High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis.

PURPOSE: High-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. METHODS AND MATERIALS: Patients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. RESULTS: A total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. CONCLUSIONS: These data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.

Clinical Outcomes of Hypofractionated Whole Breast Irradiation in Early Stage, Biologically High-Risk Breast Cancer.

PURPOSE: Adoption of hypofractionated whole breast irradiation (HWBI) for patients with early-stage, biologically high-risk breast cancer remains relatively low. We compared clinical outcomes of conventionally fractionated whole breast irradiation (CWBI) versus moderate HWBI in this patient population. METHODS AND MATERIALS: We queried a prospectively maintained database for patients with early-stage (T1-2, N0, M0) breast cancer who received whole breast irradiation with either CWBI or moderate HWBI at a single institution. We included only patients with biologically high-risk tumors (defined as either estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, human epidermal growth factor receptor 2 amplified, and/or patients with a high-risk multigene assay) who received systemic chemotherapy. Inverse probability of treatment weighting was used to compare treatment cohorts and to estimate 5-year time to event endpoints. Hazard ratios (HR) and 95% confidence interval (CI) were determined based on Cox proportional hazards model. RESULTS: We identified 300 patients, of whom 171 received CWBI and 129 received HWBI. There was a statistically significant difference in median age at diagnosis, 59 years for CWBI versus 63 years for HWBI (P = .004), and in median follow-up time, 97 months for CWBI versus 55 months for HWBI (P < .001). After accounting for differences in patient and tumor characteristics with inverse probability of treatment weighting, we found similar 5-year freedom from local recurrence (HR, 0.76; 95% CI, 0.14-4.1), freedom from regional recurrence (HR, 3.395% CI 0.15-69), freedom from distant metastasis (HR 3.9, 95% CI 0.86-17), and disease-free survival (HR 0.84; 95% CI, 0.3-2.4), between those treated with CWBI and those treated with HWBI. Results were similar among each of the 3 high-risk subtypes. CONCLUSIONS: Our data support the use of moderate HWBI in patients with early-stage, biologically high-risk breast cancer.

The Role of Far Cortical Endosteal Fixation for the Treatment of Medial Malleolus Fractures: A Biomechanical Study.

The traditional method for fixation of medial malleolus fractures has been with partially threaded (PT) lag screws extending beyond the physeal scar. The purpose of this study was to evaluate the biomechanical strength of an innovative method of fixation for medial malleolus fractures using a fully threaded (FT) lag screw that extends to the far endosteal cortex. Medial malleolus fractures were simulated in 12 matched cadaver pairs. A single PT 4.0-mm cancellous lag screw was placed in 1 ankle. The contralateral ankle of the same matched pair received an FT 3.5-mm cortical lag screw that extended to the far lateral tibial cortex and achieved endosteal purchase. Final torque of both screw configurations was recorded, and radiographs were taken to confirm appropriate screw placement. Average torque for the PT cancellous screws was 5.02 ± 2.34 in-lb. Average torque for the FT cortical screw was 7.63 ± 3.86 in-lb (p = .002). Visual and radiographic inspections revealed no displacement of the fracture site with use of the FT endosteal lag screw. Our results indicate superior biomechanical torque with far endosteal fixation with use of an FT cortical lag screw versus a traditional PT cancellous lag screw in a cadaver model. Far endosteal fixation is an alternative surgical option for medial malleolus fractures that provides added strength compared with PT lag screws and may obviate downsides associated with bicortical fixation.

Large database utilization in health outcomes research in pancreatic cancer: an update.

We sought to review published aggregate dataset studies on pancreatic cancer in the national and international settings, discuss the advantages and disadvantages these datasets possess, and possible future directions. A combination of Google Scholar, PubMed, and MEDLINE were used with search terms "pancreatic cancer" + "resectable" + "national cancer database", "pancreatic cancer" + "unresectable" + "national cancer database" and more broadly "borderline resectable pancreatic cancer", "locally advanced pancreatic cancer", "unresectable pancreatic cancer", and "resectable pancreatic cancer". Original articles and abstracts from this search were included, including data from the Surveillance, Epidemiology, and End Results (SEER) database, National Cancer Database (NCDB), and SEER-Medicare within the United States (US), as well as international database studies. Multiple database studies have been published regarding the role for radiotherapy in resected pancreatic cancer (n=6), the timing of additional therapy in resectable pancreatic cancer (n=4), and the role for radiotherapy and resection in locally advanced pancreatic cancer (LAPC) (n=4). Studies from both SEER and NCDB found a survival benefit to post-operative radiotherapy. In resectable pancreatic cancer, neoadjuvant treatment was found to be superior to adjuvant (NCDB). Chemoradiotherapy was found to be more beneficial than chemotherapy alone in LAPC, and patients who received highly-conformal or stereotactic body radiotherapy (SBRT) had improved survival compared to either conformal radiotherapy or chemotherapy alone. These studies also found that up to 10% of patients underwent resection, with a 90% margin-negative rate, and either one-half to one-third the risk of death of non-surgical patients. Criticism of large datasets includes lack of granularity of performance status, diagnosis, treatment, and outcomes-related data compared to properly administered prospective trials, as well as cross-over between treatment arms that cannot be accounted for, and concerns over quality of data represented. The US has witnessed a growing number of comparative effectiveness studies in pancreatic cancer. When taken together, certain themes emerge that are consistent with both single-institution data and clinical trials. These studies have also provided insight into questions not readily answerable by clinical trials. However, they require caution in interpretation.