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Locally advanced breast cancer requires surgical management via lumpectomy or mastectomy with or without systemic therapy followed by chest wall or breast (CW) and comprehensive nodal irradiation (CNI). Radiation (RT) dose constraints for the heart and ipsilateral lung have been developed based on photon RT. Proton therapy (PBT) can deliver significantly lower doses of RT to these organs-at-risk (OARs) and may warrant adjustments to OAR planning goals. The RT plans of consecutive patients undergoing adjuvant CW-CNI RT with PBT within a single center were reviewed. A inital treatment volume, comprised of CW/intact breast + CNI (CTV_init) structure, including the CW and CNI but excluding any boost plans was analyzed. Frequency distributions were generated based on doses received by the heart, lungs, and esophagus for validated dosimetric parameters. Frequency distributions were generated and then stratified by laterality and compared using the Kruskal-Wallis H test. The 75th, 85th, and 95th percentiles for each dosimetric parameter were calculated, overall and by laterality. The 75th percentile (Q3), was used as a suggested primary goal, and the 95th percentile was used as a suggested secondary goal. One hundred and seventy-two plans were analyzed. Forty-nine plans were right-sided, 107 were left-sided, and 16 were bilateral. The overall Q3 of the mean and V25 of the heart were 1.5 Gy and 1.7%, respectively. The mean and V25 to the heart differed significantly by laterality. Pulmonary values were similar to current recommendations. For all lateralites, the median volume of the esophagus receiving 70% prescription dose was ≤1 cm3. We present the first dosimetric study providing complete OAR dose-volume histograms data for patients undergoing adjuvant pencil-beam scanning-PBT for locally advanced breast cancer, with detailed information on central tendencies, ranges and distributions of data. We have provided suggested planning goals and metrics for the lungs, heart, and esophagus; the latter 2 differing significantly from current Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints and classical photon goals. [ABSTRACT FROM AUTHOR]

Regional nodal irradiation improves disease-free and distant disease–free survival in patients with high-risk breast cancer (BC). Trials demonstrating this used 2- or 3-dimensional conformal radiation therapy (2-dimensional or 3-dimensional [3D] conformal radiotherapy [CRT]) fields based on bony anatomy. Modern volumetric-modulated arc therapy (VMAT) and pencil beam scanning proton therapy (PBSPT) may underdose regional nodes (RNs) not contoured but covered by 3D CRT. Multiple atlases guide modern treatment planning. This study addresses the risk of underdosing when relying on published atlases and treating with 3D CRT, VMAT, and PBSPT. Targets per the Radiation Therapy Oncology Group (RTOG), European Society for Radiotherapy and Oncology (ESTRO), and Radiotherapy Comparative Effectiveness Consortium (RADCOMP) atlases were contoured on a representative patient CT scan. 3D CRT plans based on anatomic borders and VMAT and PBSPT plans for each set of target volumes were generated. Positron emission tomography/computed tomography (PET/CT) scans were reviewed. CT-positive and 18F-fluorodeoxyglucose (18F-FDG)–avid RNs (n = 389) were mapped from 102 patients with locally advanced (n = 51; median 2; range, 1-8 nodes) and metastatic (n = 51; median 4; range, 1-19 nodes) BC: axillary (AX; n = 284), supraclavicular (SCV; n = 60), and internal mammary nodal (IMN; n = 45). 18F-FDG-avid RNs falling within the 95% isodose line were considered adequately covered. 3D CRT plans provided excellent RN coverage. Low AX nodes were covered (≥99%) in all plans. Underdosing of 18F-FDG–avid RNs falling in the high AX (78%-92%), SCV (52%-75%), and IMN (84%-89%) volumes was observed following the RTOG and ESTRO atlases for VMAT and PBSPT plans. Use of the RADCOMP atlas provided coverage of these areas (89%-100%) with slightly increased heart and lung doses. Atlas guided VMAT/PBSPT plans provided cumulative nodal coverage as follows: ESTRO (89%/88%), RTOG (93%/91%), and RADCOMP (98%/96%). VMAT and PBSPT for regional nodal irradiation in patients with high-risk BC risks underdosage in the high AX, SCV, and IMN nodal regions unless comprehensive target delineation is performed. [ABSTRACT FROM AUTHOR]

Abstract Purpose A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT). Methods and Materials A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted. Results The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively. Conclusions Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making. [ABSTRACT FROM AUTHOR]

The ability to deliver highly conformal radiation therapy using intensity-modulated radiation therapy and particle therapy provides for new opportunities to improve patient outcomes by reducing treatment-related morbidities following radiation therapy. By reducing the volume of normal tissue exposed to radiation therapy (RT), while also allowing for the opportunity to escalate the dose of RT delivered to the tumor, use of conformal RT delivery should also provide the possibility of expanding the therapeutic index of radiotherapy. However, the ability to safely and confidently deliver conformal RT is largely dependent on our ability to clearly define the clinical target volume for radiation therapy, which requires an in-depth knowledge of histopathologic extent of different tumor types, as well as patterns of recurrence data. In this article, we provide a comprehensive review of the histopathologic and radiographic data that provide the basis for evidence-based guidelines for clinical tumor volume delineation. [ABSTRACT FROM AUTHOR]

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps.Methods and Materials: Active PBT clinical trials were identified from clinicaltrials.gov and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted.Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% of trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy.Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities. [ABSTRACT FROM AUTHOR]

An increasing proportion of cancer care will be delivered to elderly patients. There is a wide range of health status among the elderly, and “chronological age” may differ substantially from “biological age.” Biomarkers of aging may be used to better determine a patient''s biological age and would have potential clinical implications for the treatment of elderly patients with cancer. In this article, the authors review the current status of biomarkers related to aging and how these biomarkers may relate to treatment decisions for elderly patients with cancer. They also discuss potential implementation strategies for such biomarkers into future clinical trials. [Copyright &y& Elsevier]

Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT. NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/– memantine), performed longitudinal NCF testing, and included an optional blood draw for APOE analysis. NCF test results were compared at baseline and over time with mixed-effects models. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm and APOE carrier status. APOE results were available for 45% of patients (n = 227/508). NCF did not differ by APOE e4 carrier status at baseline. Mixed-effects modeling showed that APOE e4 carriers had worse memory after WBRT compared with APOE e4 noncarriers (Hopkins Verbal Learning Test–Revised total recall [least square mean difference, 0.63; P =.0074], delayed recognition [least square mean difference, 0.75; P =.023]). However, APOE e4 carrier status was not associated with time to NCF failure (hazard ratio, 0.86; 95% CI, 0.60-1.23; P =.40). Memantine delayed the time to NCF failure, regardless of carrier status (hazard ratio, 0.72; 95% CI, 0.52-1.01; P =.054). APOE e4 carriers with brain metastases exhibited greater decline in learning and memory, executive function, and the Clinical Trial Battery Composite score after treatment with WBRT (+/– memantine), without acceleration of onset of difference in time to NCF failure. [ABSTRACT FROM AUTHOR]

Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS for resected brain metastases (BM). Most reported studies of preoperative SRS used single-fraction SRS (SF-SRS). The goal of this study was to compare outcomes and toxicity of preoperative SF-SRS with multifraction (3-5 fractions) SRS (MF-SRS) in a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases–PROPS-BM). Patients with BM from solid cancers, of which at least 1 lesion was treated with preoperative SRS followed by planned resection, were included from 8 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included prior or planned whole brain radiation therapy. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Propensity score matched (PSM) analyses were performed. The study cohort included 404 patients with 416 resected index lesions, of which SF-SRS and MF-SRS were used for 317 (78.5%) and 87 patients (21.5%), respectively. Median dose was 15 Gy in 1 fraction for SF-SRS and 24 Gy in 3 fractions for MF-SRS. Univariable analysis demonstrated that SF-SRS was associated with higher cavity local recurrence (LR) compared with MF-SRS (2-year: 16.3% vs 2.9%; P =.004), which was also demonstrated in multivariable analysis. PSM yielded 81 matched pairs (n = 162). PSM analysis also demonstrated significantly higher rate of cavity LR with SF-SRS (2-year: 19.8% vs 3.3%; P =.003). There was no difference in adverse radiation effect, meningeal disease, or overall survival between cohorts in either analysis. Preoperative MF-SRS was associated with significantly reduced risk of cavity LR in both the unmatched and PSM analyses. There was no difference in adverse radiation effect, meningeal disease, or overall survival based on fractionation. MF-SRS may be a preferred option for neoadjuvant radiation therapy of resected BMs. Additional confirmatory studies are needed. A phase 3 randomized trial of single-fraction preoperative versus postoperative SRS (NRG-BN012) is ongoing (NCT05438212). [ABSTRACT FROM AUTHOR]

Purpose: Black men in the United States suffer significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for prostate cancer.Methods: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective IRB-approved protocol. Pearson Chi-Squared analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure.Results: One hundred and sixty-seven patients were included in the analysis (Black: n=81 [48.5%]) with a median follow-up of 88.4 months. Black patients were from lower income communities (P <0.01), had greater social vulnerability (P <0.01), and had a longer interval between diagnosis and treatment (P = 0.011). Overall cumulative FFBF was 92.3% (95% CI: 87.8% - 96.8%) at 5 years and 87.7% (95% CI: 82.0% - 93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = 0.114) and Black race was not independently predictive of failure (HR 1.51 [95% CI: 0.56 - 4.01]; P = 0.42). Overall survival was comparable between racial groups (P = 0.972). Only nadir PSA was significantly associated with biochemical failure on MVA (HR = 3.57 [95% CI: 02.44 - 5.22]; P <0.001).Conclusions: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities clinical outcomes. [ABSTRACT FROM AUTHOR]

• Details of technique, including beam angles, anatomic criteria, and image guidance. • Descriptions of target coverage and doses to OARs, and acute toxicity profiles. • Figures/images as visual guides for beam arrangements and expected dose distributions. Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs. A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed. Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV_eval was 50.4 Gy (45.0–50.4). Median 95% CTV_eval coverage was 99.5% (95–100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93–1.02). Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic. [ABSTRACT FROM AUTHOR]

Purpose: This population-based analysis compared prostate cancer–specific mortality (PCSM) in a cohort of patients with high-risk prostate cancer after nonsurgical treatment with external beam radiation therapy (EBRT), brachytherapy (BT), or combination (BT + EBRT). Methods and Materials: We identified from the Surveillance, Epidemiology and End Results database patients diagnosed from 1988 through 2002 with T1–T3N0M0 prostate adenocarcinoma of poorly differentiated grade and treated with BT, EBRT, or BT + EBRT. During this time frame, the database defined high grade as prostate cancers with Gleason score 8–10, or Gleason grade 4–5 if the score was not recorded. This corresponds to a cohort primarily with high-risk prostate cancer, although some cases where only Gleason grade was recorded may have included intermediate-risk cancer. We used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on PCSM. Results: There were 12,745 patients treated with EBRT (73.5%), BT (7.1%), or BT + EBRT (19.4%) included in the analysis. The median follow-up time for all patients was 6.4 years. The use of BT or BT + EBRT increased from 5.1% in 1988–1992 to 31.4% in 1998–2002. Significant predictors of use of BT or BT + EBRT were younger age, later year of diagnosis, urban residence, and earlier T-stage. On multivariate analysis, treatment with either BT (hazard ratio, 0.66; 95% confidence interval, 0.49–0.86) or BT + EBRT (hazard ratio, 0.77; 95% confidence ratio, 0.66–0.90) was associated with significant reduction in PCSM compared with EBRT alone. Conclusion: In patients with high-grade prostate cancer, treatment with brachytherapy is associated with reduced PCSM compared with EBRT alone. Our results suggest that brachytherapy should be investigated as a component of definitive treatment strategies for patients with high-risk prostate cancer. [Copyright &y& Elsevier]

Purpose: Acute skin toxicity in the form of radiation dermatitis (RD) or skin hyperpigmentation (SH) is a common problem experienced by patients undergoing breast irradiation. Proton radiation has been thought to deliver higher doses to skin compared with photon radiation because of differences in the physical properties between photons and protons; however, limited literature exists directly comparing toxicity outcomes.Methods and Materials: The highest recorded grades of acute RD and SH were analyzed in 86 patients undergoing adjuvant radiation therapy to the breast with or without regional lymph nodes after lumpectomy (breast-conserving surgery) or mastectomy with either proton pencil-beam scanning (n = 39) or photon (n = 47) radiation therapy within a single institution to analyze differences in severity of acute skin reactions. For 34 of 47 photon and 33 of 39 proton patients, a "skin" contour was retroactively created in our treatment planning systems, and multiple dosimetric parameters were calculated to quantify objective radiation doses received by skin.Results: On χ2 analysis, the highest reported grade of RD was significantly higher in women undergoing proton radiation compared with photon radiation; grade ≥2 RD was present in 69.2% versus 29.8% of patients receiving proton and photon therapy, respectively (P = .002). Rates of grade 3 RD were 5.1% versus 4.3% for proton versus photon radiation, respectively (P = .848). Overall, there were no significant differences in rates of SH between modalities. There were no grade 4 to 5 toxicities in either cohort.Conclusions: In a comparison with patients receiving photon radiation, a significantly higher rate of grade ≥2 RD was observed in patients undergoing proton radiation, with very low rates of grade 3 toxicity in both groups. Rates of SH did not differ significantly between modalities. Women should be counseled regarding the possibility of increased grade 2 toxicities, although this might present a dosimetric advantage for physicians when treating patients in the postmastectomy setting or when skin was involved on presentation. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. [ABSTRACT FROM AUTHOR]

Purpose: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time.Methods and Materials: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time.Results: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065).Conclusions: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings. [ABSTRACT FROM AUTHOR]

Purpose There is limited evidence to guide treatment decision making for patients with early stage uterine carcinosarcoma (UCS) regarding the use of pelvic external beam radiation therapy (RT) vs. vaginal brachytherapy (BT) after hysterectomy. We analyzed a population-based database to compare survival outcomes after adjuvant BT vs. pelvic external beam RT for patients with Stages I–II UCS. Methods and Materials We searched the Surveillance, Epidemiology, and End Results registry to identify a cohort of patients with International Federation of Gynecology and Obstetrics I/II UCS diagnosed during 1998–2010, who received a total hysterectomy and for whom radiotherapy type was known. χ 2 tests were used to test associations between patient characteristics and radiotherapy type. Overall and cancer-specific survival, measured from date of diagnosis, were summarized within each covariate. Cox proportional hazards models were used to model the impact of RT type on survival while adjusting for other factors. Results A total of 1581 subjects were identified, including 803 (50.8%) no radiotherapy; 636 (40.2%) external beam radiotherapy ± BT; and 142 (9.0%) BT alone. The use of BT alone increased from 4.5% in 1988–1999 to 12.5% in 2005–2010. Multivariate models of overall and cause-specific survival showed that radiotherapy type was not associated with survival after adjustment for other covariates. Conclusions For patients with Stages I–II UCS, adjuvant radiotherapy type did not influence survival after hysterectomy. This study addresses an existing evidence gap and identifies a trend toward increasing utilization of BT alone. Prospective trials are warranted to provide high-quality evidence to guide adjuvant therapy decisions for these patients. [ABSTRACT FROM AUTHOR]

Purpose To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms. Results The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic factors and outcomes for a large observational cohort of female patients with urethral cancer in the Surveillance, Epidemiology, and End Results database. Methods: We identified 722 women diagnosed with urethral cancer from 1983 to 2008 in the Surveillance, Epidemiology, and End Results database. Descriptive statistics were used to explore the epidemiology, standard treatment practices, and tumor characteristics. A total of 359 women with nonmetastatic primary urethral cancer were identified for cancer-specific and survival analysis. Kaplan-Meier plots and log-rank tests were performed for each potential covariate. A multivariate Cox proportional hazards model was performed to evaluate age, demographic factors, T stage, nodal status, histologic findings, surgery, and radiotherapy. Results: The median overall survival time was 42 months (95% confidence interval 35-57), and the 5- and 10-year overall survival rate was 43% and 32%, respectively. The median cancer-specific survival (CSS) time was 78 months, and the 5- and 10-year CSS rate was 53% and 46%, respectively. On multivariate analysis, black race, Stage T3-T4 tumors compared with T1, node-positive disease, nonsquamous histologic features, and advanced age were associated with shortened CSS. Surgery was associated with longer CSS. Black patients presented with a statistically significant greater T stage. Conclusion: Advanced age, T stage, node-positive disease, nonsquamous histologic features, and black race were associated with reduced CSS, and surgical resection was associated with longer CSS. We found that black patients present with more advanced tumors and have shorter CSS than white women with urethral cancer. [ABSTRACT FROM AUTHOR]