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Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan ((90)Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by (90)Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery of complete blood counts (CBC), (90)Y-IT was administered at a dose of 0.3 or 0.4 mCi/kg depending on platelet counts. Hematologic toxicity was monitored through weekly CBC. Response was measured by positron emission tomography/CT or CT 3-4 months after (90)Y-IT. Results: Only 2 patients required prolonged breaks between EBRT and (90)Y-IT. The median time after (90)Y-IT for platelets to recover to >100,000/ml was 55 days (range, 41-128 days). Platelet counts for 1 patient, who had received 4 previous chemotherapy regimens, never reached 100,000/ml. The complete and overall responses to combined therapy as measured 3-4 months after (90)Y-IT were 64%. No patients relapsed within the EBRT field. With a median follow-up of 36.1 months, 6 patients have relapsed, 2 of whom have died. Median progression-free survival was 17.5 months. Conclusions: In contrast to prior failure analysis data for RRBFL patients treated with (90)Y-IT alone, a brief course of EBRT prevented relapse in sites of BD. EBRT used to pretreat bulky sites may improve clinical outcomes and potentially extend survival when combined with (90)Y-IT. [ABSTRACT FROM AUTHOR]

Inspired by Simone's maxims, a physician shares their search for restoring joy and meaning in modern medicine.

Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether HSD3B1 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3βHSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3βHSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3βHSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating DNA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele.

Purpose: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear., Methods and Materials: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression., Results: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38)., Conclusions: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to assess prostate-specific antigen (PSA) testing rates in persons experiencing homelessness (PEH), identify factors associated with screening, and compare PSA screening rates in PEH with a matched cohort of persons not experiencing homelessness (non-PEH)., Materials and Methods: We identified 9,249 potentially eligible PEH cared for at a large metropolitan hospital system from an institutional registry of all patients who presented to the health care system as homeless from 2014 to 2021. Homelessness was defined by the presence of the Z-code for homelessness (Z59), the listed address matching to the address of a homeless shelter or other transitional housing or a positive screen for homelessness. A matched cohort of 10,000 non-PEH was generated for comparison. Univariate chi-square analysis and multivariate logistic regression were performed to evaluate variables associated with PSA testing., Results: A total of 1,605 PEH and 3,413 non-PEH were eligible for PSA screening within the study timeframe. Half of PEH were Black (50%). Medicaid was the most common insurance (51%), followed by Medicare (18%). PEH were less likely to have a PCP (58% v 81%, P < .001) and had a significantly lower PSA testing rate (13% v 34%, P < .001) compared with non-PEH. Univariate analysis revealed that PSA testing was more common in PEH who were employed ( P < .001), had private insurance or Medicare ( P < .001), or had an established primary care provider (PCP; P < .001). Multivariate analysis confirmed that having a PCP (OR, 2.54; 95% CI, 1.62 to 4.00; P < .001) significantly increased the likelihood of PSA testing in PEH., Conclusion: PEH experience low rates of prostate cancer screening. Interventions to increase screening in this population, including increased PCP access, are needed., Competing Interests: Omar Y. MianConsulting or Advisory Role: BayerUncompensated Relationships: Veracyte Rahul D. TendulkarHonoraria: Varian Medical Systems Sarah S. KilicStock and Other Ownership Interests: Pfizer, Bristol Myers Squibb Foundation, Novocure John H. SuhConsulting or Advisory Role: Philips Inc, Novocure Zachary S. MayoEmployment: Edwards LifesciencesStock and Other Ownership Interests: Dexcom, Johnson & Johnson, AbbVieNo other potential conflicts of interest were reported.

Background: Patients with high-risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost., Methods: The authors compared quality-adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external-beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low-dose-rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479)., Results: Treatment strategies were compared using the incremental cost-effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost-effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost-effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost., Conclusions: EBRT with LDR brachytherapy boost may be a cost-effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high-value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost-effective care, despite no change in overall survival., (© 2022 American Cancer Society.)

Background: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial., Methods: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM)., Results: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model., Conclusions: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Salvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era., Objective: To characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes., Design, Setting, and Participants: A multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median follow-up of 5 years., Outcome Measurements and Statistical Analysis: Variables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation., Results and Limitations: Factors associated with BF after SRT include PSA DT <6 mo, initial postoperative PSA ≥0.2 ng/ml, higher pre-SRT PSA, lack of androgen deprivation therapy, a higher Gleason score (GS), negative margins, seminal vesicle invasion, lack of pelvic nodal radiation, radiation total dose <66 Gy, a longer RP to SRT interval, and older age (p < 0.05 for each). Factors associated with DM include PSA DT <6 mo, pre-SRT PSA, a higher GS, and negative margins. Factors associated with PCSM include PSA DT not calculable or <6 mo and a higher GS. Nomograms were generated to estimate the risks of BF (concordance index [CI] 0.74), DM (CI 0.77), and PCSM (CI 0.77). Limitations include retrospective nature, broad treatment eras, institutional variations, and multiple methods available for the estimation of PSA DT., Conclusions: Postoperative PSA kinetics, particularly pre-SRT PSA and PSA DT, are strongly associated with adverse oncologic outcomes following SRT and should be considered in management decisions., Patient Summary: In this report of men with prostate cancer who developed a prostate-specific antigen (PSA) recurrence after prostatectomy, we found that PSA levels after surgery and how quickly a PSA level doubles significantly impact the chance of prostate cancer recurrence after salvage radiation therapy. Based on this information, we created a tool to calculate a man's chance of cancer recurrence after salvage radiation therapy, and these estimations can be used to discuss whether additional treatment with radiation should be considered., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain., Objective: To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT)., Design, Settings, and Participants: This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021., Exposures: High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs)., Main Outcomes and Measures: The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months)., Results: This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01)., Conclusions and Relevance: These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.

Purpose/objective(s): To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with 125 I interstitial brachytherapy benefit from androgen deprivation therapy (ADT)., Materials/methods: We reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive 125 I interstitial brachytherapy with or without ADT from 1998-2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression., Results: Of 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p<0.001), to older patients (p<0.001), corresponding with increasing PSA (p<0.001) and Grade Group (p<0.001). Median follow-up was 4.9 years (0.3-17.6 years). On multivariable analysis accounting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥0.05 each)., Conclusion: Among patients with UIR, HR, and VHR PCa, the addition of ADT to 125 I interstitial brachytherapy was not associated with improved outcomes, and no subgroup demonstrated benefit. Our findings do not support the use of ADT in combination with 125 I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Importance: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear., Objectives: To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools., Design, Setting, and Participants: This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021., Exposures: Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy., Main Outcomes and Measures: PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index., Results: Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database., Conclusions and Relevance: These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

Background: Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques., Methods: A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI., Results: A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68-3.2%) and WBI (1.7%, 95% HPD 0.92-2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI., Conclusions: IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques., (© 2021. Society of Surgical Oncology.)

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., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown., Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment., Design, Setting, and Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020., Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT)., Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models., Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001)., Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

Purpose: To report trends in the number and types of applicants and matched trainees to radiation oncology in comparison to other specialties participating in the National Resident Matching Program (NRMP) between 2010 and 2020., Methods and Materials: Data from the NRMP and Electronic Residency Application System (ERAS) were obtained for 18 medical specialties between 2010 and 2020. We assessed the numbers and types of applicants and matched trainees relative to available positions in the NRMP and Supplemental Offer and Acceptance Program (SOAP)., Results: In the 2020 NRMP, 122 US MD senior graduates preferentially ranked radiation oncology, a significant decrease from a median of 187 between 2010 to 2019 (interquartile range [IQR], 170-192; P < .001). Across all 18 specialties, radiation oncology experienced the greatest declines in the 2020 NRMP cycle relative to 2010 to 2019, in both the number of ERAS applicants from the United States and Canada (-31%) and the percentage of positions filled by US MD or DO senior graduates (-28%). Of 189 available positions, 81% (n = 154) filled in the NRMP prior to the SOAP, of which 65% (n = 122) were "matched" by US MD senior graduates who preferentially ranked radiation oncology as their top choice of specialty, representing a significant decrease from a median of 92% between 2010 to 2019 (IQR, 88%-94%; P = .002). The percentages of radiation oncology programs and positions unfilled in the NRMP prior to the SOAP were significantly increased in 2020 compared with 2010 to 2019 (programs: 29% vs 8% [IQR, 5%-8%; P < .001]; positions: 19% vs 4% [IQR, 2%-4%; P <.001]). Despite >99% (n = 127 of 128) of US MD or DO senior applicants preferring radiation oncology successfully matching to a radiation oncology position in the 2020 NRMP, 16 of 35 remaining unfilled positions were filled via the SOAP. Radiation oncology was the top user of the SOAP across all specialties participating in the 2020 NRMP, filling 15% of total positions versus a median of 0.9% (IQR, 0.3%-2.3%; P <.001)., Conclusions: The supply of radiation oncology residency positions now far exceeds demand by graduating US medical students. Efforts to nullify a market correction revealed by medical student behavior via continued reliance on the SOAP to fill historical levels of training positions may not be in the best of interest of trainees, individual programs, or the specialty as a whole., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment., Methods: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR)., Results: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%., Conclusion: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Purpose: To quantify how the quality of US medical students accepted to radiation oncology (RO) training programs, as defined by National Resident Matching Program (NRMP) metrics, has changed over time., Methods and Materials: We examined NRMP data of senior US medical students matched into RO training programs from 2007 to 2018. Metrics include United States Medical Licensing Exam (USMLE) Step 1 and 2-Clinical Knowledge scores, research output, percentage with PhD, and percentage in Alpha Omega Alpha (AOA), among others. Linear regression analysis assessed the statistical significance of changes in available metrics of matched RO residents over time. The Student t test and χ 2 test compared quality metrics between matched students in RO versus all other specialties., Results: From 2007 to 2018, the mean USMLE Step 1 and 2-Clinical Knowledge for RO residents significantly increased from 235 to 247 (1.0 point/year; 95% confidence interval [CI], 0.70-1.52; P = .002) and from 237 to 253 (1.3 points/year; 95% CI, 1.27-1.62; P <.001), respectively. The mean number of research experiences and abstracts/presentations/publications increased from 3.7 to 6.1 (0.2/year; 95% CI, 0.12-0.29; P = .003) and from 6.3 to 15.6 (0.78/year; 95% CI, 0.60-1.04; P <.001), respectively. The percentage of RO residents inducted into AOA increased from 24.2% to 35.2%, whereas those with a PhD remained stable (∼21%). Matched RO residents had statistically superior metrics versus all other specialties for USMLE Step 1 scores (mean +13.5 points; 95% CI, 7.26-19.67; P <.001), research experience (mean +2.04; 95% CI, 1.11-2.97; P <.001), abstracts/presentations/publications (mean +6.80; 95% CI, 3.38-10.22; P = .001), percentage with a PhD (22.2% vs 4.1%; P <.001), and percentage in AOA (29.5% vs 15.8%; P <.001)., Conclusions: RO resident quality, defined by routinely reported NRMP metrics, increased from 2007 to 2018. Furthermore, RO resident quality is significantly higher than in all other specialties combined for most metrics. Whether the recent decline in medical student interest in RO will correlate with reduced NRMP quality metrics is unknown., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Opinion Statement: Due to its relatively indolent disease course, the sensitivity of PSA testing, and the emergence of novel PET imaging, metastatic prostate cancer is particularly likely to present with a limited volume of disease. Patients with up to five metastatic lesions should be considered for an oligometastatic treatment approach. Systemic therapy remains the cornerstone of treatment for these patients. The optimal type and duration are unknown; however, the addition of a second agent to ADT appears to be beneficial. Multiple recent studies have found significant benefits to the integration of systemic therapy and local metastasis-directed therapies (MDT), including radiation and surgery, to the prostate and metastatic sites. MDT may also be used in select patients wishing to delay the initiation of systemic therapy. For patients with isolated regional nodal recurrences, whole pelvic radiotherapy or extensive lymphadenectomy is preferred, in combination with ADT.

Competing Interests: No other authors have conflicts of interest to disclose.

Objectives: Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious., Materials and Methods: Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx., Results: Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%., Conclusions: Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.

Adjuvant radiation therapy has been associated with improved local control following breast-conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3-6 weeks or partial breast irradiation over 1-3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early-stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I-II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x-ray. Patients were treated at a single institution between 2011 and 2019. Follow-up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow-up of 23 months (range: 0-73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor-positive, 175 (87.9%) progesterone receptor-positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low-risk patients, demonstrated low rates of recurrence and reproducibility in a multi-disciplinary setting. Further follow-up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings., (© 2019 Wiley Periodicals, Inc.)

Patients were treated at a single institution to a dose of 30 Gy in five fractions delivered every other day using image-guided intensity modulated radiation therapy (IMRT) partial breast irradiation. A total of 34 patients were treated with a median follow-up of 4.6 months. The rate of acute Grade 1 dermatitis was 23.5% (n = 8), and Grade 1 fatigue was 17.6% (n = 6), with no Grade 2 or higher acute toxicities. The rate of chronic Grade 1 dermatitis was 25.0% (n = 6), Grade 1 fat necrosis 4.2% (n=1), with no patients demonstrating other chronic toxicities. Image-guided APBI delivered with IMRT is associated with low rates of acute and chronic toxicity though additional follow-up is warranted., (© 2019 Wiley Periodicals, Inc.)

Purpose: To validate the 2019 NCCN subgroups of favorable- and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification., Methods: We included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis., Results: Of 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3-214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00-4.10; p < 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78-5.50, p < 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6-6.1%) vs. 17.0% (95% CI, 13.6-20.5%; p < 0.001), and for distant metastasis were 1.6% (95% CI, 0.5-2.6%) vs. 5.4% (95% CI, 3.3-7.4%; p < 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54-3.36; p < 0.001) and 2-3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89-6.76; p < 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34-4.53, p = 0.004; 2-3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49-9.10, p < 0.001)., Conclusions: These findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The toxicity profile of breast reconstruction with postmastectomy radiation therapy (PMRT) varies by technique and timing, and long-term data are limited. We compared rates of complications requiring reoperation (CRR) and reconstruction failure (RF) between immediate autologous reconstruction (I-AR), immediate tissue expander/implant reconstruction (I-TE/I), delayed autologous reconstruction (D-AR), and delayed tissue expander/implant reconstruction (D-TE/I) in patients receiving PMRT., Methods and Materials: Patients who received autologous reconstruction (AR) or tissue expander/implant reconstruction (TE/I) and PMRT between 2000 to 2008 were included. Reconstruction was immediate if performed on the same day as mastectomy followed by PMRT (I-AR or I-TE/I) or delayed if after PMRT (D-AR and D-TE/I). CRR was defined as an unplanned return to the operating room for infection, dehiscence, necrosis, hematoma, or hernia (with AR) and extrusion, leak, or contracture (with TE/I). RF was defined as unplanned conversion to another reconstruction technique or to flat chest wall. Cumulative incidence of CRR and RF was calculated using Kaplan-Meier and compared using the log-rank test. Logistic regression was used to identify variables associated with CRR and RF., Results: Two hundred four patients were included. Median follow-up was 8 years. There were 127 AR cases (63%) and 77 TE/I cases (38%). At 5 years, CRR was 18%, 38%, 34%, and 70% (P = .010) and RF was 4%, 22%, 7%, and 56% (P < .0001) for I-AR, I-TE/I, D-AR, and D-TE/I, respectively. On multivariate analysis, TE/I (hazard ratio [HR] 2.0; P = .011), body mass index ≥30 (HR 3.9; P = .002), and smoking (HR 2.7; P = .001) were significant predictors for CRR, and TE/I (HR 6.6; P < .0001), diabetes (HR 4.1; P = .044), and hypertension (HR 3.5; P = .005) were significant for RF. When excluding RF because of infection, the rate of RF was not significantly different among the 4 groups (P = .23)., Conclusions: With PMRT, TE/I reconstruction in the immediate and delayed setting is associated with higher CRR and RF compared with AR. Patient factors should guide selection of technique. Efforts to reduce rates of RF with TE/I should focus on minimizing risks for infection., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Salvage mastectomy (SM) is the standard of care for patients with local recurrence (LR) after breast conservation therapy (BCT), often with immediate reconstruction. Complications of reconstruction are a concern for these patients, and long-term data are limited. We sought to compare rates of complications requiring re-operation (CRR) and reconstruction failure (RF) between autologous reconstruction (AR) and tissue expander/implant reconstruction (TE/I). Patients with locally recurrent breast cancer after BCT, treated with SM and immediate AR or TE/I between 2000 and 2008, were identified. CRR was defined as unplanned return to operating room for wound infection, dehiscence, necrosis (including flap, skin, or fat), hematoma, or hernia (for AR) and extrusion, leak, or capsular contracture (for TE/I). RF was defined as conversion to another reconstruction technique or to flat chest wall. This study included 103 patients with 107 reconstructions. Median follow-up was 6.6 years. CRR and RF were significantly higher with TE/I (n = 34) compared to AR (n = 73) at 5 years (50.9% vs 25.5%; P = 0.02) and (42.1% vs 5.8%; P < 0.001). On univariate analysis (UVA), TE/I (HR = 2.14; P = 0.02) and diabetes (HR = 5.10; P = 0.007) were significant predictors for CRR. On UVA, TE/I (HR = 7.30; P < 0.001) and older age at reconstruction (HR = 1.03; P = 0.003) were significant predictors for RF. In this population of previously irradiated patients, TE/I was associated with significantly higher CRR and RF. Complications continue to occur up to 10 years after TE/I. AR should be considered in appropriately selected patients, though TE/I may remain a reasonable option in patients without high-risk factors for surgical complications., (© 2019 Wiley Periodicals, Inc.)

Purpose: We assessed the impact of cribriform pattern and/or intraductal carcinoma on Gleason 7 prostate cancer treated with external beam radiotherapy., Methods: We evaluated men with Gleason 7 (Grade Groups 2 and 3) prostate cancer treated with dose escalated external beam radiotherapy with or without androgen deprivation. We reviewed biopsies for the presence of cribriform pattern and/or intraductal carcinoma. Study end points included biochemical recurrence-free, distant metastasis-free and disease specific survival., Results: In the 237 patients median followup was 117 months (range 3 to 236). According to National Comprehensive Cancer Network® risk groups 24% of patients were at favorable intermediate risk, 53% were at unfavorable intermediate risk and 23% were at high risk. The rate of cribriform pattern without intraductal carcinoma, cribriform pattern with intraductal carcinoma, intraductal carcinoma without cribriform pattern and none of these morphologies was 36%, 13%, 0% and 51%, respectively. On multivariable analysis cribriform pattern with intraductal carcinoma (HR 4.22, 95% CI 2.08-8.53, p <0.0001), prostate specific antigen 10 to 20 ng/ml (HR 1.97, 95% CI 1.03-3.79, p=0.04) and prostate specific antigen greater than 20 ng/ml (HR 2.26, 95% CI 1.21-4.23, p=0.01) were associated with worse biochemical recurrence-free survival. On multivariable analysis only cribriform pattern with intraductal carcinoma was associated with inferior distant metastasis-free survival (HR 4.18, 95% CI 1.43-12.28, p=0.01) and disease specific survival (HR 14.26, 95% CI 2.75-74.04, p=0.0016). Factors associated with cribriform pattern with or without intraductal carcinoma included Grade Group 3, high risk group and 50% or more positive biopsy cores. When stratified by neither morphology present, cribriform pattern without intraductal carcinoma and cribriform pattern with intraductal carcinoma the differences in biochemical recurrence-free, distant metastasis-free and disease specific survival were statistically significant (p=0.00042, p=0.017 and p <0.0001, respectively)., Conclusions: Cribriform pattern with intraductal carcinoma was associated with adverse outcomes in men with Gleason 7 prostate cancer treated with external beam radiotherapy while cribriform pattern without intraductal carcinoma was not so associated. Future studies may benefit from dichotomizing these 2 histological entities.

Purpose: Long-term outcomes with hypofractionated radiation therapy for prostate cancer are limited. We report 10-year outcomes for patients treated with intensity modulated radiation therapy (IMRT) for localized prostate cancer with 70 Gy in 28 fractions at 2.5 Gy per fraction., Methods and Materials: The study included 854 consecutive patients with localized prostate cancer treated with moderately hypofractionated IMRT and daily image guidance at a single institution between 1998 and 2012. Patients with a single intermediate risk factor were considered to have favorable intermediate-risk (FIR) disease, and those with multiple intermediate risk factors were considered unfavorable (UIR). Biochemical relapse-free survival, clinical relapse-free survival, and overall survival were analyzed using Kaplan-Meier analysis. Prostate cancer-specific mortality (PCSM) was analyzed using competing risk regression. All grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 4.03, and cumulative incidence rates of GU and GI toxicity were calculated., Results: The median follow-up was 11.3 years (maximum, 19 years). For patients with low-risk (LR), FIR, UIR, and high-risk (HR) disease, the 10-year biochemical relapse free survival rates were 88%, 78%, 71%, and 42%, respectively, (P < .0001). The 10-year clinical relapse free survival were 95%, 91%, 85%, and 72% for patients with LR, FIR, UIR, and HR, respectively, (P < .0001). For all patients, the 10-year actuarial overall survival rate was 69% (95% confidence interval, 66%-73%), and the 10-year PCSM was 6.8% (95% confidence interval, 5.1%-8.6%) overall. For patients with LR, FIR, UIR and HR disease, the 10-year PCSM rates were 2%, 5%, 5%, and 15%. Long-term grade ≥3 GU or GI toxicity remained low with 10-year cumulative incidences of 2% and 1%, respectively., Conclusions: High-dose moderately hypofractionated IMRT with daily image guidance for localized prostate cancer demonstrates favorable 10-year oncologic outcomes with a low incidence of toxicity. This fractionation schedule appears to be acceptable for patients across all risk groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To report trends in applicant interview experiences and post-interview communication (PIC) between the 2016 and 2018 radiation oncology interview cycles., Methods and Materials: An anonymous survey was sent to all 203 residency applicants to a single institution during the 2018 Match, and the results were compared to a similar 2016 survey., Results: Response rates in 2018 and 2016 were 53% and 56%, respectively. Applicants from 2018 were asked less frequently than 2016 applicants about where else they were interviewing (71% vs 84%, P = .024) and how highly they planned to rank a program (11% vs 23%, P = .018). A higher proportion of 2018 programs explicitly discouraged PIC (median, 53% vs 33%, P < .0001), and more 2018 respondents chose not to send any thank-you notes/emails (42% vs 17%, P < .0001). When comparing 2018 results to 2016, no significant differences were observed in the proportion of applicants who notified their top program that they would rank that program highly (54% vs 60%, P = .354). No difference was observed in the rate of reported distress associated with a sense of obligation to send PIC (49% vs 46%, P = .664), and similar rates of respondents said they would feel relieved if PIC was discouraged (94% vs 89%, P = .223). Most respondents again reported that they would prefer a policy to actively discourage applicants from notifying their top programs of their high rank (60% vs 66%, P = .974)., Conclusions: Compared to 2016, respondents in 2018 reported that fewer programs are engaging in potential Match violations, and more are actively discouraging PIC, possibly as a result of increased awareness from recent publications. A similar number of applicants continued to engage in "gamesmanship," but more are choosing not to send thank-you notes/emails. Most respondents continue to prefer a policy discouraging PIC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Few data exist in the literature regarding outcomes of men with prostate cancer (CaP) who are receiving immunosuppression from prior organ transplantation. The aim of this study was to evaluate biochemical disease-free survival, distant metastasis-free survival, overall survival, and toxicity in patients with organ transplants who were later treated with definitive radiotherapy for CaP., Patients and Methods: Our institutional CaP registry was reviewed to identify patients who had undergone an organ transplantation before CaP diagnosis. Between 1999 and 2013, a total of 28 organ transplant recipients treated with definitive radiotherapy for CaP were identified. Treatment consisted of either I-125 low-dose-rate brachytherapy or external-beam radiotherapy. All patients were receiving immunosuppressive medications., Results: The median age was 66 years. Median follow-up time was 30 months. Twenty-four patients (86%) were treated with brachytherapy, and 4 patients (14%) were treated with external-beam radiotherapy. Nine patients (32%) had low-risk CaP, 14 (50%) had intermediate-risk CaP, and 5 (18%) had high-risk CaP. At the time of last follow-up, 2 patients had died, 1 from metastatic CaP and 1 from other causes. The 3-year biochemical disease-free survival was 95.8%. The 3-year distant metastasis-free survival was 93.1%. The 3-year overall survival was 93.8%. One patient developed grade 3 late gastrointestinal toxicity., Conclusion: This represents one of the largest reported series of outcomes in patients with organ transplantation and CaP. Organ transplant recipients treated with prostate radiotherapy have excellent 3-year outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) represent two adjuvant radiation therapy options after breast-conserving surgery. We performed a cost and cost-effectiveness analysis of an external beam image guided APBI technique compared with HWBI., Methods and Materials: HWBI was defined as 40 Gy in 15 fractions to the whole breast with or without a 10-Gy/5-fraction boost. APBI was 30 Gy in 5 fractions per Livi et al and was evaluated as both intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy. The decision analytical model measured effectiveness in quality-adjusted life years. Micro-costing was conducted to estimate the true cost of the different treatment regimens, and incremental cost-effectiveness analysis was performed., Results: Based on micro-costing, the cost of HWBI was $4551 with boost and $3666 without boost, compared with $2966 for APBI. Including indirect costs, HWBI with boost cost $6160, HWBI without boost cost $4940, and APBI cost $3569. Cost savings for APBI compared with HWBI with and without boost was $1585 and $700 based on direct costs and $2591 and $1371 including indirect costs. APBI was also more effective, at 0.2300 quality-adjusted life years compared with 0.2289 for HWBI with or without boost. Thus, APBI was both less costly and more effective. Basing cost on Medicare reimbursement (IMRT) leads to APBI again dominating HWBI, but basing cost for APBI on reimbursement billed as stereotactic body radiation therapy leads to HWBI being far more cost-effective., Conclusions: Image guided partial breast irradiation is less costly to deliver and has slightly improved efficacy compared with HWBI, with or without a boost. IMRT APBI should be considered a standard-of-care option in appropriately selected patients based on efficacy and value., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Oncotype DX recurrence score (RS) predicts risk of distant disease recurrence, and can guide chemotherapy recommendations in hormone positive, human epidermal growth factor 2-negative, early stage breast cancer. The present study aimed to evaluate the pattern of oncotype testing, RS and adjuvant treatment in patients undergoing intraoperative radiotherapy (IORT). Single center prospective data registry was queried for patients receiving IORT between October 2011 and February 2017. Patient demographics, tumor characteristics, RS, systemic therapy and recurrence information were analyzed. A total of 150 women with mean age of 70.8 years were included. The majority had invasive ductal cancer (60.6%) with 1.0 cm average tumor size and no lymph node involvement (99%). Oncotype testing was performed in 36 patients (24.3%). Low risk score (<18) was confirmed in 19 women (53%); intermediate risk score (18-30) in 16 women (44%); and high risk score (>30) in one woman (3%). Patients with RS testing had significantly increased tumor sizes (1.2 vs. 1.0 cm; P<0.001) and were younger (68.5 vs. 71.3 years; P=0.02) compared with those not tested. A total of 4/150 patients (2.6%) received chemotherapy; two received chemotherapy based on RS testing. Based on the current selection criteria for IORT, oncotype testing rarely results in a high-risk score or utilization of chemotherapy for IORT patients. The present study supports selective use of RS testing in IORT patients and confirms that biologically low-risk patients are being selected for IORT based on current guidelines.

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast-conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I-III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET-alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET-alone based on the CALGB 9343/PRIME-II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC-ESTRO trial/ASTRO guidelines/ABS guidelines/GEC-ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET-alone. This analysis shows that a large proportion of patients with node-negative breast cancer are eligible for HFRT, APBI and/or ET-alone after breast-conserving surgery., (© 2018 Wiley Periodicals, Inc.)

Background: Interview experiences and postinterview communication during the residency match process can cause distress for applicants, and deserve further study., Objective: We both quantified and qualified the nature of various interview behaviors during the 2015-2016 National Resident Matching Program (NRMP) Match and collected applicant perspectives on postinterview communication and preferences for policy change., Methods: An anonymous, 31-question survey was sent to residency candidates applying to 8 residency programs at a single academic institution regarding their experiences at all programs where they interviewed., Results: Of 6693 candidates surveyed, 2079 (31%) responded. Regarding interview experiences, applicants reported being asked at least once about other interviews, marital status, and children at the following rates: 72%, 38%, and 17%, respectively, and such questions arose at a reported mean of 25%, 14%, and 5% of programs, respectively. Female applicants were more frequently asked about children than male applicants (22% versus 14%, P  < .0001). Overall, 91% of respondents engaged in postinterview communication. A total of 70% of respondents informed their top program that they had ranked it highly; 70% of this subset reported associated distress, and 78% reported doing this to improve match success. A total of 71% would feel relief if postinterview communication was actively discouraged, and 51% would prefer applicants to be prohibited from notifying programs of their rank., Conclusions: Applicants to several residency programs reported being asked questions that violate the NRMP Code of Conduct. The majority of applicants would prefer postinterview communication to be more regulated and less prevalent., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background: Outcomes with postprostatectomy salvage radiation therapy (SRT) are not ideal. Little evidence exists regarding potential benefits of adding whole pelvic radiation therapy (WPRT) alone or in combination with androgen deprivation therapy (ADT)., Objective: To explore whether WPRT and/or ADT added to prostate bed radiation therapy (PBRT) improves freedom from biochemical failure (FFBF) or distant metastases (DM)., Design, Setting, and Participants: A database was compiled from 10 academic institutions of patients with postprostatectomy prostate-specific antigen (PSA) >0.01 ng/ml; pT1-4, Nx/0, cM0; and Gleason score (GS) ≥7 treated between 1987 and 2013. Median follow-up was 51 mo., Interventions: WPRT and/or ADT in addition to PBRT., Outcome Measurements and Statistical Analyses: FFBF and DM were calculated using cumulative incidence estimation. Multivariable analysis (MVA) utilized cumulative incidence regression., Results and Limitation: Median pre-SRT PSA was 0.5 ng/ml for 1861 patients. Median follow-up for patients not experiencing biochemical failure (BF) was 55 mo. MVA showed increased BF for PBRT versus WPRT (hazard ratio [HR] 1.82, p<0.001) and no ADT versus ADT (HR 1.70, p<0.001). WPRT was associated with a 5-yr FFBF of 62% versus 49% (p<0.001) for PBRT. ADT use was associated with improved 5-yr FFBF (55% vs 50%, p=0.012). No significant differences in DM cumulative incidence were found., Conclusions: For patients with GS ≥7 receiving SRT, clinicians should weigh FFBF benefits of WPRT and ADT against toxicities. Future studies should explore the impact of WPRT on quality of life, clinical progression, and overall survival., Patient Summary: We evaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning)., (Copyright © 2017 European Association of Urology. All rights reserved.)

Importance: Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear., Objective: To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features., Design, Setting, and Participants: This multi-institutional, propensity score-matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017., Main Outcomes and Measures: Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias., Results: Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram., Conclusions and Relevance: Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Context: Currently, salvage radiotherapy (SRT) is the only known curative intervention for men with recurrent disease following prostatectomy. Critical issues in the optimal selection and management of men being considered for SRT include the threshold prostate-specific antigen (PSA) value at which to initiate treatment (ie, pre-SRT PSA) and the role of concurrent hormonal therapy (HT)., Objective: To review the published evidence pertaining to the optimal timing for SRT and the role of concurrent HT., Evidence Acquisition: MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, and guideline statements from professional organizations were queried from January 1, 2000 through January 10, 2018., Evidence Synthesis: Thirty-three independent reports, including two randomized trials evaluating HT with SRT, were identified. Retrospective data suggest that SRT initiation at lower pre-SRT PSA levels is associated with better clinical outcomes. Prospective data suggest an overall survival benefit with concurrent HT that manifests during long-term follow-up, with the caveat that hypothesis-generating subgroup analyses suggest that this benefit may be limited to patients with higher pre-SRT PSA levels. Patients with adverse risk factors, such as Gleason grade group 4-5 disease, are likely to benefit the most from earlier SRT initiation and/or the use of HT., Conclusions: Given the limitations of the available data, it is imperative that physicians participate in shared decision-making, with the recommendation tailored for each man's desire to maximize oncologic benefit (with a risk of overtreatment) versus potential quality-of-life optimization (with a risk of undertreatment). Within that framework, a significant body of retrospective data supports initiation of SRT at low pre-SRT PSA values, without an arbitrary absolute threshold. Prospective data suggest a benefit of HT, but this benefit may be greatest in patients with a pre-SRT PSA that is higher than the typical level in most patients receiving "early" SRT. Further research is necessary before absolute recommendations can be made., Patient Summary: Two ways to potentially improve outcomes following salvage radiotherapy for prostate cancer that recurs after prostatectomy are to start treatment at a lower prostate-specific antigen level and to use concurrent hormonal therapy. Our review suggests that the available evidence is imperfect, but highlights that both measures are likely to improve clinical outcomes in general, but perhaps not uniformly and/or consistently for all patients. Physician-patient shared decision-making and further research are critical., (Copyright © 2018 European Association of Urology. All rights reserved.)

Urethral adenocarcinoma of males is a rare disease with limited prospective data to define optimal treatment. Surgical excision remains the primary treatment for early-stage disease. Multimodality therapy with a combination of chemotherapy, radiation, or surgery has been explored in patients with locally advanced disease. We present the case of a 45-year-old-man with a locally recurrent urethral adenocarcinoma after initial surgical resection managed successfully with combined weekly cisplatinum and radiation therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purposes: The aim of this study was to evaluate a dual marker-based and soft-tissue based image guidance for inter-fractional corrections in stereotactic body radiotherapy (SBRT) of prostate cancer., Methods/materials: We reviewed 18 patients treated with SBRT for prostate cancer. An endorectal balloon was inserted at simulation and each treatment. Planning margins were 3 mm/0 mm posteriorly. Prior to each treatment, a dual image guidance protocol was applied to align three makers using stereoscopic x ray images and then to the soft tissue using kilo-voltage cone beam CT (kV-CBCT). After treatment, prostate (CTV), rectal wall, and bladder were delineated on each kV-CBCT, and delivered dose was recalculated. Dosimetric endpoints were analyzed, including V 36.25 Gy for prostate, and D 0.03 cc for bladder and rectal wall., Results: Following initial marker alignment, additional translational shifts were applied to 22 of 84 fractions after kV-CBCT. Among the 22 fractions, ten fractions exceeded 3 mm shifts in any direction, including one in the left-right direction, four in the superior-inferior direction, and five in the anterior-posterior direction. With and without the additional kV-CBCT shifts, the average V 36.25 Gy of the prostate for the 22 fractions was 97.6 ± 2.6% with the kV x ray image alone, and was 98.1 ± 2.4% after applying the additional kV-CBCT shifts. The improvement was borderline statistical significance using Wilcoxon signed-rank test (P = 0.007). D 0.03 cc was 45.8 ± 6.3 Gy vs. 45.1 ± 4.9 Gy for the rectal wall; and 49.5 ± 8.6 Gy vs. 49.3 ± 7.9 Gy for the bladder before and after applying kV-CBCT shifts., Conclusions: Marker-based alignment alone is not sufficient. Additional adjustments are needed for some patients based kV-CBCT., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.