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Immunotherapy has emerged as a promising therapeutic option for advanced or unresectable hepatocellular carcinoma (HCC). However, survival remains poor with only a subset of patients deriving benefit. This trial investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in HCC.In this multicenter phase 1 randomized trial, patients with advanced or unresectable HCC received liver SBRT (40 Gy in 5 fractions) followed by either nivolumab alone or nivolumab plus ipilimumab. The primary endpoint was dose-limiting toxicity occurring within 6 months of SBRT. Secondary endpoints included overall response rate, progression-free survival, overall survival (OS), distant disease control, and local control of the irradiated tumor. Disease status and response endpoints were assessed radiographically every 8 weeks until progression or initiation of nonprotocol therapy. Response was determined using both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and iRECIST.Fourteen patients were enrolled across 3 centers. Thirteen patients were evaluated for study endpoints. The study was closed early because of slow accrual. The median follow-up time was 42.7 months. Dose-limiting toxicities within 6 months occurred in 2 (15.4%) of 13 patients: 1 of 6 patients in the nivolumab arm (16.7%; 90% confidence interval [CI], 0.9%-58.2%) and 1 of 7 patients in the nivolumab plus ipilimumab arm (14.3%; 90% CI, 0.7%-52.1%). Grade 3 adverse events occurred in 8 (61.6%), 5 (71.4%), and 3 (50.0%) patients in the overall nivolumab plus ipilimumab and nivolumab cohorts. Grade 3 hepatotoxicity occurred in 4 (30.8%), 3 (42.9%), and 1 (16.7%) patients in the respective cohorts. Clinical outcomes favored the nivolumab plus ipilimumab arm compared with nivolumab alone, including an overall response rate of 57% (4 of 7 patients; 90% CI, 23%-87%) versus 0% (0 of 6 patients; 90% CI, 0%-39%), median progression-free survival of 11.6 months (90% CI, 4.5 months to not reached) versus 2.7 months (90% CI, 1.3-4.7 months), and median OS of 41.6 months (90% CI, 4.5 months to not reached) versus 4.7 months (90% CI, 2.0-16.2 months) (all P.05). With combination immunotherapy, 3-year OS was 57% (90% CI, 23%-81%), with 2 patients alive after 42.7 months without progression and negative PET.In this first prospective trial investigating the combination of SBRT and immunotherapy for HCC, multimodal therapy demonstrated acceptable safety. SBRT with nivolumab plus ipilimumab compared favorably to outcomes of immunotherapy alone and warrants further investigation.

There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.

The incidence of anal cancer in the United States has increased in recent years, primarily related to the increasing incidence of HPV-associated anal squamous cell carcinoma, which is estimated to represent 80%-95% of anal cancers. Similar to head and neck cancer, HPV association has been demonstrated to be a strong positive prognostic factor in patients with anal cancer. Encouraging results from a number of studies investigating treatment de-escalation for HPV-associated oropharyngeal cancer support the notion that similar attempts may be feasible in HPV-associated anal cancer; however, the data to support this hypothesis are currently lacking. Studies are needed to determine how, if at all, HPV status should impact the management of patients with anal cancer. This review summarizes the relationship between HPV association and outcomes for patients with anal cancer, and how HPV status may impact the treatment of patients with anal cancer going forward.

Purpose Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. Methods and Materials We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework. Results A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. Conclusions There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.

Purpose Conventional imaging rarely localizes the site(s) of prostate cancer recurrence in patients undergoing evaluation for salvage radiation therapy (sRT) after radical prostatectomy (RP). LOCATE (NCT02680041) was a prospective, multicenter study investigating the impact of 18F-fluciclovine positron emission tomography and computed tomography (PET/CT) on the management of patients with biochemical recurrence of prostate cancer after curative-intent radiation or RP and negative or equivocal conventional imaging. Our objective was to determine the impact of 18F-fluciclovine PET/CT on treatment decisions for men planning to undergo sRT for biochemical recurrence post-RP. Methods and Materials We conducted a subgroup analysis of post-RP patients enrolled in LOCATE who were planning to undergo sRT with or without hormonal therapy based on prescan documentation. 18F-Fluciclovine PET/CT was performed according to standardized procedures. The treatment plan postscan was compared with the prescan plan, and Fisher exact test was used to determine the impact of prescan prostate-specific antigen (PSA) and Gleason sum (GS) on positivity and anatomic patterns of uptake. Results A total of 114 patients (median prescan PSA 0.42 [interquartile range, 0.3-1.1] ng/mL) met selection criteria (54% of patients in LOCATE). Forty-eight (42%) had 18F-fluciclovine-avid lesions. Twelve patients (11%) had positive findings only in the prostate bed, 24 (21%) had positivity only in the pelvis (prostate bed or pelvic nodes), and 24 (21%) had extrapelvic findings. PSA >0.5 ng/mL and GS ≥8 were associated with a higher risk of extrapelvic positivity (P Postscan, 55 (48%) patients had a management change; 37 (32%) had a change in overall treatment approach (ie, omission of sRT); and 18 (16%) had sRT target modification. Conclusions 18F-Fluciclovine PET/CT is positive in nearly half of patients planning to undergo post-RP sRT with negative/equivocal conventional imaging, with findings frequently leading to changes in management. PSA >0.5 ng/mL and GS ≥8 are associated with a higher risk of extrapelvic positive findings.

Background Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes. Methods A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS). Results After a median follow‐up of 103 months, 10‐year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10‐year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10‐year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count, 482 men received primary radiotherapy for non‐metastatic prostate cancer and those men with pre‐treatment platelet count in the lowest quartile experienced worse 10‐year freedom from biochemical failure (61% vs 81%, P

Background Fiducial markers are frequently used before treatment for image‐guided patient setup in radiation therapy (RT), but can also be used during treatment for image‐guided intrafraction motion detection. This report describes our implementation of automatic marker detection with periodic kV imaging (TrueBeam v2.5) to monitor and correct intrafraction motion during prostate RT. Methods We evaluated the reproducibility and accuracy of software fiducial detection using a phantom with 3 implanted fiducial markers. Clinical implementation for patients with intraprostatic fiducials receiving volumetric modulated arc therapy (VMAT) utilized periodic on‐board kV imaging with 10 s intervals during treatment delivery. For each image, the software automatically identified fiducial locations and determined whether their distance relative to planned locations were within a 3 mm tolerance. Motion was corrected if either ≥2 fiducials in a single image or ≥1 fiducial in sequential images were out of tolerance. Results Phantom studies demonstrated poorer performance of linear fiducials compared to collapsible fiducials, and wide variability to accurately detect fiducials across eight software settings. For any given setting, results were relatively reproducible and precise to ~0.5 mm. Across 17 patients treated with a median of 20 fractions, the software recommended a shift in 44% of fractions, and a shift was actually implemented after visual confirmation of movement greater than the 3 mm threshold in 20% of fractions. Adjustment of our approach led to improved accuracy for the latter (n = 7) patient subset. On average, table repositioning added 3.0 ± 0.3 min to patient time on table. Periodic kV imaging increased skin dose by an estimated 1 cGy per treatment arc. Conclusions Periodic kV imaging with automatic detection of motion during VMAT prostate treatments is commercially available, and can be successfully implemented to mitigate effects of intrafraction motion with careful attention to software settings.

Rationale and Objectives To investigate whether pre-treatment quantitative multiparametric MRI can predict biochemical outcome of prostate cancer (PCa) patients treated with primary radiotherapy (RT). Materials and Methods Fifty-one patients with biopsy confirmed PCa underwent prostate multiparametric MRI on 3T MR scanner prior to RT. Thirty-seven men (73%) were treated with external beam RT alone, 12 men (24%) were treated with brachytherapy monotherapy, and two men (4%) were treated with external beam RT with brachytherapy boost. The index lesion was outlined by a radiologist and quantitative apparent diffusion coefficient (ADC), T2 and DCE parameters were measured. Biochemical failure was defined using the Phoenix criteria. Results After a median follow-up of 65 months, seven patients had biochemical failure. ADC had an area under the receiver operating characteristic curve of 0.71 for predicting RT outcome with significantly lower ADC (0.78 ± 0.17 vs 0.96 ± 0.26 µm2/ms, p = 0.04) of the index lesion in men with biochemical failure. Ideal ADC cutoff point (Youdens index) was 0.96 µm2/ms which had a sensitivity of 100% and specificity of 48% for predicting biochemical failure. Kaplan-Meier analysis showed that lower ADC values were associated with significantly lower freedom from biochemical failure (FFBF, p = 0.03, no failures out of 20 men if ADC ≥ 0.96 µm2/ms; seven of 31 with failures if ADC Conclusion Our results suggest that quantitative ADC values of the index lesion may predict biochemical failure following primary radiotherapy in patients with PCa. Lower ADC values were associated with inferior biochemical control.

PURPOSE The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.

Purpose/Objective(s) A data registry was established upon implementation of a program of intra-operative radiation therapy (IORT) using high-dose rate brachytherapy. We evaluated the initial experience of patients with locally recurrent gastrointestinal (GI) cancers to help inform future patient selection and optimal multi-modal treatment management. Materials/Methods All patients treated with surgical resection and IORT at a tertiary referral center were prospectively enrolled in a registry after program implementation in 2015. Candidates for IORT included patients who presented with disease likely to be resected with either close or positive margins based on multi-disciplinary evaluation. Patient, disease, and treatment characteristics including radiation history and acute (within 90 days, Clavien-Dindo grade) were recorded. IORT was administered using a HAM applicator, with field size and location determined intra-operatively, prescribed to 1 cm depth with lead blocking as appropriate. Patterns of failure and toxicity were analyzed. Time to event analysis was conducted using Kaplan Meier method, and contingency tables and chi square statistics evaluated differences in frequency of events. Results Twenty-one patients were identified with locally recurrent GI cancer (rectal 62%, colon 29%, and anal cancer, 9%) who underwent surgical resection and IORT with curative intent. Median age was 58 years. All patients had a history of pelvic external beam radiotherapy (EBRT, median 50.4 Gy); 9 (43%) were treated with pre-operative reirradiation (median dose 43 Gy, median 2 mo prior to surgery). The median IORT dose was 12.5 Gy (range 10-15). Resection was pathologically complete (R0, n = 9), or with microscopic (R1, n = 11) or macroscopic residual (R2, n = 1). Median follow up was 20 months. Twelve (57%) patients had failure at the site of IORT, at a median 7 mo. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF-1y 75% for R0 vs 15% for R1/2, P = 0.0065) but not re-irradiation EBRT or IORT dose (P > 0.05). Pelvic failure beyond the IORT site occurred in 5 (24%) patients at a median 5 mo, and 13 (62%) had eventual distant metastases, at a median 5.5 months. Ultimately, only 3 patients (14%) were disease free at last follow-up. The median hospital stay was 6 days, the 90-day readmission rate was 25%, and acute grade 3 toxicity was observed in 43%, with abscess/sepsis most common (n = 5, 24%). Grade 3 toxicities and 90-day admission were not associated with resection status or EBRT (all P > 0.1). There were no 90-day grade 4/5 toxicities. Conclusion In patients treated with surgical excision and IORT for locally recurrent GI cancer, the ability to achieve a clear resection margin is a critical determinant of in-field local control. Patient selection should consider the chance for R0 resection, as well as the risk of regional or distant progression, when evaluating patients for this aggressive multi-modal treatment.

Purpose Urethral cancer is rare, with limited data guiding treatment. A national hospital-based registry was used to evaluate the role of local therapy in these patients. Methods and Materials We performed a retrospective cohort study of patients who, between 2004 and 20013, received a diagnosis of T0-4N0-2 M0 urethral cancer. Local therapy was radiation therapy (RT), surgery (S), or S and RT (S+RT). The Cox proportional hazards model was used to assess the impact of therapy type on overall survival (primary endpoint). Subgroup analysis by extent of disease (early stage [T0-2 N0] vs locally advanced [T3+ or N+]) and histology was performed. Results In our study, 2614 patients had a median follow-up of 28 months. Three-year overall survival was 54%. In 501 patients with locally advanced disease, S+RT was associated with improved survival versus S alone (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.42-0.80). There was no difference for patients with squamous cell carcinoma by treatment type, but patients with adenocarcinoma (RT vs S: HR 0.20; 95% CI, 0.07-0.60) or transitional cell carcinoma (S+RT vs S: HR 0.45, 95% CI, 0.26-0.77) had improved OS with RT as part of treatment. In 1705 early-stage patients, there was no association with survival when comparing S+RT versus S. Conclusions For patients with locally advanced disease and transitional cell carcinoma undergoing S, the addition of RT is associated with improved overall survival and should be considered. An RT-based approach may be preferred for adenocarcinoma, but there was no clear association with survival by therapy type for squamous cell carcinoma. This study is hypothesis generating; prospective trials are necessary.

Purpose Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. Methods and materials 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. Results With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. Conclusions More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

PURPOSE/OBJECTIVE(S) Hematuria is a potentially distressing late toxicity of post-prostatectomy radiotherapy (PPRT). Because of the potential for a long latent period between PPRT and symptoms, it may be underreported in the literature. We examined incidence and severity of this toxicity in a cohort with long term follow-up. MATERIALS/METHODS A prospectively maintained database was queried for men treated with PPRT with a minimum potential follow-up of 4 yrs. Late (≥ 90 d) genitourinary toxicity and hematuria were characterized using physician-assigned RTOG/CTCAE grading and patient-reported outcomes, inclusive of clinical visits, urinalysis, and procedure notes from each patient's complete electronic medical record. Freedom from grade 2+ hematuria (FFG2H; macroscopic hematuria) and grade 3+ hematuria (FFG3H; hematuria requiring intervention) were estimated. Patient and treatment characteristics were assessed for association with FFG2H on univariable analysis (UVA) using log-rank tests. The Cox model was used to create a multivariable model (MVA) for FFG2H including all covariates with P < 0.1 on UVA. Quality of life (QOL) was assessed using EPIC-26. RESULTS 216 consecutive men underwent PPRT from 2007-2016 with a median dose to the prostate bed of 68.4 Gy. 66% and 64% of men were treated with androgen deprivation therapy (median 4 mo) and pelvic nodal radiotherapy (median 50.4 Gy), respectively. Median time from prostatectomy to PPRT was 20 mo. With a median follow-up of 72 mo, the incidence of grade 1+, 2+, and 3+ hematuria was 39%, 35%, and 7%, respectively. 8-yr FFG2H and FFG3H were 55% and 91%, respectively. On UVA, the percentage of bladder receiving 65 Gy (V65, median 43%) was found to correlate with FFG2H, while V70 and V40 were not. FFG2H was 43% among men with a bladder V65 ≥ 43% versus 66% in men with a V65 < 43% (P = 0.004). On MVA, inferior FFG2H was most strongly associated with anticoagulant/antiplatelet therapy (AC/AP; HR 3.25, P < 0.001), followed by bladder V65 ≥ 43% (HR 1.97, P = 0.004) and history of medication allergies (HR 1.73, P = 0.049), after controlling for age ≥ 65 yrs (HR 1.23, P = .374) and diabetes mellitus (HR 0.49, P = 0.098). 23% of men underwent at least one cystoscopy with the majority demonstrating RT-related changes and no other potential etiology; however, one man was diagnosed with a superficial bladder cancer. 7% had an emergency room visit due to hematuria. Hematuria was typically managed conservatively; only 6% required intervention (most commonly hyperbaric oxygen and cautery, each at 3%). 11% of men experienced recurrent hematuria, at a median 26 mo after initial symptoms. QOL data to be presented. CONCLUSION Hematuria is a common late toxicity, even 5-10 yrs after PPRT, especially in men on AC/AP. The vast majority of episodes are transient and self-limited. Bladder V65 represents a potential dosimetric factor which can be used to predict or mitigate the risk of hematuria.

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.

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.

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.

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.

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.

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.

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.

To the Editor:We appreciate the interest taken in our analysis of pelvic failures after radical cystectomy (1, 2). We agree with the comments made that our study supports several notions that have more recently come to light: (1) after radical cystectomy, pelvic recurrences occur at a rate that is higher than historically reported, in up to 30% to 50% of selected patients; (2) adjuvant chemotherapy does not appear to substantially reduce the risk of pelvic failure; and (3) histology does not appear to influence the pattern of pelvic failure. Additionally, our analysis presents a few new considerations for this clinical situation: (1) margin-positive resections do not necessarily increase the risk of failure at the cystectomy bed alone; (2) a reasonable proportion of local and regional failures may occur without concurrent distant disease, suggesting a chance to influence survival with improved local and regional control; and (3) a low proportion of patients demonstrates evidence of recurrence in the cystectomy bed, suggesting a relatively higher value in covering nodal regions at risk and a possible means to reduce the risks of adjuvant local therapy. Our conclusions must be considered in the context of the retrospective, single-institution nature of the study, so we await prospective trials to help substantiate our findings. The recent presentation by Zaghloul et al (3) from the Egyptian NCI indicates that pelvic control can be reduced by adjuvant radiation therapy (3-year local-regional relapsefree survival 87%vs 69%,P

Renal cell carcinoma accounts for 2%-3% of all visceral malignancies. Preoperative imaging can provide important staging and anatomic information to guide treatment decisions. Size of the primary tumor and degree of local invasion, such as involvement of perinephric fat or renal sinus fat, and tumor thrombus in renal veins and inferior vena cava are important detriments to local staging of primary tumor. Both kidneys are assessed for presence of other synchronous lesions. The ACR Appropriateness Criteria ® are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and application by the panel of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

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.

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.

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: To report the tolerability and efficacy of twice-daily whole-abdomen irradiation (WAI) for non-Hodgkin’s lymphoma (NHL). Methods and Materials: Of 123 patients treated for NHL with WAI, 37% received previous chemotherapy, 28% received WAI as part of comprehensive lymphatic irradiation (CLI), and 32% received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy, followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0 Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured weekly. Results: At a median follow-up of 4.3 years, local control was 72% and overall survival was 55% at 5 years. Median time of WAI was 42 days for once-daily treatment and 32 days for twice-daily treatment. Patients receiving twice-daily WAI did not have a significantly higher rate of acute side effects (e.g., nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute thrombocytopenia was the most frequent side effect of treatment; 24 of 96 patients (25%) with available hematologic data had Grade 3+ toxicity. There was no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction. Multiple regression indicated that patients with four or less involved sites and disease size ≤6 cm had improved local control and overall survival. Conclusions: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small doses per fraction (0.8–1 Gy/fx) are effective, tolerated well in the acute setting, and associated with a low rate of late toxicity.

Purpose: Our aim was to report the control rate of radiographically positive retropharyngeal (RP) nodes with radiation therapy (RT) and to correlate posttreatment imaging with clinical outcome. Methods and Materials: Sixteen patients treated with definitive RT for head-and-neck cancer had radiographically positive RP nodes (size >1 cm in largest axial dimension, or presence of focal enhancement, lucency, or calcification), and both pre-RT and post-RT image sets available for review. An additional 21 patients with unconfirmed radiographically positive RP nodes had post–RT imaging, which consisted of computed tomography (CT) at a median of 4 weeks after completing RT. Patients with positive post-RT RP nodes underwent observation with serial imaging. Results: Of 16 patients with pre-RT and post-RT images available for review, 9 (56%) had a radiographic complete response, and of 21 patients with unconfirmed positive RP nodes with post-RT images available for review, 14 (67%) had a radiographic complete response. In all, 14 patients with incomplete response on post–RT imaging experienced control of their disease with no further therapy, and no RP node or neck failures were noted during a median follow-up of 2.8 years. Six patients with positive post-RT RP nodes had serial imaging available for review, and none demonstrated radiographic progression of disease. Conclusions: Radiographic response at 4 weeks may not accurately reflect long-term locoregional control, as RP nodes may continue to resolve over time. The highest index of suspicion should be reserved for patients with progressive changes in size, focal lucency, or focal enhancement on serial imaging after RT.