A brief review of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost for high-risk prostate

For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P \u3c 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted

Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital‐based analysis of patterns of care, RT fractionation scheme, and overall survival

Abstract Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P  .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center

Intensity-modulated radiotherapy for prostate cancer

Radiation therapy (RT) is a curative treatment modality for localized prostate cancer. Over the past two decades, advances in technology and imaging have considerably changed RT in prostate cancer treatment. Treatment has evolved from 2-dimensional (2D) planning using X-ray fields based on pelvic bony landmarks to 3-dimensional (3D) conformal RT (CRT) which uses computed tomography (CT) based planning. Despite improvements with 3D-CRT, dose distributions often remained suboptimal with portions of the rectum and bladder receiving unacceptably high doses. In more recent years, intensity-modulated radiation therapy (IMRT) has become the standard of care to deliver external beam RT. IMRT uses multiple radiation beams of different shapes and intensities delivered from a wide range of angles to \u27paint\u27 the radiation dose onto the tumor. IMRT allows for a higher dose of radiation to be delivered to the prostate while reducing dose to surrounding organs. Multiple clinical trials have demonstrated improved cancer outcomes with dose escalation, but toxicities using 3D-CRT and escalated doses have been problematic. IMRT is a method to deliver dose escalated RT with more conformal dose distributions than 3D-CRT and has been associated with improved toxicity profiles. IMRT also appears to be the safest method to deliver hypofractionated RT and pelvic lymph node radiation. The purpose of this review is to summarize the technical aspects of IMRT planning and delivery, and to review the literature supporting the use of IMRT for prostate cancer

Measuring the impact of medicines regulatory interventions - systematic review and methodological considerations

Aim: Evaluating the public health impact of regulatory interventions is important but there is currently no common methodological approach to guide this evaluation. This systematic review provides a descriptive overview of the analytical methods for impact research.Methods: We searched MEDLINE and EMBASE for articles with an empirical analysis evaluating the impact of European Union or non-European Union regulatory actions to safeguard public health published until March 2017. References from systematic reviews and articles from other known sources were added. Regulatory interventions, data sources, outcomes of interest, methodology and key findings were extracted.Results: From 1,246 screened articles, 229 were eligible for full-text review and 153 articles in English language were included in the descriptive analysis. Over a third of articles studied analgesics and antidepressants. Interventions most frequently evaluated are regulatory safety communications (28.8%), black box warnings (23.5%) and direct healthcare professional communications (10.5%). 55% of studies measured changes in drug utilisation patterns, 27% evaluated health outcomes and 18% targeted knowledge, behaviour, or changes in clinical practice. Unintended consequences like switching therapies or spill-over effects were rarely evaluated. Two thirds used before-after time series and 15.7% before-after cross-sectional study designs. Various analytical approaches were applied including interrupted time series regression (31.4%), simple descriptive analysis (28.8%) and descriptive analysis with significance tests (23.5%).Conclusion: Whilst impact evaluation of pharmacovigilance and product-specific regulatory interventions is increasing, the marked heterogeneity in study conduct and reporting highlights the need for scientific guidance to ensure robust methodologies are applied and systematic dissemination of results occurs.</p