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Purpose International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

Purpose Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P =.02), grade 3+ neutropenia (33% vs 8%, P =.04), and grade 2+ thrombocytopenia (32% vs 7%, P =.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 ( P Conclusions Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total "marrow reserve" can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

Purpose To present the most updated American College of Radiology (ACR) Appropriateness Criteria formed by an expert panel on the appropriate delivery of external beam radiation to manage stage T1 and T2 prostate cancer (in the definitive setting and post-prostatectomy) and to provide clinical variants with expert recommendations based on accompanying Appropriateness Criteria for target volumes and treatment planning. Methods and materials The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a panel of multidisciplinary experts. The guideline development and revision process includes an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In instances in which evidence is lacking or equivocal, expert opinion may supplement available evidence to recommend imaging or treatment. Results The panel summarizes the most recent and relevant literature on the topic, including organ motion and localization methods, image guidance, and delivery techniques (eg, 3-dimensional conformal intensity modulation). The panel presents 7 clinical variants, including (1) a standard case and cases with (2) a distended rectum, (3) a large-volume prostate, (4) bilateral hip implants, (5) inflammatory bowel disease, (6) prior prostatectomy, and (7) a pannus extending into the radiation field. Each case outlines the appropriate techniques for simulation, treatment planning, image guidance, dose, and fractionation. Numerical rating and commentary is given for each treatment approach in each variant. Conclusions External beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature, these Appropriateness Criteria can aid clinicians in determining the appropriate treatment delivery and personalized approaches for individual patients.

Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

Purpose We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated in the contemporary era. Methods Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated. Results Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM). Conclusion Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.

Urinary incontinence is a potential side effect of prostatectomy and intensity modulated radiation therapy (IMRT) for prostate cancer. There are limited data on dosimetric parameters that may predict for poor continence recovery in men who receive postoperative IMRT.Eighty-seven men with nonmetastatic prostate cancer who underwent prostatectomy followed by adjuvant (13%) or salvage (87%) IMRT were identified. The Expanded Prostate Cancer Index composite questionnaire was prospectively collected at baseline, 6 weeks, and 6, 12, 18, 24, 36, and 48 months post-IMRT. Relevant critical structures were contoured and dose-volume metrics collected. The primary endpoint was urinary continence global score. Longitudinal analysis using a generalized estimating equation model was performed.There was no statistically significant change in Expanded Prostate Cancer Index composite urinary continence global scores over time as compared with baseline (all P.05). In univariate analysis, bladder volume receiving 70 Gy (V70 Gy) and penile bulb V70 Gy were associated with urinary continence (odds ratio, 0.82; P.05). In a multivariable model that included body mass index, distance between vesicourethral junction and genitourinary diaphragm, time from surgery, use of antihypertensive medications, age, diabetes, and bladder V70 Gy, only bladder V70 Gy (odds ratio, 0.82; P = .03) was associated with outcome. After 2 years, there was a significant difference in global score for those with V70 Gy42.27 versus ≥42.27 mL (all P.05 at 2 and 3 years post-IMRT).There was no significant change in patient-reported urinary continence scores after postprostatectomy IMRT. Bladder V70 Gy was independently associated with a decrease in urinary continence scores. Further evaluation is necessary to optimize quality of life in these men.

195 Background: This study evaluated the ability of the combined clinical cell-cycle risk score (CCR) to prognosticate the risk of prostate cancer metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). Methods: The CCR score is a validated model that combines the cell cycle progression score (CCP) with the UCSF Cancer of the Prostate Risk Assessment score (CAPRA). The CCR score and a CCR-based multimodality threshold score (2.112) were evaluated in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Center (NCCN) intermediate- or high-risk localized disease (N = 741) who received single (RT) or multimodality therapy (ADT with RT). Effects of prognostic variables were analyzed using Kaplan-Meier and Cox regression methods. Results: Median follow-up was 5.9 years. CCR predicted metastasis [hazard ratio (HR) 2.21, 95% Confidence Interval (CI) 1.70-2.87, p < 0.001]. The CCR score was a better prognosticator of metastasis (C-index 0.78) than either NCCN-risk group (C-index 0.70), CAPRA score (C-index 0.71), or CCP score (C-index 0.69) alone. In bivariate analyses, the CCR score remained highly prognostic for metastasis when comparing any ADT vs none (HR 2.19, 95% CI 1.62 to 2.97, p < 0.001), ADT duration as a continuous variable (HR 2.05, 95% CI 1.54-2.72, p < 0.001), or ADT use given as less than or at the recommended duration for each NCCN risk group (HR 2.22, 95% CI 1.71-2.88, p < 0.001). Men with CCR scores either below or above the threshold (2.112) had a 10-year risk of metastasis of 4.2% and 25.3%, respectively. For men below the threshold receiving RT alone versus RT+ADT, the 10-year risk of metastasis was 4.2% and 3.9%, respectively. Conclusions: CCR is a highly precise and accurate predictor of metastasis in men undergoing dose-escalated RT, with or without ADT. CCR adds clinically actionable information relative to guideline recommended therapies that are based on NCCN risk groups or CAPRA alone. Men with scores below the multimodality threshold may not significantly reduce their 10-year risk of metastasis with the addition of ADT.

Novel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT).One hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis.A PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776).mpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT.

We applied an established prognostic model to high-risk prostate cancer (HRPC) patients treated with radiotherapy (RT) and evaluated the influence of clinical and treatment variables on treatment outcomes.In total, 1075 HRPC patients undergoing definitive radiotherapy (RT) between 1995 and 2010 were retrospectively reviewed. Median follow-up was 62.3 months. Patients received either dose-escalated external beam radiotherapy (n=628, EBRT) or combined-modality radiotherapy (n=447, pelvic RT and low-dose rate brachytherapy boost, CMRT). 82.9% received androgen-deprivation therapy (ADT). A prognostic model stratified patients into predefined groups (good, intermediate, and poor). Kaplan-Meier methods and Cox proportional hazards regressions assessed biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM) and overall mortality (OM). C-indices analyzed predictive value.The model was prognostic; C-indices for BF, DM, PCSM and OM were: 0.62, 0.64, 0.61, and 0.57. On multivariate analysis, CMRT and longer ADT (≥24 mo) were associated with improved BF, DM, and PCSM. Gleason score (GS) 9-10 was the strongest predictor of PCSM. C-indices for BF, DM, PCSM, and OM using a 4-compartment model incorporating GS 9-10 were: 0.62, 0.65, 0.68, and 0.56. In poor-prognosis patients (GS 8-10+additional risk factors), CMRT+LTADT (12 mo) had 10-year PCSM (3.7%±3.6%), comparing favorably to 25.8%±9.2% with EBRT+LTADT.The model applies to high-risk RT patients; GS 9-10 remains a powerful predictor of PCSM. Comparing similar prognosis patients, CMRT is associated with improved disease-specific outcomes relative to EBRT. In poor-prognosis patients, CMRT+LTADT yields superior 10-year PCSM, potentially improving RT treatment personalization for those with HRPC.

Background Limited long-term data characterize patient-reported quality of life (QOL) following postprostatectomy intensity-modulated radiation therapy (PPRT), and predictors of decline are poorly defined. Objective To identify modifiable dosimetric and clinical risk factors impacting QOL and late toxicity following PPRT. Design, setting, and participants A prospective cohort study of consecutive men with prostate cancer who received PPRT between 2007 and 2015 at a single academic institution. Intervention Patients were prospectively evaluated using the Expanded Prostate Cancer Index Composite (EPIC-26) QOL instrument. Radiation Therapy Oncology Group/Common Toxicity Criteria for Adverse Events toxicity grades were assigned at every follow-up visit. Treatment was delivered to the prostate bed (median 68 Gy) ± pelvic lymphatics (65%, median 50.4 Gy) with daily image guidance. Androgen deprivation therapy was concomitantly administered to 132 (66%) men for a median of 4 mo. Outcome measurements and statistical analysis Changes were deemed relevant if they exceeded the minimally clinically important difference (MCID), as calculated by a distribution-based method. Generalized estimating equation models and Cox regression were used for QOL and late toxicity univariate and multivariable analysis. Results and limitations Overall, 199 men were identified with a median follow-up of 33 mo. Overall urinary function (UF), bowel function (BF), sexual function (SF), and urinary irritation/obstruction (UI/UO) scores were never lower than the MCID. Between 8% and 18% of men experienced a small multidomain (1× MCID) decline, and 0–8% experienced a moderate multidomain decline (2× MCID) at a given time point up to 84 mo after PPRT. The rates of freedom from grade 2 or higher (Gr2+) genitourinary (GU) and gastrointestinal (GI) toxicity were 94% and 95%, respectively, at 4 yr. Factors associated with worse QOL or toxicity included longer time to PPRT (UC and UF), higher BMI (UF, BF, and late GI toxicity), older age (BF, SF, and late GU toxicity); hormone therapy (SF), total dose (late GI toxicity), tobacco history (BF), and higher bladder V70 Gy (UC, UF, and late GU toxicity). Conclusions Long-term QOL and late toxicity are favorable following postprostatectomy radiation therapy. Identifiable clinical and dosimetric risk factors may guide decision making to optimize urinary, sexual, and bowel function. Patient summary The following study provides a detailed report of favorable patient-reported quality of life and late side-effect profiles of radiation therapy following surgery for localized prostate cancer. Our findings provide patients guidance on what symptoms to expect if they are planning to undergo radiation therapy in this setting. It also allows physicians to counsel patients appropriately, and modify certain clinical and radiation-related risk factors to optimize quality of life.

The purpose of this study was to investigate the utility of pre-treatment multiparametric magnetic resonance imaging (mpMRI) in a modern cohort of intermediate and high-risk prostate cancer patients treated with primary radiotherapy.One hundred twenty three men with National Comprehensive Cancer Network (NCCN) intermediate or high-risk prostate cancer were treated with primary EBRT and/or brachytherapy and had evaluable pre-treatment mpMRI with endorectal coil. Images were assessed for the presence of radiographic extraprostatic extension (rEPE), seminal vesicle invasion (rSVI), lymph node involvement (LNI), sextant involvement, and largest axial tumor diameter. Imaging characteristics were analyzed along with clinical risk factors against freedom from biochemical failure (FFBF). Median follow-up time was 50 months.Fourteen (11%) men developed biochemical failure. The 5-year FFBF was 94% in intermediate-risk patients and 82% in high-risk patients (p0.01). mpMRI findings including rEPE (29% vs. 66%, p0.01), rSVI (6% vs. 25%, p0.01), LNI (1% vs. 30%, p0.01), and largest axial tumor size15 mm (27% vs. 48%, p = 0.02) were identified in men with intermediate vs. high risk prostate cancer, respectively. mpMRI features associated with 5-y FFBF biochemical failure on univariate analysis included rEPE (80% vs 98%), rSVI (55% vs. 96%), LNI (65% vs. 93%), and largest axial tumor size15mm (81% vs. 94%, all p0.01). Men without any high risk MRI finding had a 5-y FFBF of 100% vs. 81% (p0.01). Adverse imaging features (HR 8.9, p0.01) were independently associated with biochemical failure in a bivariate model analyzed alongside clinical risk category (HR 3.2, p = 0.04).Pre-treatment mpMRI findings are strongly associated with biochemical outcomes in a modern cohort of intermediate and high-risk patients treated with primary radiotherapy. mpMRI may aid risk stratification beyond clinical risk factors in men treated with radiation therapy; further study is warranted to better understand how mpMRI can be used to individualize therapy.

Background Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported. Materials and methods 52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded. Results Median follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively. Conclusions In this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.

In this edition of the Gastrointestinal Oncology Scan, our group has selected several interesting updates of large wellknown randomized trials, and a recent phase 2 trial, that shed further light on earlier results and highlight ongoing areas of debate. These offer a nice complement to some of our earlier Oncology Scans, bringing you the best literature around the journal landscape in gastrointestinal cancers (1-4). The first is the CROSS trial, a landmark study from the Netherlands, which established preoperative radiation given concurrently with carboplatin and paclitaxel, as opposed to surgery alone, as the standard of care for esophageal cancer (5). The follow-up publication provides patterns of failure data, which confirms the expected local control benefit of radiation therapy (6). The second trial is an update on the well-known German Rectal Trial, which cemented preoperative chemoradiation as standard therapy for locally advanced rectal cancer (7). The updated analysis provides important data on the correlation of pathologic response and disease outcome(8).Thequestionofadjuvantchemotherapy for patients with rectal cancer is highlighted in the third update of the EORTC 22921 trial (9). Many clinicians extrapolate from colon cancer data to support the use of adjuvant chemotherapy for high-risk patients. The long-term results of this trial question the soundness of that approach. Finally, the last report we discuss is a phase 2 trial from investigators at Memorial-Sloan Kettering using preoperative chemotherapy alone for locally advanced rectal cancer (10). The results suggest that for carefully selected patients, radiation may be omitted without a compromise in outcome. This approachisnowbeingtestedinarandomizedprospectivetrial.

Androgen deprivation therapy (ADT) is an important adjunctive therapy to external beam radiation therapy (RT) for the definitive management of prostate cancer. The role of ADT is well-established for locally advanced or high-risk disease in conjunction with standard doses of RT, but less defined for intermediate-risk disease or with dose-escalated RT. The goal of this review is to summarize evidence evaluating the combination of ADT/RT, focusing on recent trials and current controversies as they pertain to the practicing clinician. The benefit of ADT on biochemical control is maintained with dose-escalated RT according to recently reported phase III studies. Furthermore, there is now prospective, randomized evidence to support the addition of ADT to RT in the post-prostatectomy setting. ADT continues to play an important role for prostate cancer patients receiving dose-escalated RT. Future research is needed to identify subgroups most likely to benefit from this combination.

Objective To create a validated tool to measure digital rectal examination proficiency and aid with teaching of the examination. Design The Digital Rectal Examination Clinical Tool was created using a modified Delphi method with 5 urologists and 5 radiation oncologists. The instrument was then validated in a population of preclinical medical students examining male urological teaching associates, and clinical trainees (third- and fourth-year medical students and urology resident physicians) examining prospectively enrolled subjects. Trainees completed paired examinations with an attending urologist, and responses were scored with reference to the attending responses. Setting The instrument was validated at the University of Virginia in the urology clinic, endoscopic operating room, and main operating room settings. Participants We tested the instrument on consenting subjects consisting of male urologic teaching associates ( n = 12), clinic patients ( n = 4), and operating room patients ( n = 64). The participants were undergraduate ( n = 302) and graduate ( n = 9) medical trainees. Results In preclerkship trainees, improved scores in subjects without abnormal compared to those with abnormal findings demonstrated validity. In clinical trainees, scores on the Digital Rectal Examination Clinical Tool increased by 2% for each additional year of training, demonstrating construct validity. Conclusions We used an expert panel to create a novel instrument for measuring digital rectal examination proficiency and validated it with preclinical and clinical trainee cohorts at our institution.

Background Outcomes with postprostatectomy salvage radiation therapy (SRT) are not ideal. Little evidence exists regarding potential benefits of adding whole pelvic radiation therapy (WPRT) alone or in combination with androgen deprivation therapy (ADT). Objective To explore whether WPRT and/or ADT added to prostate bed radiation therapy (PBRT) improves freedom from biochemical failure (FFBF) or distant metastases (DM). Design, setting, and participants A database was compiled from 10 academic institutions of patients with postprostatectomy prostate-specific antigen (PSA) >0.01 ng/ml; pT1-4, Nx/0, cM0; and Gleason score (GS) ≥7 treated between 1987 and 2013. Median follow-up was 51 mo. Interventions WPRT and/or ADT in addition to PBRT. Outcome measurements and statistical analyses FFBF and DM were calculated using cumulative incidence estimation. Multivariable analysis (MVA) utilized cumulative incidence regression. Results and limitation Median pre-SRT PSA was 0.5 ng/ml for 1861 patients. Median follow-up for patients not experiencing biochemical failure (BF) was 55 mo. MVA showed increased BF for PBRT versus WPRT (hazard ratio [HR] 1.82, p p p p =0.012). No significant differences in DM cumulative incidence were found. Conclusions For patients with GS ≥7 receiving SRT, clinicians should weigh FFBF benefits of WPRT and ADT against toxicities. Future studies should explore the impact of WPRT on quality of life, clinical progression, and overall survival. Patient summary We evaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning).

303 Background: Androgen deprivation therapy (ADT) improves disease control in intermediate (IR) and high risk (HR) prostate cancer (PCa) treated with radiation therapy (RT), but also causes toxicity which may be worse in men of older age or with comorbidity. We hypothesized that dual agent ADT, replacing GnRH agonist for an oral 5-alpha-reductase inhibitor (5AR), would improve hormonal health-related quality of life (HRQOL) without compromising PCa outcomes. Methods: Patients with localized IR or HR PCa, age > 70 years and/or with Charlson comorbidity index (CCI) score > 2 were treated with bicalutamide and finasteride or dutasteride (oADT). A synchronous standard of care (SOC) cohort received bicalutamide and GnRH agonist. Median RT dose was 78 Gy. Dual agent ADT was given for 4 months (mo), while 5AR or GnRH agonist continued for an additional 2 years. The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26) hormonal HRQOL global score at 6 mo, with success defined as < 30% decline, requiring 40 men in the oADT group. Secondary endpoints included a log-rank comparison of freedom from biochemical failure (FFBF), and overall survival (OS). Results: Between 1/2011 and 8/2018, 40 and 30 men were prospectively enrolled in the oADT and SOC cohorts, respectively, with similar CCI scores > 2 (73% vs 66%, p=0.58), and age (mean 71, p=0.99). Median follow-up was 36 mo. Global scores for hormonal HRQOL at baseline, 6 mo, and 2 yr were 89, 88, 84 for the oADT group, and 92, 81, 83 for the SOC group; the declines from baseline to 6 mo (p=0.04) and 2 yr (p=0.05) were smaller in the oADT group. Sexual HRQOL was better preserved at 6 mo (p

Kimberly S Corbin,1 Hedy L Kindler,2 Stanley L Liauw31Department of Radiation Oncology, Memorial Medical Center, Springfield, IL, USA; 2Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA; 3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USAAbstract: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in the gastrointestinal tract. Over the last decade, the management and prognosis of GISTs has changed dramatically with molecular characterization of the c-kit mutation and the adoption of targeted systemic therapy. Currently, the standard of care for resectable tumors is surgery, followed by adjuvant imatinib for tumors at high risk for recurrence. Inoperable or metastatic tumors are treated primarily with imatinib. Despite excellent initial response rates, resistance to targeted therapy has emerged as a common clinical problem, with relatively few therapeutic solutions. While the treatment of GISTs does not commonly include radiotherapy, radiation therapy could be a valuable contributing modality. Several case reports indicate that radiation can control locally progressive, drug-resistant disease. Further study is necessary to define whether radiation could potentially prevent or delay the onset of drug resistance, or improve outcomes when given in combination with imatinib.Keywords: GIST, imatinib, radiotherapy

Herpes zoster, a viral disease that is characterized by a painful and blistering eruption in the skin, represents reactivation of latent varicella zoster (chickenpox) virus infection. In high-risk groups such as elderly or immunocompromised patients, the incidence of zoster can be as high as 50%. Radiation oncologists are likely to see zoster because cancer, and cancer therapy, can adversely affect immune function. A few reports suggest that radiation therapy is a risk factor for zoster, and that the skin eruption is often in or near the radiation treatment field. The diagnosis is typically made through clinical history and exam, but several tests are available to confirm the diagnosis and differentiate it from other infections or dermatitis. Effective management consists of prompt antiviral medication, acute pain control, appropriate precautions to limit transmission, and referral to specialists in certain cases. Despite appropriate therapy, up to 18% of patients can develop persistent postherpetic neuralgia, defined as pain more than 4 months after resolution of the rash. Several classes of pain medication are available to treat acute or long-term pain. Vaccination against zoster is recommended for patients aged 60 years or older, as it can reduce the incidence and severity of zoster.

BACKGROUND The objective of this study was to examine the effect of tobacco use on disease control and late gastrointestinal and genitourinary toxicity in men undergoing external beam radiotherapy (EBRT) for prostate cancer. METHODS In total, 633 men with known tobacco history at consultation underwent definitive EBRT between 1988 and 2008. Tobacco use was defined as positive (current or prior) or negative (never). The median EBRT dose was 74 gray (Gy). In univariate analysis, tobacco use and other prognostic factors were compared with disease control and toxicity. Multivariable analysis included tobacco use and the covariates that were associated with outcome on univariate analysis (P

Medical students often choose to pursue a career in radiation oncology with limited meaningful exposure to the field. We previously identified factors that were most influential to an applicant's rank list order. Here, we sought to assess if residency graduates had differing views regarding those factors. We also polled recent graduates' attitudes of the current job market.An anonymous, internet-based survey was developed and distributed to graduates of radiation oncology residencies from 2003 through 2006 and 2012 through 2015 to assess the importance of factors with regard to residency selection, training, and job securement and attitudes toward the job market within the United States.Responses were received from 198 of 848 (23%) of those invited to participate. The respondents were divided into 2 cohorts for analysis, an "early" cohort (2001-2009) and a "contemporary" cohort (2010-2016). Respondents recalled "quality of clinical training," "perceived happiness of residents," and "sense of community among faculty and residents" as the 3 most important factors influencing the rank list. Postresidency, the most valued factors of the residency experience were "quality of clinical training," "geographic location," and "faculty mentorship." Factors that were assigned the greatest differential value in hindsight to influence the rank list included "faculty mentorship," "willingness of faculty to call employer," and "quality of alumni base." Sixty-four percent of respondents reported the job market to be difficult or very difficult. This perception was more common among contemporary graduates (P.05). Sixty percent of respondents reported "far too many" or "somewhat too many" residency positions for the actual job needs in the United States.After training, residency graduates place higher value on factors in residency that can directly improve job procurement. This finding is more common among more recent graduates, potentially a result of the perception of a tightening job market with too many radiation oncologists in training.

PURPOSE To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer METHODS:: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. RESULTS The panel summarized the most recent and relevant literature on the topic and voted on 4 clinical variants illustrating the appropriate management of locally advanced, high-risk cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. CONCLUSIONS Aggressive local approaches including surgery followed by adjuvant XRT, beam combined with androgen deprivation therapy, and beam combined with brachytherapy have resulted in unpresented success in locally advanced, high-risk prostate cancer. By combining most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate integration of available therapeutic modalities.

Purpose To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test ( P =.531 and P =.397 for grade 2+ and 3+ LRT, respectively). Conclusions In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study.

Purpose To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP. The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA ≤0.3 ng/mL ( P 3 and was directly associated with PSA ( r =0.5, P =.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins ( r =0.8, P Conclusions Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT.

Purpose To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy. Methods and Materials The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography–based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity. Conclusions Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians.

Radiation oncology trainees frequently learn to contour through clinical experience and lectures. A hands-on contouring module was developed to teach delineation of the postoperative prostate clinical target volume (CTV) and improve contouring accuracy.Medical students independently contoured a prostate fossa CTV before and after receiving educational materials and live instruction detailing the RTOG approach to contouring this CTV. Metrics for volume overlap and surface distance (Dice similarity coefficient, Hausdorff distance (HD), and mean distance) determined discordance between student and consensus contours. An evaluation assessed perception of session efficacy (1 = "not at all" to 5 = "extremely"; reported as median[interquartile range]). Non-parametric statistical tests were used.Twenty-four students at two institutions completed the module, and 21 completed the evaluation (88% response). The content was rated as "quite" important (4[3.5-5]). The module improved comfort contouring a prostate fossa (pre 1[1-2] vs. post 4[3-4], p.01), ability to find references (pre 2[1-3] vs. post 4[3.5-4], p0.01), knowledge of CT prostate/pelvis anatomy (pre 2[1.5-3] vs. post 3[3-4], p.01), and ability to use contouring software tools (pre 2[2-3.5] vs. post 3[3-4], p=.01). After intervention, mean DSC increased (0.29 to 0.68, p0.01) and HD and mean distance both decreased, respectively (42.8 to 30.0, p.01; 11.5 to 1.9, p.01).A hands-on module to teach CTV delineation to medical students was developed and implemented. Student and expert contours exhibited near "excellent agreement" (as defined in the literature) after intervention. Additional modules to teach target delineation to all educational levels can be developed using this model.

Purpose To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure–free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% ( p = 0.138) and the 5-year OS rate was 87% vs. 80% ( p = 0.159). On multivariate analysis, percent positive cores (PPC) ( p = 0.002) and GS ( p = 0.008) were significantly associated with BFFS, with ADT showing a trend ( p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% ( p = 0.019), GS 4+3 ( p = 0.078), and number of risk factors greater than 1 ( p = 0.022). Only intensity-modulated radiotherapy use ( p = 0.012) and GS ( p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.

Purpose To determine the total setup error and the required planning target volume (PTV) margin for prostate bed without image guided radiotherapy (IGRT), and to demonstrate the feasibility and dosimetric benefit of IGRT post prostatectomy using surgical clips. Materials and methods Seventeen patients were treated with intensity modulated radiotherapy (IMRT) to the prostate bed with a 1 cm PTV margin. Three-dimensional shifts of the surgical clips inside the prostate bed were measured with respect to the isocenter from 364 orthogonal kV image pairs, and the total setup error was calculated to determine the required PTV margin. Alternative IMRT plans using 5 mm or 1 cm PTV expansion were generated and compared for rectal and bladder sparing. Results Surgical clips were reproducibly and reliably identified. The mean (standard deviation) shifts in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP), axes were: −0.1 mm (1.7 mm), 0.6 mm (2.4 mm), and −2.1 mm (2.6 mm), respectively. The required PTV margins were calculated to be 6, 8, and 9 mm in the LR, AP, and SI axis, respectively. A PTV expansion of 5 mm, compared to 1 cm, significantly reduced V65 Gy to the rectum by 10%. Conclusions In the absence of IGRT, a non-uniform PTV margin of 6 mm LR, 8 mm AP, and 9 mm SI should be considered. Use of clips as fiducial markers can decrease the total setup error, enable a smaller PTV margin, and improve rectal sparing.

To evaluate the prognostic significance of the first postsurgery carcinoembryonic antigen (CEA) level in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation (nCRT) and total mesorectal excision.A total of 100 patients underwent nCRT and had baseline and posttreatment CEA levels recorded within 6 months of surgery. The median radiotherapy dose was 50.4 Gy. Eighty-six patients received adjuvant 5-fluorouracil-based chemotherapy. Prognostic factors were analyzed for possible associations with freedom from failure (FFF) by univariate and multivariate analyses. Median follow-up was 30 months.The median CEA (ng/ml) levels at baseline before nCRT, after nCRT, and after total mesorectal excision were 3.6, 1.7, and 1.3, respectively. Pathologic complete response was observed in 22%. FFF at 36 months was 78%. Local failure and distant failure occurred in 4 and 20% of the patients, respectively. On univariate analysis, pathologic complete response, margin status, and both pretreatment and postsurgery CEA levels were associated with recurrence (all P0.05). On multivariate analysis, pathologic complete response (P0.007), margin status (P0.001), and postsurgery CEA level (P = 0.003), but not baseline CEA level (P = 0.2), were found to be associated with recurrence.After nCRT for rectal cancer, postsurgery CEA level may have more prognostic value than pretreatment level. Patients with a postsurgery CEA level of2.5 ng/ml have higher rates of recurrence and may warrant closer surveillance.

Purpose To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose–volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V 70 ), 65 Gy (V 65 ), and 40 Gy (V 40 ). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V 70 ≤10%, V 65 ≤20%, and V 40 ≤40%; 92% for men with rectal V 70 ≤20%, V 65 ≤40%, and V 40 ≤80%; and 85% for men exceeding these criteria ( p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years ( p = 0.07). No bladder dose–volume relationships were associated with the risk of GU toxicity. Conclusions IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

To report the urinary outcome of men treated for prostate cancer with external beam radiotherapy (EBRT) who have pretreatment obstructive urinary symptoms (International Prostate Symptom Score [IPSS] ≥ 15).We treated 368 patients with EBRT for localized prostate cancer, and pre- and post-radiotherapy (RT) IPSSs were recorded. In total, 80 men had an IPSS ≥ 15, 48% of whom were taking genitourinary (GU) medications before RT. The IPSS was followed over time and analyzed as a pretreatment factor against Radiation Therapy Oncology Group acute and late GU toxicity.The median follow-up was 44 months. Among men with a pre-RT IPSS ≥ 15, the median IPSS at baseline, first follow-up, and last follow-up was 18 (range, 15 to 34), 17 (range, 0 to 32), and 13 (range, 0 to 34), respectively. The mean patient declines in IPSS from baseline to first and last follow-up were -3.6 points (p0.0004) and -6.9 points (p0.0001), respectively. At last follow-up, 43 men (54%) took GU medications. Pre-RT IPSS ≥ 15 vs. ≤ 14 was associated with a higher incidence of Grade ≥ 2 acute GU toxicity (64% vs. 42%, p = 0.0005), and 4-year freedom from Grade ≥ 2 late GU toxicity was 38% vs. 64% (p0.0001). There was no greatly increased risk of Grade ≥ 3 late GU toxicity for men with IPSS ≥ 15 (4-year freedom from Grade ≥ 3 late GU toxicity of 90% vs. 96%, p = 0.0964).Although the improvement is not immediate, men with moderate to severe obstructive GU symptoms can have improvement in urinary function after EBRT, without significant risk for severe morbidity.

Objective: To use the Surveillance, Epidemiology, and End Results (SEER) registry to analyze age-specific time trends in the use of radiotherapy (RT) (external beam radiotherapy [EBRT], brachytherapy [brachy], and combination therapy [combo]) as first-line treatment for prostate cancer. Methods: A total of 820,649 prostate cancer patients in the SEER public-use registry (1973-2004) with diagnosis year, treatment, and age information available were identified. Modality use time-trend curves were plotted for patients 45 to 85 + years of age, grouped in 5-year intervals. A nonparametric (Spearman) test was used to assess the correlation between diagnosis year and (a) percentage use of RT and (b) relative percentage use of EBRT, brachy, and combo therapy. Results: Over the study period from 1973 to 2004, RT use increased in patients ≥65 years of age, but has remained stable in patients

Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported.52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded.Median follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively.In this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.

Purpose To describe genitourinary (GU) toxicity in men with a history of transurethral resection of the prostate (TURP) treated with external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials Seventy-one men with a history of TURP were treated with EBRT for prostate cancer. The median time from TURP to EBRT was 15 months. The median EBRT dose was 70 Gy, and 21 men (30%) received androgen deprivation therapy (ADT). Acute GU toxicity and late GU toxicity were scored by Radiation Therapy Oncology Group criteria and compared with a cohort of 538 men without prior TURP. The median follow-up for men with TURP and men without TURP was 40 months and 50 months, respectively ( p = 0.7605). Results The rate of acute Grade 2 GU toxicity or higher was 41%, and was increased with a history of more than 1 TURP (73% vs. 31%, p = 0.0036). The 4-year rate of freedom from late Grade 3 GU toxicity or higher was 84%, and was decreased with ADT (45% vs. 95% without ADT, p = 0.0024). By last follow-up, maximal GU toxicity tended to resolve ( p p = 0.6911). Compared to men without a prior TURP, TURP patients had a lower rate of freedom from late Grade 3 toxicity or higher (84% vs. 96%, p = 0.0483). Multivariate analysis suggested a higher rate of late Grade 3 toxicity or higher with TURP (risk ratio, 2.87; p = 0.0612) and EBRT dose of 74 Gy or greater (risk ratio, 2.26; p = 0.0521). Conclusions Men treated for prostate cancer with EBRT after TURP have a higher risk of severe GU toxicity; however, the overall incidence is low, and toxicity tends not to persist.

Purpose There has been growing interest in the potential anticancer activity of statins based on preclinical evidence of their antiproliferative, proapoptotic, and radiosensitizing properties. The primary objective of this study was to determine whether statin use is associated with improved clinical outcomes in patients treated with radiotherapy (RT) for prostate cancer. Patients and Methods In total, 691 men with prostate adenocarcinoma treated with curative-intent RT between 1988 and 2006 were retrospectively analyzed. Of those, 189 patients (27%) were using statins, either during initial consultation or during follow-up. Lipid panels were collected (n = 298) a median of 5 months before RT start. Median follow-up was 50 months after RT. Results Statin use was associated with improved freedom from biochemical failure (FFBF; P < .001), freedom from salvage androgen deprivation therapy (FFADT; P = .0011), and relapse-free survival (RFS; P < .001). Improved FFBF for statin users was seen in low-, intermediate-, and high-risk groups (P = .0401, P = .0331, and P = .0034, respectively). The improvement in FFBF with statin use was independent of ADT use or radiation dose. On multivariable analysis, statin use was associated with improved FFBF (P < .001) along with pretreatment prostate-specific antigen ≤ 8.4 (P < .001), stage less than T2b (P = .0111), and Gleason score < 7 (P = .0098). On univariate analysis, pretreatment total cholesterol < 187 (89% v 80%; P = .0494) and low-density lipoprotein (LDL) < 110 (96% v 85%; P = .0462) were associated with improved 4-year FFBF. Conclusion Statin use was associated with a significant improvement in FFBF, FFADT, and RFS in this cohort of men treated with RT for prostate cancer. The favorable effect of statins may be mediated by direct effect or via the LDL-lowering effect of these medications.

Importance Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. Objective To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. Design, Setting, and Participants This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Main Outcomes and Measures Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Results Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Conclusions and Relevance Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Objectives: Although specialized (urology/radiotherapy [RT]) databases have been used to measure practice patterns in nonmetastatic prostate cancer, the Surveillance, Epidemiology, and End Results (SEER) registry has not yet been employed for this task in detail. Our objectives were to analyze time trends in the use of surgery and RT and type of RT (external beam RT [EBRT], brachytherapy [Brachy] or combination EBRT + Brachy [Combo]). Methods: Eight lakh twenty-three thousand two hundred ninety-four patients in the SEER public-use registry (1973―2004) were identified. Modality time-trend curves were plotted for the whole group and by (a) grade (well-differentiated [WD], moderately differentiated [MD], and poorly differentiated [PD]) and (b) stage (modified AJCC stage 0-I, stage II, and stage III). A nonparametric (Spearman) test was used to assess correlation of diagnosis year with (a) percentage use of RT and (b) percentage use of EBRT, Brachy, and Combo. Results: RT use steadily increased from 9.1% in 1973 to 26.0% in 2004 (P < 0.001). Within RT, EBRT use decreased from 99.3% to 59.3% (P < 0.001), Brachy use increased from 0.0% to 29.6% (P < 0.001), and Combo use increased from 0.0% to 11.1% (P < 0.001). Similar time-trend curves to the overall group were observed for all grades and for stage 0 to II patients; stage III time trends were somewhat more static. Conclusions: Our SEER analysis demonstrated an expected rise in RT use (and relative increase in Brachy) paralleling the rise in evidence for modem EBRT and Brachy efficacy/safety. Within stated limitations, these results can serve as national benchmarks to assess prevailing referral patterns in a given institution or region.

BACKGROUND: Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer. METHODS: The study cohort consisted of 662 patients with adenocarcinoma of the prostate who received radiotherapy (RT) with curative intent. Among those 622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin). All patients received external-beam RT, permanent seed implantation, or a combination of both. Prostate-specific antigen (PSA) values were monitored for biochemical control of disease. RESULTS: At a median follow-up of 49 months, the biochemical control rate at 4-years was significantly better in patients who received ACs at 91% compared with 78% in patients who did not receive ACs (P = .0002). The distant metastasis rate at 4 years also was reduced in the AC group compared with the non-AC group (1% vs 5%; P = .0248). In subgroup analysis, the improvement in biochemical control was significant only for patients with high-risk disease. Along with Gleason score, T classification, and initial PSA, the use of AC therapy was associated independently with improved biochemical control in multivariate analysis. CONCLUSIONS: AC therapy was associated with an improvement in biochemical control in patients with prostate cancer who received RT with curative intent. The effect was most prominent in patients who had high-risk disease. Cancer 2010. © 2010 American Cancer Society.