Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Using standardized workflows and quantitative data-driven management to reduce time interval from simulation to treatment initiation.

PURPOSE: External beam radiotherapy is a complex process, involving timely coordination among multiple teams. The aim of this study is to report our experience of establishing a standardized workflow and using quantitative data and metrics to manage the time-to-treatment initiation (TTI). METHODS AND MATERIALS: Starting in 2014, we established a standard process in a radiation oncology-specific electronic medical record system (RO-EMR) for patients receiving external beam radiation therapy in our department, aiming to measure the time interval from simulation to treatment initiation, defined as TTI, for radiation oncology. TTI data were stratified according to the following treatment techniques: three-dimensional (3D) conformal therapy, intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT). Statistical analysis was performed with the Mann-Whitney test for the respective metrics of aggregate data for the initial period 2012- 2015 (PI) and the later period 2016-2019 (PII). RESULT: Over 8 years, the average annual number of treatments for PI and PII were 1760 and 2357 respectively, with 3D, IMRT, and SBRT treatments accounting for 53, 29, 18% and 44, 34, 22%, respectively, of the treatment techniques. The median TTI for 3D, IMRT, and SBRT for PI and PII were 1, 6, 7, and 1, 5, 7 days, respectively, while the 90th percentile TTI for the three techniques in both periods were 5, 9, 11 and 4, 9, 10 days, respectively. From the aggregate data, the TTI was significantly reduced (p = 0.0004, p < 0.0001, p < 0.0001) from PI to PII for the three treatment techniques. CONCLUSION: Establishing a standardized workflow and frequently measuring TTI resulted in shortening the TTI during the early years (in PI) and maintaining the established TTI in the subsequent years (in PII).

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Intratumoral androgen biosynthesis associated with 3ß-hydroxysteroid dehydrogenase 1 promotes resistance to radiotherapy in prostate cancer.

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 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) 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 3ßHSD1 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 3ßHSD1. 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, 3ßHSD1 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.

Transperineal ultrasound is a good alternative for intra-fraction motion monitoring for prostate stereotactic body radiotherapy.

PURPOSES: To report our experience in a prospective study of implementing a transperineal ultrasound system to monitor intra-fractional prostate motion for prostate stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: This IRB-approved prospective study included 23 prostate SBRT patients treated between 04/2016 and 11/2019 at our institution. The prescription doses were 36.25 Gy to the Low-Dose planning target volume (LD-PTV) and 40 Gy to the High-Dose PTV (HD-PTV) in five fractions with 3 mm planning margins. The transperineal ultrasound system was successfully used in 110 of the 115 fractions. For intra-fraction prostate motion, the real-time prostate displacements measured by ultrasound were exported for analysis. The percentage of time prostate movement exceeded a 2 mm threshold was calculated for each fraction of all patients. T-test was used for all statistical comparisons. RESULTS: Ultrasound image quality was adequate for prostate delineation and prostate motion tracking. The setup time for each fraction under ultrasound-guided prostate SBRT was 15.0 ± 4.9 min and the total treatment time per fraction was 31.8 ± 10.5 min. The presence of an ultrasound probe did not compromise the contouring of targets or critical structures. For intra-fraction motion, prostate movement exceeded 2 mm tolerance in 23 of 110 fractions for 11 of 23 patients. For all fractions, the mean percentage of time when the prostate moved more than 2 mm in any direction during each fraction was 7%, ranging from 0% to 62% of a fraction. CONCLUSION: Ultrasound-guided prostate SBRT is a good option for intra-fraction motion monitoring with clinically acceptable efficiency.

Contour similarity and its implication on inverse prostate SBRT treatment planning.

PURPOSE: Success of auto-segmentation is measured by the similarity between auto and manual contours that is often quantified by Dice coefficient (DC). The dosimetric impact of contour variability on inverse planning has been rarely reported. The main aim of this study is to investigate whether automatically generated organs-at-risk (OARs) could be used in inverse prostate stereotactic body radiation therapy (SBRT) planning and whether the dosimetric parameters are still clinically acceptable after radiation oncologists modify the OARs. METHODS AND MATERIALS: Planning computed tomography images from 10 patients treated with SBRT for prostate cancer were selected and automatically segmented by commercially available atlas-based software. The automatically generated OAR contours were compared with the manually drawn contours. Two volumetric modulated arc therapy (VMAT) plans, autoRec-VMAT (where only automatically generated rectums were used in optimization) and autoAll-VMAT (where automatically generated OARs were used in inverse optimization) were generated. Dosimetric parameters based on the manually drawn PTV and OARs were compared with the clinically approved plans. RESULTS: The DCs for the rectum contours varied from 0.55 to 0.74 with a mean value of 0.665. Differences of D95 of the PTV between autoRec-VMAT and manu-VMAT plans varied from 0.03% to -2.85% with a mean value of -0.64%. Differences of D0.03cc of manual rectum between the two plans varied from -0.86% to 9.94% with a mean value of 2.71%. D95 of PTV between autoAll-VMAT and manu-VMAT plans varied from 0.28% to -2.9% with a mean value -0.83%. Differences of D0.03cc of manual rectum between the two plans varied from -0.76% to 6.72% with a mean value of 2.62%. CONCLUSION: Our study implies that it is possible to use unedited automatically generated OARs to perform initial inverse prostate SBRT planning. After radiation oncologists modify/approve the OARs, the plan qualities based on the manually drawn OARs are still clinically acceptable, and a re-optimization may not be needed.

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis.

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.

Prostate Cancer Screening Disparities in Persons Experiencing Homelessness.

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.

Cost effectiveness of treatment strategies for high risk prostate cancer.

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.

Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.

BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes. OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status. RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033). CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures. PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

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.

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy.

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.

125I Interstitial brachytherapy with or without androgen deprivation therapy among unfavorable-intermediate and high-risk prostate cancer.

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 125I 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 125I 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 125I 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 125I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy.

No Longer a Match: Trends in Radiation Oncology National Resident Matching Program (NRMP) Data from 2010-2020 and Comparison Across Specialties.

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.

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients.

PURPOSE: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. METHODS AND MATERIALS: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). RESULTS: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). CONCLUSIONS: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.