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.

Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts.

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.

Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer.

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.

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

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.

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

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.

Brachytherapy of the head and neck: An University of California Los Angeles guide to morbidity reduction.

The head and neck (H&N) region is among the most intricate and functional part of our anatomy. Major functional nerves and blood vessels with importance that affect the entire body emanate from the base of skull. Brachytherapy plays an important role as a single modality therapy in early cancer of the lip and oral cavity and a supplemental role in the pharynx or in advanced or recurrent disease. Morbidity in the H&N is intensely personal and disabling. Its avoidance is critical in determining the success or failure of a treatment program, and it is essential to preservation of quality of life. This article summarizes the current literature regarding morbidity related to H&N brachytherapy to aid patients and physicians to achieve optimal outcomes.

Clinical Outcomes for Patients With Gleason Score 10 Prostate Adenocarcinoma: Results From a Multi-institutional Consortium Study.

PURPOSE: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. METHODS AND MATERIALS: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. RESULTS: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ2 test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048). CONCLUSIONS: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.

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

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

Head and neck cancer reirradiation with interstitial high-dose-rate brachytherapy.

BACKGROUND: As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation. METHODS: Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis. RESULTS: For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities. CONCLUSION: Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.

Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification.

OBJECTIVES: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. METHODS: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal-ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. RESULTS: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. CONCLUSIONS: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.

A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy.

OBJECTIVES: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. MATERIALS AND METHODS: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. RESULTS: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. CONCLUSIONS: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.

OBJECTIVE: To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. METHODS: Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. RESULTS: In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P<0.01). Similarly, 43% who selected the Internet as their primary information source endorsed treatment regret versus 10% who selected their urologist, and 7% who selected their radiation oncologist (P<0.01). On multivariate regression, only patients who selected the Internet as their primary information source were more likely to endorse treatment regret (odds ratio, 46.47; P<0.001) and a worse treatment perception (odds ratio, 83.33; P<0.001). CONCLUSIONS: Patients who used the Internet as their primary information source were significantly more likely to endorse treatment regret and a worse than expected overall treatment experience. These data highlight the potential dangers of Internet-based resources and the importance for physicians to proactively counsel patients.

Clinical outcomes using image-guided interstitial brachytherapy for definitive cervical cancer patients with high-risk clinical target volumes greater than 30 cc.

PURPOSE: Given the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable. METHODS: A retrospective review of 37 cervical cancer patients with high-risk clinical target volumes (HR-CTVs) ≥30 cc treated with interstitial image-guided brachytherapy (IS IGBT) was performed. All patients received external beam radiotherapy to a median dose of 45 Gy, followed by IS IGBT delivered in a single implant to a median dose of 6 Gy × 5 fractions. Median HR-CTV was 59 cc. A median HR-CTV D90 of 87.44 Gy was achieved. Kaplan-Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks. RESULTS: Median followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8-94.5%), 56.8% (CI: 41.3-78.1%), and 54.4% (CI: 39.4-75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively (p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively (p = 0.021). DISCUSSIONS: IS IGBT can achieve a high D90 to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS. CONCLUSIONS: Efforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes.

American College of Radiology-American Brachytherapy Society practice parameter for electronically generated low-energy radiation sources.

BACKGROUND: This collaborative practice parameter technical standard has been created between the American College of Radiology and American Brachytherapy Society to guide the usage of electronically generated low energy radiation sources (ELSs). It refers to the use of electronic X-ray sources with peak voltages up to 120 kVp to deliver therapeutic radiation therapy. MAIN FINDINGS: The parameter provides a guideline for utilizing ELS, including patient selection and consent, treatment planning, and delivery processes. The parameter reviews the published clinical data with regard to ELS results in skin, breast, and other cancers. CONCLUSIONS: This technical standard recommends appropriate qualifications of the involved personnel. The parameter reviews the technical issues relating to equipment specifications as well as patient and personnel safety. Regarding suggestions for educational programs with regard to this parameter,it is suggested that the training level for clinicians be equivalent to that for other radiation therapies. It also suggests that ELS must be done using the same standards of quality and safety as those in place for other forms of radiation therapy.

Pretreatment 3T multiparametric MRI staging predicts for biochemical failure in high-risk prostate cancer treated with combination high-dose-rate brachytherapy and external beam radiotherapy.

PURPOSE: To determine whether pretreatment 3T multiparametric MRI (mpMRI) staging impacts biochemical recurrence-free survival (BRFS) or distant metastasis-free survival (DMFS) for men with high-risk prostate cancer treated with combination high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT). MATERIALS AND METHODS: This institutional review board-approved retrospective study included a cohort of 37 men with high-risk prostate cancer treated with HDR brachytherapy and EBRT after 3T mpMRI. Kaplan-Meier analysis was used to evaluate whether mpMRI evidence of extracapsular extension or seminal vesicle invasion (SVI) resulted in differences in BRFS or DMFS. Pretreatment and treatment-related variables were evaluated for association with biochemical failure (Phoenix definition) and distant metastatic failure using univariate Cox regression analysis. RESULTS: The median prostate-specific antigen at diagnosis was 9 ng/mL (range 2-100). Biopsy Gleason score (bGS) was ≤8 in 38% and nine in 62%. Clinical T-category was T1-T2 in 89%, T3a in 8%, and T3b in 3%. With a median followup of 30.6 months, actuarial 3-year BRFS and DMFS were 76% and 86%, respectively. Kaplan-Meier analysis revealed that mpMRI evidence of extracapsular extension or SVI resulted in significantly higher rates of both biochemical recurrence and distant failure. Using Cox regression analysis, only mpMRI evidence of SVI vs. no SVI predicted for biochemical failure (hazard ratio 13.98, p = 0.0055). CONCLUSIONS: For high-risk prostate cancer treated with combination HDR brachytherapy and EBRT, mpMRI evidence of SVI predicted for biochemical failure, whereas traditional pretreatment variables did not. Therefore, pretreatment 3T mpMRI appears useful for identifying men who may benefit from treatment intensification.

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy.

PURPOSE: Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center's experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary). METHODS: All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003-December 2013 were retrospectively reviewed. Only patients with ≥18 months of follow-up who had lesions contiguous with the optic disc (0 mm of separation) were included. The tumor apex prescription dose was 85 Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity. RESULTS: Thirty-four patients were included with a median follow-up of 44.1 months (range 18.2-129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%-100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up. CONCLUSIONS: I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of radionuclide-based high-dose-rate brachytherapy.

Brachytherapy is a radiation therapy method in which radionuclide sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. This practice parameter refers only to the use of radionuclides for brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides such as iridium-192 at dose rates of 20 cGy per minute (12 Gy per hour) or more to a designated target point or volume. High-dose-rate (HDR) brachytherapy is indicated for treating malignant or benign tumors where the treatment volume or targeted points are defined and accessible.

Exploring Value From the Patient's Perspective Between Modern Radiation Therapy Modalities for Localized Prostate Cancer.

PURPOSE: Patients' perspectives on their treatment experiences have not been compared between modern radiation modalities for localized prostate cancer. We evaluated treatment regret and patients' perceptions of their treatment experiences to better inform our understanding of a treatment's value. METHODS AND MATERIALS: Patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), or high-dose-rate (HDR) brachytherapy between 2008 and 2014 with at least 1 year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities versus the reality, and treatment regret by means of a validated tool. RESULTS: Three hundred twenty-nine consecutive patients were surveyed, with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and posttreatment follow-up time were 68 years and 47 months, respectively. Eighty-two percent of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathologic features and a median initial prostate-specific antigen of 5.8 ng/mL. Thirteen percent expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. The incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret versus 18% with HDR and 19% with IMRT (P<.01). On multivariable logistic regression, patients treated with HDR versus SBRT were 7.42 times more likely to have regret, and patients treated with IMRT versus SBRT were 11.11 times more likely to have regret (P<.01 and P<.01, respectively). Significantly more patients treated with SBRT selected that their actual long-term toxicities were significantly less than originally expected, compared with IMRT and HDR patients (SBRT 43% vs IMRT 20% vs HDR 10%, P<.01). CONCLUSIONS: We found significant differences in patients' experiences between SBRT, IMRT, and HDR, with significantly less treatment regret and less toxicity than expected among SBRT patients. The majority of patients with regret would now opt for active surveillance; therefore, pretreatment counseling is essential.

American Brachytherapy Society Task Group Report: Long-term control and toxicity with brachytherapy for localized breast cancer.

PURPOSE: There has been significant controversy regarding the equivalency of accelerated partial breast irradiation to whole-breast irradiation. With the recent publication of a large, randomized trial comparing these two treatment modalities, an update on the current state of knowledge of brachytherapy-based accelerated partial breast irradiation, with respect to local control and toxicities, would be useful to practitioners and patients. METHODS AND MATERIALS: A systematic literature review was conducted examining articles published between January 2000 and April 2016 on the topics "brachytherapy" and "breast." A total of 67 articles met inclusion criteria, providing outcomes on local tumor control and/or toxicity for breast brachytherapy. RESULTS: Reported 5-year local failure rates were 1.4-6.1% for multicatheter interstitial brachytherapy (MIB) and 0-5.7% for single-entry brachytherapy catheters when delivered to patients with standard selection criteria. Toxicity profiles are acceptable, with cosmetic outcomes comparable to whole-breast irradiation. The reported rates of infection were 0-12%. Symptomatic fat necrosis was found in 0-12% and 0-3.2% of patients treated with MIB and single-entry brachytherapy catheters, respectively. Late Grade ≥3 telangiectasias and fibrosis were reported in 0-8% and 0-9.1% of patients treated with MIB, respectively. These side effects were less common with single-entry brachytherapy catheters (0-2.0% and 0%, respectively). CONCLUSIONS: Breast brachytherapy is a treatment technique that provides acceptable rates of local control in select patients, as demonstrated by Level I evidence. The side effect profile of this treatment is well documented and should be shared with patients when considering this treatment modality.

High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer.

PURPOSE: Outcomes using high-dose-rate (HDR) brachytherapy monotherapy (without androgen deprivation therapy or external beam radiation therapy) for National Comprehensive Cancer Network-defined intermediate-risk (IR) patients are limited. We report our long-term data using HDR monotherapy for this patient population. METHODS AND MATERIALS: One-hundred ninety IR prostate cancer patients were treated 1996-2013 with HDR monotherapy. Biochemical prostate-specific antigen (PSA) failure was per the Phoenix definition. Acute and late genitourinary and gastrointestinal toxicities were graded according to Common Toxicity Criteria of Adverse Events, version 4. Kaplan-Meier (KM) biochemical progression-free survival (BPFS), cause-specific survival, and overall survival rates were calculated. Univariate analyses were performed to determine relationships with BPFS. The median patient age was 66 years (43-90), and the median initial PSA was 7.4 ng/mL. The Gleason score was ≤6 in 26%, 3 + 4 in 62%, and 4 + 3 in 12%. The median treatment BED1.5 was 254 Gy; 83% of patients were treated with a dose of 7.25 Gy × six fractions delivered in two separate implants. RESULTS: With a median follow-up of 6.2 years, KM BPFS at 5/8 years was 97%/90%, cause-specific survival at 8 years was 100%, and overall survival at 5/8 years was 93%/88%. Late genitourinary toxicities were 36.3% Grade 1, 18.9% Grade 2, and 3.7% Grade 3. Late gastrointestinal toxicities were 6.3% Grade 1, 1.1% Grade 2, and no Grade ≥3. Of the patients with no sexual dysfunction before treatment, 68% maintained potency. Age, initial PSA, T stage, Gleason score, prostate volume, and percent positive cores did not correlate with BPFS. Stratifying by favorable vs. unfavorable IR groups did not affect BPFS. CONCLUSIONS: HDR brachytherapy monotherapy represents a safe and highly effective treatment for IR prostate cancer patients with long-term follow-up.