e16541 Background: Bone metastases are a debilitating aspect of prostate cancer progression. Stereotactic Body Radiotherapy (SBRT) has gained momentum as a treatment option for oligometastatic prostate cancer (OPC). We report on a large multi-center cohort of OPC treated by SBRT techniques in the community setting. Methods: This is an IRB approved retrospective study of men undergoing SBRT for OPC at 32 centers. Cumulatively, 121 men with a median age of 74 years were treated to 188 lesions. The median follow-up was 7.8 months. Most men had received prior androgen deprivation therapy (84%). Systemic therapy included abiraterone (14%), docetaxel-based chemotherapy (13%), Sipuleucel-T (10%), enzalutamide (9%), and Radium 223 (6%). Three percent had undergone surgery and 21% had received prior radiation therapy to bone lesion(s). Technetium-99 bone scan (59%), Na-F18 PET/CT bone scan (23%), and MRI (21%) were commonly used for diagnostic evaluation and/or treatment planning. The spine was the most common radiated site (67%). Fractionation schedules varied but most commonly: 8 Gy x 3 (34%), 5 Gy x 5 (19%), 6 Gy x 5 (10%). Results: Prior to SBRT, 83% of patients had clinically significant bone pain. At follow up, 76% noted a significant improvement in pain (p = .02) as their best response post SBRT. Only 2 patients had no pain relief and 1 patient had increased pain. No acute toxicity was reported in 93%; Grade 1-2 esophagitis was the most common side effect (3%). Late toxicity was noted in one case of Grade 1 lung fibrosis. Fractionation scheme or location of the OPC did not appear to influence outcome or morbidity. Conclusions: These data suggest SBRT is a well-tolerated treatment option that offers statistically significant, clinically relevant pain control for OPC. While a variety of fractionation schemes are employed, virtually all SBRT patients maintain a prolonged level of pain relief. Given the results of the present study and the recent improvements in systemic therapies for OPC, further studies to evaluate the combination of these treatments are warranted.

Stereotactic body radiation therapy (SBRT) offers promise as a developing standard of care for localized prostate cancer. As compared to a conventional schedule, hypofractionated treatment may produce higher tumor control rates while maintaining an equivalent biologic effective dose (BED) to normal tissues for late effects and reducing BED for acute effects. Most previous single institution studies have specifically focused on patients with low risk prostate cancer with limited data available in intermediate (IRPC) or high risk prostate cancer. We describe toxicity and biochemical progression free survival outcomes of linear accelerator based SBRT boost for IRPC. This is a multi-center (9) retrospective review of prospectively collected data for a total of 60 patients; thirty-eight patients (63%) were treated on an IRB approved prospective trial. IRPC patients that included clinical stage T2b (7%) or PSA > 10 ng/ml and < 20 ng/ml (25%) or Gleason score of 7 (82%), received 45 Gy of IMRT in 25 fractions followed by a SBRT boost of 5.5 Gy per fraction for 4 fractions. Cone beam CT image guidance was used prior to each fraction for correction of target setup error. Twenty-three percent of patients received concomitant androgen deprivation therapy (ADT); forty-six patients (77%) deferred concomitant ADT. NCI CTCAE v3.0 was used to assess urinary and rectal toxicity at baseline, during treatment, and then at 1, 3, 6, 9, 12, 18, 24, 30, and 36 months after treatment. Biochemical determinations were made at concurrent follow up time points. IPSS and IEFF scores were also obtained at baseline and at follow up. Median follow up was 21.5 months (range 2.9-87.2). No patient (0%) had a biochemical failure, using the combined ASTRO Phoenix definition. Mean PSA (ng/ml) at baseline was 8.5; 2.9 at 1, 1.7 at 3, 1.3 at 6, 0.8 at 9, 1.0 at 12, 0.7 at 18, 0.4 at 24, 0.3 at 30 months after treatment respectively. With respect to toxicity, Grade 3-5 Genitourinary (GU) toxicity was 3%, with 2 patients experiencing grade 3 (3%), and no patient experiencing grade 4 or 5 toxicity. The most common GU toxicity was urinary frequency/urgency, experienced by 35% of patients at baseline, peaking during treatment to 65%, declining to 24% by 12 months and thereafter remaining stable. Grade 3-5 Gastrointestinal (GI) toxicity was 2%, with 1 patient experiencing grade 3 (2%), and no grade 4 or 5 toxicity. Diarrhea was the most common side effect seen, 24% during treatment, all Grade 1. This toxicity resolved rapidly, with 4% at 12 months and 0% thereafter. Linear accelerator based SBRT boost for IRPC produces a rapid biochemical response with favorable urinary and rectal toxicity following treatment. Interestingly, a clinically significant number of patients had GU symptoms at baseline which improved over time. Further follow up is needed to determine long-term toxicity and disease control outcomes.

Significant improvements on radiation dose planned and delivered have occurred with the advent of intensity modified radiation therapy (IMRT) and image guided RT (IGRT). However, the fundamental questions remains: is dose planned equivalent to dose delivered? In an effort to look at this fundamental question, a total of 490 prostate patients' plans were analyzed. Daily online computed tomographic (CT)-based image guidance was performed for all treatment fractions. To evaluate the actual dose deposited to the patient, an adaptive dose recalculation (ADR) process was used. As such, the dose was computed in each one of the daily CTs. A deformable registration code provides deformation maps that are used to map back the dose to the planning CT. Adding the dose mapped back can generate the cumulative dose. In this way we can compare the planned dose with the adaptive cumulative dose that was computed. Table 1 displays the comparison results between the delivered dose and the planned dose. For the delivered dose the one computed with the ADR process was used. For the target we consider as deviation (+) or (-) for the chosen criteria. For the organs at risk we consider as deviation when the actual dose is larger than the planned dose.Poster Viewing Abstracts 2593; Table 1Structure/Criteria% of patients where actual and planned dose differ by < 2%% of patients where actual and planned dose differ by < 5%% of patients where actual and planned dose differ by < 10%PTV Dmean86.9398.97100PTV D9564.2887.3596.33Rectum D2079.3490.5995.91Rectum D5074.0287.3294.48Rectum D6068.9186.0994.27Rectum D7564.2183.2393.86Bladder D2080.4992.4099.18Bladder D5075.5788.7197.33Bladder D6073.5186.0495.89Bladder D7570.2380.0494.66 Open table in a new tab For modern RT practice with routine online IGRT, there appears to be further room for improvement in delivered dose relative to planned dose. Only 80% to 90% of patients had variation ≤5% for most dosimetric endpoints due primarily to intrafraction motion and deformation.

Purpose/Objective(s)External beam photon radiation therapy (XRT) is an accepted curative treatment option for men with localized prostate cancer. This cohort of patients may include those of widely disparate chronological ages. As age may influence treatment, morbidity, and response, we examined and compared treatment technique and outcome for older and younger men treated for this diagnosis.Materials/MethodsAn institutional review board–approved chart review of our institution’s database of definitive RT for localized prostate cancer returned 416 patients treated during 2009 to 2011. Age ranged from 49 to 88 years, with 7% aged 60 or less, 37% aged 61 to 70, 46% aged 71 to 80, and 9% aged greater than 80 years. Stage was T1 in 70% (n=292), T2 in 24% (n=100), and T3 in 3% (n=13). The T stage was not noted in 11 patients. The Gleason score was 6 in 47% of patients, 7 in 38%, 8 in 8%, and 9 in 5%. Hormones were delivered to 41% of patients. Photon radiation was delivered by intensity modified RT in all cases with 97% also undergoing image guidance. Radiation dose was generally 81 Gy. The mean rectal dose was 32.7 Gy, and the mean bladder dose was 28.4 Gy. Only 7.5% of patients were reported to have whole-pelvic XRT.ResultsPatients have been followed a mean of 11.2 months (range 1.5 – 35.1 months). Acute genitourinary (GU) complications were mild with 86% reported as Grade 0, 1, or 2. Acute gastrointestinal (GI) complications were also mild with 86% reported as grade 0, 1, or 2. No Late GU complications were reported in 90% of men and no late GI complications were reported in 96%. Only 3% of patients had any treatment interruption. Local failure has not been seen and 99% of patients are alive at last follow-up. No deaths attributed to prostate cancer have been reported. On univariate analysis and comparing age groups (<60, 61-70, 71-80, >80 years), no significant differences are noted in T stage, Gleason Score, treatment techniques or dose, GI or GU morbidity (acute or chronic), outcomes, or treatment break among other variables. A statistically significant difference favoring the use of hormonal blockade in patients older than 70 years (P<.03) was noted. There was biochemical failure in 4 patients (1%). Only Gleason Score predicted significantly for biochemical failure (P=.03). There was no difference when analyzing by T stage, dose, treatment field, or age.ConclusionAge should not be a major determinant in delivering definitive photon RT for localized prostate cancer. Elderly patients can be treated identically to younger patients with the expectation of similar outcomes. No increase in acute or chronic morbidity was noted based on age, and treatment breaks were not related to age. Outcomes appear identical in terms of disease control and cancer-specific survival. Older gentlemen were more commonly treated with the addition of hormonal blockade, though this may represent undertreatment of younger men in an attempt to preserve sexual function. Purpose/Objective(s)External beam photon radiation therapy (XRT) is an accepted curative treatment option for men with localized prostate cancer. This cohort of patients may include those of widely disparate chronological ages. As age may influence treatment, morbidity, and response, we examined and compared treatment technique and outcome for older and younger men treated for this diagnosis. External beam photon radiation therapy (XRT) is an accepted curative treatment option for men with localized prostate cancer. This cohort of patients may include those of widely disparate chronological ages. As age may influence treatment, morbidity, and response, we examined and compared treatment technique and outcome for older and younger men treated for this diagnosis. Materials/MethodsAn institutional review board–approved chart review of our institution’s database of definitive RT for localized prostate cancer returned 416 patients treated during 2009 to 2011. Age ranged from 49 to 88 years, with 7% aged 60 or less, 37% aged 61 to 70, 46% aged 71 to 80, and 9% aged greater than 80 years. Stage was T1 in 70% (n=292), T2 in 24% (n=100), and T3 in 3% (n=13). The T stage was not noted in 11 patients. The Gleason score was 6 in 47% of patients, 7 in 38%, 8 in 8%, and 9 in 5%. Hormones were delivered to 41% of patients. Photon radiation was delivered by intensity modified RT in all cases with 97% also undergoing image guidance. Radiation dose was generally 81 Gy. The mean rectal dose was 32.7 Gy, and the mean bladder dose was 28.4 Gy. Only 7.5% of patients were reported to have whole-pelvic XRT. An institutional review board–approved chart review of our institution’s database of definitive RT for localized prostate cancer returned 416 patients treated during 2009 to 2011. Age ranged from 49 to 88 years, with 7% aged 60 or less, 37% aged 61 to 70, 46% aged 71 to 80, and 9% aged greater than 80 years. Stage was T1 in 70% (n=292), T2 in 24% (n=100), and T3 in 3% (n=13). The T stage was not noted in 11 patients. The Gleason score was 6 in 47% of patients, 7 in 38%, 8 in 8%, and 9 in 5%. Hormones were delivered to 41% of patients. Photon radiation was delivered by intensity modified RT in all cases with 97% also undergoing image guidance. Radiation dose was generally 81 Gy. The mean rectal dose was 32.7 Gy, and the mean bladder dose was 28.4 Gy. Only 7.5% of patients were reported to have whole-pelvic XRT. ResultsPatients have been followed a mean of 11.2 months (range 1.5 – 35.1 months). Acute genitourinary (GU) complications were mild with 86% reported as Grade 0, 1, or 2. Acute gastrointestinal (GI) complications were also mild with 86% reported as grade 0, 1, or 2. No Late GU complications were reported in 90% of men and no late GI complications were reported in 96%. Only 3% of patients had any treatment interruption. Local failure has not been seen and 99% of patients are alive at last follow-up. No deaths attributed to prostate cancer have been reported. On univariate analysis and comparing age groups (<60, 61-70, 71-80, >80 years), no significant differences are noted in T stage, Gleason Score, treatment techniques or dose, GI or GU morbidity (acute or chronic), outcomes, or treatment break among other variables. A statistically significant difference favoring the use of hormonal blockade in patients older than 70 years (P<.03) was noted. There was biochemical failure in 4 patients (1%). Only Gleason Score predicted significantly for biochemical failure (P=.03). There was no difference when analyzing by T stage, dose, treatment field, or age. Patients have been followed a mean of 11.2 months (range 1.5 – 35.1 months). Acute genitourinary (GU) complications were mild with 86% reported as Grade 0, 1, or 2. Acute gastrointestinal (GI) complications were also mild with 86% reported as grade 0, 1, or 2. No Late GU complications were reported in 90% of men and no late GI complications were reported in 96%. Only 3% of patients had any treatment interruption. Local failure has not been seen and 99% of patients are alive at last follow-up. No deaths attributed to prostate cancer have been reported. On univariate analysis and comparing age groups (<60, 61-70, 71-80, >80 years), no significant differences are noted in T stage, Gleason Score, treatment techniques or dose, GI or GU morbidity (acute or chronic), outcomes, or treatment break among other variables. A statistically significant difference favoring the use of hormonal blockade in patients older than 70 years (P<.03) was noted. There was biochemical failure in 4 patients (1%). Only Gleason Score predicted significantly for biochemical failure (P=.03). There was no difference when analyzing by T stage, dose, treatment field, or age. ConclusionAge should not be a major determinant in delivering definitive photon RT for localized prostate cancer. Elderly patients can be treated identically to younger patients with the expectation of similar outcomes. No increase in acute or chronic morbidity was noted based on age, and treatment breaks were not related to age. Outcomes appear identical in terms of disease control and cancer-specific survival. Older gentlemen were more commonly treated with the addition of hormonal blockade, though this may represent undertreatment of younger men in an attempt to preserve sexual function. Age should not be a major determinant in delivering definitive photon RT for localized prostate cancer. Elderly patients can be treated identically to younger patients with the expectation of similar outcomes. No increase in acute or chronic morbidity was noted based on age, and treatment breaks were not related to age. Outcomes appear identical in terms of disease control and cancer-specific survival. Older gentlemen were more commonly treated with the addition of hormonal blockade, though this may represent undertreatment of younger men in an attempt to preserve sexual function.

THE PROCEEDINGS OFACRO 2015 Abstracts of Oral and Poster Presentations, 25th Annual Meeting of the American College of Radiation Oncology, May 14–16, 2015 | Hyatt Regency Crystal City, Arlington, Virginias of Oral and Poster Presentations, 25th Annual Meeting of the American College of Radiation Oncology, May 14–16, 2015 | Hyatt Regency Crystal City, Arlington, Virginia Chair of the Scientific Program Committee: Arnab Chakravarti, MD, FACRO ORAL PRESENTATIONS Thursday, May 14, 2015 (5:15–6:15 pm) Abstracts Submitted by Trainee are identified by an *

For stereotactic body radiation therapy (SBRT) of lung tumors, random setup, anatomical variations, and the small number of treatment fractions delivered, may together significantly impact the actual dose received by the tumor and surrounding normal structures. We compared planned and actual dosimetry for 101 SBRT lung treatments to determine the effect of setup and anatomical changes on actual dose. This was a retrospective review of prospectively collected data for 101 patients treated with lung SBRT. The number of fractions per patient ranged from 3 to 10. A surrogate for the actual dose was computed using an adaptive dose recalculation (ADR) code. The ADR used the acquired CT prior to each fraction and calculated the fractional dose. A deformable registration code was used to generate daily contours. The deformable registration deformation maps also allowed for cumulative doses (as surrogate of the actual dose) to be calculated and compared to the planned doses. Daily and cumulative doses and DVHs were then evaluated and compared to the planned dosimetry. In all cases, we were able to compare the planned dose to the actual dose delivered using the adaptive dose recalculation code. The mean dose to the PTV was within +/- 5% respective to plan for 93 percent of the patients. The maximum PTV mean dose deviation respective to plan was 7% for one patient. Lung mean dose was within +/- 4% for 91% of the patients with a maximum deviation of 8.1%. Maximum dose to the esophagus was within +/- 5% for 76% of the patients with a maximum deviation of 25%. The dose to 33% of the volume for the heart was within +/- 10% for 90% of the patients with a maximum deviation of 55%. Maximum dose to the spinal cord was within +/- 10% respect to plan for 88% of the patients with a maximum deviation of 46%. Plan and actual dosimetry may differ due to setup and anatomical variations among patients treated with lung SBRT. Even when all observed variations were within acceptable tolerances, the use of planned dose (rather than in actual dose) as the dosimetric surrogate may lead to inaccurate representations of the actual dosimetric outcome during treatment.

Whole-pelvis radiotherapy or a short-course (approximately 4 months) of androgen deprivation therapy yield an all-cause mortality benefit among patients with unfavorable-risk prostate cancer. However, the combination of these 2 treatments does not further improve mortality outcomes, suggesting a shared therapeutic mechanism.Background: The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). Patients and Methods: A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. The median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration, 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason score >= 7; prostate-specific antigen >= 10 ng/mL; or stage >= T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. The interaction between radiation volume and ADT use was assessed. Results: After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = .01), or with ADT use (AHR, 0.71; 95% CI, 0.58-0.90; P = .004). However, a combination of WPRT and ADT did not further improve ACM compared with either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the radiotherapeutic treatment volume and ADT (AHR, 1.61; 95% CI, 1.004-2.58; P = .048). Conclusion: Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, although a combination of the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes. (C) 2015 Elsevier Inc. All rights reserved.

e16070 Background: In 2008, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific-antigen based screening for prostate cancer in men age > 75, and in 2012 recommended against screening in all men. It is unknown whether these guidelines have changed the number or risk profile of patients presenting to radiation oncology care. Methods: We conducted a retrospective study of patients who presented with localized prostate cancer in 2007-2013 to a network of radiation oncology clinics in southwest Florida. In the area, the provider network (21st Century Oncology) supplies nearly all radiation oncology services. We assessed trends in total patient volume and determined the risk distribution of a random sample of patients, using risk groups defined by the National Comprehensive Cancer Network. We applied this risk distribution to the total patient volume to estimate the number of patients presenting in each risk group. Results: The number of patients presenting with prostate cancer ...

To determine whether extent of prostate radiation therapy (i.e., whole-pelvic radiation therapy [WPRT] versus prostate/seminal-vesicle radiation therapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). A multi-institutional cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. Median age was 72 years, and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason ≥7; prostate-specific antigen [PSA] ≥10ng/mL; or stage ≥T2b). Cox regression was applied to determine whether the radiation treatment volume affected risk of ACM. Interaction between radiation volume and ADT use was assessed. After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR] 0.58; 95% confidence interval [CI] 0.38-0.89; P=.01), or with ADT use (AHR 0.71; 95% CI 0.58–0.90; P=.004). However, combining WPRT and ADT did not further improve ACM in comparison to either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the RT treatment volume and ADT (AHR 1.61; 95% CI 1.004–2.58; P=.048). Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, though combining the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes.

Radiation therapy and immunotherapy in partnership may have the capability of delivering a therapeutic effect exceeding the sum of its parts. The possible relationship has been demonstrated in murine models and has been extended to a variety of clinical trials. Though the standard notion of whole body radiation therapy is immunosuppressive, there is growing evidence toward the contrary for focal radiation therapy. Furthermore, if immunotherapeutic techniques can retune the immune system against cancerous cells, they should have obvious benefits for advanced treatments moving forward. Herein, we explore the promise in combining radiation therapy and immunotherapy with distinct focus on potential morbidities and toxicities through analysis of completed clinical trials.

PURPOSE: To determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer.METHODS AND MATERIALS: We analyzed 5972 men with Tlc-T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed.RESULTS: ADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02-4.17; p = 0.04]) or not (ABER, 1.8 [95% CI, 1.05-3.20; p = 0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p = 0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR = 2.21 [1.04-4.68]; p = 0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33-1.22]; p = 0.17).CONCLUSIONS: ADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

BackgroundSipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient's own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen.MethodsData relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation.ResultsData from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development.ConclusionsThere is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.

Penile cancer is rare. Modern treatment paradigms are based on therapies that may not be representative of current techniques. We analyzed current treatment and outcomes for this group of patients. An IRB approved chart review of all 31 histologically proven primary penile cancers diagnosed over the last 15 years in the 21st Century Oncology database were analyzed. These men ranged in age from 37-89 yrs, mean 67, and were mainly white with high Karnofsky performance status (mean of 90). Presenting signs and symptoms were most commonly penile pain and mass. Pelvis CT scans and MRI were used to stage most patients. Only 1 patient underwent PET/CT at diagnosis. Surgical intervention to the primary tumor ranged from circumcision to radical penectomy. Most commonly wide excision or partial penectomy was accomplished. Groin nodal dissection was undertaken for palpable disease. Radiation was delivered as part of primary therapy in 20 pts (64.5%) and to recurrent surgical failures in 11 pts (35.5%). Daily external beam radiation therapy (XRT) of 1.8-2 Gy achieved a mean total dose of 59 Gy (range, 19.8-75.2 Gy) to the penis/inguinal nodes. Treatment delivery was equally IMRT, 3D or 2D. IGRT was employed in 26%. A total of 5 patients underwent chemotherapy. All patients have been followed. Acute complications were generally mild to moderate with cutaneous morbidity the most common following XRT (90%). Late complications were mainly urethral stenosis (13%). Local control at the penis was 97%. Regional failure in the groin occurred in 8 pts (26%). Three patients failed distantly. At last follow up 58% of patients are alive. In univariate analysis age, Karnofsky, XRT dose, primary or recurrent disease, surgery type, and nodal treatment did not affect survival. Penile cancer patients generally undergo wide local excision or partial penectomy followed by XRT. Nearly one third of patients in this series underwent XRT following tumor recurrence. In addition, overall only 50% of patients had XRT to the groins. Considering that regional failure in the groin remains the most common site of tumor recurrence or progression, more intense therapy to this anatomy may play an important role in improving disease control.

Study Type – Therapy (retrospective cohort analysis)Level of Evidence 2bWhat's known on the subject? and What does the study add?Prostate cancer is generally considered to be high risk when the prostate‐specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high‐risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined‐modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation‐based regimens have been attempted but failed to accrue.OBJECTIVE To assess the risk of prostate cancer‐specific mortality after therapy with radical prostatectomy (RP) or combined‐modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen‐suppression therapy (AST) in men with Gleason score 8–10 prostate cancer. PATIENTS AND METHODS Men with localised high‐risk prostate cancer based on a Gleason score of 8–10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT. Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer‐specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors. RESULTS As of January 2009, with a median (interquartile range) follow‐up of 4.62 (2.4–8.2) years, there were 21 prostate cancer‐specific deaths. Treatment with RP was not associated with an increased risk of prostate cancer‐specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–5.6, P= 0.3). Factors associated with an increased risk of prostate cancer‐specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3–16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1–7.2; P= 0.03) as compared with T1c, 2a. CONCLUSION Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer‐specific mortality in men with Gleason score 8–10 prostate cancer.

Purpose/Objective(s): Adrenocortical carcinoma (ACC) is a rare and highly malignant tumor usually diagnosed in an advanced stage.Radiation therapy (RT) has been a poorly studied and under-utilized therapeutic option.To our knowledge, this report represents one of the largest that examines the role of both palliative and adjuvant RT in ACC.Materials/Methods: This retrospective analysis reviewed treatment courses for 14 patients with pathologically confirmed ACC treated between 1997 and 2012.Two patients were treated adjuvantly following surgery, and 12 were treated with palliative intent.Patients presented with Stage II (n Z 4), Stage III (n Z 7), and Stage IV (n Z 3) disease.Patients had a mean age of 48.7 years at the time of RT, and had received a mean of 1.5 separate chemotherapy courses and 1.2 surgical resections prior to receiving RT at a mean of 15.0 months after diagnosis.Results: In total, twenty sites were treated, two of which were in an adjuvant setting, and eighteen of which were for palliative indications in twelve patients as follows: [1] pain/neuropathy (n Z 10); [2] prophylactic aggressive treatment of recurrences (n Z 3); and [3] prevention of imminent metastatic complications including cord compression (n Z 2), hemoptysis (n Z 1), severe mass effect on surrounding organs (n Z 1), and brain metastasis (n Z 1).Sites were treated to a mean dose of 36.3Gy (range: 17.5 -60 Gy) in an average of 2.53 Gy/fx (range: 1.8-4 Gy).At a mean follow-up of 12.1 months for the entire cohort, 13 had either a clinical and/or a radiographic response.Of the two patients treated adjuvantly, one patient did not have a local recurrence during a 14.3-month period of observation, and one did not recur locally until 14.5 months later.At a mean follow-up of 11.0 months (range: 0 -39.9 months) for the patients receiving palliative RT, tumor shrinkage of 30% or greater was observed in 22% with improvement in symptoms recorded at 80% of sites.In field disease progression occurred in 39% of lesions at a mean of 5.1 months after RT.Ten patients developed out-of-field progression or new distant disease.Twelve patients required one or more additional treatments at some point after RT including systemic chemotherapy (n Z 12), surgery (n Z 2), chemoembolization (n Z 1), and radiofrequency ablation (n Z 1).Acute RTOG/EORTC toxicities observed in six patients included three grade 1, three grade 2 and one grade 3.No patient suffered acute grade 4 or any RTOG/EORTC late grade 1 toxicity.Conclusion: This report is one of the largest to date examining the role of modern radiation techniques in the management of ACC.We conclude that RT can be effective in the management of metastatic ACC, palliating local symptoms, and preventing complications from large metastases.RT should be considered as an option in multi-modality management of ACC patients.

An increased risk of death due to androgen deprivation therapy (ADT) has not been observed in randomized trials of mainly healthy men, but there may be subgroups of men with specific comorbidities who are at risk for harm from ADT. Records of 5,972 men treated for T1c-T3b prostate cancer using brachytherapy-based radiation therapy, with or without neoadjuvant ADT, were retrospectively reviewed. Cox multivariable regression analysis with propensity scoring was used to determine if ADT use was associated with increased all-cause mortality in men divided into 5 different comorbidity groups: (1) history of myocardial infarction (MI) or congestive heart failure (CHF) without revascularization (n = 245), (2) history of MI or CHF with revascularization such as angiography, stent placement, or bypass (n = 250), (3) history of coronary artery disease (CAD) without CHF or MI (n = 549), (4) hypertension, hypercholesterolemia, or diabetes mellitus without CAD (n = 2,201), and (5) no cardiac comorbidity (n = 2,727). ADT was only associated with an increased risk of death in groups 1 and 2. In men with a history of MI or CHF but no revascularization, the adjusted hazard ratio (AHR) for death due to ADT was 1.81 (95% CI: 1.02-3.17, p = 0.03). In those with history of MI or CHF who underwent revascularization, the AHR was 2.08 (95% CI: 1.03-4.20, p = 0.04). There was no significant association observed between ADT use and risk of death among those with CAD but not CHF/MI, those with hypertension, hypercholesterolemia or diabetes mellitus, or those without any cardiac comorbidities. Men with a history of CHF or MI (who comprised only 8.28% of the study population) had an increased risk of death if treated with ADT, regardless of whether or not they were revascularized. An increased risk of mortality due to ADT was not observed among men with only CAD or other cardiac comorbidities. Future randomized trials testing the value of ADT should stratify by comorbidity, and clinicians should continue to carefully weigh the risks and benefits of ADT in men with a history of CHF or MI.

BACKGROUND:Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown. OBJECTIVE:To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD. DESIGN, SETTING, AND PARTICIPANTS:This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage <T3); and 1360 men with localized or locally advanced, high-risk PCa consecutively treated in a community-based, multi-institutional setting between 1991 and 2006. CAD risk factors included at least a history of diabetes mellitus, hypercholesterolemia, or hypertension. The median follow-up for men with low-, intermediate-, and high-risk PCa were 4.1, 4.4, and 4.6 yr, respectively. INTERVENTIONS:Men were treated with or without a median duration of 4 mo of NHT followed by brachytherapy with or without supplemental external-beam radiation therapy (EBRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Cox regression multivariable analyses were performed to assess whether NHT use affected the risk of ACM in men with low-, intermediate-, and high-risk PCa, adjusting for age; year of brachytherapy; supplemental EBRT use; the presence of CAD risk factors; treatment propensity score; and known PCa prognostic factors, including pretreatment PSA level, biopsy Gleason score, and clinical stage. RESULTS AND LIMITATIONS:NHT use was associated with a significantly increased risk of ACM in men with low-risk PCa (adjusted hazard ratio [HR]: 1.27; 95% confidence interval [CI], 1.07-1.51; p<0.01) but not in men with intermediate-risk (adjusted HR: 1.13; 95% CI, 0.96-1.35; p=0.15) or high-risk PCa (adjusted HR: 0.86; 95% CI, 0.66-1.13; p=0.28). Using an interaction model for the low-risk group, NHT use was associated with a significantly increased risk of ACM in the subgroup of men with at least a single CAD risk factor (adjusted HR: 1.36; 95% CI, 1.07-1.74; p=0.01) but not for men with no CAD risk factors (adjusted HR: 1.19; 95% CI, 0.95-1.51; p=0.13). CONCLUSIONS:For men with no or at least a single risk factor for CAD, NHT use is associated with an increased risk of ACM in the setting of low-risk but not intermediate- or high-risk PCa. This effect is driven by the subgroup of men with at least a single risk factor for CAD. These results warrant prospective validation given the widespread use of NHT for prostate downsizing prior to brachytherapy.

A study was undertaken to determine the impact of prior coronary revascularization (angioplasty, stent, or coronary artery bypass graft) on the risk of all‐cause mortality after neoadjuvant hormonal therapy (HT) for prostate cancer (PC) in men with a history of coronary artery disease (CAD)‐induced congestive heart failure (CHF) or myocardial infarction (MI).

Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates (<= 20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates.Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume <= 20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer specific mortality (PCSM), respectively, after adjustment for other known prognostic factors.Results: 443 patients (6.9%) had a prostate volume <= 20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume <= 20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for <= 20 cc vs. > 20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4).Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume <= 20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding. (C) 2011 Elsevier Inc.