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Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P.001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up.Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received anThe 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P.001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm.Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

Purpose: The aim of this study was to investigate whether a delay in radiotherapy is associated with a poorer biochemical control for prostate cancer. Methods: The time to treatment (TTT) from diagnosis of prostate cancer to radiotherapy was analyzed with respect to prostate-specific antigen (PSA) control in 1024 hormone-naive patients. The Kaplan-Meier PSA control curves for patients with TTT less than the median were compared with those for patients with TTT greater than the median in 3 predefined risk groups. Statistical significant differences in PSA control were further analyzed using Cox multivariate analysis with pretreatment PSA, Gleason score, T stage, and radiotherapy dose as covariates. Results: The median TTT and median follow-up are 3.7 months and 49 months respectively. Patients with a longer TTT have a statistically significant better PSA control than patients with a shorter TTT if they have intermediate- or high-risk disease. However in multivariate analysis TTT was not found to be significant in predicting PSA control, with pretreatment PSA and Gleason score emerging as highly significant in predicting PSA failure in both intermediate- and high-risk disease. Conclusion: In this study in prostate cancer patients in British Columbia, there was no evidence that a longer time interval between diagnosis and radiotherapy was associated with poorer PSA control.

Purpose: Comparing radiation therapy utilization rates (RTUR) to those predicted by best evidence is a useful measure of the equity and accessibility of service delivery. In this study the RTUR for melanoma was established for British Columbia, Canada, and compared with the rate suggested by the evidence. Demographic variables, specifically age, gender, and geography that influenced the RTUR were examined with a view to identifying methods of improving underutilization. Methods and Materials: The RTUR in the management of malignant melanoma was taken from British Columbia Cancer registry data for 1986 to 1998. Variations in utilization based on age, gender, health authority, stage of disease, and referral patterns were analyzed. Results: An RTUR of 11% was identified. This was consistent over time. Referral rates decreased between 1986 and 1998. RT is used mostly for later stage disease. Males were more likely to receive RT than females, related to later stage of disease in men. Referral rates decreased, but RTUR for referred cases increased, in health authorities that did not have a cancer center. Conclusions: Use of RT is influenced by age and by stage of disease. Overall RTUR in British Columbia is lower than suggested by best evidence. Referral patterns are influenced by geography. RTUR was higher in males, consistent with a different pattern of disease in males compared with females.

Purpose: To determine predictive factors for postimplant erectile dysfunction (ED) in a cohort of patients, according to prospectively collected data; specifically, to assess the impact of penile bulb volume and D50 and D95 (dose covering 50% and 95% of the penile bulb volume, respectively) on ED. Methods and Materials: Three hundred forty-two patients were identified who were potent before implant and who had at least 2 years’ follow-up. Patient, tumor, treatment, and dosimetric data were collected on all patients. Postimplant ED was defined according to both physician-documented and patient-documented outcome data. Binary logistic regression analysis was used to create multivariable models of predictors for ED at 1, 2, and 3 years after implant. Results: Physician-documented rates of ED were 57%, 48%, and 38% at 1, 2, and 3 years after implant, respectively. Patient-documented rates of ED were 70% and 66% at 1 and 2 years, respectively. Multivariable analyses revealed age and degree of preimplant erectile function to be consistently significant predictors of ED. Use of hormones was significant at the 1-year physician-documented ED endpoint but not thereafter, in keeping with the time course of testosterone recovery. Penile bulb volume, D50, and D95 were not found to be predictive for ED at any time point, in contrast to previous studies. In addition, planning ultrasound target volume, number of needles, and institutional case sequence number were significant predictors of ED at various time points, consistent with a traumatic etiology of ED. Conclusions: We found no evidence to support penile bulb dosimetry as an independent predictive factor for ED after implant, using physician-documented or patient-documented outcomes.

Purpose To determine the relationship between prostate-specific antigen (PSA) failure and cause-specific and overall survival in prostate cancer patients treated with radical radiotherapy. Methods and materials Patients with and without PSA failure were compared with respect to overall survival and cause-specific survival in a cohort of 1786 patients. The relationship between PSA failure and survival was further investigated among six subgroups defined by three tumor risk groups (high, intermediate, and low risk based on T stage, Gleason score, and presenting PSA) and two age groups (

Purpose To evaluate the late toxicity profile of prostate cancer patients treated with external beam radiotherapy, to investigate the possible risk factors for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA) is a factor. Methods and materials The study population consisted of 1192 patients with ≥24 months' follow-up. Late GI and GU toxicities were scored with a modified Radiation Therapy Oncology Group/Subjective, Objective, Management, and Analytic scale. All patients were treated with external beam radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either conventional or three-dimensional conformal techniques. Of the 1192 patients, 40% received NAA (median 5 months). Risk factors investigated on multivariate analysis were age, past medical history, use of pelvic fields, dose, fractionation, use and duration of neo- and adjuvant androgen ablation, and acute toxicity (Grade 2 or greater). Results The median follow-up for the group was 49 months (range 24–105). The incidence of late Grade 2-3 GI or GU toxicity was 30% at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk factors of significance in relation to the development of late Grade 3 GU toxicity were coexisting GU disease ( p = 0.02), prior transurethral resection of the prostate or transurethral resection of bladder tumor ( p p = 0.012). For late Grade 3 GI toxicity, short-term (≤2 months) NAA ( p = 0.0002) and coexisting GI disease ( p = 0.017) were risk factors. Conclusion Short-term (≤2 months) NAA, but not longer durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The possible mechanism of this phenomenon is unclear.

Nadir+2 ng/mL 84.7% (5.6%) 71.1% (8.2%) O0.4 ng/mL 65.3% (6.4%) 59.2% (8.0%) O0.2 ng/mL 46.3% (7.6%) 38.8% (8.2%) LDR-PB boost Nadir+2 ng/mL 88.7% (4.8%) 86.2% (5.4%) O0.4 ng/mL 86.6% (5.2%) 84.3% (5.6%) O0.2 ng/mL 85.3% (5.2%) 82.1% (6.0%)

Purpose To review the published literature pertaining to radiation oncology in undergraduate medical education. Methods and Materials Ovid MEDLINE, Ovid MEDLINE Daily Update and EMBASE databases were searched for the 11-year period of January 1, 1998, through the last week of March 2009. A medical librarian used an extensive list of indexed subject headings and text words. Results The search returned 640 article references, but only seven contained significant information pertaining to teaching radiation oncology to medical undergraduates. One article described a comprehensive oncology curriculum including recommended radiation oncology teaching objectives and sample student evaluations, two described integrating radiation oncology teaching into a radiology rotation, two described multidisciplinary anatomy-based courses intended to reinforce principles of tumor biology and radiotherapy planning, one described an exercise designed to test clinical reasoning skills within radiation oncology cases, and one described a Web-based curriculum involving oncologic physics. Conclusions To the authors' knowledge, this is the first review of the literature pertaining to teaching radiation oncology to medical undergraduates, and it demonstrates the paucity of published work in this area of medical education. Teaching radiation oncology should begin early in the undergraduate process, should be mandatory for all students, and should impart knowledge relevant to future general practitioners rather than detailed information relevant only to oncologists. Educators should make use of available model curricula and should integrate radiation oncology teaching into existing curricula or construct stand-alone oncology rotations where the principles of radiation oncology can be conveyed. Assessments of student knowledge and curriculum effectiveness are critical.

Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

Purpose: To compare the efficacy of pion radiation therapy with conventional external beam photon therapy, for the treatment of locally advanced stage T3/4, N0, M0 adenocarcinoma of the prostate. Methods and Materials: Two hundred seventeen eligible patients were randomly allocated to either photon or pion therapy. No adjuvant hormone therapy was used. Results: Median follow-up was 42 months (range 2–90). Acute bladder toxicity was worse in the pion arm, p = 0.002, but other acute toxicity did not differ. Late grade 2 toxicity was significantly less in the pion arm (29% at 5 years versus 48%, p = 0.002), but late grade 3 or 4 toxicity did not differ. Clinical local control was not significantly different between treatment arms (64% after 5 years with photons, 56% with pions, p = 0.6). Cause-specific and overall survival also did not differ ( p = 0.7). There was a significant delay in time to first failure in the photon arm, largely as a result of decreased biochemical relapse, p = 0.01. A multivariate analysis is presented. Conclusion: Pion therapy was well tolerated, with increased acute toxicity and significantly decreased late tissue injury. This contrasts with the late toxicity observed with higher LET particle therapy such as neutron therapy. No improvement in local control with pion therapy was observed.

This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas.Eighty-four patients were randomized to pion therapy (33-34.5 Gy pi), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS)or = 50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms.Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms.In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma.