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5008 Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. The aim of this randomized trial (Clinical Trials.gov, #NCT00223171) was to compare outcomes of RT combined with either 36 or 18 months of ADT. Methods: Patients with HRPC were randomized to pelvic and prostate RT combined with 36 (arm 1) or 18 months (arm 2) of ADT. Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results: 630 patients were randomized, 310 to arm 1 and 320 to arm 2. With a median follow-up of 9.4 years, 290 patients had died (147 arm 1 vs. 143 arm 2). The 10-year OS rate was 62.4% (95% confidence interval [CI] 56.4%, 67.8%) for arm 1 and 62.0% (95% CI 56.1%, 67.3%) for arm 2 (p = 0.8412) with a global hazard ratio (HR) of 1.024 (95% CI 0.813-1.289, p = 0.8411). QoL analysis showed a significant difference (p < 0.001) in 6 scales and 13 items favoring 18 months ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. Conclusions: In HRPC, ADT combined with RT can be safely reduced from 36 to 18 months without compromising outcomes or QoL. 18 months of ADT represents a new standard of care in HRPC. Funded by AstraZeneca Pharmaceuticals Clinical trial information: NCT00223171.

129 Background: Low testosterone is generally associated with a higher overall mortality rate. We previously published that an increase in neutrophils is associated with lower overall survival in a large population of patients with localized prostate cancer. In this study, we tested a combination of both testosterone and neutrophils to predict for overall survival in a prospective cohort of patients treated with radiotherapy for localized prostate cancer. Methods: 414 patients from our institutional database were enrolled prospectively in phase 2 or 3 studies. To be included in this present analysis, patients had to have a baseline testosterone and complete blood count before enrollment in their respective study. Thirty-three patients were excluded for missing data for a total of 381 (92%) patients were included for analysis. Multivariate cox proportional hazards models were used to analyze the influence of white blood count (WBC = neutrophils + lymphocytes) and testosterone level on biochemical recurrence (Phoenix definition) and overall survival (OS). A cutoff level for testosterone of 10.4 nmol/l ( = 300ng/dL) was used as an indicator of hypogonadism and a WBC cutoff of 6.2 (109/L) representing the median value of this study population. Results were adjusted for cancer characteristics, comorbidities and androgen deprivation therapy. Results: Median age (range) was 71 (52-82) years. The median follow-up for biochemical recurrence and OS analysis were 72 and 78 months, respectively. WBC and testosterone were not predictive of biochemical recurrence, but CAPRA score 6-10 vs. ≤ 2 was (HR 5.39, 95% CI 1.19-24.45). WBC ≥ 6.2 alone was not associated with OS (HR 0.66, 95% CI 0.30-1.46), but when combined with a testosterone > 10.3 nmol/l, it was associated with a HR of 2.96 (95%CI 1.45-6.06) when compared to a WBC < 6.2, P-interaction = 0.01. Conclusions: A combination of high WBC and normal testosterone levels seem to be associated with increased mortality in patients with localized prostate cancer. Validation in larger samples is needed and could help to identify patients with increased risk of mortality within the first 6-7 years post treatment.

96 Background: To investigate the impact of 5-alpha-reductase inhibitors (5-ARIs) usage on radiotherapy outcomes for localized prostate cancer. Methods: From our institutional database of over 2500 patients, we identified 203 patients on a 5-ARI. They were all treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients receiving a 5-ARI were analyzed according to the following prostate cancer progression criteria: a) progression of Gleason score or increase in cancer volume on the biopsy, b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. Results: At a median follow-up of 36 months (interquartile range [IQR] 22-52 months), 10 (4.9%) patients experienced BF. 52% of men demonstrated none of the progression criteria, 37% showed only one prostate cancer progression criteria and 11% showed two. Using a univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) but not Gleason progression (p = 0.3) were a significant predictive factor of BF. With separate multivariate analysis adjusted for the CAPRA score (HR 1.7, 95% CI 1.2-2.3, p = 0.003), a rising PSA (HR 5.7, 95% CI 1.1-28.8, p = 0.04) and the number of cancer progression factors (HR 2.9, 95%CI 1.2-7.0, p = 0.02) remained adverse risk factors. Both Gleason score progression (p = 0.4) and first biopsy positive for cancer (p = 0.13) failed to remain significant. Age and obesity were not significant factors in univariate or multivariate analysis. Conclusions: A PSA progression experienced while under 5-ARI treatment before EBRT or brachytherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

BACKGROUND AND PURPOSE: To be radiopaque, BAVM embolization products must contain high-atomic-number materials, which may also attenuate photon beams delivered with radiosurgery. This “shielding effect” has been invoked to explain why radiation therapy may be less effective for previously embolized BAVMs. To evaluate the impact of embolization material on radiation dose, we measured and compared the dose delivered to the center of an AVM model, before and following embolization with various materials in a LINAC. MATERIALS AND METHODS: Two in vitro AVM models were constructed by drilling interconnected tubular perforations in plastic water phantoms to simulate nidal vessels. Phantoms were designed to allow the positioning of a radiation detector at their center. One model was embolized with Onyx 18 and a second model, with a combination of Indermil, Lipiodol, tungsten powder, and Onyx 18. The radiation delivered was compared between embolized and nonembolized controls following irradiation with a standard 250-cGy dose. RESULTS: The mean dose of radiation delivered to the model embolized with Onyx alone was 244 ± 5 cGy before and 246 ± 5 cGy following embolization. The mean dose of radiation delivered to the model embolized with various agents was 242 ± 5 cGy before, and 254 ± 5 cGy after embolization. CONCLUSIONS: Embolic material did not reduce the radiation dose delivered by a LINAC to the center of our experimental BAVM models. The shielding effect may be compensated by scattered and reflected radiation.

Objectives: To analyze the relationship between body mass index (BMI), fat tissue distribution, and total testosterone (TT) levels in men with localized prostate cancer (PCa). Methods: Two hundred and thirty-eight patients with either intermediate-risk PCa (60.5%) or high-risk PCa (39.5%) treated by external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), were analyzed. The visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were identified from patient's radiotherapy planning computed tomography (CT) images. Patients were divided into two groups: the first included patients whose TT levels were hypogonadal; the second included patients whose TT levels were normal. Results: There was a correlation between VAT and BMI (r=0.627). In an univariate model, BMI (p = 0.0174) and VAT (p=0.0228) were both predictive for low TT; age (p=0.579) was not. In a multivariate analysis taking into account the non-linear relationship between a low TT and BMI, BMI was the only predictive factor of a low TT (p=0.0304). An increase in BMI from 15 to 35 kg/m2 was associated with a fairly linear increase in the probability of having a low TT level; an increase in BMI of 5 kg/m2 resulted in an increase in probability of a low TT of 10%. On the other hand, a BMI >35 kg/m2 had a lower probability of a low TT level. Conclusions: There is a non-linear relationship between hypogonadal TT levels and BMI. VAT was not an independent predictor for low TT levels. Our results emphasize the important relationship between low TT and obesity in patients with PCa. Categories: Urology, Radiation Oncology

To analyze the value of the Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) in patients with D'Amico low- or intermediate-risk prostate cancer treated with different radiation techniques.We analyzed 744 patients treated with either external beam radiotherapy (52.7%) or permanent-seed prostate brachytherapy (47.3%) without any androgen deprivation. External beam radiotherapy dose levels were extreme hypofractionation (45 Gy in 9 fractions) in 10%, 76-79.2 Gy (in 1.8-2.0 Gy per fraction) in 32.7%, and 70.2-74 Gy in 10%. All patients had a minimum of 36-month follow-up. Cox regression analysis was used for univariate and multivariate analysis to predict for bF, as per the Phoenix definition (prostate-specific antigen-nadir + 2 ng/mL).Median follow-up for patients without bF was 56 months (range, 36-114 months). In univariate analysis, CAPRA score as a continuous variable was predictive of bF (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.23-1.79; P.001), and in multivariate analysis adjusted for treatment type, the HR was 1.39 (95% CI, 1.14-1.71; P = .002). D'Amico intermediate-risk vs low-risk patients had an HR for bF of 1.93 (95% CI, 1.07-3.47; P = .029) in univariate analysis, but the difference was not statistically significant anymore after adjustment for treatment type, (P = .206). The area under the curve of the CAPRA score as a continuous variable at 3 and 5 years was 0.66 and 0.62, respectively (P = .005 for both years).The CAPRA score is predictive of bF. Each 1-point rise increased the risk of bF by 39%, which is comparable to surgical series.

Vascular changes after radiotherapy of the central nervous system are well known. Recently, pro-liferative vascular lesions have been reported. We present the case of an 18-year-old male who developed a cavernous hemangioma 5 years after radiotherapy for a low-grade glioma at the same site in the brain. Short review of the literature and hypothesis follow the case presentation.

Objective:To assess the feasibility, toxicity, and local control of stereotactic radiosurgery followed by accelerated external beam radiotherapy (AEBR) for patients with glioblastoma multiforme.Materials and methods:Six males and eight females, with a median age of 67.5 years (range 45-78 years), entered the study. Karnofsky performance status was 90 for five, 80 for six, and 60 for three patients. Following surgery, the patients were left with a residual mass 4 cm. Radiosurgery was delivered with a single dose of 20 Gy to the 90% isodose surface corresponding to the contrast-enhancing edge of the tumour. A total AEBR dose of 60 Gy in 30 fractions was delivered using a concomitant boost technique over four weeks.Results:Median survival time was 40 weeks (range 17-80 weeks). Actuarial survivals at 12 and 18 months were 43% and 14%, respectively. The median time to progression was 25 weeks (range 2-77 weeks). One patient developed a seizure on the day of stereotactic radiosurgery. Two patients experienced somnolence at 47 and 67 days post-radiotherapy. Eight patients remained steroid-dependent. Radiological evidence of leukoencephalopathy was observed in one patient, and brain necrosis in two additional patients at 30 and 63 weeks. One of these two patients with brain necrosis developed complete loss of vision in one eye, and decreased vision in the contralateral eye at 63 weeks.Conclusion:Stereotactic radiosurgery followed by AEBR was feasible but was associated with late complications. The use of such radiosurgical boost for patients with glioblastoma multiforme should be reserved for those patients entering controlled clinical trials.

A 44-year-old male presented with a 3-week history of clumsiness and numbness of the left hemibody. CT scan and MRI revealed a 2 cm mass in the right hemisphere of the cerebellum. The patient underwent a sub-occipital craniotomy with gross total resection of the intra-parenchymal lesion. On pathology, the lesion was found to be compatible with a mesenchymal chondrosarcoma. The patient received adjuvant radiation treatment and remains free of disease 60 months after completion of treatment. Mesenchymal chondrosarcomas are neoplasms that rarely arise intra-cranially. Thirty cases have been found in the literature. Our case resembles more closely six of these cases because the tumour had no dural attachment. We describe our case in more detail and review similar cases found in the English literature.

2054Background: The randomized multicenter RTOG 9402 trial showed a significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (R...

Background: Transient tumor progression is difficult to diagnose and is challenging for the physician.

Purpose To evaluate the technical quality of external beam radiotherapy for prostate cancer in Canada. Methods This was a multi-institution, retrospective study of a random sample of patients undergoing radiotherapy (RT) for prostate cancer in Canada. Patterns of care were determined by abstracting details of the patients' management from original records. The quality of patient's technical care was measured against a previously published, comprehensive suite of quality indicators. Results 32 of the 37 RT centres participated. The total study population of 810 patients included 25% low-risk, 44% intermediate-risk, and 28% high-risk cases. 649 received external beam RT (EBRT) only, for whom compliance with 12 indicators of the quality of pre-treatment assessment ranged from 56% (sexual function documented) to 96% (staging bone scan obtained in high-risk patients). Compliance with treatment-related indicators ranged from 78% (dose to prostate ⩾74Gy in intermediate risk patients not receiving hormone therapy) to 100% (3DCRT or IMRT plan). Compliance varied among centres; no centre demonstrated 100% compliance on all indicators and every centre was 100% compliant on at least some indicators. The number of assessment-related indicators ( n =13) with which a given centre was 100% compliant ranged from 4 to 11 (median 7) and the number of the treatment-specific indicators ( n =8) with which a given centre was 100% compliant ranged from 6 to 8 (median 8). ADT therapy was utilised in most high-risk cases (191, 92.3%). Conclusions While patterns of prostate cancer care in Canada vary somewhat, compliance on the majority of quality indicators is very high. However, all centres showed room for improvement on several indicators and few individual patients received care that met target benchmarks on all quality measures. This variation is particularly important for indicators such as delivered dose where impact on disease outcome is known to exist, and suggests that quality improvement programmes have the potential to further improve quality of care.

Background Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. Materials and Methods We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Results Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Conclusions Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

Purpose Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk ( n = 152), intermediate-risk ( n = 142), or high-risk ( n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level ( p = .017) and National Comprehensive Cancer Network risk group ( p = .0022). On multivariate analysis, statin use was associated with a PSA level p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08–0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02–0.59, p = .02). Conclusion Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

We tested the potential role of abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues, waist circumference (WC) and body mass index (BMI) as prognostic factors in patients with intermediate-risk prostate cancer (clinical stage T1b-2b, and Gleason Score (GS)=7 and prostate-specific antigen PSA level15 ng ml(-1), or GS ≤ 6 and PSA between 10 and 20 ng ml(-1)) treated with ultrasound-based image-guided radiotherapy.VAT, SAT and WC (measured from planning abdominal computed tomography) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity indices significantly predicted biochemical disease free-survival (bDFS).Of the 112 eligible patients, 30 (27%) were obese. Median BMI at baseline was 27.5 kg m(-2) (range, 19.2-51.5 kg m(-2)). Greater abdominal adiposity, WC and BMI were significantly associated with younger age at diagnosis and increased prostate volume (P=0.003 and P=0.002, respectively). No significant correlation between obesity measures and T-stage, GS, PSA or percentage of positive cores at biopsy was found. On Cox regression analyses, none of the obesity measures predicted for bDFS. No association was observed between obesity indices and surrogate markers of biochemical failure as PSA nadir (nPSA) or time to nPSA.Abdominal adiposity, WC and BMI are associated with younger age at diagnosis and greater prostate volume but not with an increased risk of biochemical failure in patients with intermediate-risk prostate cancer.

Among men who underwent permanent seed prostate brachytherapy, we aimed to: 1) investigate: whether development of lower urinary tract symptoms (LUTS) after permanent seed prostate brachytherapy was associated with suboptimal erectile function before brachytherapy, and 2) identify factors that are associated with normal erectile function before brachytherapy.We analyzed data from 215 consecutive patients with low- or intermediate-risk prostate cancer who received permanent seed brachytherapy at our center. Erectile function at baseline (prior to brachytherapy) was assessed using the Mount Sinai Erectile Function Score (MSEFS). Urinary symptoms at baseline and at 1 month and 4 months after brachytherapy were measured using the International Prostate Symptom Score (IPSS) questionnaire. Multiple linear regression, and a multivariable mixed linear model were used to analyze differences in IPSS from baseline to 1 month and 4 months after brachytherapy. Multiple logistic regression was used to investigate factors associated with normal erectile function at baseline.A total of 124 patients had data available for baseline, and 1 month and 4 months after brachytherapy. Having normal erectile function (MSEFS of 3) versus suboptimal erectile function (MSEFS 0 to 2) was not associated with increases in IPSS from baseline to 1 month or 4 months after brachytherapy. Larger increases in IPSS were found in subjects who had smaller prostates (regression coefficient = -0.36) or higher seed radioactivity (regression coefficient = 0.33). Patients with higher baseline IPSS were less likely to have normal erectile function (MSEFS = 3) before brachytherapy (odds ratio = 0.88).Normal erectile function prior to brachytherapy was not associated with worse IPSS after brachytherapy. However, patients with a higher IPSS before brachytherapy also had worse erectile function before brachytherapy, which may point to a common pathway.

Purpose To develop a set of indicators of the quality of radiotherapy (RT) for localized prostate cancer. Methods and materials Following a comprehensive review of the literature to identify candidate quality indicators, we utilized a modified Delphi technique to develop a set of indicators of the quality of RT for localized prostate cancer. The first Delphi round consisted of an online survey in which radiation oncologists were asked to rate the importance of the candidate quality indicators. The second round was a face-to-face meeting of a smaller group of radiation oncologists to discuss, rate, and rank a final set of quality indicators. Results The literature review identified 57 candidate quality indicators. After the two rounds of the Delphi process, a final set of 25 indicators was agreed upon. The set includes quality indicators covering all aspects of prostate cancer radical RT management: pre-treatment assessment, external beam RT, brachytherapy, androgen deprivation therapy, and follow-up. Conclusions This new set of quality indicators is more comprehensive than others described in the literature, and can be applied to patterns of care studies that assess the quality of RT for prostate cancer. The process used to develop this set of indicators can be readily adapted for use in other contexts.

Purpose To compare low (mean 0.44, SD ± 0.0163 mCi) with high source activity (0.61 ± 0.0178 mCi) in I 125 permanent seed brachytherapy regarding seed loss, dosimetric outcome, and toxicity. Methods and Materials The study included 199 patients with prostate cancer treated by permanent seed brachytherapy alone: the first 105 with seeds of lower activity (first cohort), the following 94 with higher seed activity (second cohort). The V100, V150, V200, and D90 were analyzed on the CT scan 30 days after implantation (CTD30). The V100, V150, and D2 of the rectum were also calculated on CTD30. Seed loss was determined 30 days after implantation. Urinary toxicity was measured with the International Prostate Symptom Score (IPSS) questionnaire. Results Lower seed activity was associated with lower V150 and V200 ( p = 0.01 and p ≤ 0.001, respectively) on CTD30. More patients had a V100 p = 0.098 for D90 and p = 0.029 for V100) on CTD30. There was no difference between cohorts in dose to the rectum ( p = 0.325–0.516) or difference in patients' IPSS score from baseline ( p = 0.0.117–0.618), although there was a trend toward more urinary toxicity at 4 and 8 months for high activity seeds. Seed loss as a percentage of implanted seeds was not different ( p = 0.324). Conclusions Higher seed activity (I 125 ≥ 0.6 mCi) results in at least equal V100 and D90 on CTD30. However, dose inhomogeneity and a trend toward more urinary toxicity at 4 and 8 months after treatment may lead to a higher long-term urinary complications.

Purpose To identify dosimetric parameters predictive of a good prostate seed I 125 quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. Methods and Materials We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I 125 brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of ≥90% and a D90 of ≥140 Gy on the basis of CT-D28 values. Results On CT-D28, 72.4% of patients had a V100 of ≥90% and 74.8% had a D90 of ≥140 Gy. AUROC for a V100 of ≥90% was 0.665 ( p = 0.004) on PRE-TRUS and 0.619 ( p = 0.039) on POST-TRUS. AUROC for D90 of ≥140 Gy was 0.602 ( p = 0.086) on PRE-TRUS and 0.614 ( p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. Conclusions Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography–based dosimetry.

27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience & resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel & Urinary domains EPIC instrument(EPIC B&U). Secondary objectives included acute & late GI & GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a & PSA < 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) > 5 points & in EPIC urinary domain score > 2 points were felt to be clinically significant. The frequency for > 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for > 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( > 80%). The 1 year FREQE-B for 5 fr was 23.5% (p < 0.001) & 12 fr was 23.1% (p < 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p < 0.001) & 12 fr was 34.7% (p < 0.001). Conclusions: This study confirms that based on changes in EPIC B&U (baseline to 1-year), acute & late toxicity, both the 5 & 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy & toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]

3 Background: Previous reports suggested that AAT when combined with salvage RT following RP in patients may improve prostate cancer control outcomes. Methods: Post-RP patients with pT3pN0 or with pT2pN0 and positive margins who had or developed elevated PSA levels from 0.2 to 4.0 ng/ml were randomized on a phase III, double-blind, trial of RT + placebo (64.8 Gy in 36 fractions of 1.8 Gy) vs. RT + AAT (24 months bicalutamide, 150 mg daily) during and after RT. The primary end-point was overall survival. Trial design required 725 patients and provided 80% power to detect a reduction in death rate by at least 28.5% and a 1-sided significance level of 0.046. Results: From 3/98 to 3/03, 761 eligible patients (median age 65) were randomized to RT + AAT (384) or RT + placebo (377). 248 patients (33%) were pT2pN0 and 513 (67%) were pT3pN0. 671 (88%) had a PSA nadir after RP of < 0.5 ng/ml. 649 (85%) had an entry PSA value of

34 Background: The purpose of this analysis was to establish causes of death in a population of intermediate-risk (IR) and high-risk (HR) prostate cancer treated on two phase III trials. Methods: From October 2000 to September 2010, 1,230 patients were randomized: 630 with HR (ClinicalTrials.gov, #NCT00223171) and 600 with IR (#NCT00223145). HR was defined as T3-4, PSA >20 g/ml, Gleason >7 (with at least one of these 3 factors). IR was defined as T1-T2, Gleason < 6 and PSA 10-20 ng/ml or T1-T2, Gleason 7 and PSA < 20 ng/ml. Causes of death were compiled until July 2015 and were established from data sent by the different investigators and centrally reviewed. Causes of death were mainly based on data from clinical records, then by family members, obituaries, death certificates and family physicians. Results: The median follow-up for the 1,230 patients was 7.5 years (HR 8 vs. IR 6.8 years, p

Patient-Reported Outcomes in NRG Oncology/RTOG 0938, a Randomized Phase 2 Study Evaluating 2 Ultrahypofractionated Regimens (UHRs) for Prostate Cancer H. Lukka, P. Stephanie, D. Bruner, J.P. Bahary, C.A.F. Lawton, J.A. Efstathiou, R. Kudchadker, L. Ponsky, S.A. Seaward, I.S. Dayes, D.D. Gopaul, J.M. Michalski, G. Delouya, I.D. Kaplan, E.M. Horwitz, M. Roach, III, W.H. Pinover, D.C. Beyer, H.M. Sandler, and L.A. Kachnic; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada, NRG Oncology Statistics and Data Management Center, Philadelphia, PA, Emory University, Atlanta, GA, Hopital Notre-Dame du CHUM, Montreal, QC, Canada, Medical College of Wisconsin, Milwaukee, WI, Massachusetts General Hospital, Harvard Medical School, Boston, MA, MD Anderson Cancer Center, Houston, TX, United States, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, Kaiser Permanente Northern California, Santa Clara, CA, United States, McMaster University, Hamilton, ON, Canada, Grand River Regional Cancer Centre, Kitchener, ON, Canada, Washington University School of Medicine, St. Louis, MO, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, Beth Israel Deaconess Medical Center, Boston, MA, Fox Chase Cancer Center, Philadelphia, PA, University of California, San Francisco, San Francisco, CA, Abington Memorial Hospital, Abington, PA, United States, Foundation for Cancer Research and Education, Phoenix, AZ, Cedars-Sinai Medical Center, Los Angeles, CA, Boston Medical Center, Boston, MA

Hospitalization final 90 days of life 48.3% 64.0% .0004 Hospitalization final 30 days of life 31.5% 61.5%

Prostate cancer is the second cause of cancer related death in North American men. We investigated the frequency of familial clustering in a French-Canadian population of prostate cancer cases.Between October 2004 and September 2005, 179 consecutively seen patients with localized prostate cancer identified each of their parents as being of French-Canadian descent. They were asked for their family history of cancer in first-degree relatives, age at diagnosis, whether affected relatives were alive, age and markers of tumor aggressiveness, including prostate specific antigen, Gleason and disease stage. ANOVA was used to compare the distribution of quantitative factors according to qualitative factors identified in our population. Differences between qualitative factors were assessed by the Fisher exact test. All p values were 2-sided.Mean age at diagnosis was 67 years. A total of 45 French-Canadian patients (25.1%) had at least 1 first-degree relative with prostate cancer, including 34 (19%) with 1 first-degree relative, 9 with a father-son pair, 25 with a brother-brother pair and 11 (6.1%) with at least 2 first-degree relatives. In our series the frequency of familial clustering defined by at least 1 relative with prostate cancer was high. We found a higher percent of French-Canadian men with at least 1 first-degree relative with prostate cancer than what was previously reported for an unselected population in Canada (25.1% vs 14.7%, p0.0001).Those preliminary results open a new perspective to a better understanding of familial prostate cancer in the Province of Quebec.

2002 Background: TMZ is efficacious in recurrent anaplastic glioma and newly diagnosed glioblastoma. The primary objective was to compare the overall survival (OS) of patients with AA treated with ...

4 Background: RTOG 0126 is a phase III trial for localized prostate cancer (PC) testing whether dose escalation to 79.2Gy with 3DCRT or IMRT will improve overall survival (OS). Methods: Stage cT1b-T2b with Gleason Score (GS) 2-6 and PSA ≥ 10 and

Background and Purpose— Endovascular treatment of intracranial aneurysms is safe and effective but is associated with angiographic recurrences. Beta radiation prevents recanalization after coil embolization in experimental models. We wanted to assess the feasibility of using radioactive coil embolization to improve long-term results of endovascular treatment. Methods— Platinum coils were ion-implanted with 0.13 to 0.26 μCi/cm of 32 P. Forty-one patients aged 34 to 84 years with 44 aneurysms with a high propensity for recurrences were included. Radioactive coils were introduced into aneurysms to reach a target volumetric activity of 0.018 μCi/mm 3 . Nonradioactive coils were also used to ensure the same safety and the same angiographic results as the standard procedure. Angiographic results, procedure-related complications, and neurological events during follow-up were recorded. Angiographic follow-up data are available in 36 lesions 6 months after treatment. Results— Forty of 44 aneurysms (91%) could be treated with radioactive coils. Target activities could be reached in 88% of lesions that could actually be coiled (35/40). Total activities ranged from 1.72 to 80.9 μCi, for a mean of 20.13±20.80 μCi. Procedure-related complications occurred in 7% of patients. Initial angiographic results were satisfactory (complete occlusions or residual necks) in 75% of lesions. Angiographic recurrences occurred in 11 (31%) of patients followed, within the expected range for standard coils. There was no complication from beta radiation during a mean follow-up period of 10 months. Conclusions— Radioactive coil embolization is feasible; target volumetric activities can be reached in most aneurysms considered for endovascular treatment.

Purpose To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. Methods and materials Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of ≥60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m 2 of TMZ was given on Days 1–5 of RT. In Arm 1, 200 mg/m 2 of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m 2 of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. Results A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. Conclusion The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Purpose/Objective(s): To report the long-term survival and toxicity outcomes with the use of ultra-high-dose intensity modulated radiation therapy (IMRT) to a dose of 86.4 Gy for patients with localized prostate cancer. Materials/Methods: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk-grouping system. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen-deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range 1-14 years). Results: The 5and 10-year actuarial prostate-specific antigen (PSA) relapse-free survival outcomes for low-, intermediate-, and high-risk groups were 98.8 and 96.3%, 89.1 and 75.4%, and 76.1 and 65.8% (p < 0.001), respectively. On multivariate analysis, T stage (p Z 0.002), Gleason score (p < 0.001), and pretreatment PSA (iPSA) (p Z 0.008) were predictors for biochemical relapse. The 5and 10-year actuarial DMFS for low-, intermediate-, and high-risk groups was 99.4 and 96.8%, 97.4 and 93.6%, and 90.1 and 74.4% (p < 0.001), respectively. On multivariate analysis, T stage (p < 0.001), Gleason score (p < 0.001), and iPSA (p < 0.033) were predictive for DM. No prostate cancer-related deaths were observed in the low-risk group. The 5and 10-year actuarial CSS for intermediateand high-risk groups was 99.4 and 93.8%, and 96.6 and 82.2% (p Z 0.008), respectively. On multivariate analysis, only T stage (p Z 0.016) and Gleason score (p Z 0.003) were predictive for prostate cancer-related death. The incidence of grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicities were 4.4% and 17.1%, respectively. Late grade 3 GI and GU toxicity was experienced in 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This represents the largest cohort of patients treated with ultra-high-dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes and is well tolerated with acceptable toxicity. Author Disclosure: D. Spratt: None. X. Pei: None. J. Yamada: None. M.A. Kollmeier: None. B. Cox: None. Z. Zhang: None. M.J. Zelefsky: None.

BACKGROUND: Recent results of R9802 (Buckner et al; J Clin Oncol 32:5s, 2014 (suppl; abstr 2000)) demonstrated that PCV given with RT at the time of initial diagnosis prolongs both progression-free survival (PFS) and overall survival (OS) for all patients enrolled in the trial. Herein, we report the impact of treatment on PFS and OS based upon specific histologic type. METHODS: Eligibility criteria included age 40 with any extent of resection, and supratentorial grade ll oligodendroglioma (O), oligo-astrocytoma (OA), or astrocytoma (A). Patients were stratified by age, histology, Karnofsky Performance Status, and presence versus absence of contrast enhancement on the preoperative imaging study and randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. In an exploratory analysis, we used the log rank test to compare survival and progression free survival (PFS) distributions for each histologic type. RESULTS: 251 eligible patients were accrued from 1998 to 2002: 107 had O, 79 had OA, and 65 had A. In total, 67% have progressed and 55% have died. Median PFS (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 4.0 vs 10.4 (p < 0.001); 6.0 vs not reached (NR) (p < 0.001); 3.0 vs 8.9 (p = 0.01); and 1.8 vs 3.7 (p = 0.06) years. Median survival times (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 7.8 vs 13.3 (p = 0.002); 10.8 vs NR (p = 0.008); 5.9 vs 11.4 (p = 0.05); and 4.4 vs 7.7 (p = 0.31) years. CONCLUSIONS: For grade 2 glioma patients with less than gross total tumor resection or >40 years of age, PCV + RT prolongs both OS and PFS compared with RT alone. The observed benefit is most definitive for O and OA patients.

2000 Background: Early results of R9802 (Shaw et al: J Clin Oncol. 2012; 30(25):3065-70) demonstrated that PCV given with RT at the time of initial diagnosis prolongs progression-free survival (PFS...

5 Background: To evaluate long-term quality of life (QOL) in 630 patients with high-risk prostate cancer (HRPC) treated in a prospective randomized phase III trial (PCS IV clinical trials, Gov. # NCT 00223171). Methods: Patients were randomized to radiotherapy (RT) plus 36 or 18 months of androgen deprivation therapy (ADT). QOL was assessed by two validated tools: EORTC30 (30 items) and PR25 (25 items). The 55 items were regrouped into 21 scales: 15 for EORTC30 and six for PR25. All items and scales scores were linearly transformed to a 0 to 100 points scale. A p value less than 0.01 was considered statistically significant and a difference between groups in mean scores of greater than or equal to 10 points as clinically relevant. Patient-reported outcomes were filled out before treatments, every six months during ADT, four months after and then once a year for five years. All items and scales scores were analysed with general linear model with repeated measures to evaluate changes between groups and over time periods. Results: Three hundred ten patients were randomized to 36 months and 320 to 18 months of ADT, with a median follow-up of 79 months, there was no difference in survival outcomes. The global adherence to QOL questionnaires was 72.4% (10,052 out of 13,880). When comparing the two groups, 6 out of 21 scales (physical, emotional, and social functioning, fatigue, hormonal treatment-related symptoms, and sexual active) and 14 out of 55 items (trouble with long walks, stay in bed during the day, weakness, tenseness, worry, irritable, depressed, close to a toilet, blood in stools, hot flushes, enlarged breasts, interested in sex, sexually active, enjoyable sex) were statistically significant (p< 0.01) in favor of the 18 months ADT group. None of the 21 scales reached clinical relevance (mean scores greater than or equal to 10 points) sexual active being the highest score with 9.0 points of difference. For the 14 statistically significant items, interest in sex with 9.9 points and sexually active with 8.1 points were close to clinical relevance and hot flushes with 24 points and enjoyable sex with 18 points had important clinical relevance at 42 months. Conclusions: In HRPC treated with RT and ADT, reducing the duration of ADT from 36 to 18 months improves QOL, without a negative impact on survival. Source of Funding: AstraZeneca Pharmaceuticals grant. Clinical trial information: PCS IV clinical trials, Gov. # NCT 00223171.

PURPOSE: This phase II study tested the efficacy and safety of tirapazamine (Sanofi Synthelabo Research, Malvern, PA), a bioreductive agent, in glioblastoma multiforme (GBM) patients. The patients were staged according to a model constructed by a recursive partitioning analysis (RPA) of glioma patients in prior Radiation Therapy Oncology Group (RTOG) trials and compared with a matched standard population, as predicted by the model. PATIENTS AND METHODS: A total of 124 patients diagnosed with a GBM were treated with radiation therapy and intravenous tirapazamine between January 27,1995, and April 25,1997. All patients received 60 Gy in 2-Gy fractions. Tirapazamine was delivered three times a week for 12 treatments during radiotherapy. Fifty-five patients received tirapazamine at 159 mg/m2. A second dose level, 260 mg/m2, was opened, and 69 patients were entered. RESULTS: There was no significant survival advantage to the drug in any RPA class at either dose level. The median survival time was 10.8 months for the patient population treated with the 159-mg/m2 dose of tirapazamine and 9.5 months for the group treated with the 260-mg/m 2 dose of tirapazamine. Survival times by RPA class for patients receiving tirapazamine at 159 mg/m2 were 27.4 months (class III), 10.8 months (class IV), 7.9 months (class V), and 3.8 months (class VI). Survival times by RPA class for patients receiving tirapazamine at 260 mg/m2 were 16.2 months (class III), 10.3 months (class IV), 5.1 months (class V), and 1.3 months (class VI). Patients in RPA class III treated in the 159 mg/m2 dose arm had a notably longer survival than patients in the RTOG database RPA class III, but the difference did not reach statistical significance. There were no fatal toxicities. Grade 3/4 toxicities were more frequent at the higher dose level. CONCLUSION: Survival in the population treated with radiation and tirapazamine was equivalent to the control population. Patients in RPA class III treated with radiation and tirapazamine at the 159-mg/m2 dose had a longer survival when compared with the historical controls. The improvement in survival did not reach statistical significance. Toxicity was acceptable in both treatment arms, but grade 3/4 toxicities were more frequent in the higher dose regimen.