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In this Technical Note, we describe an in‐house video goggles feedback system assembled using several commercially available products. This goggle video feedback system is currently being used at University of Louisville and Mayo Clinic for both CT simulation and linac treatment delivery. The setup details, including specific recommendations, are provided, along with an alternative option for using the video goggles system.PACS number: 07.07Hj

The purpose of this study was to introduce a planning strategy for dynamic conformal arc therapy (DCAT), named negative margin technique (NMT), and evaluate its dosimetric gain in lung stereotactic body radiation therapy (SBRT). In DCAT, the field aperture is continuously conformed to the planning target volume (PTV) with an aperture margin (AM) to compensate for the penumbra effect with gantry rotation. It is a common belief the AM should be positive (or at least ‘zero'). However, the radial penumbra width becomes significantly wider because of continuously overlapped beams in arc delivery. Therefore, we hypothesize if the ‘negative margin’ is applied in the radial direction, it would improve the PTV dose conformation while reducing normal tissue dose. For verification, trial plans were made using the NMT and compared with ‘zero margin (ZM)’ plans for five lung SBRT cases representing different situations depending on the location of the PTV and organs at risk. All plans met 95% PTV coverage with the prescription dose and spared the spinal cord below the tolerance. Two conventional conformation indices (the ratio of prescription isodose volume to the PTV (CI100) and the ratio of 50% prescription isodose volume to the PTV (CI50)) and a modified conformation index were investigated. The maximum dose at 2 cm from the PTV and the percent of lung volume receiving 20 Gy were also evaluated. Another planning simulation was performed with a total of ten randomly selected lung SBRT cases to mimic actual practice. In this simulation, optimization with ZM was first performed and further optimization using the NMT was processed for cases that could not meet a goal of with the ZM optimization. In all cases, both the and values were significantly reduced (overall, and for and , respectively). The modified conformation index values also showed similar improvement (overall, increase). Reduction of was also observed in all cases . values decreased in all cases but one (, excluding the increased case). In the random group simulation, it was possible to achieve the goal with just one NMT trial for five out of six cases that did not meet the goal in the ZM optimization. Interestingly, however, one case needed as many as six iterations to get the goal. The NMT turned out to be an effective planning strategy that could bring significant improvement of dose conformation. The NMT can be easily implemented in most clinics with no prerequisite.PACS number: 87.55.D‐

303 Background: Small cell (SC) neuroendocrine carcinoma of the prostate has very poor prognosis and does not respond well to androgen receptor (AR)-targeted therapies. Neuroendocrine prostate carcinomas are increasingly recognized to show a spectrum of morphologic changes, and may not always be distinguishable from adenocarcinoma (adeno) based on morphology alone. Here we hypothesize that SC carcinoma harbor a unique gene expression signature that, when measured in primary prostatic adenocarcinoma, may help guide subsequent management. Methods: In total, 617 whole genome expression profiles were retrieved from the Decipher GRID providing gene expression data for 1.4 million markers. 17 morphologically-diagnosed SC carcinoma samples were compared to 32 Gleason 8-10 and 77 Gleason 6 RP adeno samples with no prior treatment and no evidence of metastasis, and this comparison was used to define SC Genomic Fingerprint (SCGFt) through adjusted median fold difference and Wilcoxon test. An additional 493 RP adeno from Mayo Clinic and John Hopkins Hospital were used to evaluate the utility of the SCGFt for predicting outcome. Results: Based on genomic prognostic tests calculated using the Decipher assay including Decipher, Penney and microarray-derived Cell Cycle Progression, SC carcinomas have very poor prognosis compared to high grade adeno. A total of 356 genes defined the SCGFt with 258 gene upregulated in SC and 98 down-regulated. PEG10, HELLS and RB1-loss program are the most overexpressed genes in SC and AR-related genes the most down-regulated. As expected, SC lacked ERG and alternative ETS expression and showed relatively low SPINK1 expression. A median summarization of the 356 genes in SCGFt was used to build a small cell genomic score (SCGS). Evaluating SCGS in RP adeno cohorts showed that patients with high SCGS are at higher risk of developing metastasis after RP in a natural history cohort or after adjuvant hormonal therapy based on Kaplan Meier analysis (both p< 0.001). When restricted to patients with high Decipher scores, SCGS provided independent prognostic information. Conclusions: SC carcinoma has a distinct genomic profile that may be useful for treatment management of patients with adenocarcinoma.

256 Background: B7-H3 (CD276), part of the B7 superfamily, has been shown to play an immunomodulatory role, however its regulation, receptor and mechanism of action remain unclear. Protein levels of B7-H3 have been previously shown to relate to prostate cancer outcomes and currently, humanized monoclonal antibodies are being developed for clinical use (MGA271, Macrogenics). Here we use genomic expression data to examine the relationship of B7-H3 to prostate cancer outcomes and molecular subtypes. Methods: Prostatectomy tissue from 905 patients were profiled using the Affymetrix HuEx 1.0 ST microarray. Kruskal-Wallis tests were used to identify significant associations of B7-H3 expression with clinico-pathologic variables, and survival analysis were used to evaluate the prognostic value of B7-H3. Pearson’s correlation analyses were also performed to assess the relationship of B7-H3 expression with molecular subtypes and individual transcripts. Androgen receptor (AR) occupancy of promoter regions was derived in silico from chromosomal immune-precipitation (ChIP) data. Results: B7-H3 expression was positively associated with Gleason score (p < 0.01) and tumor stage (p < 0.01). High B7-H3 expression also correlated with the development of metastasis and prostate cancer specific mortality (HR of 3.4 and 2.4 respectively, p < 0.05 for both), but this was not significant on multi-variable analysis. B7-H3 was positively associated with ERG+ disease (n = 670, r = 0.85, p < 0.05) and AR expression (n = 670, r = 0.46, p < 0.001). B7-H3 was found to be one of the most correlated genes with AR (95th percentile) and ChIP analysis revealed AR binding upstream of B7-H3, suggesting potential androgen dependent regulation. Conclusions: B7-H3 expression correlates with high Gleason grade and advanced prostate cancer stage with higher quartiles of expression portending poor oncologic outcomes in two independent prostatectomy cohorts. B7-H3 expression appears to relate to the androgen receptor.

12 Background: In 3 published randomized trials, adjuvant radiation therapy (ART) for prostate cancer (PCa) resulted in improved progression free survival. However, the impact on metastases and overall survival is unclear. To date, there have been no published prospective trials examining the impact of salvage radiation therapy (SRT) in this disease state. Hence, we conducted a retrospective, nonrandomized comparative study of ART, SRT, or no radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathologic features, APF). Methods: 422 PCa men treated at 4 institutions with RP and having APF were analyzed with a primary end point of clinical metastasis. ART (n = 111), early SRT (n = 70) and delayed SRT (n = 83) were defined by PSA levels of < 0.2, 0.2 to 0.5, and ≥ 0.5 ng/mL, respectively, prior to RT initiation. Remaining 157 men who did not receive additional therapy prior to metastatic onset formed the no RT arm. Clinical-genomic risk was assessed by CAPRA-S and Decipher. Cox multivariable (MVA) model was used to evaluate the impact of treatment on outcome. Results: During study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on MVA for metastatic outcome (both p < 0.05). On MVA adjusting for clinical-genomic risk, delayed SRT and no RT had an HR of 4.31 (95%CI, 1.20-15.47) and 5.42 (95% CI, 1.59-18.44) for metastasis compared to ART. No significance difference was observed between early SRT and ART (p = 0.28). Men with low to intermediate CAPRA-S and low Decipher have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. Conclusions: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and men to balance risks of morbidity with improved oncologic outcomes. This analysis provides the most robust and accurate quantification of risk for these men. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

106 Background: Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Methods: Expression profiles of 1023 PCa patients treated with RP were obtained from the Decipher GRID database. These were split into training (n=529) and validation (n=494) sets and stratified by the receipt of adjuvant ADT (n=243) or no adjuvant ADT (n=780). A literature review of ADT resistance and neuroendocrine genes identified 1,557 genes as candidates. This set was further filtered, using logistic regression to select a 52-gene ADT resistance signature (ARS). ARS was trained using a generalized linear model with lasso regularization. Survival c-index and Kaplan Meier was used to compare survival differences between treated and untreated patients with high and low ARS scores (defined by median split). Results: In validation cohorts, the ARS was predictive of metastasis in cohorts receiving adjuvant ADT (10-year metastasis free survival c-index of 0.69 (95% CI 0.59-0.78) as compared to 0.45 (95% CI 0.29-0.61) in patients not treated with ADT). Similarly in a separate cohort of untreated patients that received no ADT until after metastatic onset, ARS was not prognostic (c-index 0.53). Among ADT treated patients, those with low ARS scores had a 10 year MFS of 87%, versus 70% in those with high ARS scores (p<0.001). In the subset of men who received ADT after metastatic onset and who developed castrate-resistant prostate cancer (CRPC, n = 41), median time to treatment failure was 1 year in patients with high ARS compared to 2 years for those with low ARS scores (p=0.07). Conclusions: A 52-gene ADT resistance signature was developed which showed significant differences in metastasis-free survival among adjuvant hormone treated but not untreated patients.

103 Background: Beginning in 2014, the National Comprehensive Cancer Network (NCCN) recognized very high-risk (VHR) prostate cancer (cT3b-T4, or primary Gleason pattern 5, or more than 4 biopsy cores with Gleason score 8-10, or multiple HR features) as a classification distinct from high-risk (HR) disease. Using prospectively collected institutional data, we describe contemporary treatment patterns and short-term outcomes in the VHR population. Methods: Men who underwent radical prostatectomy (RP) between January 2010 and June 2015 were identified using the Johns Hopkins RP database, and trends in management were compared across the study period. Pathological and short-term clinical outcomes were assessed in men with VHR cancer. Non organ-confined disease (NOCD) was defined as ≥ pT3 disease or lymph node positivity, persistent postoperative PSA as ≥ 0.2 ng/mL, and biochemical recurrence (BCR) as a PSA ≥ 0.2 ng/mL following an initial undetectable postoperative PSA. Results: During the study period, 4,954 men underwent RP, of which 161 (3.2%) men had VHR cancer at diagnosis. The annual proportion of men who underwent RP with VHR cancer increased over the study period (chronologically 1.8%, 1.0%, 3.3%, 4.1%, 5.6%, and 5.2%; p<0.001). Sixteen percent of men with VHR disease were enrolled in pre-surgical clinical trials, with an increase from 0% of men in 2010 to 19.1% in 2015 (p=0.11). At RP, 39% of the VHR cohort had seminal vesicle invasion, 26% had lymph node involvement, and a total of 74% had NOCD. Following surgery, 33% of men had PSA persistence, and 40% experienced either PSA persistence or BCR during follow-up (median 13.4 months). Of 136 men with at least one follow-up assessment, 15 (11.0%) developed metastasis; 33% of the cohort was treated with radiation therapy, 42% with androgen deprivation, and 15% with docetaxel. Conclusions: The VHR population carries the greatest risk of clinical progression following local treatment. Over the past five years, we have observed increasing surgical treatment and clinical trial enrollment at our institution. Continued assessment of post-operative interventions and outcomes will help to facilitate counseling and establish point estimates from which to power clinical trials.

284 Background: Frameless stereotactic radiosurgery (SRS) is single fraction radiation therapy delivered to an intracranial lesion. Rather than with a rigid head frame, frameless SRS uses a thermoplastic mask for immobilization. The benefit of this mask includes the ability to simulate and treat the patient at different times, ease of patient set-up and improved patient comfort. Clinically, frameless SRS is used for primary brain tumors and metastatic lesions. The length of the treatments may vary based on a number of factors, including total treatment dose, number of monitor units, number and arrangement of beams, and equipment manipulations. This is a single institution review of patients treated with SRS with positional checks made before, during and at the completion of treatment to evaluate intrafraction motion. Methods: Patients were treated with SRS at Mayo Clinic Florida between 2010 and 2011. All patients were immobilized with a thermoplastic mask and treated on a Varian IX Clinac. KV Cone beam CT was taken prior to the initiation of treatment to verify the treatment position. Cone beam CT’s were also performed at the midpoint and conclusion of treatment. The same physician analyzed all cone beam CT’s. Adjustments were recorded in each dimension and analyzed to determine intrafraction motion. Results: Intrafraction motion was evaluated during six separate SRS cases. The mean displacements at mid-treatment were 0.67±0.52 mm, 0.50±0.55 mm, 0.83±0.75 mm, and 1.35±0.78 mm in the medial/lateral, superior/inferior, anterior/posterior, and vectoral direction, respectively. The mean post-treatment displacements were 0.17±0.41 mm, 0.67±0.82 mm, 0.50±0.84 mm, and 1.11±0.96 mm in the medial/lateral, superior/inferior, anterior/posterior, and vectoral direction, respectively. Estimated overall margins to accommodate intrafraction motion in 90% of patients were 2.63 mm and 2.69 mm at mid-treatment and post-treatment, respectively. Conclusions: The majority of intrafraction motion occurred during the first portion of treatment. Intrafraction motion during the course of frameless SRS treatment is not negligible and approximately a 2.5 mm margin should be taken into account during the planning process.

Background: The objective of this study is to determine the time-dependent dissipation of extrinsic wrist ligament tension following the application external fixation with axial distraction of the wrist in a cadaveric model. Methods: Six paired fresh-frozen cadaveric specimens underwent mechanical testing simulating external fixation with 1 arm of each pair osteotomized to simulate a distal radius fracture. The change in tension was then recorded over 24 hours. Results: The rate of stress relaxation decreased with time. The average loss in tension in the control arms and osteotomized arms was 55% and 59%, respectively, over a 24-hour period. There was no statistically significant difference in the stress relaxation behavior between the 2 groups. Conclusion: This study further supports the recommendation that comminuted distal radius fractures treated with an external fixator should have Kirschner wire augmentation or other additional means of fixation to help maintain fracture length and alignment. The results of this study call in to question the efficacy of ligamentotaxis alone through external fixation as the sole means of maintaining reduction of displaced, unstable distal radius fractures.