Faculty Bibliography

OBJECTIVE:To characterize the impact of androgen-deprivation therapy (ADT) on the incidence of cardiovascular events (CE) in prostate cancer patients treated with radiotherapy (RT). MATERIALS AND METHODS/METHODS:There were 2211 patients with localized prostate cancer treated with RT from 1988 to 2008 at our institution. There were 991 patients (44.8%) who received ADT at the time of RT for a median of 6.1 months. Salvage ADT was initiated prior to CE in 365 men (16.5%) at a median of 5.5 years (range: 0.6 to 18.4 years) after RT and continued for a median of 4.3 years. A nomogram was constructed to predict the 10-year risk of CE "post-RT" (i.e., after RT). RESULTS:Patients receiving ADT at the time of RT exhibited significantly higher 10-year incidence of CE (19.6%, 95% CI 17.0%-22.6%) than those not receiving ADT (14.3%, 95% CI 12.2%-16.7%, P = .005). On multivariate analysis, both ADT at the time of RT (P = .007) and the time of salvage (P = .0004) were associated with increased CE risk, as were advanced age (P  =  .02), smoking (P  =  .0007), history of diabetes (P  =  .0007), and history of CE before RT (P  <  .0001). A nomogram using patient age, smoking status, history of pre-RT CE, history of diabetes, and ADT use at the time of RT predicted the rate of 10-year CE with a C-index of 0.81 (95% CI, 0.72-0.88). CONCLUSION/CONCLUSIONS:While ADT is often an essential part of prostate cancer treatment, patients should be counseled regarding increased risks of CE and prophylactic efforts should be considered to mitigate that risk.

PURPOSE/OBJECTIVE:We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. METHODS:Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48 months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. RESULTS:At 48 months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57-20.01; and delta 10.5, 95% CI, 3.78-17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. CONCLUSIONS:Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient.

PURPOSE/OBJECTIVE:Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. METHODS AND MATERIALS/METHODS:We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. RESULTS:Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. CONCLUSIONS:IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt.

PURPOSE:Prostate low-dose-rate (LDR) brachytherapy involves implantation of radioactive seeds permanently into the prostate gland. During receptive anal intercourse, the penis of the partner may come in close proximity to the implanted prostate gland. We estimate the potential intrarectal dose rates and suggest guidance on radiation precautions. METHODS AND MATERIALS:One hundred two patients were included in the study. After implantation, with patients under anesthesia in the dorsal lithotomy position, a new set of ultrasound (US) images and a CT scan were obtained. The images were fused, radioactive seeds and US probe locations were determined on the CT, and prostate, bladder, and rectal contours were drawn on the US. Dose rates (cGy/h) were calculated for the portion of the US probe spanning the prostate for several dose-volume histogram parameters. RESULTS:Twenty patients were treated with (125)I and 82 patients with (103)Pd. Average dose rates at Day 0 to the portion of the US probe spanning the prostate were 2.1 ± 1.3 cGy/h and 2.5 ± 0.8 cGy/h for patients treated with (125)I and (103)Pd, respectively. After 60 days, average calculated probe dose drops to 1.0 ± 0.6 cGy/h and 0.2 ± 0.1 cGy/h for (125)I and (103)Pd, respectively. CONCLUSIONS:During the immediate weeks after prostate seed implant, the estimated intrarectal dose rates are higher in (103)Pd compared to (125)I. As (103)Pd decays faster than (125)I, 2 months after the implant, radiation exposure from (103)Pd becomes lower than (125)I. Receptive anal intercourse time should be kept as low as possible during 2 and 6 months after low-dose-rate brachytherapy of the prostate with (103)Pd and (125)I, respectively.

PURPOSE:Value, defined as outcomes over costs, has been proposed as a measure to evaluate prostate cancer (PCa) treatments. We analyzed standardized outcomes and time-driven activity-based costing (TDABC) for prostate brachytherapy (PBT) to define a value framework. METHODS AND MATERIALS:Patients with low-risk PCa treated with low-dose-rate PBT between 1998 and 2009 were included. Outcomes were recorded according to the International Consortium for Health Outcomes Measurement standard set, which includes acute toxicity, patient-reported outcomes, and recurrence and survival outcomes. Patient-level costs to 1 year after PBT were collected using TDABC. Process mapping and radar chart analyses were conducted to visualize this value framework. RESULTS:A total of 238 men were eligible for analysis. Median age was 64 (range, 46-81). Median followup was 5 years (0.5-12.1). There were no acute Grade 3-5 complications. Expanded Prostate Cancer Index Composite 50 scores were favorable, with no clinically significant changes from baseline to last followup at 48 months for urinary incontinence/bother, bowel bother, sexual function, and vitality. Ten-year outcomes were favorable, including biochemical failure-free survival of 84.1%, metastasis-free survival 99.6%, PCa-specific survival 100%, and overall survival 88.6%. TDABC analysis demonstrated low resource utilization for PBT, with 41% and 10% of costs occurring in the operating room and with the MRI scan, respectively. The radar chart allowed direct visualization of outcomes and costs. CONCLUSIONS:We successfully created a visual framework to define the value of PBT using the International Consortium for Health Outcomes Measurement standard set and TDABC costs. PBT is associated with excellent outcomes and low costs. Widespread adoption of this methodology will enable value comparisons across providers, institutions, and treatment modalities.