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Supplementary Figures 1-3

S1. VSV-hIFNβ treatment followed by RT caused S-phase cell cycle arrest of prostate cancer cells. S2. VSV treatment in combination with radiation therapy increases the GFP or Luciferase expression in vitro and in vivo. S3. C57BL/6 CD8 Re-challenge study with VSV-mIFNβ+RT followed by CD8 depletion.

Purpose/Objective(s)Accurate target delineation/contouring is essential for radiation treatment planning and radiotherapy efficacy. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. The purpose of this study was to track the concordance of radiation oncology residents’ contours with faculty physicians’ contours over the course of one year to assess for patterns.Materials/MethodsResidents in PGY levels of 2-4 were asked to contour target volumes which were compared to the finalized, faculty physician-approved contours. Concordance between resident and faculty physician contours was determined by calculating the Jaccard Concordance Index (JCI), ranging from 0 or no agreement to 1 or complete agreement. Mutivariate mixed effect models were used to assess the association of JCI to the fixed effect of PGY level and its interactions with cancer type and other baseline characteristics. Post hoc means of JCI were compared between PGY levels after accounting for multiple comparisons using a Tukey’s method.ResultsIn total, 958 structures from 314 patients collected during the 2020-2021 academic year were studied. The mean JCI was 0.77, 0.75, and 0.61 for the levels of PGY-4, PGY-3, and PGY-2, respectively. JCI score in PGY-2 was found lower than those of PGY-3 and PGY-4 respectively (P’sConclusionTracking and comparing the concordance of resident contours and faculty physician contours is an intriguing method of assessing resident performance in contouring and target delineation and could potentially serve as a quantitative metric in radiation oncology resident evaluation, which is lacking currently. However, additional study is necessary before this technique can be incorporated into residency assessments.

Introduction The aim of this study was to perform a Surveillance, Epidemiology, and End Results (SEER) analysis on the effect of radiotherapy (RT) on survival among patients with prostate ductal adenocarcinoma (DA), a rare variant of prostate cancer. Patients and Methods Cases of T1 to 4 N0 M0 prostate DA diagnosed between 2004 and 2013 were extracted from SEER. The association between categorical variables and radiation therapy was assessed for statistical significance using the χ2 test or Fisher exact test. Difference in continuous variables across the RT groups was assessed for statistical significance using the 2-sample t test or non-parametric test. The distribution of overall survival (OS) and disease-specific survival (DSS) between the RT groups was assessed using the Kaplan-Meier method and the log rank test and after propensity matching. The association between hazards of death (HR) and covariates was examined using Cox proportional hazards model. A 2-sided P-value of .05 was used to determine statistical significance. Results A total of 205 patients met inclusion criteria. On univariate analysis, RT was associated with significant improvement in OS and DSS. On multivariate Cox regression, RT significantly decreased risk of death for both OS and DSS (HR, 0.516; 95% confidence interval [CI], 0.273-0.978 and HR, 0.232; 95% CI, 0.082-0.658, respectively). After propensity score matching, RT demonstrated a persistent improvement in both OS and DSS. Conclusions RT decreased risk of death for both OS and DSS in patients with node-negative, nonmetastatic prostate DA on multivariable analysis. RT was also associated with improved OS and DSS after propensity matching.

Cushing's syndrome (CS) is associated with high morbidity and fivefold excess mortality. Ectopic ACTH syndrome accounts for 20% of CS cases. It is crucial to identify and localize the source of extrapituitary ACTH secretion because surgical resection of the primary, often malignant, tumor has a high probability of cure with complete remission in 80% of cases. A 72-year-old female was admitted to a community hospital for lateral chest pain after a fall. She endorsed progressive weight gain, new HTN, emotional lability and worsening cognition over the prior 6 months. ACTH and cortisol levels were elevated. MRI brain failed to identify a pituitary lesion. CT chest showed multiple rib fractures and anterior mediastinal mass which was biopsied. While awaiting pathology results, IPS sampling attempted but aborted due to pulmonary edema necessitating ICU care. She was transferred to our institution for planned TSR of suspected pituitary adenoma. Examination showed Cushingoid features. Labs showed hypokalemia, high cortisol and high ACTH. MRI pituitary showed normal sella. MRI spine showed multilevel vertebral compression fractures. CT chest showed interval growth of mediastinal mass. A 1 mg dexamethasone suppression test failed to suppress ACTH and cortisol, confirming ACTH dependent hypercortisolism. A high dose 8 mg dexamethasone test failed to suppress ACTH and cortisol, a 10 mcg DDAVP stimulation test showed a flat response, with ACTH and cortisol levels remaining comparable before and after DDAVP injection. Dynamic testing therefore consistent with ectopic ACTH dependent hypercortisolism. Gallium-68 DOTA-TATE PET Scan demonstrated uptake in mediastinal mass suggestive of somatostatin receptor positive neuroendocrine tumor. Biopsy specimens processed at our institution showed cells positive for epithelial markers Cytokeratin and PAX8. Sample showed neuroendocrine differentiation with positive staining for Chromogranin A, synaptophysin and CD 117. Findings consistent with neuroendocrine thymic neoplasm. The patient was started on oral ketoconazole to control hypercortisolism. Surgical resection of tumor was planned with intent to cure CS. Ultimately, due to proximal myopathy and multiple vertebral fractures her performance status was too poor for safe tumor resection. Unfortunately, she died of complications related to CS while attempting preoperative rehabilitation. This case illustrates the importance of a timely, systematic evaluation for ACTH source in ACTH dependent hypercortisolism. Delay in CS diagnosis and localizing correct ACTH source led to missing the window of fitness for curative surgery. If ACTH is elevated, the most common source is pituitary neoplasia, however ectopic ACTH production must be ruled out. Dynamic testing including high dose dexamethasone suppression test, CRH and DDAVP stimulation tests should be used for preliminary localization of ACTH production. IPS sampling is invasive with greater potential for complications, as in the case of our patient. Therefore, it is only indicated if there are conflicting results from different dynamic tests and imaging studies. Presentation: No date and time listed

We review a case of inoperable early stage breast cancer treated definitively with the use of stereotactic ablative radiotherapy (SABR). A 57-year-old female with a history of decompensated cirrhosis with early stage breast cancer was treated with 25 Gy in one fraction. At her 7-month follow up visit, there was a complete resolution of disease on imaging. This case represents a novel approach for the treatment of breast cancer with SABR when surgery is contraindicated.

Purpose To characterize inventions and assess trends in brachytherapy innovation based on brachytherapy-related patents awarded across the past 2 decades and provide insights that will help inform future research and entrepreneurship in the field. Methods The United States Patent and Trademark Office database was searched for patents awarded between 1999 and 2018 with a classification code corresponding to the broadest brachytherapy search category. Patent characteristics were stratified and compared by geographic location, affiliation, and theme of invention. Results There were 202 brachytherapy-related patents awarded from 2009 to 2018, which indicates a 56% increase in patent productivity and brachytherapy innovation compared with the previous decade from 1999 to 2008. Patents had an industry affiliation in 83% of cases from 1999 to 2008 and in 76% of cases from 2009 to 2018. Meanwhile, academic participation in brachytherapy patent innovation rose from 4% to 11% in that time. The focus and theme of inventions evolved across time, with radiation sources being the most common theme from 1999 to 2008 and falling to third place in 2009–2018. Conversely, development of brachytherapy-related patents involving exogenous agents such as drug-conjugates, radiosensitizers, and adjuncts to treatment increased substantially in the subsequent decade. While no collaboration was observed between academia and industry between 1999 and 2008, notable partnerships emerged in the subsequent decade which amounted to almost 5% of all patents awarded between 2009 and 2018. Conclusions There has been an increase in overall brachytherapy patent production over time, and this has been accompanied by a greater variety of distinct patent themes. Collaboration between industry and academia is rare. Knowledge of brachytherapy patents may inform future research innovation in this field.

Background The role of post mastectomy radiation therapy (PMRT) in patients with N1mic breast cancer has not been well defined. A retrospective analysis was performed using the SEER database to evaluate the impact of PMRT on survival in patients with N1mic breast cancer. Materials and methods Women with T1-T2, N1mic, M0 breast cancer who had undergone mastectomy were analyzed. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log rank test while multivariate analysis was performed with Cox proportional hazards regression. Sub-cohort analysis with propensity score matching was used to assess differences in survival among patients undergoing PMRT vs no PMRT. Comparisons were considered statistically significant at P, Highlights • In women with N1mic breast cancer, there was no difference in overall survival with or without adjuvant radiation. • CSS was worse among women undergoing adjuvant radiation on univariate analysis, but not on multivariate analysis. • After propensity score matching, no significant difference was observed in survival between women undergoing PMRT vs no PMRT.

Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors.

Purpose: To investigate the relationships between circulating tumor cells (CTCs), free circulating DNA (fcDNA) and biochemical response in prostate cancer patients treated primarily versus salvage radiotherapy (RT). Methods and Materials: Blood was collected prospectively from patients, enrolled in two institutional Phase II trials for primary and salvage RT. Three blood samples were collected at: (i) prior to treatment [RT or androgen deprivation therapy (ADT)], (ii) last week of RT, and (iii) three months post-RT. CTCs were quantified in 31 samples from 12 primary patients and 30 samples from 12 salvage patients; fcDNA were analyzed in 11 primary (28 samples) and 5 (9 samples) salvage patients. CTCs were visualized by immunofluorescence after microfilter capture and fcDNA was quantified using real-time Polymerase chain reaction (PCR). CTCs and fcDNA were correlated with early biochemical response by subdividing patients into early favorable and unfavorable response at 3 months after RT. Results: For those treated primarily, there was a direct correlation with CTC counts and prostate specific antigen (PSA) pre-RT that changed to a reciprocal relationship 3 months post-RT. CTCs increased significantly (p=0.03) at 3 months after primary RT in the biochemical favorable patients, while no significant association was observed for fcDNA. Correspondingly, post-RT fcDNA levels were inversely related to CTC counts. In salvage patients, the number of CTCs was related to pre-RT PSA, but it was not correlated to RT response. In post-RT series, a significant direct correlation was observed between CTCs and PSA. Conclusion: Our preliminary studies suggest that RT affects CTC counts, which are thus associated with prostate cancer biochemical response. A larger cohort with longer follow-up will be needed to establish the association with more recognized treatment endpoints.

To perform a retrospective analysis of the epidemiology and role of surgery on survival in patients with urethral clear cell carcinoma (UCCC) using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. UCCC cases diagnosed from January 1, 1973, to December 31, 2014, were extracted from SEER. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log-rank test. Multivariate analysis was performed with Cox proportional hazards regression models to determine the predictive performance of covariates with respect to overall survival (OS) and disease-specific survival (DSS), reported as hazard ratio (HR) with 95% CIs. Comparisons were considered statistically significant at P

OBJECTIVES Primary pancreatic signet ring cell carcinoma (SRCC) is a rare histologic variant of pancreatic carcinoma. A population-based analysis of pancreatic SRCC was performed to determine the predictive effects of epidemiological factors and treatment interventions on overall survival (OS) and disease-specific survival (DSS). MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results registry was searched for pancreatic SRCC cases diagnosed between January 1, 1973 and December 31, 2013. Statistical analysis was performed using the Fisher exact test, χ(2) analysis, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. RESULTS The mean age among 497 patients was 66.6 years (SD, 11.9). Most patients were white (82.7%) and male (54.5%). The 1-, 2-, and 5-year OS rates were 17%, 9%, and 4%, respectively, while the corresponding 1-, 2-, and 5-year rates for DSS were 18%, 10%, and 5%, respectively. On univariable analysis; age, site, grade, stage, and treatment were predictive of OS and DSS (P

Heart failure remains a major public health concern with high burden of morbidity and mortality despite advances in pharmacotherapy, device therapy, and surgical and percutaneous techniques. Cardiac regeneration may have a role to play in these patients with a huge unmet need for these therapies in patients with chronic ischemic heart disease, post-infarct heart failure, dilated cardiomyopathy, and heart failure with preserved ejection fraction. In this review, we focus on the pre-clinical and translational basis for different modes of cardiac regenerative medicine and then critically appraise the clinical evidence amassed from pivotal clinical trials focused on cardiac regeneration for ischemic and non-ischemic cardiomyopathies. Cardiac regenerative medicine is rapidly evolving with novel approaches involving cell-based, cell-free, tissue engineering, and hybrid therapies to achieve myocardial regeneration and repair. Further studies are warranted with a robust comparison arm with optimal contemporary medical therapy to translate regenerative therapies to a clinical reality.

Basal cell carcinoma (BCC ) is the most common human malignancy. Systemic therapy with a sonic hedgehog (SHH) pathway inhibitor plays an important role in the treatment of advanced BCC . Literature on concurrent use of radiation therapy (RT ) with SHH inhibitors has been minimal and has solely been focused on vismodegib. We present a case report of a patient with recurrent basal cell carcinoma involving the high-risk area of the face, who was denied surgery due to comorbidities and difficulty in obtaining complete tumor removal without cosmetic or functional impairment. The patient received combined treatment of fractionated radiation with concurrent sonidegib and had complete clinical response with no significant toxicities. This is the first reported case on the use of concurrent RT with sonidegib for management of recurrent basal cell carcinoma of the head and neck.

BACKGROUND Short instructional videos can make learning more efficient through the application of multimedia principles, and video animations can illustrate the complex concepts and dynamic processes that are common in health sciences education. Commercially produced videos are commonly used by medical students but are rarely integrated into curricula. OBJECTIVE Our goal was to examine student engagement with medical education videos incorporated into a preclinical Cardiovascular Systems course. METHODS Students who took the first-year 8-week Cardiovascular Systems course in 2019 and 2020 were included in the study. Videos from Osmosis were recommended to be watched before live sessions throughout the course. Video use was monitored through dashboards, and course credit was given for watching videos. All students were emailed electronic surveys after the final exam asking about the course’s blended learning experience and use of videos. Osmosis usage data for number of video views, multiple choice questions, and flashcards were extracted from Osmosis dashboards. RESULTS Overall, 232/359 (64.6%) students completed surveys, with rates by class of 81/154 (52.6%) for MD Class of 2022, 39/50 (78%) for MD/MPH Class of 2022, and 112/155 (72.3%) for MD Class of 2023. Osmosis dashboard data were available for all 359 students. All students received the full credit offered for Osmosis engagement, and learning analytics demonstrated regular usage of videos and other digital platform features. Survey responses indicated that most students found Osmosis videos to be helpful for learning (204/232, 87.9%; P=.001) and preferred Osmosis videos to the traditional lecture format (134/232, 57.8%; P CONCLUSIONS Commercial medical education videos may enhance curriculum with low faculty effort and improve students’ learning experiences. Findings from our experience at one medical school can guide the effective use of supplemental digital resources for learning, and related evaluation and research.

To compare brachytherapy to external beam radiation therapy (EBRT) with respect to overall survival (OS) and disease-specific survival (DSS) among NSCLC patients undergoing limited surgical resection. All cases of T1-4 N0 M0 NSCLC undergoing limited resection and either brachytherapy or EBRT diagnosed between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test and Fisher’s exact analysis were used to analyze categorical variables while Student’s t-test was used to analyze continuous variables. Univariate analysis to assess for differences in survival with respect to covariates was performed with the log-rank test. Multivariable analysis was performed with Cox proportional hazards regression models among the entire cohort and after sub-stratification by T stage. Among 543 patients, 471 underwent EBRT and 72 underwent brachytherapy. Brachytherapy demonstrated improved OS and DSS on univariate analysis as compared to EBRT (p

Background Short instructional videos can make learning more efficient through the application of multimedia principles, and video animations can illustrate the complex concepts and dynamic processes that are common in health sciences education. Commercially produced videos are commonly used by medical students but are rarely integrated into curricula. Objective Our goal was to examine student engagement with medical education videos incorporated into a preclinical Cardiovascular Systems course. Methods Students who took the first-year 8-week Cardiovascular Systems course in 2019 and 2020 were included in the study. Videos from Osmosis were recommended to be watched before live sessions throughout the course. Video use was monitored through dashboards, and course credit was given for watching videos. All students were emailed electronic surveys after the final exam asking about the course’s blended learning experience and use of videos. Osmosis usage data for number of video views, multiple choice questions, and flashcards were extracted from Osmosis dashboards. Results Overall, 232/359 (64.6%) students completed surveys, with rates by class of 81/154 (52.6%) for MD Class of 2022, 39/50 (78%) for MD/MPH Class of 2022, and 112/155 (72.3%) for MD Class of 2023. Osmosis dashboard data were available for all 359 students. All students received the full credit offered for Osmosis engagement, and learning analytics demonstrated regular usage of videos and other digital platform features. Survey responses indicated that most students found Osmosis videos to be helpful for learning (204/232, 87.9%; P=.001) and preferred Osmosis videos to the traditional lecture format (134/232, 57.8%; P Conclusions Commercial medical education videos may enhance curriculum with low faculty effort and improve students’ learning experiences. Findings from our experience at one medical school can guide the effective use of supplemental digital resources for learning, and related evaluation and research.

Vesicular stomatitis virus (VSV) expressing IFNβ induces apoptosis in multiple tumor models while maintaining an excellent safety profile. VSV-IFNβ is oncoselective due to permissive replication in cells with an altered IFN pathway. The human VSV-IFNβ (hIFNβ) vector is currently used in clinical trials as a standalone therapy; however, we hypothesized that oncolytic virotherapy might be more effective when used in combination with radiotherapy (RT). We investigated the synergistic effects of RT and VSV-hIFNβ in the subcutaneous PC3 and orthotopic LNCaP prostate xenograft models and a syngeneic RM9 prostate tumor model. VSV-IFNβ combined with RT amplified tumor killing for PC3 and LNCaP xenografts, and RM9 tumors. This was attributed to the induction of proapoptotic genes leading to increased VSV-IFNβ infection and replication, VSV expression, and oncolysis. In the RM9 tumors, combination therapy resulted in a robust antitumor immune response. Treated RM9 tumor-bearing mice demonstrated an increase in CD8+ and CD4+ T-cell numbers, 100% resistance to tumor rechallenge, and reduced resistance to reimplantation challenge with CD8+ knockdown. RT enhanced the activity of VSV-mediated oncolysis via attenuation of the innate antiviral response, resulting in increased VSV replication and the generation of an adaptive immune response earmarked by an increase in CD8+ lymphocyte numbers and antitumor activity. Local tumor irradiation combined with VSV-IFNβ affects tumor cell death through direct and systemic activity in conjunction with pronounced antitumor immunity. Implications: Radiotherapy enhances VSV-mediated oncolysis and anti-tumor immunity, indicating that the ombination has promise for very high risk prostate cancer.

4545 Background: Palliative care improves quality of life for both patients and caregivers but may be underutilized due to socioeconomic barriers to access. An NCDB analysis was performed to analyze the effect of socioeconomics on palliative care receipt among patients with metastatic renal cell carcinoma. Methods: A retrospective hospital-based analysis was performed using the National Cancer Database to identify variables that significantly affect receipt of palliative care among patients diagnosed with metastatic renal cell carcinoma diagnosed between 2004 and 2016. Sub-cohort analysis was also performed among patients with the most severe disease. Multivariate binominal logistic regression was performed to determine the association of underlying socioeconomics with receipt of palliative care. The odds of receiving palliative care based on socioeconomic factors was reported as odds ratios (OR) with 95% CI. Results: There were 50405 patients meeting inclusion criteria with 40448 (80.2%) undergoing no palliation and 9957 (19.8%) undergoing palliative care. Both Black and Spanish/Hispanic patients had decreased odds of receiving palliative care (OR, 0.816, 95% CI, 0.753 to 0.885 and OR, 0.599, 95% CI, 0.540 to 0.665, respectively). Increasing age, papillary histology, increasing income, and increasing distance were also significantly associated with decreased odds of receiving palliation while treatment at an integrated network cancer program or comprehensive community cancer program and higher educational attainment were associated with increased odds of receiving palliative care. Similar findings were demonstrated among patients with the most severe disease. Limitations include the retrospective design and potential underlying selection biases of this study. Conclusions: Significant associations between receipt of palliative care and socioeconomic factors exist among patients with metastatic renal cell carcinoma. In this study among patients with metastatic renal cancer, we found associations between socioeconomics and palliative care access including age, race, Spanish/Hispanic origin, income, education, and other factors.

Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease.

5059 Background: Stereotactic body radiotherapy (SBRT) is being increasingly used for renal cell carcinoma (RCC) treatment in non-surgical candidates. However, no studies have compared survival between nephrectomy and SBRT. The National Cancer Database (NCDB) database was used to assess overall survival in patients undergoing SBRT vs nephrectomy. Methods: All cases of T1-T4, N0, M0 RCC diagnosed between 2004 and 2016 were extracted from the NCDB. Only patients undergoing either nephrectomy or SBRT, but not both, were included in the final analysis. Primary outcome was overall survival, defined as time in months from diagnosis to death due to any cause. Descriptive statistics were calculated for all variables. Univariate survival analysis was performed using the Kaplan Meier method and log rank test. Multivariate Cox proportional hazards regression models were performed to determine the predictive performance of covariates with respect to overall survival, reported as hazard ratio [HR] with 95% CIs. Nephrectomy patients were propensity score matched to SBRT patients for sub-cohort survival analysis. Comparisons were considered statistically significant at P < 0.05. Results: There were 243,754 patients meeting inclusion criteria with 243,488 undergoing nephrectomy and 266 undergoing SBRT. Five year OS rates were 53% and 80% for SBRT and nephrectomy, respectively (P < 0.001). On multivariate Cox regression, SBRT was associated with an increased risk of death as compared to nephrectomy (HR, 2.05; 95% CI, 1.72 – 2.44; P < 0.001). Sex, race, insurance coverage, comorbidity index, tumor grade, lymphovascular invasion status, T-stage, tumor size, and academic status of treatment facility were also independent predictors of survival. After propensity score matching of 266 SBRT patients to 266 nephrectomy patients, there were no significant differences in baseline characteristics between the groups. However, SBRT continued to demonstrate worse survival and an increased risk of death as compared to nephrectomy (HR, 1.85; 95% CI, 1.41 – 2.44; P < 0.001). Conclusions: Among node-negative, non-metastatic RCC patients, SBRT is associated with inferior survival outcomes as compared to nephrectomy, even after correcting for underlying differences in demographics, tumor characteristics, socioeconomic status, and comorbidities. These results indicate that nephrectomy should remain the standard of care for RCC patients, with SBRT reserved for non-surgical candidates.

1550 Background: Clear cell carcinoma (CCC) of the urethra is a very rare histologic variant of urethral adenocarcinoma. The majority of studies have been case reports and case series with no large population based studies. A retrospective analysis was performed with the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) database to establish the epidemiology of urethral CCC and determine the clinical factors associated with survival. Methods: All cases of clear cell carcinoma of the urethra diagnosed from January 1, 1973 to December 31, 2014 were extracted from SEER. Age at diagnosis, sex, marital status, race, grade, stage, surgery, radiation, chemotherapy, overall survival (OS), disease specific survival (DSS), and survival months were extracted for analysis. Descriptive statistics were calculated for all variables. Univariable analysis to assess for differences in survival with respect to covariates was performed using the log rank test. Multivariable analysis was performed with Cox proportional hazards regression models to determine the predictive performance of covariates with respect to OS and DSS, reported as hazard ratio [HR] with 95% CIs. Comparisons were considered statistically significant at P < 0.05. Results: Sixty one cases were extracted for analysis. The mean ± SD was 63.0 ± 13.9 years. Fifty eight (95.1%) patients were female with 53 (86.8%) locoregional cases at presentation. There were 50 (82%), 18 (29.5%), and 12 (23.0%) patients who underwent surgery, radiation, and chemotherapy, respectively. On univariable analysis, the following covariates were associated with both OS and DSS: age, stage, and surgery (all p < 0.001; log rank test). On multivariable analysis, surgery was a predictor for improved OS and DSS (HR, 0.178; 95% CI [0.068; 0.464]) and HR, 0.166; 95% CI [0.196; 2.132], respectively). Additionally, both increasing age and distant disease were associated with worse OS and DSS. Neither radiation nor chemotherapy were significantly associated with OS or DSS. Conclusions: Surgery improves OS and DSS in patients with urethral CCC. While neither radiation nor chemo were significantly associated with survival, additional studies are necessary to determine how these therapeutic interventions may impact prognosis.

An important key to clinical management of prostate cancer patients is to determine early those who will benefit from primary treatment and are not good candidates for active surveillance (AS). We describe a 67-year-old gentleman with a long history of stable prostate specific antigen (PSA) levels and a negative biopsy. After slight PSA rise and low volume Gleason score (GS) 6 biopsy, the patient was considered for primary treatment or AS. A multiparametric (MP )MRI exam revealed a suspicious lesion in the anterior apex of the prostate. Biopsies were carried out on a 3D-ultrasound prostate biopsy system with MRI-fusion. The location of the target area was challenging and could have been missed using standard 12-core biopsy template. The pathology determined Gleason 3+4 disease in 30% of the core from this region. Consequently, the patient underwent radiotherapy (RT). MP-MRI was also used to follow the changes from pre- to post-RT.

BRG1 is a catalytic subunit of the human SWI/SNF-like BAF chromatin remodeling complexes. Recent findings have shown that inactivation of BRG1 sensitizes mammalian cells to various DNA damaging agents, including ultraviolet (UV) and ionizing radiation. However, it is unclear whether BRG1 facilitates nucleotide excision repair (NER). Here we show that re-expression of BRG1 in cells lacking endogenous BRG1 expression stimulates nucleotide excision repair of UV induced DNA damage. Using a micropore UV radiation technique, we demonstrate that recruitment of the DNA damage recognition protein XPC to sites of UV lesions is significantly disrupted when BRG1 is depleted. Chromatin immunoprecipitation of the endogenous DDB2 protein, which is involved in recruiting XPC to UV-induced CPDs (cyclobutane pyrimidine dimers), shows that elevated levels of BRG1 are associated with DDB2 in chromatin in response to UV radiation. Additionally, we detected slow BRG1 accumulation at sites of UV lesions. Our findings suggest th...

Background The incidence of shoulder and elbow injuries in adolescent baseball players is rapidly increasing. One leading theory about this increase is that breaking pitches (such as the curveball) place increased moments on the dominant arm and thereby increase the risk of injury. Hypothesis There is no difference in the moments at the shoulder and elbow between fastball and curveball pitches in adolescent baseball pitchers. Study Design Controlled laboratory study. Methods Thirty-three adolescent baseball pitchers with a minimum of 2 years of pitching experience underwent 3-dimensional motion analysis using reflective markers aligned to bony landmarks. After a warm-up, pitchers threw either a fastball or curveball, randomly assigned, from a portable pitching mound until 3 appropriate trials were collected for each pitch technique. Kinematic and kinetic data for the upper extremities, lower extremities, thorax, and pelvis were collected and computed for both pitch types. Statistical analysis included both the paired sample t test and mixed model regression. Results There were lower moments on the shoulder and elbow when throwing a curveball versus when throwing a fastball. As expected, speed for the 2 pitches differed: fastball, 65.8 ± 4.8 mph; and curveball, 57.7 ± 6.2 mph (P Conclusion In general, the moments on the shoulder and elbow were less when throwing a curveball than when throwing a fastball. In each comparison, the fastball demonstrated higher moments for each individual pitcher for both joints. Clinical Relevance The findings based on the kinematic and kinetic data in this study suggest that the rising incidence of shoulder and elbow injuries in pitchers may not be caused by the curveball mechanics. Further evaluation of adolescent and adult baseball pitchers is warranted to help determine and subsequently reduce the risk of injury.

Document the biomechanics of the pitching motion to help provide insight about the etiology of common injuries seen in adolescent baseball pitchers.Kinematic and kinetic data for the upper and lower extremities, thorax, and pelvis were collected from 24 adolescent pitchers, using modern three-dimensional computerized motion-analysis techniques.Original information regarding forearm and wrist motion was reported in this study and were consistent with expected motions for the fastball pitch. Average excursion of motion was: pronation/supination 63 +/- 15 degrees, wrist flexion/extension 44 +/- 14 degrees, and ulnar/radial deviation 12 +/- 4 degrees. Explosive forearm motion occurred between ball release (BR) and maximal glenohumeral internal rotation (GH-MIR) with a peak pronation velocity of 2051 +/- 646 degrees.s(-1). The majority of internal/external and abduction/adduction shoulder motion was attributed to the glenohumeral motion. Internal glenohumeral rotation range of motion was 125 +/- 13 degrees and mean peak internal glenohumeral rotation velocity was 3343 +/- 453 degrees.s(-1). Thorax and pelvic motion peak velocities and accelerations occurred before the peak elbow varus moment, which occurred at 59% of the pitch cycle (PC). The peak shoulder, elbow, and wrist velocities and accelerations occurred after the peak elbow varus moment. The pelvis squared to the plate at 51 +/- 10% PC and the thorax at 59 +/- 7% PC with maximal glenohumeral external rotation (GH-MER) at 65% PC and BR at 78 +/- 3% PC. The data collected in this study were consistent with the literature, with the exception of joint velocities and moments, which were lower than those in one published study.We have established the kinematic and kinetic parameters of the adolescent baseball pitch. These measured parameters and the differences between adolescent pitchers and their adult counterparts can be used to examine and help determine the causes of the rapid increase in adolescent pitching injuries.

Biomechanical model assumptions affect the interpretation of the role of the muscle or joint moments to the segmental power estimated by induced acceleration analysis (IAA). We evaluated the effect of modeling the pelvis and trunk segments as two separate segments (8 SM) versus as a single segment (7 SM) on the segmental power, support of the body, knee and hip extension acceleration produced by the joint moments during the stance phase of normal walking. Significant differences were observed in the contribution of the stance hip abductor and extensor moments to support, ipsilateral knee and hip acceleration, and ipsilateral thigh and upper body power. The primary finding was that the role of the stance hip moment in generating ipsilateral thigh and upper body power differed based on degrees of freedom in the model. Secondarily, the magnitude of contributions also differed. For example, the hip abductor and extensor moments showed greater contribution to support, hip and knee acceleration in the 8 SM. IAA and segment power analysis are sensitive to the degrees of freedom between the pelvis and trunk. There is currently no gold standard by which to evaluate the accuracy of IAA predictions. However, modeling the pelvis and trunk as separate segments is closer to the anatomical architecture of the body. An 8 SM appears to be more appropriate for estimating the role of joint moments, particularly to motion of more proximal segments during normal walking.

Purpose: Diagnostic prostate biopsies are subject to sampling bias. We hypothesize that quantitative imaging with multiparametric (MP)-MRI can more accurately direct targeted biopsies to index lesions associated with highest risk clinical and genomic features. Methods: Regionally distinct prostate habitats were delineated on MP-MRI (T2-weighted, perfusion and diffusion imaging). Directed biopsies were performed on 17 habitats from 6 patients using MRI-ultrasound fusion. Biopsy location was characterized with 52 radiographic features. Transcriptome-wide analysis of 1.4 million RNA probes was performed on RNA from each habitat. Genomics features with insignificant expression values (