumab). Local control (LC), symptomatic radiation necrosis (RN) and overall survival (OS), stratified by receipt of ICI, were estimated using Kaplan-Meier survival curves. Symptomatic RN was defined by a pt’s need for medication intervention to manage their symptoms. Univariate and step-wise multivariate analyses (MVA) with propensity adjustments were performed. One-hundred and sixty-nine pts were treated with SRS to 314 BMs and followed for 7.1 months (median). Sixty-two BMs were treated with SRS + ICI, received in the 3 months prior (n=20, 32.3%), 3 months after (n=31, 50%) or concurrently (n= 11, 18%) with SRS. Three pts received concurrent or sequential dual anti CTLA-4 and PD-1 therapy. The one-year LC rate for BMs treated with SRS + ICI was 95.2% compared to 85.2% for BMs treated with SRS alone (p=0.18). OS was similar between the groups (SRS: 40% vs. SRS+ICI: 38%, p=0.80). At one-year, 9.3% of BMs treated with SRS + ICI developed symptomatic RN vs. 8.5% of BMs treated with SRS alone (p=0.85). After MVA with propensity adjustments, non-squamous histology was associated with improved LC (HR 0.33, 95% CI 0.11-0.98, p=0.045) and resected BMs were associated with inferior LC (gross total resection: HR 2.57, 95% CI 0.71-9.29, p=0.15, sub-total resection: HR 10.79, 95% CI 3.43-33.97, p<0.0001). BMs ≥2 cm predicted for symptomatic RN (HR 10.72, 95% CI 4.16-27.60, p<0.0001). This experience suggests that SRS + ICI is safe and not associated with increased risk of symptomatic, grade 2+ RN. Apprehension regarding increased toxicity with SRS + ICI may prompt clinicians to change their standard treatment practices for SRS, for example by lowering the dose prescribed to a BM. This experience suggests this may not be necessary and SRS + ICI may not increase the risk of symptomatic RN. Although there was a trend towards improved LC for BMs treated with SRS + ICI, this difference was not statistically significant. Further follow-up is needed to fully analyze these findings.

There has been a rapid increase in the use of frameless SRS in place of the frame-based SRS for treatment of brain metastases (BM). Compared to the frame-based SRS, intra-fraction motion management is a major challenge for the frameless SRS. With advanced immobilization and patient monitoring technologies, intra-fraction motion can be reduced. The purpose of this study is to analyze intra-fraction motion with LINAC-based SRS using a frameless radiosurgery platform that uses an integrated 3D optical surface monitoring system for intra-fraction motion management. This retrospective study includes 97 LINAC-SRS treatments delivered to 60 patients of BM with an integrated 3D surface imaging software for intra-fraction monitoring. Every treatment was delivered with a 6MV FFF beam at a dose-rate of 1400MU/min. Each treatment had at least 3 non-coplanar arcs with a minimum of 3 couch rotations. The patients were immobilized using an open-faced rigid SRS-thermoplastic mask with an opening encompassing the eyes, nose, and part of their forehead. Each patient was first aligned using a high-quality cone-beam CT (CBCT) with 1mm slice thickness and positioned using a 6 degrees of freedom couch. The patient's face was monitored during treatment delivery through the surface monitoring system. During delivery, beam holds occurred if patient motion exceeded pre-defined tolerance (1mm translation/1° rotation) for > 5 seconds. An additional CBCT was performed following the delivering of two arcs to assess for any intra-fraction motion. Each CBCT was then registered to the planning CT using the automated intensity-based registration algorithm, followed by confirmation with a manual check. The intra-fraction shifts (RL, AP, and SI) and rotation (yaw, roll, and pitch) data were retrospectively recorded and analyzed. The total magnitude of the patient intra-fraction motion for all ninety-seven SRS treatments as recorded through shifts were 0.4 mm (mean) ± 0.3 mm (stv). Translational shifts were 0.0±0.3 mm in RL, 0.0±0.3 mm in AP, 0.0±0.3 mm in SI, while the rotational variations were 0.0±0.4° in yaw, 0.0±0.2° in roll, and 0.0±0.2° in pitch. In total, 93.8%(n=91/97) delivered treatments had intra-fraction motion that was ≤1mm and ≤1 degree. Minimal intra-fraction motion was observed during frameless-based LINAC-SRS treatments when using an integrated 3D surface image tracking; Only 6% percent of treatments experienced motion that was >1mm or >1 degree. A planning target margin of ≤1 mm may be considered adequate during the planning process to account for intra-fraction motion in the majority of all cases.

There has been a rapid increase in the use of multi-fraction stereotactic radiosurgery (MF-SRS) as an alternative to single-fraction stereotactic radiosurgery (SF-SRS) for the treatment of brain metastases (BM), particularly when access to deliver SF-SRS is limited. Recent studies suggest MF-SRS affords decreased risk of radiation necrosis with similar (or improved) rates of local control compared to SF-SRS. Here, we evaluate treatment outcomes for patients treated with SF-SRS compared to MF-SRS for the treatment of BM across multiple centers affiliated with a single NCI-designated comprehensive cancer center. One hundred and sixty-nine patients with a total of 314 metastatic brain lesions treated with SF-SRS (n = 65 patients; 162 lesions) or MF-SRS (n = 104 patients; 152 lesions) were retrospectively analyzed. Patient-, disease- and tumor-specific parameters were collected. Probability of local control (LC) and symptomatic radiation necrosis (RN) (defined as ≥ grade 2 by CTCAEv5) from the date of first SRS fraction stratified by SF-SRS vs MF-SRS was estimated using Kaplan-Meier survival curves. Univariate (UVA) and step-wise multivariate analyses (MVA) with propensity score adjustments were performed to adjust for confounders. Median follow-up for the entire patient cohort was 7.1 months. Median size of BM was 7 mm (SF-SRS) and 16 mm (MF-SRS) (P < 0.0001). Thirty-one percent (n = 20) and 32% (n = 33) of patients had prior whole brain irradiation in the SF-SRS and MF-SRS groups, respectively, and 93% (n = 151) and 86% (n = 130) of lesions were treated definitively. Median dose of SF-SRS was 24Gy (range, 8-24) and median BED of MF-SRS was 43 Gy (range, 15-60). One-year OS for the entire cohort was 45%. One-year LC was 90.9% (SF-SRS) versus 80.8% (MF-SRS) (P = 0.03). MF-SRS (HR 2.5, CI 1.04-6.13; P = 0.04) and lesion size 2cm (HR 2.7, CI 1.18-6.19; P = 0.02) were significantly associated with a higher rate of local failure on UVA. On MVA, only MF-SRS remained significant after propensity score adjustment for confounders including lesion size (HR 2.6, CI 1.23-5.63; P = 0.01). The one-year rate of symptomatic RN was 9.1% (SF-SRS) and 8.8% (MF-SRS) (P = 0.5). In a MVA for radiation necrosis, lesion size 2cm was the only variable significantly associated with a higher risk of developing symptomatic RN (HR 3.6, 95% CI 1.52-8.40; P = 0.003). In contrast to prior studies, SF-SRS was associated with significantly improved local control and no significant difference in rates radiation necrosis when compared to MF-SRS. Future studies are warranted to determine the optimal BED for local control when treating with MF-SRS.

A novel breast specific stereotactic radiosurgery device (BSRD) was invented at our institution. Over the last several years the device has been systematically evaluated demonstrating the stereotactic accuracy of its patented breast immobilization system and dosimetric benefits in comparison to external beam radiotherapy, proton beam radiotherapy and brachytherapy. Based on these evaluations, an Investigator Device Exemption (IDE) was obtained through the FDA and a study was developed and approved to test its feasibility. This report is the 1st clinical experience of this device on this pre-FDA approved feasibility study. This protocol was approved through the Institutional Review Board. Eligible patients were > 60 years, recommended to undergo whole breast radiation(WBRT) without nodal radiation, had a tumor bed(TB) well visualized on CT simulation and the TB volume was < 25% of the WB. Once deemed eligible, patients received a single fraction of 8 Gy using the BSRD to the TB + 1cm prior to WBRT (40 Gy in 15 fx or 50 Gy in 25 fx). The primary objective of this trial was to ensure the adequacy of the radiation dose distribution(DD) with a secondary endpoint of acute toxcity. Dosimetric parameters evaluated in the protocol included planning tumor volume(PTV) coverage, PTV max dose, PTV min dose, and maximum dose to the skin, chest wall, rib, lung and heart. In order to meet the primary endpoint of feasibility, the two stage design by Simon was utilized. This tests the null hypothesis that the true proportion of patients for whom BSRD treatment planning is able to generate an acceptable DD is < 60%. Seventeen patients will be accrued, with a planned interim analysis in the 1st stage after 8 patients, where the DD needs to be acceptable in 6 or more in order to move forward to stage 2. Between 3/18/16 and 12/21/16, 9 patients signed consent for treatment and 8 patients underwent successful treatment. One patient, who was found not to eligible after simulation, was treated with conventional WBRT off study. The TB volume ranged from 2.86 to 20.38cc, while the PTV ranged from 21.69 to 89.56cc. The median(range) skinmax, lungmax, heartmax, and PTVmax dose were 2.04Gy(1.13-2.87), 1.40(0.1-1.98), 1.01(0.1-2.2) and 8.71 Gy(8.35-9.26), respectively. One patient with a deep seeded TB had a minor deviation and received a dose over the prescription dose to the chest wall, while a second patient had inadequate coverage of the PTV(major deviation). Acute toxicity related to the device has been minimal with one patient developing small blisters related to the immobilization device that was seen immediately following removal of the device. Based on an adequate dose distribution seen in 7 of the 1st 8 patients, stage 2 was initiated. The plan is to complete accrual this spring and submit the results for FDA approval.

Partial breast irradiation (PBI) has held the promise of shortened courses of radiotherapy with reduced exposure of normal tissues. However, initial postoperative results with PBI have been met with higher than expected rates of fair to poor cosmesis. Preoperative approaches increase patient eligibility, reduce target volumes, and improve dosimetry. At our institution, a novel breast-specific stereotactic radiotherapy (BSRT) device has been developed which employs a dynamic dose-painting technique with 36 noncoplanar Co-60 beams that rotate around the breast in the prone position. We sought a dosimetric comparison of BRST to a frameless robotic radiosurgery system (FRRS). Ten previously treated breast cancer patients were enrolled on an IRB-approved protocol and underwent CT simulation in the prone position with the BSRT patented vacuum-assisted breast immobilization cup. The preoperative gross tumor volume was simulated with a spherical target of equal diameter to each patient's pathologic tumor size inside the lumpectomy cavity. Clinical (15mm) and planning (PTV) (3mm) target volumes were based upon recent trials and the device's measured localization uncertainty. BSRT and FRRS plans were generated for each case requiring similar PTV coverage with maximal sparing of surrounding normal tissue. For FRRS planning, the CT image was rotated to simulate supine position as FRRS technique is unable treat prone. The dose to the normal ipsilateral breast, skin, heart, lung, and chest wall were recorded for several percentages of the prescribed dose (Vx%). All volumes and plans were generated by a trained physician/physicist team. Wilcoxon rank sum tests were utilized for statistical comparison. Despite the geometric advantage provided to the FRRS by prone breast anatomy and the vacuum-assisted breast cup immobilization, the BSRT device provided substantially improved sparing of nearly all normal tissues. On average, the BSRT especially reduced the normal breast tissue V5%/V20%/V50%/V80%/V100% by a relative 37.0%/40.8%/24.5%/32.3%/48.8% (p≤0.013) (Table 1), metrics which have been directly linked to cosmetic outcomes [Hepel et al. 2009]. BSRT also relatively reduced the heart max by 46.1% (p=0.005) and the skin V15% by 52.8% (p=0.005). Low and moderate doses to the lung and chest wall were similarly very low with both techniques (p>0.05). This novel BSRT device offers substantial and clinically meaningful dose reductions to the uninvolved normal breast tissue and the majority of organs at risk as compared to FRRS. These differences would be even further magnified under conventional set up for FRRS. The benefits of BSRT will be tested clinically in the pre-operative setting early in 2018.Abstract 3720; Table 1Mean dosimetric parameters BSRT vs. FRRSBSRTFRRSV5% Breast41.3%65.7%V20% Breast17.1%28.9%V50% Breast8.0%10.6%V80% Breast4.2%6.2%V100% Breast2.1%4.1%V15% Skin11.6%24.5%Heart Max7.6%14.1% Open table in a new tab

A dedicated stereotactic breast specific radiation therapy device was developed as a novel partial breast delivery unit. The first clinical unit was installed at our institution and commissioned to treat the first patient in the spring of 2016 using an FDA-approved study. A commissioning protocol was developed for the clinical implementation of this technology, reporting on the performance of the GammaPod system. The GammaPod treatment unit is comprised of a rotating hemispherical source carrier containing 36 Co-60 sources and a concentric rotating tungsten collimator providing beam diameters of 15 and 25 mm. Commissioning tests were developed to include safety, mechanical, geometric, and dosimetric performance of the treatment unit, control system, and treatment planning systems. Several dosimetric systems were utilized that included area survey meters, stereotactic size ion chambers, radiochromic film, and OSL detectors. Dosimetric measurements were performed using acrylic as well as polyethylene phantoms and also performed directly in patient breast cups filled with water and using a manually controlled 3-dimensional chamber positioning system. A commissioning protocol is provided with lists of performance tests for safety systems, mechanical, geometric, and dosimetric accuracy of GammaPod. Using this procedure, mechanical accuracy of the couch positioning system was measured over a 40-mm range using both mechanical methods (<0.2 mm) as well as the location of the radiation isocenter (<0.5 mm). The couch sag from the presence of varying weights was measured and modelled to be 0.1 mm per 10 kg of patient weight. The congruence of the radiation profile and mechanical positioning system was measured through several treatment table loading and unloading procedures over a period of 1 month and determined to be −0.1±0.1, 0.2±0.1, and 0.2±0.2 mm in x, y, and z directions, respectively. Single isocenter dose profiles were also measured in all 3 cardinal directions using radiochromic film. Dose profile widths were found to be within 0.2 mm of corresponding MC simulations for single isocenter 15- and 25-mm shots. Overall dosimetric and spatial accuracy of the system was also determined through a variety of plan dosimetric verifications as well as end-to-end tests. The first GammaPod treatment unit for breast-specific stereotactic radiation therapy was successfully installed and commissioned for commencement of patient treatments in 2016. A clinical commissioning protocol was devised to verify the integrity of the GammaPod system and characterize its performance in terms of safety profiles as well as its mechanical and dosimetric accuracy. We report our commissioning experience with the first clinical GammaPod unit in the world.

The first stereotactic radiation therapy system dedicated for breast cancer, the GammaPod™, has been installed and commissioned at our institution and expected to treat its first patient in March 2016. We describe our institutional design of the clinical processes and protocols as well as the quality control systems put in place for its safe and effective use. The GammaPod™ system is comprised of the treatment unit, the vacuum-assisted stereotactic breast cup immobilization device (BCID), an automatic patient loader for treatment planning imaging, and the dedicated treatment planning system. A multidisciplinary team of radiation oncologists, medical physicists, radiation therapists, and nurses designed and reviewed various sub-processes and generated process maps for different stages of GammaPod™ treatment to aid in the seamless execution of treatments. In the first single-institution clinical trial, which will test both the feasibility of delivering a high focal dose of radiation and the safety of the system, patients who receive whole-breast radiotherapy (WBRT) as part of their breast conservation therapy (BCT) will be given a single-fraction 8 Gy boost treatment using GammaPod™ prior to WBRT. Preliminary procedures were studied for 24 previously imaged volunteers used to test the reproducibility of the BCID through an IRB-approved protocol. The duration and adequacy of the procedure as well as the time spent for each of the processes were recorded throughout the experimentation period. A comprehensive clinical process map was developed for safe and efficient execution of this novel stereotactic technology. The use of a BCID for the stereotactic localization and immobilization of the breast requires a fast-paced but well-defined process. The single day image-and-treat workflow starts with selection and installation of the appropriate breast cup by the clinical team. In the preliminary testing, the average time for the initial BCID setup was 27±11 minutes. Out of 24 patients enrolled in the study, we had difficulty mounting the BCID due to patient comfort and body hiatus for 4 patients and were not able to find an appropriate breast cup size for 1 patient. For the remaining patients, CT imaging was performed in prone position with the help of the automated patient loader and images were then transferred to the treatment planning system. Patient plans were ready for treatment execution in 33±3 minutes after the completion of imaging. Throughout the entire process, several quality checklists and safety measures were also implemented to further improve the accuracy and efficiency of treatments. A clinical workflow was developed for the first installation of GammaPod™ stereotactic radiotherapy technology. Process mapping and identification of the causes and effects of potential failures relating to the workflow improves the quality of GammaPod™ treatments and increases safety and efficiency for the use of this technology.

Perform a dosimetric comparison of IMPT PBI to BSRT. The BSRT device consists of 36 noncoplanar Co-60 sources that focus on a single isocenter that dynamically delivers the treatment through a rotating collimator. Dosimetrically, both techniques have advantages regarding normal tissue sparing in comparison to external beam PBI. External beam PBI has recently been shown to have worse cosmesis compared to conventional fractionation; therefore, if PBI is to be considered a standard treatment, improvements are required to result in better cosmesis. The aim of the present analysis is to compare which modality results in better normal tissue sparing, particularly to the normal breast tissue. We hypothesized that BSRT would result in better sparing of normal breast tissue. Nine patients previously treated with breast-conserving therapy including radiation for early-stage breast cancer underwent CT simulation with the BSRT breast cup immobilization device (BCID) as part of an IRB-approved study. When utilizing the BSRT BCID, reproducibility studies have validated a planning target volume (PTV) margin of 3 mm. For proton therapy a similar immobilization device does not exist. In order to not skew results based on volumetric differences in PTV when utilizing different margins, an analysis was performed for both modalities utilizing a 10-mm margin consistent with that used in external beam therapies. For IMPT, single field optimization using 2 fields was utilized for added robustness. Dosimetrists were given identical treatment planning goals. Plans were then compared using 2-sided Wilcoxon signed rank tests for doses to normal structures. BSRT resulted in decreased doses of RT to the following normal structures compared to IMPT: whole breast (WBV) V20% (P=0.03), V50% (P=0.03), V80% (P=0.02), and V100% (P=0.02); ipsilateral lung V15% (P=0.05) and skin V15% (P=0.05). BSRT resulted in increased max hot spot compared to IMPT PBI (P=0.02). There was no benefit of BSRT compared to IMPT when comparing heart V15%, heart max dose, whole breast V5%, chest wall V15% and V25%, and lung V25%. The relative benefit in mean doses received by the WBV20, WBV50, WBV80, WBV100 with BSRT were 18%, 20%, 17%, and 11%, respectively. BSRT resulted in decreased doses of radiation to the normal breast tissue even when standardizing PTV margins due to lack of a similar immobilization device for IMPT. These doses are significantly decreased further when using the BSRT specific PTV margin (3 mm). Previous published data indicates a relationship between cosmetic outcome with low, intermediate and high doses of radiation to the breast. BSRT has the potential to further improve long-term fibrosis/cosmetic outcomes compared to other external beam therapies when used as a modality for PBI.

Preparing for all three parts of the Therapy ABR Physics boards is more than just studying as much material as possible. There will always be material that is missed and gaps in one's knowledge. Therefore it is crucial to understand how the materials relate to each other and to clinical experiences in order to fill those gaps.Each part of the board exam presents its own difficulties:Part I: Determining what material to study, most of which have been learned a long time ago.Part II: Solving a vast array of clinical calculations rapidly by handPart III: Gaining crucial clinical experiences and being able to explain orally how they are performed and what they mean.All three require different skill sets and preparation, from memorizing vast amounts of material, to rapidly recognizing and solving calculations, to being able to easily and confidently respond to oral questions about all aspects of working in the clinic and why those clinical methods and procedures are performed that way. This symposium is not a comprehensive review of all required study material. Instead it focuses on the previously mentioned problems and required skill sets that are needed for each part of the board exam. Expert Medical Physicists will share their experiences and methods to help students best prepare for the challenges of each individual exam.Learning Objectives: How to Prepare for Part 1 by determining study material How to Prepare for Part 2 by learning to solve clinical calculations rapidly How to Prepare for Part 3 by determining critical clinical experiences and learning how to answer questions orally

Preparing for all three parts of the Therapy ABR Physics boards is more than just studying as much material as possible. There will always be material that is missed and gaps in one's knowledge. Therefore it is crucial to understand how the materials relate to each other and to clinical experiences in order to fill those gaps. Each part of the board exam presents its own difficulties: Part I: Determining what material to study, most of which have been learned a long time ago. Part II: Solving a vast array of clinical calculations rapidly by hand Part III: Gaining crucial clinical experiences and being able to explain orally how they are performed and what they mean. All three require different skill sets and preparation, from memorizing vast amounts of material, to rapidly recognizing and solving calculations, to being able to easily and confidently respond to oral questions about all aspects of working in the clinic and why those clinical methods and procedures are performed that way. This symposium is not a comprehensive review of all required study material. Instead it focuses on the previously mentioned problems and required skill sets that are needed for each part of the board exam. Expert Medical Physicists will share their experiences and methods to help students best prepare for the challenges of each individual exam. Learning Objectives: How to Prepare for Part 1 by determining study material How to Prepare for Part 2 by learning to solve clinical calculations rapidly How to Prepare for Part 3 by determining critical clinical experiences and learning how to answer questions orally

Purpose: This work carries out the commissioning and validation of the Mobius3D and MobiusFX software tools, which can replace the time-consuming measurement-based patient specific quality assurance (PSQA). Methods: The beam model supplied by Mobius3D was validated against a 21EX linac's beam measured data. Complex patient (VMAT) plans using Eclipse treatment planning system (TPS) was used to test the consistency between Mobius3D (calculates dose using patient image and field data) and MobiusFx (calculates dose using treatment dynalog files). Dose difference and gamma analysis (3%/3mm) between Mobius3D and MobiusFx were used to assess treatment plan and treatment delivery consistency. An end-to-end test was performed to validate Mobius3D and MobiusFx against ion chamber measurements. Effect of the dosimetric leaf gap (DLG) on Mobius3D dose calculation was additionally investigated. Results: Mobius3D beam model parameters matched within 1%-3% with our beam measured data. A comparison of Mobius3D and MobiusFx dose matrices for VMAT planned prostate cases showed (0.33±0.07)% mean dose difference with gamma values above 95%. The end-to-end test showed dose differences of 1% between Mobius3D and MobiusFx. Dependence of Mobius3D dose calculation upon DLG was explored by introducing a ±0.5 mm change in the default value for DLG. This change resulted in agreement differences above 2% Conclusion: Use of reference beam data would appear to speed up commissioning process for the clinical implementation of Mobius3D. However, careful consideration is required when comparing the information provided by the software, since large dose variations can be seen when the proper parameters are not optimized. The plan and delivered dose were in good agreement; hence MobiusFx has the potential to significantly speed up the PSQA process and at the same time helps to verify treatment parameters that are not possible with measurement-based PSQA.

Preparing for all three parts of the Therapy ABR Physics boards is more than just studying as much material as possible. There will always be material that is missed and gaps in one's knowledge. Therefore it is crucial to understand how the materials relate to each other and to clinical experiences in order to fill those gaps. Each part of the board exam presents its own difficulties: Part I: Determining what material to study, most of which might have been learned a long time ago. Part II: Solving a vast array of clinical calculations rapidly by hand, which are usually done by a computer. Part III: Gaining crucial clinical experiences and being able to explain orally how they are performed and what they mean. All three require different skill sets and preparation, from memorizing vast amounts of material, to rapidly recognizing and solving calculations, to being able to easily and confidently respond to oral questions about all aspects of working in the clinic and why those clinical methods and procedures are performed that way. This symposium is not a comprehensive review of all required study material. Instead it focuses on the previously mentioned problems and required skill sets that are needed for each part of the board exam. Expert Medical Physicists and Medical Faculty will share their experiences and methods to help students best prepare for the challenges of each individual exam along with helping students cope with the anxiety of the exam process.LEARNING OBJECTIVES1. How to Prepare for Part 1 by determining study material 2. How to Prepare for Part 2 by learning to solve clinical calculations rapidly 3. How to Prepare for Part 3 by determining critical clinical experiences and learning how to answer questions orally.

Purpose: Anti‐microbial silver wound dressing may be useful as a bolus material. This study measures the water‐equivalent‐thickness of a silver wound dressing to characterize it for clinical use. This nylon‐mesh dressing, with its permanently plated silver surface (546 mg Ag/100 cm2) may meet the need for bolus with fine variability of thickness and self‐sterilization. Methods: A percent depth dose (PDD) curve was measured in plastic water (CNMC Best Medical) using a parallel plate chamber (PTW N34001) for an 8×8 cm field size, 6 MV beam, 100 cm SSD with a linear accelerator. Measurements were repeated under varying thicknesses (0.5 mm, 1mm, and 2 mm) of silver dressing material, 10 cm × 11 cm (Silverlon™ Antimicrobial silver wound contact dressing WCD‐466). Control measurements were also made in a small water tank. Results: For every layer of dressing added (∼0.5mm) the PDD shifts to the left along the depth axis. A 2 mm offset applied to the position values of the 2 mm (4‐layers) PDD curve causes superposition with the control PDD. This suggests that 2 mm of silver dressing performs similarly to 2 mm of plastic water. This was verified with measurements under clinical setup conditions, 100 cm to the top of the parallel plate chamber, ie. to skin, with bolus placed on top, under 2 mm plastic water (73.40%) and under 2 mm silver dressing (73.41%). Measurements in a water tank for this equivalent depth agree within 1%. Conclusion: The bolus properties of silver‐mesh dressing appear to be water‐equivalent. Silver dressings can be used as bolus and may be particularly beneficial when fine variations are desired or when maintaining an anti‐microbial environment is of particular value.