Prognostic Value of BAP1 and Preferentially Expressed Antigen in Melanoma (PRAME) Immunohistochemistry in Uveal Melanomas.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.

Complications of Acute Posterior Vitreous Detachment.

PURPOSE: To evaluate the risk factors for retinal tear (RT) or rhegmatogenous retinal detachment (RRD) associated with acute, symptomatic posterior vitreous detachment (PVD) in a large comprehensive eye care setting. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 8305 adult patients in the Kaiser Permanente Northern California Healthcare System (KPNC) during calendar year 2018 who met inclusion criteria. METHODS: The KPNC electronic medical record was queried to capture acute, symptomatic PVD events. Each chart was reviewed to confirm diagnoses and capture specific data elements from the patient history and ophthalmic examination. MAIN OUTCOME MEASURES: Presence of RT or RRD at initial presentation or within 1 year thereafter. RESULTS: Of 8305 patients who presented with acute PVD symptoms, 448 (5.4%) were diagnosed with RT and 335 (4.0%) were diagnosed with RRD. When considering variables available before examination, blurred vision (odds ratio [OR], 2.7; confidence interval [CI], 2.2-3.3), male sex (OR, 2.1; CI, 1.8-2.5), age < 60 years (OR, 1.8; CI, 1.5-2.1), prior keratorefractive surgery (OR, 1.6; CI, 1.3-2.0), and prior cataract surgery (OR, 1.4; CI, 1.2-1.8) were associated with higher risk of RT or RRD, whereas symptoms of flashes were mildly protective (OR, 0.8; CI, 0.7-0.9). Examination variables associated with a high risk of RT or RRD included vitreous pigment (OR, 57.0; CI, 39.7-81.7), vitreous hemorrhage (OR, 5.9; CI, 4.6-7.5), lattice degeneration (OR, 6.0; CI, 4.7-7.7), and visual acuity worse than 20/40 (OR, 3.0; CI, 2.5-3.7). Late RTs or RRDs occurred in 12.4% of patients who had vitreous hemorrhage, lattice degeneration, or a history of RT or RRD in the fellow eye at initial presentation but only 0.7% of patients without any of these 3 risk factors. Refractive error had an approximately linear relationship with age at presentation of PVD, with myopic patients presenting at a younger age (r = 0.4). CONCLUSIONS: This study, based in a comprehensive eye care setting, found the rate of RT and RRD associated with acute PVD to be lower than rates previously reported by retina subspecialty practices. Several patient features strongly predicted the presence of initial and late complications of acute PVD.

Multi-center analysis of intraocular biopsy technique and outcomes for uveal melanoma: Ocular Oncology Study Consortium report 4.

PURPOSE: To investigate the relationship between surgical approach for intraocular tumor biopsy of uveal melanoma and tumor morphologic features such as size and intraocular location and the effect of these variables on diagnostic yield and biopsy outcome. METHODS: Consecutive patients from nine Ocular Oncology centers with uveal melanoma (UM) undergoing tumor biopsy immediately preceding I125 plaque brachytherapy with tissue sent for gene expression profiling (GEP) testing were reviewed retrospectively. RESULTS: Three hundred sixty patients were included (50% men, mean age 60.2 years). Overall biopsy yield was 99% and 83% for GEP and cytopathology, respectively. Surgeon choice of biopsy approach (trans-vitreal vs. trans-scleral) was found to associate with both tumor location and tumor thickness. A trans-scleral rather than trans-vitreal approach was used more commonly for anteriorly located tumors (92% vs. 38% of posterior tumors, p < 0.001) and thicker tumors (86% vs. 55% of thin tumors, p < 0.001). When performing trans-vitreal biopsies, ocular oncologists with previous vitreoretinal surgery fellowship training were more likely to use wide-field surgical viewing systems, compared with indirect ophthalmoscopy (82.6% vs. 20.6%, p < 0.001). Surgical complications were rare and occurred more frequently with trans-vitreal biopsies (3.6% vs. 0.46%, p = 0.046). CONCLUSIONS: In this multi-center analysis of UM tumor biopsy, surgical yield was high for obtaining tumor tissue for GEP and cytopathology analysis with both trans-scleral and trans-vitreal techniques. Fellowship-trained ocular oncologists' preferred intraocular biopsy techniques associated strongly with tumor location, tumor thickness, and fellowship training of the surgeon. Short-term complication rates were low.

CORRELATION OF GENE EXPRESSION PROFILE STATUS AND AMERICAN JOINT COMMISSION ON CANCER STAGE IN UVEAL MELANOMA.

PURPOSE: To study the relationship between gene expression profile (GEP) subclass and American Joint Committee on Cancer (AJCC) stage in patients with uveal melanoma (UM). METHODS: A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Three hundred sixty eligible patients had UM and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with GEP testing between January 1, 2010, and October 28, 2014. Patient demographics and UM features were analyzed by both GEP and AJCC status. RESULTS: Gene expression profile class divided the cohort into three groups: Class 1a (n = 186), Class 1b (n = 77), and Class 2 (n = 113). When classified using AJCC staging criteria, we found the following: Stage I in 91 cases (25.3%), Stage IIA in 143 cases (39.7%), Stage IIB in 89 cases (24.7%), Stage IIIA in 36 cases (10%), and Stage IIIB in 1 case (0.3%). There were no Stage IV cases, as lymph node and metastatic data were not collected as a part of this study. Among Stage I tumors, both high tumor height and high largest basal diameter were associated with a higher frequency of Class 2 status (P < 0.05). As UMs progress to a larger AJCC tumor group (T1-T4), the odds ratio of having a worse prognosis based on GEP class was 1.75 (95% CI, 1.36-2.25; P < 0.001). Similarly, as UMs progress to a higher AJCC stage, the odds ratio of having a worse prognosis based on GEP class was 1.69 (95% CI, 1.36-2.10; P < 0.001). CONCLUSION: This report details the differences in clinical features between GEP subclasses and how they are distributed among the AJCC stages. When the tumors were grouped by AJCC staging criteria, both larger AJCC tumor (T) group and worsening AJCC stage were associated with worsening predicted prognosis, based on GEP subclass.

RELATIONSHIP OF CLINICAL FEATURES AND BASELINE TUMOR SIZE WITH GENE EXPRESSION PROFILE STATUS IN UVEAL MELANOMA: A Multi-institutional Study.

PURPOSE: To study the relationship between gene expression profile subclass and clinical features in a multicenter cohort of patients with uveal melanoma. METHODS: A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Eligible patients had uveal melanoma and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with gene expression profile testing between January 1, 2010, and October 28, 2014. Data were collected regarding patient demographics, baseline tumor clinical features, and gene expression profile results. Statistical analyses were performed using the Fisher's exact test, Wilcoxon rank-sum test, Kruskal-Wallis test, and proportional-odds cumulative logit modeling. RESULTS: Inclusion criteria were met for 379 patients. Gene expression profile class divided the cohort into two main groups, Class 1 (n = 263) and Class 2 (n = 113). Class 1 tumors were further subdivided into Class 1a (n = 186) and Class 1b (n = 77). The differences between Class 1 and Class 2 tumors were similar to previous studies, except the finding of Class 2 tumors being more likely to have associated exudative retinal detachment (P < 0.001). There was no statistically significant difference between Class 1 and Class 2 tumors based on the presence of lipofuscin, drusen, or subretinal fluid. Class 1a tumor patients, compared with Class 1b, were significantly older (P = 0.034). Class 2 tumors, when compared with Class 1b, were associated with increasing patient age (P < 0.001), larger tumor height (P = 0.010), ciliary body involvement (P = 0.001), exudative retinal detachment (P = 0.024), and anterior tumor location (P < 0.001). When the tumors were grouped into Collaborative Ocular Melanoma Study size categories, increasing tumor size category was significantly associated with Class 2 status: 6% of small tumors, 32% of medium tumors, and 53% of large tumors were Class 2. CONCLUSION: In a multi-institutional setting, we found that the only significant difference in clinical features between Class 1a and Class 1b tumors was that patients with Class 1a tumors were older at the time of diagnosis. We also found that Class 1a and Class 1b have clinical features distinct from Class 2 tumors. The distribution of the gene expression profile subclasses among the size groups was similar to reported time-to-metastasis data among the same size groupings. Our clinical findings support the current molecular classification-based survival data previously reported in uveal melanoma.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial.

BACKGROUND: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. METHODS: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. FINDINGS: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. INTERPRETATION: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. FUNDING: National Cancer Institute.

MOLECULAR PROGNOSTICS FOR UVEAL MELANOMA.

PURPOSE: To review laboratory methods, currently available commercial tests, caveats and clinical tips regarding prognostic analysis of uveal melanoma tissue. METHODS: A review of the literature was performed focused on the genetic abnormalities found in uveal melanoma cells, their correlation to the development of metastases, the validity of various laboratory approaches in their detection, and the existing commercially available tests for uveal melanoma prognostication. RESULTS: Numerous laboratory methods exist for analyzing genetic material obtained from uveal melanoma cells. Older tests have been gradually replaced with contemporary methods that are simpler with greater accuracy. Two commercially available assays exist which have not been directly compared-a gene expression profiling test has been validated directly through a large, prospective multicenter study and a DNA-based test which uses laboratory methods supported by extensive historical data. CONCLUSION: There are myriad laboratory methods for prognostic analysis of uveal melanoma tissue. These tests were historically only available to those with access to an outfitted laboratory. Newer commercially available assays have increased the accessibility of prognostic biopsy for uveal melanoma. The various caveats that exist when considering and performing prognostic biopsy of uveal melanoma are discussed.

Association between Tumor Regression Rate and Gene Expression Profile after Iodine 125 Plaque Radiotherapy for Uveal Melanoma.

PURPOSE: Gene expression profile (GEP) testing segregates uveal melanoma (UM) into 2 main prognostic classes. It is unknown if a greater tumor regression response after iodine 125 (I125) brachytherapy correlates with class 2 GEP status. The purpose of this study was to determine whether there is a significant relationship between the rate of UM height regression and GEP classification testing after I125 plaque brachytherapy. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Adult UM patients treated with I125 plaque brachytherapy who had concurrent tumor biopsy at the time of surgery with a GEP test result from January 1, 2010 through June 30, 2014. METHODS: Baseline clinical data and GEP class assignments were obtained. The ultrasonographic tumor height was recorded at baseline and at 3, 6, 9, and 12 months and at the most recent final follow-up visits. Subanalysis of paired cases based on pretreatment ultrasound height was performed. Statistical analysis was performed using Wilcoxon rank-sum tests, the Fisher exact test, and Kaplan-Meier analysis. MAIN OUTCOME MEASURES: Percentage change in tumor height from baseline. RESULTS: A total of 353 patients were included in the study. Median follow-up was 2.1 years (range, 0.5-5.3 years). Gene expression profile status was class 1 in 247 tumors (70%) and class 2 in 106 tumors (30%). Increased patient age, larger tumor dimensions, and greater tumor thickness were associated with class 2 GEP status (P = 0.006, P < 0.001, and P < 0.001, respectively). The percentage reduction in tumor height from baseline was significantly greater in class 1 than class 2 tumors at 3 months (17.5% vs. 11.8%; P = 0.007) and 6 months (26.8% vs. 17.1%; P = 0.007), respectively, but there was no significant difference in reduction between class 1 and 2 tumors at 9 months (P = 0.26) and 12 months (P = 0.57) after treatment. Class 1A and 1B tumors showed similar reduction compared with class 2 tumors (P < 0.05). CONCLUSIONS: Class 1 UM tumors tend to regress more rapidly than class 2 tumors in the first 6 months after plaque radiotherapy. Class 1A and 1B tumors regress at similar rates after plaque radiotherapy.

Cost of phacovitrectomy versus vitrectomy and sequential phacoemulsification.

PURPOSE: To evaluate and compare the cost of combined pars plana vitrectomy and phacoemulsification/intraocular lens implantation (phacovitrectomy) to a sequential approach to the surgical procedures for patients with an indication for vitrectomy and a visually significant cataract. METHODS: The total cost of both the combined and sequential approaches to surgery were calculated by combining the surgeon, ambulatory surgical center, and anesthesiology fees as reimbursed by Medicare. A univariate sensitivity analysis was also performed to examine the sensitivity of our estimations to changes in surgical duration. RESULTS: Phacovitrectomy afforded a 17% to 20% per-patient cost savings to Medicare (depending on the type of vitrectomy) compared with vitrectomy with sequential phacoemulsification. The conclusion that phacovitrectomy was less expensive than sequential surgery was robust in sensitivity analysis. CONCLUSION: Phacovitrectomy seems to be significantly less costly to Medicare than a sequential approach to surgery for patients with an indication for vitrectomy and a visually significant cataract.

Prostate-specific antigen response after short-term hormone therapy plus external-beam radiotherapy and outcome in patients treated on Radiation Therapy Oncology Group study 9413.

BACKGROUND: The objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes. METHODS: The phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA ≤0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure. RESULTS: For 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30). CONCLUSIONS: The current results indicated that failure to obtain a PSA-CR (PSA ≤0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation.

The effect of procedure room temperature and humidity on LASIK outcomes.

OBJECTIVE: To determine whether procedure room temperature or humidity during LASIK affect refractive outcomes in a large patient sample. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 202 394 eyes of 105 712 patients aged 18 to 75 years who underwent LASIK at an Optical Express, Inc., location in their United Kingdom and Ireland centers from January 1, 2008, to June 30, 2011, who met inclusion criteria. METHODS: Patient age, gender, flap creation technique, pre- and 1-month post-LASIK manifest refraction, and ambient temperature and humidity during LASIK were recorded. Effect size determination and univariate and multivariate analyses were performed to characterize the relationships between LASIK procedure room temperature and humidity and postoperative refractive outcome. MAIN OUTCOME MEASURES: One month post-LASIK manifest refraction. RESULTS: No clinically significant effect of procedure room temperature or humidity was found on LASIK refractive outcomes. When considering all eyes in our population, an increase of 1°C during LASIK was associated with a 0.003 diopter (D) more hyperopic refraction 1 month postoperatively, and an increase in 1% humidity was associated with a 0.0004 more myopic refraction. These effect sizes were the same or similar when considering only myopic eyes, only hyperopic eyes, and subgroups of eyes stratified by age and preoperative refractive error. CONCLUSIONS: Neither procedure room temperature nor humidity during LASIK were found to have a clinically significant relationship with postoperative manifest refraction in our population.

Glaucoma severity and medication adherence in a county hospital population.

OBJECTIVE: To assess the association between disease severity and adherence with glaucoma medications in a county hospital population. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 126 patients diagnosed with glaucoma receiving intraocular pressure (IOP)-lowering medication were recruited from the San Francisco General Hospital Ophthalmology Clinic. METHODS: Subjects completed an oral questionnaire to assess demographic information, knowledge of glaucoma, and perceptions of glaucoma medication adherence. Glaucoma disease severity was classified according to the American Academy of Ophthalmology's Preferred Practice Pattern guidelines. Medication adherence was measured for each patient by obtaining pharmacy refill data and calculating medication possession ratio (MPR), that is, the ratio of total days' supply of medication during a 365-day period. Adherence was measured retrospectively over the 18-month period before study entry. Subjects with an MPR >80% were considered adherent. MAIN OUTCOME MEASURE: Medication adherence. RESULTS: Subjects with mild or moderate glaucoma were more likely to be nonadherent to their prescribed glaucoma medications than those with severe disease (adjusted odds ratio [OR], 1.54; 95% confidence interval [CI], 1.03-2.31; P = 0.04). Age, gender, race, education level, years of glaucoma, number of medications, and glaucoma diagnosis were not found to be statistically significantly associated with adherence. CONCLUSION: Patients with severe glaucoma were more likely to adhere to their topical IOP-lowering medication regimen than those with milder glaucomatous disease. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Quality of Life Implications of Dose-Escalated External Beam Radiation for Localized Prostate Cancer: Results of a Prospective Randomized Phase 3 Clinical Trial, NRG/RTOG 0126.

PURPOSE: External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer. METHODS AND MATERIALS: The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time. RESULTS: In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk. CONCLUSIONS: Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.

Novel Guarded Needle Trans-Scleral Biopsy for Uveal Melanoma: A Pilot Study.

INTRODUCTION: Trans-scleral biopsy of uveal melanoma (UM) poses an inherent risk of tumor and possibly retinal perforation. We describe a novel technique for trans-scleral biopsy of UM and evaluate its safety and efficacy in an initial cohort of patients. METHODS: A retrospective, consecutive observational case series was conducted from October 14, 2019, to April 15, 2020, at Kaiser Permanente, San Francisco, CA among patients with UM of the ciliary body or anterior choroid undergoing trans-scleral fine-needle aspiration biopsy using a novel guarded needle technique. RESULTS: A total of 6 patients were included in the study, with a mean age of 64.3 (range 35-77) years (5 women 83%). Mean (±SD) tumor thickness and maximal basal diameter were 6.4 (±2.66) and 11.9 (±2.13) mm, respectively. Five out of 6 patients achieved a successful biopsy with reliable gene expression profiling (GEP) results. The only failure to obtain specimen occurred in the first attempted patient and, after a minor technique modification, all subsequent biopsies were successful. No intraoperative or short-term postoperative complications were observed in any patient. CONCLUSION: This novel trans-scleral biopsy technique appears to be safe and effective when obtaining UM tissue for GEP. This method may provide a more controlled biopsy depth thereby minimizing the risk of tumor perforation and its associated complications while still obtaining adequate biopsy yield.