The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/ml on metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. METHODS: Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. RESULTS: We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/ml was the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. CONCLUSIONS: Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer.

BACKGROUND: Limited data exist comparing intensity-modulated photon (IMRT) and proton (IMPT) radiation therapy when treating the prostate bed and pelvic lymph nodes in the postoperative setting for prostate cancer. The aim of this study was to evaluate dosimetric differences between IMRT and IMPT when treating with whole pelvis radiation therapy (WPRT) postoperatively. MATERIALS AND METHODS: IMRT and IMPT plans were generated for 10 post-prostatectomy patients treated between July and August 2020. The prescription was 50 Gy radiobiologic equivalent (GyE) (proton radiobiological effective dose 1.1) to the pelvis and 70 GyE to the prostate bed in 2 GyE per fraction. Paired 2-sided Wilcoxon signed-rank tests were used to compare clinical target volume (CTV) coverage and dose to organs at risk (OARs). RESULTS: CTV coverage was met for all plans with 99% of CTVs receiving ≥99% of prescription doses. Dose to OARs was significantly higher with IMRT than IMPT for the following endpoints: bladder V5-V65; bowel V5-V45; sigmoid V5-V50; rectum V5-V70; femoral head V40 and maximum dose; bone V5-V65. Select endpoints with significant differences included bladder V30 (63.5 vs. 44.4%, p < .001), bowel V15 (949 vs. 191 cc, p = .001) and V30 (386 vs. 121 cc, p < .001), rectum V40 (81.8 vs. 32.1%, p < .001) and V50 (47.6 vs. 24.9%, p < .001), femoral head maximum doses (46.4-47.1 vs. 38.3-38.6GyE, p < .001), and bone V10 (93.3 vs. 85.4%, p < . 001). Mean doses for all OARs were significantly higher with IMRT, including bladder (41.9 vs. 29.7GyE, p < .001), bowel (21.2 vs. 5.5GyE, p < .001), and rectum (50.8 vs. 27.3GyE, p < .001). Integral dose to 'Body - CTV' was significantly higher with IMRT (32.8 vs. 18.4 J, p < .001). CONCLUSION: IMPT provides comparable target coverage to IMRT when treating prostate cancer with WPRT in the postoperative setting while significantly reducing dose to OARs. These data can inform the future clinical management and delivery of post-prostatectomy irradiation for prostate cancer.

Radiating the prostate bed in relapsed oligometastatic prostate cancer: How comprehensive should we be?

PURPOSE: A subset of patients with high-risk pathological features at radical prostatectomy recur with oligometastatic disease. The aim of this study is to investigate the rate of prostate bed recurrence, with or without history of prostate bed irradiation (PBRT), in oligometastatic prostate cancer (OMPC) patients after metastasis-directed therapy (MDT). METHODS: We performed a retrospective analysis of hormone-sensitive OMPC patients treated initially with curative-intent radical prostatectomy followed by disease recurrence and metastasis-directed stereotactic ablative radiotherapy (SABR) at our institution. Prostate bed recurrence rates were compared between patients who had PBRT at any point (i.e., before oligometastatic diagnosis or concurrently with MDT) versus those with no history of PBRT. RESULTS: Seventy-seven patients were included, and 68.8% had received PBRT. There were no significant differences in baseline characteristics between those who had received and had not received PBRT. There were five prostate bed recurrences following MDT, specifically with a 24-month cumulative incidence of 30.4% in patients who did not have PBRT and 2.4% in those who did (p = 0.03). Three of the five recurrences were isolated to the prostate bed at time of recurrence. CONCLUSIONS: Relapsed oligometastatic prostate cancer patients who have not received maximal local consolidative therapy to the prostate bed may have higher rates of local failure. Prospective studies are warranted investigating when prostate bed irradiation should be considered for patients after radical prostatectomy who ultimately have oligometastatic prostate cancer.

A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS).

BACKGROUND: Metastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa. METHODS: Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response. DISCUSSION: The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/- radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm. TRIAL REGISTRATIONS: Clinicaltrials.gov. Identifier: NCT04037358. Date of Registration: July 30, 2019. Date of First Participant Enrolled: August 9, 2019. Date of Last Approved Amendment: October 16, 2019. Protocol Version: Version 5.

Diversity by Race, Ethnicity, and Sex within the US Psychiatry Physician Workforce.

OBJECTIVE: This study assessed the distribution of race, ethnicity, and sex within the US psychiatry physician workforce and trends from 1987 to 2016. METHODS: The authors used physician workforce data to assess differences in race, ethnicity, and sex among psychiatric practicing physicians, faculty, fellows, residents, residency applicants, and medical graduate cohorts. Binomial tests were used for comparison between individual cohorts and to US population statistics. A simple linear regression model was used to assess trends among psychiatric residents and faculty over years 1987-2016. RESULTS: Within psychiatry, historically underrepresented minorities in medicine (URMs) had less representation as residents (16.2%), faculty (8.7%), and practicing physicians (10.4%) compared with the US population (32.6%), Ps < 0.0001. Females were underrepresented as psychiatric practicing physicians (38.5%, P < .0001). There was greater URM representation among residents (16.2%) compared with that of Psychiatry faculty and practicing physicians (Ps < .0001). Racial/ethnic representation did not differ significantly compared with subspecialty fellows; however, the addiction subspecialty contained the least URM and female diversity. Historical trends indicated the proportion of female faculty (0.9%/yr) increased nearly 1.5 times faster than that of female trainees (0.6%/year). Conversely, the proportion of URM residents (0.26%/year) increased over 4 times faster than that of URM faculty (0.06%/year), with black faculty actually decreasing in proportion. CONCLUSIONS: Female and URM representation within the psychiatry physician workforce is significantly lower than US population demographics; however, trends indicate diminishing underrepresentation. While psychiatry residency remains more diverse than other specialties, specific trends identify poor minority representation among psychiatry faculty and fellows as areas needing attention.

Comparative toxicity outcomes of proton-beam therapy versus intensity-modulated radiotherapy for prostate cancer in the postoperative setting.

BACKGROUND: Despite increasing utilization of proton-beam therapy (PBT) in the postprostatectomy setting, no data exist regarding toxicity outcomes relative to intensity-modulated radiotherapy (IMRT). The authors compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes in patients with prostate cancer (PC) who received treatment with postprostatectomy IMRT versus PBT. METHODS: With institutional review board approval, patients with PC who received adjuvant or salvage IMRT or PBT (70.2 gray with an endorectal balloon) after prostatectomy from 2009 through 2017 were reviewed. Factors including combined IMRT and PBT and/or concurrent malignancies prompted exclusion. A case-matched cohort analysis was performed using nearest-neighbor 3-to-1 matching by age and GU/GI disorder history. Logistic and Cox regressions were used to identify univariate and multivariate associations between toxicities and cohort/dosimetric characteristics. Toxicity-free survival (TFS) was assessed using the Kaplan-Meier method. RESULTS: Three hundred seven men (mean ± SD age, 59.7 ± 6.3 years; IMRT, n = 237; PBT, n = 70) were identified, generating 70 matched pairs. The median follow-up was 48.6 and 46.1 months for the IMRT and PBT groups, respectively. Although PBT was superior at reducing low-range (volumes receiving 10% to 40% of the dose, respectively) bladder and rectal doses (all P ≤ .01), treatment modality was not associated with differences in clinician-reported acute or late GU/GI toxicities (all P ≥ .05). Five-year grade ≥2 GU and grade ≥1 GI TFS was 61.1% and 73.7% for IMRT, respectively, and 70.7% and 75.3% for PBT, respectively; and 5-year grade ≥3 GU and GI TFS was >95% for both groups (all P ≥ .05). CONCLUSIONS: Postprostatectomy PBT minimized low-range bladder and rectal doses relative to IMRT; however, treatment modality was not associated with clinician-reported GU/GI toxicities. Future prospective investigation and ongoing follow-up will determine whether dosimetric differences between IMRT and PBT confer clinically meaningful differences in long-term outcomes.

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA).

BACKGROUND: In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events. METHODS/DESIGN: This is a randomized, double-blind, phase II, prospective, multicenter study in adult males with biochemically recurrent prostate cancer following radical prostatectomy. Following registration, enzalutamide 160 mg or placebo by mouth (PO) once daily will be administered for 6 months. Following two months of study drug, external beam radiotherapy to 66.6-70.2 Gray (Gy) will be administered to the prostate bed over 7-8 weeks while continuing daily placebo/enzalutamide. This is followed by two additional months of placebo/enzalutamide. DISCUSSION: The SALV-ENZA trial is the first phase II placebo-controlled double-blinded randomized study to test SRT in combination with a next generation androgen receptor antagonist in men with high-risk recurrent prostate cancer after radical prostatectomy. The primary hypothesis of this study is that clinical outcomes will be improved by the addition of enzalutamide compared to standard-of-care SRT alone and pave the path for phase III evaluation of this combination. TRIAL REGISTRATIONS: ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

PURPOSE: Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). METHODS: Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1-5 fractions of 5-18 Gray. Kaplan-Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated. RESULTS: In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ≥ grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. CONCLUSIONS: Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

BACKGROUND: Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. METHODS: A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. RESULTS: The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). CONCLUSIONS: EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men.

Initial report of the genitourinary and gastrointestinal toxicity of post-prostatectomy proton therapy for prostate cancer patients undergoing adjuvant or salvage radiotherapy.

PURPOSE: To report acute and late genitourinary (GU) and gastrointestinal (GI) toxicities associated with post-prostatectomy proton therapy (PT). METHODS: The first 100 consecutive patients from 2010 to 2016 were retrospectively assessed. Baseline characteristics, prospectively graded CTCAE v4.0 toxicities, and patient-reported outcomes were reported. Late outcomes were reported for 79 patients with 3 months minimum follow up. Toxicity-free survival Kaplan-Meier curves were estimated. Logistic regression assessed associations between toxicities and clinical and treatment characteristics (p < .05 significance). RESULTS: Median age, months after surgery, and months of follow-up were respectively 64 years (range 42-77), 25 (5-216), and 25 (0-47). PT received was 70.2 Gy (RBE) (89%), salvage (93%), prostate bed only (80%), pencil beam scanning (86%), with IMRT (31%), and with androgen deprivation (34%). Acute and late maximum toxicities, respectively were: GU grade 0 (14%; 18%), 1 (71%; 62%), 2 (15%; 20%), ≥3 (0), and GI: grade 0 (66%; 73%), 1 (34%; 27%), ≥2 (0). Toxicity-free survival at 24 months was GU grade 2 (83%) and GI grade 1 (74%). Mean (±std dev) baseline International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 6.6 ± 6.1, 10.5 ± 7.3, 90.9 ± 10.8, 93.3 ± 11.2, respectively, and largely unchanged at 2 years: 6.3 ± 3.6, 11.1 ± 6.3, 92.8 ± 5.8, and 90.9 ± 10.3. On multivariate analysis, baseline IPSS (p = .009) associated with GU grade 2 acute toxicity. Bladderless-CTV median dose, V30, and V40 associated with GU grade 2 acute toxicity and maximum dose with late (Ps <0.05). For GI, on multivariate analysis, baseline bowel function (p = .033) associated with acute grade 1 toxicity. Rectal minimum and median dose, V10, and V20, and anterior rectal wall median dose and V10 through V65 associated with acute grade 1 GI toxicity (Ps < .05). CONCLUSIONS: Post-prostatectomy PT for prostate cancer is feasible with a favorable GU and GI toxicity profile acutely and through early follow up.

Data integrity systems for organ contours in radiation therapy planning.

The purpose of this research is to develop effective data integrity models for contoured anatomy in a radiotherapy workflow for both real-time and retrospective analysis. Within this study, two classes of contour integrity models were developed: data driven models and contiguousness models. The data driven models aim to highlight contours which deviate from a gross set of contours from similar disease sites and encompass the following regions of interest (ROI): bladder, femoral heads, spinal cord, and rectum. The contiguousness models, which individually analyze the geometry of contours to detect possible errors, are applied across many different ROI's and are divided into two metrics: Extent and Region Growing over volume. After analysis, we found that 70% of detected bladder contours were verified as suspicious. The spinal cord and rectum models verified that 73% and 80% of contours were suspicious respectively. The contiguousness models were the most accurate models and the Region Growing model was the most accurate submodel. 100% of the detected noncontiguous contours were verified as suspicious, but in the cases of spinal cord, femoral heads, bladder, and rectum, the Region Growing model detected additional two to five suspicious contours that the Extent model failed to detect. When conducting a blind review to detect false negatives, it was found that all the data driven models failed to detect all suspicious contours. The Region Growing contiguousness model produced zero false negatives in all regions of interest other than prostate. With regards to runtime, the contiguousness via extent model took an average of 0.2 s per contour. On the other hand, the region growing method had a longer runtime which was dependent on the number of voxels in the contour. Both contiguousness models have potential for real-time use in clinical radiotherapy while the data driven models are better suited for retrospective use.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

BACKGROUND: We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. METHODS/DESIGN: Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. DISCUSSION: The ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

Underrepresentation of Women and Minorities in the United States IR Academic Physician Workforce.

PURPOSE: To assess the United States interventional radiology (IR) academic physician workforce diversity and comparative specialties. METHODS: Public registries were used to assess demographic differences among 2012 IR faculty and fellows, diagnostic radiology (DR) faculty and residents, DR subspecialty fellows (pediatric, abdominal, neuroradiology, and musculoskeletal), vascular surgery and interventional cardiology trainees, and 2010 US medical school graduates and US Census using binomial tests with .001 significance level (Bonferroni adjustment for multiple comparisons). Significant trends in IR physician representation were evaluated from 1992 to 2012. RESULTS: Women (15.4%), blacks (2.0%), and Hispanics (6.2%) were significantly underrepresented as IR fellows compared with the US population. Women were underrepresented as IR (7.3%) versus DR (27.8%) faculty and IR fellows (15.4%) versus medical school graduates (48.3%), DR residents (27.8%), pediatric radiology fellows (49.4%), and vascular surgery trainees (27.7%) (all P < .001). IR ranked last in female representation among radiologic subspecialty fellows. Blacks (1.8%, 2.1%, respectively, for IR faculty and fellows); Hispanics (1.8%, 6.2%); and combined American Indians, Alaska Natives, Native Hawaiians, and Pacific Islanders (1.8%, 0) showed no significant differences in representation as IR fellows compared with IR faculty, DR residents, other DR fellows, or interventional cardiology or vascular surgery trainees. Over 20 years, there was no significant increase in female or black representation as IR fellows or faculty. CONCLUSIONS: Women, blacks, and Hispanics are underrepresented in the IR academic physician workforce relative to the US population. Given prevalent health care disparities and an increasingly diverse society, research and training efforts should address IR physician workforce diversity.

A case-matched study of toxicity outcomes after proton therapy and intensity-modulated radiation therapy for prostate cancer.

BACKGROUND: The authors assessed whether proton beam therapy (PBT) for prostate cancer (PCa) was associated with differing toxicity compared with intensity-modulated radiation therapy (IMRT) using case-matched analysis. METHODS: From 2010 to 2012, 394 patients who had localized PCa received 79.2 Gray (Gy) relative biologic effectiveness (RBE) delivered with either PBT (181 patients) or IMRT (213 patients). Patients were case-matched on risk group, age, and prior gastrointestinal (GI) and genitourinary (GU) disorders, resulting in 94 matched pairs. Both exact matching (risk group) and nearest-neighbor matching (age, prior GI/GU disorders) were used. Residual confounding was adjusted for by using multivariable regression. Maximum acute and late GI/GU Common Terminology Criteria for Adverse Events-graded toxicities were compared using univariate and multivariable logistic and Cox regression models, respectively. RESULTS: Bladder and rectum dosimetry variables were significantly lower for PBT versus IMRT (P ≤ .01). The median follow-up was 47 months (range, 5-65 months) for patients who received IMRT and 29 months (range, 5-50 months) for those who received PBT. On multivariable analysis, which exploited case matching and included direct adjustment for confounders and independent predictors, there were no statistically significant differences between IMRT and PBT in the risk of grade ≥ 2 acute GI toxicity (odds ratio, 0.27; 95% confidence interval [CI], 0.06-1.24; P = .09), grade ≥ 2 acute GU toxicity (odds ratio, 0.69; 95% CI, 0.32-1.51; P = .36), grade ≥ 2 late GU toxicity (hazard ratio, 0.56; 95% CI, 0.22-1.41; P = .22), and grade ≥ 2 late GI toxicity (hazard ratio, 1.24; 95% CI, 0.53-2.94; P = .62). CONCLUSIONS: In this matched comparison of prospectively collected toxicity data on patients with PCa who received treatment with contemporary IMRT and PBT techniques and similar dose-fractionation schedules, the risks of acute and late GI/GU toxicities did not differ significantly after adjustment for confounders and predictive factors.

Retroperitoneal sarcoma (RPS) high risk gross tumor volume boost (HR GTV boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists.

PURPOSE: Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. METHODS: Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. RESULTS: HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. CONCLUSIONS: Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.