Search

PURPOSE We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double‐blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695 ). Random assignment (1:1) was stratified by center, surgical margin status (R0 v R1), PSA before salvage treatment (PSA ≥ 0.5 v < 0.5 ng/mL), and pathologic Gleason sum (7 v 8‐10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6‐70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis‐free survival, and safety as determined by frequency and severity of adverse events. RESULTS Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; P = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; Pinteraction = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; Pinteraction = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA v 53% placebo) and urinary frequency (40% ENZA v 49% placebo). CONCLUSION SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.

Immunotherapy has emerged as a promising therapeutic option for advanced or unresectable hepatocellular carcinoma (HCC). However, survival remains poor with only a subset of patients deriving benefit. This trial investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in HCC.In this multicenter phase 1 randomized trial, patients with advanced or unresectable HCC received liver SBRT (40 Gy in 5 fractions) followed by either nivolumab alone or nivolumab plus ipilimumab. The primary endpoint was dose-limiting toxicity occurring within 6 months of SBRT. Secondary endpoints included overall response rate, progression-free survival, overall survival (OS), distant disease control, and local control of the irradiated tumor. Disease status and response endpoints were assessed radiographically every 8 weeks until progression or initiation of nonprotocol therapy. Response was determined using both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and iRECIST.Fourteen patients were enrolled across 3 centers. Thirteen patients were evaluated for study endpoints. The study was closed early because of slow accrual. The median follow-up time was 42.7 months. Dose-limiting toxicities within 6 months occurred in 2 (15.4%) of 13 patients: 1 of 6 patients in the nivolumab arm (16.7%; 90% confidence interval [CI], 0.9%-58.2%) and 1 of 7 patients in the nivolumab plus ipilimumab arm (14.3%; 90% CI, 0.7%-52.1%). Grade 3 adverse events occurred in 8 (61.6%), 5 (71.4%), and 3 (50.0%) patients in the overall nivolumab plus ipilimumab and nivolumab cohorts. Grade 3 hepatotoxicity occurred in 4 (30.8%), 3 (42.9%), and 1 (16.7%) patients in the respective cohorts. Clinical outcomes favored the nivolumab plus ipilimumab arm compared with nivolumab alone, including an overall response rate of 57% (4 of 7 patients; 90% CI, 23%-87%) versus 0% (0 of 6 patients; 90% CI, 0%-39%), median progression-free survival of 11.6 months (90% CI, 4.5 months to not reached) versus 2.7 months (90% CI, 1.3-4.7 months), and median OS of 41.6 months (90% CI, 4.5 months to not reached) versus 4.7 months (90% CI, 2.0-16.2 months) (all P.05). With combination immunotherapy, 3-year OS was 57% (90% CI, 23%-81%), with 2 patients alive after 42.7 months without progression and negative PET.In this first prospective trial investigating the combination of SBRT and immunotherapy for HCC, multimodal therapy demonstrated acceptable safety. SBRT with nivolumab plus ipilimumab compared favorably to outcomes of immunotherapy alone and warrants further investigation.

There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.

The incidence of anal cancer in the United States has increased in recent years, primarily related to the increasing incidence of HPV-associated anal squamous cell carcinoma, which is estimated to represent 80%-95% of anal cancers. Similar to head and neck cancer, HPV association has been demonstrated to be a strong positive prognostic factor in patients with anal cancer. Encouraging results from a number of studies investigating treatment de-escalation for HPV-associated oropharyngeal cancer support the notion that similar attempts may be feasible in HPV-associated anal cancer; however, the data to support this hypothesis are currently lacking. Studies are needed to determine how, if at all, HPV status should impact the management of patients with anal cancer. This review summarizes the relationship between HPV association and outcomes for patients with anal cancer, and how HPV status may impact the treatment of patients with anal cancer going forward.

To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer.The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. REstimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). RGleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.

Goals of care discussions (GOCD) are essential when counseling patients with cancer. Respective roles of radiation oncologists (RO) and medical oncologists (MO) in GOCD can be unclear. This study aims to clarify the dynamics and barriers to GOCD. Five hundred and fifty-four ROs and 1604 MOs at NCI-designated comprehensive cancer centers were sent an anonymous electronic survey regarding demographics, opinions, training in GOCD, GOCD frequency, and three vignettes. Response formats were Yes/No, Likert-type, and free response. Chi-square and Wilcoxon rank-sum tests were performed. Likert-type scores were reported as median [interquartile range]. There were 76 (13.7%) RO and 153 (9.5%) MO who completed surveys. Sixty-three percent of RO and 66% of MO reported GOCD with > 50% of patients (p = 0.90). GOCD were initiated for declining performance status (74%) and poor life expectancy (69%). More MO (42%) received formal GOCD training compared to RO (18%) (p

Background Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression. Methods Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. Results Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. Conclusions For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.

Purpose Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. Methods and Materials We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework. Results A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. Conclusions There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.

BACKGROUND: We explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer. METHODS: This phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD). Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival. RESULTS: Fifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26–30 Gy, P

Purpose Conventional imaging rarely localizes the site(s) of prostate cancer recurrence in patients undergoing evaluation for salvage radiation therapy (sRT) after radical prostatectomy (RP). LOCATE (NCT02680041) was a prospective, multicenter study investigating the impact of 18F-fluciclovine positron emission tomography and computed tomography (PET/CT) on the management of patients with biochemical recurrence of prostate cancer after curative-intent radiation or RP and negative or equivocal conventional imaging. Our objective was to determine the impact of 18F-fluciclovine PET/CT on treatment decisions for men planning to undergo sRT for biochemical recurrence post-RP. Methods and Materials We conducted a subgroup analysis of post-RP patients enrolled in LOCATE who were planning to undergo sRT with or without hormonal therapy based on prescan documentation. 18F-Fluciclovine PET/CT was performed according to standardized procedures. The treatment plan postscan was compared with the prescan plan, and Fisher exact test was used to determine the impact of prescan prostate-specific antigen (PSA) and Gleason sum (GS) on positivity and anatomic patterns of uptake. Results A total of 114 patients (median prescan PSA 0.42 [interquartile range, 0.3-1.1] ng/mL) met selection criteria (54% of patients in LOCATE). Forty-eight (42%) had 18F-fluciclovine-avid lesions. Twelve patients (11%) had positive findings only in the prostate bed, 24 (21%) had positivity only in the pelvis (prostate bed or pelvic nodes), and 24 (21%) had extrapelvic findings. PSA >0.5 ng/mL and GS ≥8 were associated with a higher risk of extrapelvic positivity (P Postscan, 55 (48%) patients had a management change; 37 (32%) had a change in overall treatment approach (ie, omission of sRT); and 18 (16%) had sRT target modification. Conclusions 18F-Fluciclovine PET/CT is positive in nearly half of patients planning to undergo post-RP sRT with negative/equivocal conventional imaging, with findings frequently leading to changes in management. PSA >0.5 ng/mL and GS ≥8 are associated with a higher risk of extrapelvic positive findings.

Background Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes. Methods A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS). Results After a median follow‐up of 103 months, 10‐year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10‐year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10‐year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count, 482 men received primary radiotherapy for non‐metastatic prostate cancer and those men with pre‐treatment platelet count in the lowest quartile experienced worse 10‐year freedom from biochemical failure (61% vs 81%, P

Background Fiducial markers are frequently used before treatment for image‐guided patient setup in radiation therapy (RT), but can also be used during treatment for image‐guided intrafraction motion detection. This report describes our implementation of automatic marker detection with periodic kV imaging (TrueBeam v2.5) to monitor and correct intrafraction motion during prostate RT. Methods We evaluated the reproducibility and accuracy of software fiducial detection using a phantom with 3 implanted fiducial markers. Clinical implementation for patients with intraprostatic fiducials receiving volumetric modulated arc therapy (VMAT) utilized periodic on‐board kV imaging with 10 s intervals during treatment delivery. For each image, the software automatically identified fiducial locations and determined whether their distance relative to planned locations were within a 3 mm tolerance. Motion was corrected if either ≥2 fiducials in a single image or ≥1 fiducial in sequential images were out of tolerance. Results Phantom studies demonstrated poorer performance of linear fiducials compared to collapsible fiducials, and wide variability to accurately detect fiducials across eight software settings. For any given setting, results were relatively reproducible and precise to ~0.5 mm. Across 17 patients treated with a median of 20 fractions, the software recommended a shift in 44% of fractions, and a shift was actually implemented after visual confirmation of movement greater than the 3 mm threshold in 20% of fractions. Adjustment of our approach led to improved accuracy for the latter (n = 7) patient subset. On average, table repositioning added 3.0 ± 0.3 min to patient time on table. Periodic kV imaging increased skin dose by an estimated 1 cGy per treatment arc. Conclusions Periodic kV imaging with automatic detection of motion during VMAT prostate treatments is commercially available, and can be successfully implemented to mitigate effects of intrafraction motion with careful attention to software settings.

303 Background: Six months of a GnRH agonist with SRT is a standard of care for patients with unfavorable features and a detectable PSA post-RP. FORMULA-509 was designed to evaluate whether adding six months of AAP and Apa to this regimen could improve outcomes. Methods: FORMULA-509 (NCT03141671) is an investigator-initiated, multi-center, open-label, randomized trial. Patients had PSA≥0.1 post-RP and one or more unfavorable features (Gleason 8-10, PSA>0.5, pT3/T4, pN1 or radiographic N1, PSA doubling time 0.5 vs.≤0.5) and pN0 vs pN1. Analyses within these subgroups were pre-planned. Results: 345 participants (332 evaluable) from 9 sites were randomized from 11/24/2017 to 3/25/2020 (172 bicalutamide, 173 AAP/Apa). Median follow-up was 34 (6-53) months; 29% were pN1 and 31% had PSA >0.5 ng/mL. The HR for PFS was 0.71 (90% CI 0.49-1.03), stratified one-sided log-rank p=0.06 (3-year PFS was 68.5% bicalutamide vs 74.9% AAP/Apa). The HR for MFS was 0.57 (90% CI 0.33-1.01), stratified one-sided log rank p=0.05 (3-year MFS was 87.2% bicalutamide vs 90.6% AAP/Apa). In a pre-planned analysis by stratification factors, AAP/Apa was significantly superior for patients with PSA >0.5 for PFS [HR 0.50, (90% CI 0.30-0.86), p=0.03 (2-sided); 3-year PFS 46.8% bicalutamide vs. 67.2% AAP/Apa] and for MFS [HR 0.32 (90% CI 0.15-0.72), p=0.01 (2-sided); 3-year MFS 66.1% bicalutamide vs. 84.3% AAP/Apa.] No statistically significant benefit was detected in pre-planned analyses of stratification subgroups defined by PSA≤0.5, pN0, or pN1. Adverse events were consistent with the known safety profiles of the agents being studied, with more rash and hypertension in the AAP/Apa arm. Conclusions: Although this primary analysis did not meet the pre-specified threshold for statistical significance, it does strongly suggest that the addition of AAP/Apa to SRT+6 months of ADT may improve PFS and MFS, particularly in the subgroup of patients with PSA>0.5 where a pre-planned subgroup analysis by stratification factors observed a statistically significant benefit for both PFS and MFS. Clinical trial information: NCT03141671 .

Rationale and Objectives To investigate whether pre-treatment quantitative multiparametric MRI can predict biochemical outcome of prostate cancer (PCa) patients treated with primary radiotherapy (RT). Materials and Methods Fifty-one patients with biopsy confirmed PCa underwent prostate multiparametric MRI on 3T MR scanner prior to RT. Thirty-seven men (73%) were treated with external beam RT alone, 12 men (24%) were treated with brachytherapy monotherapy, and two men (4%) were treated with external beam RT with brachytherapy boost. The index lesion was outlined by a radiologist and quantitative apparent diffusion coefficient (ADC), T2 and DCE parameters were measured. Biochemical failure was defined using the Phoenix criteria. Results After a median follow-up of 65 months, seven patients had biochemical failure. ADC had an area under the receiver operating characteristic curve of 0.71 for predicting RT outcome with significantly lower ADC (0.78 ± 0.17 vs 0.96 ± 0.26 µm2/ms, p = 0.04) of the index lesion in men with biochemical failure. Ideal ADC cutoff point (Youdens index) was 0.96 µm2/ms which had a sensitivity of 100% and specificity of 48% for predicting biochemical failure. Kaplan-Meier analysis showed that lower ADC values were associated with significantly lower freedom from biochemical failure (FFBF, p = 0.03, no failures out of 20 men if ADC ≥ 0.96 µm2/ms; seven of 31 with failures if ADC Conclusion Our results suggest that quantitative ADC values of the index lesion may predict biochemical failure following primary radiotherapy in patients with PCa. Lower ADC values were associated with inferior biochemical control.

Testis cancer is the most common solid malignancy in young males. The purpose of this guideline is to provide a useful reference on the effective evidence-based treatment of early stage testicular cancer.The systematic review utilized to inform this guideline was conducted by a methodology team at the Johns Hopkins University Evidence-based Practice Center. The methodology team searched using PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The evidence review team also reviewed relevant systematic reviews and references provided by the panel to identify articles that may have been missed by the database searches.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions.This guideline attempts to improve a clinician's ability to evaluate and treat patients with testicular cancer, but higher quality evidence in future trials will be essential to improve level of care for these patients.

Background Bladder cancer is commonly diagnosed in patients ineligible for radical cystectomy or chemoradiotherapy (chemo-RT) with cisplatin or fluorouracil with mitomycin. We assessed tolerability, efficacy, and toxicity of hypofractionated radiotherapy with capecitabine in this challenging population. Patients and Methods Patients with high-grade urothelial bladder cancer ineligible for radical cystectomy or high-intensity chemo-RT underwent maximal transurethral resection of bladder tumor followed by capecitabine (median, 825 mg/m2 per day 2 times a day) and radiation (median, 55 Gy in 2.2 Gy per fraction). Patients underwent surveillance cystoscopy and imaging, and were evaluated for toxicity, freedom from local failure and freedom from distant metastasis, progression-free survival, and overall survival. Results Eleven patients (median age, 80 years) with localized disease (n = 7), locally advanced disease (n = 3), or local-only recurrence after cystectomy (n = 1) were treated. Four patients (35%) had an Eastern Cooperative Oncology Group performance status of 2; median Charlson comorbidity index was 5. There was 1 acute grade 3 genitourinary event (9%), 6 acute grade 3 hematologic events (55%) of lymphopenia, and no acute grade 4 or higher events or hospitalizations. Ten patients (91%) completed radiotherapy, while 4 patients (36%) temporarily discontinued capecitabine. The complete response rate in the bladder was 64%. Two patients (18%) experienced late grade 1/2 genitourinary toxicities, and 1 (9%) experienced a transient late grade 4 genitourinary toxicity. With a median follow-up of 16.6 months, overall survival, progression-free survival, freedom from local failure, and freedom from distant metastasis at 1 year were 82%, 55%, 100%, and 55%, respectively, and at 2 years were 61%, 41%, 80%, and 55%, respectively. Conclusion Hypofractionated chemo-RT was well tolerated and was associated with a high rate of local control in this comorbid population, thus providing a treatment option for select bladder cancer patients.

5012 Background: We sought to investigate whether enzalutamide (ENZA) treatment, without androgen deprivation therapy, increases freedom-from-PSA-progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer post-radical prostatectomy (RP). Methods: Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double-blind, phase II, placebo-controlled, multicenter study of SRT + placebo vs SRT + ENZA. The randomization (1:1) was stratified by center, surgical margin status (R0 vs R1), PSA prior to salvage treatment (PSA ≥0.5 vs < 0.5 ng/mL), and pathologic Gleason sum (7 vs 8-10) using a minimization algorithm. Following randomization, patients received either placebo or ENZA 160 mg PO once daily for 6 months. Following 2 months of study drug therapy, external beam radiotherapy to 66.6-70.2 Gy was administered to the prostate bed (no pelvic nodes). The primary endpoint was FFPP. The trial design was powered for a HR 0.44 FFPP benefit with intended enrollment of 96 subjects and was closed as planned to enrollment on March 2020 short of that goal. Secondary endpoints were time to local recurrence (LR) within the radiation field, metastasis‐free survival (MFS), and safety as determined by frequency and severity of adverse events (AEs). Results: A total of 86 patients were randomized with a median follow-up of 34 (range 0-52) months. The median pre-SRT PSA was 0.3 (range 0.06-4.6) ng/mL, 56/86 (65%) had extra-prostatic disease (pT3), 39/86 (45%) had Gleason Grade Group 4 or higher and 43/96 (50%) had positive surgical margins. Trial arms were well balanced. FFPP was significantly improved with ENZA vs placebo, for example 2-year FFPP was 87.1% vs 68.1%, respectively, and overall with a HR 0.40 [95% confidence interval (CI), 0.17-0.92, p-value = 0.026]. Subgroup analyses demonstrate differential benefit (p-value of interaction = 0.031) of ENZA in men with pT3 (HR 0.19, 95%CI 0.05-0.67) vs pT2 disease (HR 1.29, 95%CI 0.34-4.81). There were insufficient secondary endpoint events for analysis. The most common adverse events were grade 1-2 fatigue (13% ENZA vs 9%) and urinary frequency (6 % ENZA vs 8%). Conclusions: SRT plus ENZA monotherapy for men with PSA recurrent high-risk prostate cancer following RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time. Additional molecular biomarker analyses are being pursued. Clinical trial information: NCT02203695.

PURPOSE The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.

Purpose/Objective(s) A data registry was established upon implementation of a program of intra-operative radiation therapy (IORT) using high-dose rate brachytherapy. We evaluated the initial experience of patients with locally recurrent gastrointestinal (GI) cancers to help inform future patient selection and optimal multi-modal treatment management. Materials/Methods All patients treated with surgical resection and IORT at a tertiary referral center were prospectively enrolled in a registry after program implementation in 2015. Candidates for IORT included patients who presented with disease likely to be resected with either close or positive margins based on multi-disciplinary evaluation. Patient, disease, and treatment characteristics including radiation history and acute (within 90 days, Clavien-Dindo grade) were recorded. IORT was administered using a HAM applicator, with field size and location determined intra-operatively, prescribed to 1 cm depth with lead blocking as appropriate. Patterns of failure and toxicity were analyzed. Time to event analysis was conducted using Kaplan Meier method, and contingency tables and chi square statistics evaluated differences in frequency of events. Results Twenty-one patients were identified with locally recurrent GI cancer (rectal 62%, colon 29%, and anal cancer, 9%) who underwent surgical resection and IORT with curative intent. Median age was 58 years. All patients had a history of pelvic external beam radiotherapy (EBRT, median 50.4 Gy); 9 (43%) were treated with pre-operative reirradiation (median dose 43 Gy, median 2 mo prior to surgery). The median IORT dose was 12.5 Gy (range 10-15). Resection was pathologically complete (R0, n = 9), or with microscopic (R1, n = 11) or macroscopic residual (R2, n = 1). Median follow up was 20 months. Twelve (57%) patients had failure at the site of IORT, at a median 7 mo. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF-1y 75% for R0 vs 15% for R1/2, P = 0.0065) but not re-irradiation EBRT or IORT dose (P > 0.05). Pelvic failure beyond the IORT site occurred in 5 (24%) patients at a median 5 mo, and 13 (62%) had eventual distant metastases, at a median 5.5 months. Ultimately, only 3 patients (14%) were disease free at last follow-up. The median hospital stay was 6 days, the 90-day readmission rate was 25%, and acute grade 3 toxicity was observed in 43%, with abscess/sepsis most common (n = 5, 24%). Grade 3 toxicities and 90-day admission were not associated with resection status or EBRT (all P > 0.1). There were no 90-day grade 4/5 toxicities. Conclusion In patients treated with surgical excision and IORT for locally recurrent GI cancer, the ability to achieve a clear resection margin is a critical determinant of in-field local control. Patient selection should consider the chance for R0 resection, as well as the risk of regional or distant progression, when evaluating patients for this aggressive multi-modal treatment.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.

Background Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs. Methods A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment–related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant. Results A total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n = 71), sulfa (n = 35), and aspirin or nonsteroidal antiinflammatory drugs (n = 28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model. Conclusions Men with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.

Goals of care discussions (GOCD) are essential when counseling patients with cancer. Respective roles of radiation oncologists (RO) and medical oncologists (MO) in GOCD can be unclear. This study aims to clarify the dynamics and barriers to GOCD.Five hundred and fifty-four ROs and 1604 MOs at NCI-designated comprehensive cancer centers were sent an anonymous electronic survey regarding demographics, opinions, training in GOCD, GOCD frequency, and three vignettes. Response formats were Yes/No, Likert-type, and free response. Chi-square and Wilcoxon rank-sum tests were performed. Likert-type scores were reported as median [interquartile range].There were 76 (13.7%) RO and 153 (9.5%) MO who completed surveys. Sixty-three percent of RO and 66% of MO reported GOCD with 50% of patients (p = 0.90). GOCD were initiated for declining performance status (74%) and poor life expectancy (69%). More MO (42%) received formal GOCD training compared to RO (18%) (p 0.01). MO were more comfortable conducting GOCD than RO (p 0.01). RO-conducted GOCD were rated to be less important by MO compared to RO (p 0.05). Thirty-six percent of MO reported being "not at all" or "somewhat" comfortable with RO-conducted GOCD. RO-initiated GOCD with new patients were rated less appropriate by RO compared to MO perceptions of RO-initiated GOCD (p 0.01).While MO and RO conduct GOCD with similar frequency, MO are more comfortable conducting GOCD and are more likely to have formal training. MO rate importance of RO involvement lower than RO. Further research is needed to understand interdisciplinary dynamics that may impact GOCD and subsequent patient care outcomes.

Purpose Urethral cancer is rare, with limited data guiding treatment. A national hospital-based registry was used to evaluate the role of local therapy in these patients. Methods and Materials We performed a retrospective cohort study of patients who, between 2004 and 20013, received a diagnosis of T0-4N0-2 M0 urethral cancer. Local therapy was radiation therapy (RT), surgery (S), or S and RT (S+RT). The Cox proportional hazards model was used to assess the impact of therapy type on overall survival (primary endpoint). Subgroup analysis by extent of disease (early stage [T0-2 N0] vs locally advanced [T3+ or N+]) and histology was performed. Results In our study, 2614 patients had a median follow-up of 28 months. Three-year overall survival was 54%. In 501 patients with locally advanced disease, S+RT was associated with improved survival versus S alone (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.42-0.80). There was no difference for patients with squamous cell carcinoma by treatment type, but patients with adenocarcinoma (RT vs S: HR 0.20; 95% CI, 0.07-0.60) or transitional cell carcinoma (S+RT vs S: HR 0.45, 95% CI, 0.26-0.77) had improved OS with RT as part of treatment. In 1705 early-stage patients, there was no association with survival when comparing S+RT versus S. Conclusions For patients with locally advanced disease and transitional cell carcinoma undergoing S, the addition of RT is associated with improved overall survival and should be considered. An RT-based approach may be preferred for adenocarcinoma, but there was no clear association with survival by therapy type for squamous cell carcinoma. This study is hypothesis generating; prospective trials are necessary.

Radical Cystectomy and trimodality therapy with maximal transurethral resection of bladder tumor followed by concurrent chemoradiotherapy are standard curative treatment options for patients with muscle-invasive bladder cancer (MIBC). There are no robust randomized data available to determine the comparative effectiveness between these treatment modalities. Both treatment approaches are supported by National Comprehensive Cancer Network (NCCN) and American Urological Association guidelines (1,2). However, fundamental differences in the two therapeutic approaches and associated risks create a divergent choice for clinicians and patients, which can introduce some complexity in decision making.

Purpose Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. Methods and materials 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. Results With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. Conclusions More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Salvage radiation therapy (SRT) is an effective treatment for recurrent prostate cancer (PCa) after radical prostatectomy. We report the long-term outcome of men who developed biochemical recurrence (BCR) after SRT and were treated14 years ago.In total, 61 patients treated with SRT from 1992 to 2000 at our institution were identified. Survival was calculated by Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters.The median follow-up was 126 months (interquartile range, 66-167 mo). Thirty-four (56%) had prostate-specific antigen (PSA) failure after SRT. At 10 years, overall survival (OS) was 67%, freedom from PSA failure (FFPF) was 33%, prostate cancer-specific survival (PCSS) was 84%, and distant metastases-free survival (DMFS) was 84%. Pathologic T-stage, Gleason score, seminal vesicle involvement, and pre-SRT PSA were associated with FFPF. For patients who failed SRT, the median time to BCR after SRT was 30 mo. A total of 19 (68%) received androgen deprivation therapy. The median OS was 13.6 years. At 10 years from time of BCR, OS was 59%, PCSS was 73%, DMFS was 75%, and castration-resistant-free survival was 70%. Early SRT failure correlated with significantly decreased DMFS and PCSS. Ten-year DMFS from SRT was 43% (BCR≤1 y) versus 91% (BCR1 y).Extended follow-up demonstrates that despite SRT failure, PCSS remains high in select patients. Early failure (≤1 y after SRT) predicted for significantly worse outcome and may represent a subgroup with more aggressive disease that may be considered for further prospective clinical studies.

PURPOSE/OBJECTIVE(S) Hematuria is a potentially distressing late toxicity of post-prostatectomy radiotherapy (PPRT). Because of the potential for a long latent period between PPRT and symptoms, it may be underreported in the literature. We examined incidence and severity of this toxicity in a cohort with long term follow-up. MATERIALS/METHODS A prospectively maintained database was queried for men treated with PPRT with a minimum potential follow-up of 4 yrs. Late (≥ 90 d) genitourinary toxicity and hematuria were characterized using physician-assigned RTOG/CTCAE grading and patient-reported outcomes, inclusive of clinical visits, urinalysis, and procedure notes from each patient's complete electronic medical record. Freedom from grade 2+ hematuria (FFG2H; macroscopic hematuria) and grade 3+ hematuria (FFG3H; hematuria requiring intervention) were estimated. Patient and treatment characteristics were assessed for association with FFG2H on univariable analysis (UVA) using log-rank tests. The Cox model was used to create a multivariable model (MVA) for FFG2H including all covariates with P < 0.1 on UVA. Quality of life (QOL) was assessed using EPIC-26. RESULTS 216 consecutive men underwent PPRT from 2007-2016 with a median dose to the prostate bed of 68.4 Gy. 66% and 64% of men were treated with androgen deprivation therapy (median 4 mo) and pelvic nodal radiotherapy (median 50.4 Gy), respectively. Median time from prostatectomy to PPRT was 20 mo. With a median follow-up of 72 mo, the incidence of grade 1+, 2+, and 3+ hematuria was 39%, 35%, and 7%, respectively. 8-yr FFG2H and FFG3H were 55% and 91%, respectively. On UVA, the percentage of bladder receiving 65 Gy (V65, median 43%) was found to correlate with FFG2H, while V70 and V40 were not. FFG2H was 43% among men with a bladder V65 ≥ 43% versus 66% in men with a V65 < 43% (P = 0.004). On MVA, inferior FFG2H was most strongly associated with anticoagulant/antiplatelet therapy (AC/AP; HR 3.25, P < 0.001), followed by bladder V65 ≥ 43% (HR 1.97, P = 0.004) and history of medication allergies (HR 1.73, P = 0.049), after controlling for age ≥ 65 yrs (HR 1.23, P = .374) and diabetes mellitus (HR 0.49, P = 0.098). 23% of men underwent at least one cystoscopy with the majority demonstrating RT-related changes and no other potential etiology; however, one man was diagnosed with a superficial bladder cancer. 7% had an emergency room visit due to hematuria. Hematuria was typically managed conservatively; only 6% required intervention (most commonly hyperbaric oxygen and cautery, each at 3%). 11% of men experienced recurrent hematuria, at a median 26 mo after initial symptoms. QOL data to be presented. CONCLUSION Hematuria is a common late toxicity, even 5-10 yrs after PPRT, especially in men on AC/AP. The vast majority of episodes are transient and self-limited. Bladder V65 represents a potential dosimetric factor which can be used to predict or mitigate the risk of hematuria.

An increasing proportion of men are undergoing radical prostatectomy for locally advanced prostate cancer. More than half of men with adverse pathologic features are expected to experience disease recurrence within 10 years. This article discusses the use of postoperative radiation therapy to decrease this risk. Evidence from 3 randomized trials and multiple retrospective studies indicates that either adjuvant or salvage radiation improve biochemical progression-free survival and may improve overall survival. Novel imaging and genomic analysis can improve patient selection for either modality, however current tests are unable to identify all patients who may benefit from additional local therapy.

Purpose International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

Purpose Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P =.02), grade 3+ neutropenia (33% vs 8%, P =.04), and grade 2+ thrombocytopenia (32% vs 7%, P =.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 ( P Conclusions Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total "marrow reserve" can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

Purpose To present the most updated American College of Radiology (ACR) Appropriateness Criteria formed by an expert panel on the appropriate delivery of external beam radiation to manage stage T1 and T2 prostate cancer (in the definitive setting and post-prostatectomy) and to provide clinical variants with expert recommendations based on accompanying Appropriateness Criteria for target volumes and treatment planning. Methods and materials The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a panel of multidisciplinary experts. The guideline development and revision process includes an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In instances in which evidence is lacking or equivocal, expert opinion may supplement available evidence to recommend imaging or treatment. Results The panel summarizes the most recent and relevant literature on the topic, including organ motion and localization methods, image guidance, and delivery techniques (eg, 3-dimensional conformal intensity modulation). The panel presents 7 clinical variants, including (1) a standard case and cases with (2) a distended rectum, (3) a large-volume prostate, (4) bilateral hip implants, (5) inflammatory bowel disease, (6) prior prostatectomy, and (7) a pannus extending into the radiation field. Each case outlines the appropriate techniques for simulation, treatment planning, image guidance, dose, and fractionation. Numerical rating and commentary is given for each treatment approach in each variant. Conclusions External beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature, these Appropriateness Criteria can aid clinicians in determining the appropriate treatment delivery and personalized approaches for individual patients.

Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

Radiation training programs are designed to prepare graduates for independent practice, with metrics in place to assess appropriateness of clinical decision-making. Here, we investigated the self-assessed preparedness of US graduates during the transition to independent practice.An anonymous, Internet-based survey was distributed to recent graduates of radiation oncology residencies (2016-2017). A Likert scale was used to assess comfort with various aspects of practice, as well as "time" to development of comfort in independent practice.Responses were obtained from 70/210 (33%), the majority reported training in programs with 5-8 residents (n = 35). Most (77%) reported designing between 500 and 900 treatment plans during training (n = 54). Only 41% of respondents reported the opportunity to review treatment plans and make decisions about safety/adequacy without attending input > 50% of the time (n = 29). Thirty percent of residents reported being responsible for seeing/managing on-treatment visits (OTVs) ≤ 75% of the time. Aspects with which practitioners reported the least comfort were understanding of billing/application to practice (2.43, IQR 2-3), orthovoltage (superficial radiation) setup and field design (2.57, IQR 1-4), and planning/delivery of prostate implants (2.82, IQR 2-4). Increased mean comfort levels were reported by those designing > 700 treatment plans in training as well as those reporting an opportunity to evaluate plans and make clinical decisions prior to attending input > 50% of the time during residency. Comfort with the delivery of stereotactic body radiation (SBRT) correlated with caseload for liver, spine, prostate, and CNS disease sites but not lung.Variations in training experiences exist across institutions. Here, a lower than expected number of residents reported seeing/managing OTVs as well as reviewing treatment plans prior to attending input during training. Overall comfort was correlated with case volume and opportunities to independently review treatment plans prior to attending input. These data highlight areas of opportunity for improving resident education with implications for ease of transition to independent clinical practice.