Lenvatinib in multimodal therapy for unresectable radioactive iodine-naïve differentiated thyroid cancer: A case report with literature review.

BACKGROUND: Patients with unresectable or metastatic differentiated thyroid carcinoma (DTC) are rare and require individualized therapy. This may require approaches not typically used in resectable disease. We report a patient treated with lenvatinib and external beam radiation therapy. CASE: An 87-year-old woman presented with cT4N1aM1 papillary thyroid carcinoma with tracheal invasion. She was not a candidate for surgery, radioactive-iodine, or radiation, so a trial of lenvatinib was offered. Her tumor showed clinical, biochemical, and radiological response after 5 months of lenvatinib, and she subsequently received external beam radiation. She enjoys good quality of life without evidence of cancer progression off therapy 21 months post-initiation of treatment. CONCLUSION: Lenvatinib may be effective in RAI-naïve advanced DTC patients as a component of individualized multimodal therapy when conventional options are not feasible.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial.

BACKGROUND: Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. METHODS: In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. DISCUSSION: This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04221165 . Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

Risk of Chronic Opioid Use After Radiation for Head and Neck Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Opioid addiction is a major public health concern. Chronic opioid use (COU) patterns after radiation for head and neck cancer (HNC) remain poorly understood. The aim of this study was to estimate the prevalence of COU and to identify its risk factors in patients with HNC undergoing curative-intent radiation therapy (RT) or chemoradiotherapy (CRT). METHODS AND MATERIALS: We performed a systematic review and meta-analysis using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from dates of inception until January 2020. COU was defined as persistent use of opioids ≥ 3 months after treatment completion. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I2 value. RESULTS: Seven retrospective studies, reporting on 1841 patients, met the inclusion criteria. Median age was 59.4 (range: 56.0-62.0) years with 1343 (72.9%) men and 498 (27.1%) women. Primary tumor locations included oropharynx (n = 891, 48.4%), oral cavity (n = 533, 29.0%), larynx (n = 93, 5.1%), hypopharynx (n = 32, 1.7%), and nasopharynx (n = 29, 1.6%). Eight hundred fifty-four (46.0%) patients had stage I/II and 952 (50.3%) had stage III-IV disease. Three hundred one (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of patients with HNC who developed COU post-RT/CRT was 40.7% at 3 months (95% confidence interval [CI]: 22.6%-61.7%; I2 = 97.1%) and 15.5% at 6 months (95% CI: 7.3%-29.7%; I2 = 94.3%). Oropharyngeal malignancies had the highest rate of COU based on primary tumor location (46.6%; 95% CI: 30.8%-63.1%; P < .0001). High proportions of COU were found in patients with a history of psychiatric disorder(s) (61.7%), former/current alcohol abuse (53.9%), and opioid requirements before radiation treatment (51.6%; P = .035). CONCLUSIONS: A significant proportion of patients who undergo RT for HNC suffer from COU. High-risk factors for COU include an oropharyngeal primary, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate COU are needed.

Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial.

BACKGROUND: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. METHODS: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. DISCUSSION: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Long-Term Results of a Randomized Trial Comparing Iridium Implant Plus External Beam Radiation Therapy With External Beam Radiation Therapy Alone in Node-Negative Locally Advanced Cancer of the Prostate.

PURPOSE: To determine the impact on long-term survival from the addition of brachytherapy to external beam radiation therapy (EBRT) in patients with prostate cancer. METHODS AND MATERIALS: Between 1992 and 1997, 104 men with cT2-3, surgically staged node-negative prostate cancer were randomized to receive either EBRT (40 Gy/20 fractions) with iridium implant (35 Gy/48 hours) or EBRT alone (66 Gy/33 fractions) to the prostate. According to T stage, Gleason score, and prostate-specific antigen level, 60% of patients had high-risk disease. Substantial improvements in biochemical control at 8 years have previously been reported. Additional follow-up was collected on deaths and metastases. RESULTS: Median follow-up was 14 years. Five patients were lost to follow-up. All other patients have been followed a minimum of 13 years. There have been 75 deaths, including 21 from prostate cancer and 25 from second cancers. No patients developing a second cancer have died from prostate cancer. There was no difference in overall survival between the 2 treatment groups: 34 deaths (67%) in the implant arm and 41 (77%) in the EBRT arm (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.63-1.59). Similarly, there was no difference in prostate cancer-specific deaths: 9 (18%) patients in the implant arm compared with 12 (23%) in the EBRT arm (HR 0.79, 95% CI 0.34-1.87). There was no statistically significant difference in the number of patients developing metastatic disease: 10 (20%) in the implant arm and 15 (28%) in the EBRT arm (HR 0.70, 95% CI 0.32-1.57). Improvements in biochemical control were maintained (HR 0.53, 95% CI 0.31-0.88). CONCLUSIONS: Despite a dramatic reduction of biochemical recurrence rates, the addition of iridium implant to EBRT did not translate into improved overall survival or prostate cancer-specific survival.

Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer.

PURPOSE: We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. PATIENTS AND METHODS: NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 µg/L or PSA of 20 to 40 µg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. RESULTS: One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. CONCLUSION: This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial.

BACKGROUND: Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. METHODS: Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. RESULTS: Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70-78 vs 66%, 60-70; hazard ratio [HR] 0·77, 95% CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). INTERPRETATION: The benefits of combined modality treatment--ADT and RT--should be discussed with all patients with locally advanced prostate cancer. FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.

Evaluating health-related quality of life and priority health problems in patients with prostate cancer: a strategy for defining the role of the advanced practice nurse.

A framework for the introduction and evaluation of APN roles emphasizes the importance of a systematic approach to role development based on the assessment of patient health needs. This study determined the health-related quality of life (HRQL) of patients with prostate cancer. The most frequent and severe patient health problems and their perceptions of priority health problems were identified and compared across five patient groups as a strategy to inform the supportive care role of the advanced oncology nurse for patients with advanced prostate cancer. The study found that the majority of men with early stage and advanced hormone sensitive prostate cancer can expect to enjoy good quality of life for several years following diagnosis. These two patient groups have common priority needs for improving their health related to sexual function, urinary frequency, urinary incontinence, and physical activity. Both groups may benefit from an advanced practice nursing (APN) role that can provide episodic supportive care for health problems occurring at different treatment stages. Conversely, it was found that men with advanced hormone refractory prostate cancer experience significantly poorer HRQL and have multiple severe health problems. These patients also have different priority needs including problems related to pain, fatigue, and decreased physical activity. Because of this, the focus of supportive care programs and interventions in advanced prostate cancer will differ for those with hormone refractory disease. They may benefit more from an APN role that can provide ongoing rather than episodic supportive care to assess and manage the multiple, new, and worsening health problems associated with progressive disease.

Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients.

PURPOSE: To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer. METHODS AND MATERIALS: Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC(6)/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy. RESULTS: Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity. CONCLUSIONS: Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.

Individual radiosensitivity and its relevance to health physics.

Radiation protection regulations have been established to reduce exposure of individuals to acceptable safe levels. These limits assume that people have similar responses to ionizing radiation and that there is no variation in individual radiation risk. The purpose of this research was to determine if apoptosis in lymphocytes can be used to assess individual sensitivity to ionizing radiation. Blood samples were taken from 54 males ranging in age from 19-85 years. Apoptosis was measured using modified flow cytometry based Annexin-FITC/7AAD and DiOC(6)/7AAD assays in different populations of lymphocytes (total mixed lymphocyte population, subset CD4+ or CD8+ lymphocytes) after exposure to in vitro doses of 0, 2, 4 or 8Gy (dose rate 0.1Gy/min). The variation in individual responses to radiation was large. The variation was the largest in the CD4+ lymphocyte sub-population. Radiation-induced apoptosis decreased with age of donor demonstrating that as people age their lymphocytes may become relatively more resistant to radiation. This research shows that individuals have marked differences in their sensitivity to radiation and protection policies may someday need to be tailored for some individuals.

Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review.

BACKGROUND AND PURPOSE: The purpose was to develop a systematic review that would address the following question: what is the role of radiopharmaceuticals in the palliation of metastatic bone pain in adults with uncomplicated, multifocal painful bone metastases whose pain is not controlled with conventional analgesic regimens? The outcomes of interest are pain response, analgesic consumption, overall survival, adverse effects and quality of life. MATERIALS AND METHODS: A systematic review of the English published literature was undertaken to provide evidence relevant to the above outcomes. RESULTS: Six randomized phase III trials, two randomized phase II trials and one randomized crossover trial of strontium-89 were reviewed. A randomized phase III trial comparing strontium-89 plus cisplatin with strontium-89 plus placebo reported a significantly higher proportion of patients experiencing pain relief for a significantly longer duration with strontium-89 plus cisplatin. A randomized phase III trial comparing adjuvant strontium-89 with placebo following radiotherapy reported a higher proportion of pain-free patients with strontium-89. Patients who received strontium-89 also experienced fewer new sites of bone pain. A second, but underpowered study failed to confirm these results. In one randomized trial of strontium-89 versus radiotherapy (hemibody or local), patients treated with strontium-89 developed fewer new sites of pain. In a second trial comparing strontium-89 versus local radiotherapy, median overall survival was improved with radiotherapy, while pain response and time-to-progression were similar in the two groups. One randomized phase III trial reported no difference in pain relief between strontium-89 and placebo. Three randomized phase III trials and two randomized phase II trials investigating samarium-153 were reviewed. In a randomized phase III trial of three different doses of samarium-153, the pain responses were similar for all three doses. In a randomized phase III trial of two different doses of samarium-153 versus placebo, the complete pain response rate was significantly higher with the higher dose of samarium-153 compared with placebo. In a randomized phase III trial comparing samarium-153 with placebo, significant differences favouring samarium-153 were reported for pain and opiate use. In addition, one randomized phase III trial, two randomized phase II trials, one randomized crossover trial and 13 phase II or phase I trials of rhenium, one phase I trial of tin-117 m and one phase II trial of phosphorus-32 were reviewed. The majority of patients treated in trials of radiopharmaceuticals where histology was specified had metastatic breast cancer (approximately 5-10% of patients reported), metastatic hormone-refractory prostate cancer (80-90% of patients reported) or metastatic lung cancer (5-10% of patients reported). Information on histologic subtype was not available for a significant proportion of patients treated on trials (30-40% of patients reported). CONCLUSIONS: Use of single-agent radiopharmaceuticals (strontium-89 and samarium-153) should be considered as a possible option for the palliation of multiple sites of bone pain from metastatic cancer where pain control with conventional analgesic regimens is unsatisfactory and where activity on a bone scan of the painful lesions is demonstrated. Ongoing clinical research should seek to establish the benefit of newer radiopharmaceuticals and radiopharmaceuticals in combination with other systemic therapies.

Randomized trial comparing two fractionation schedules for patients with localized prostate cancer.

PURPOSE: The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). PATIENTS AND METHODS: Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. RESULTS: From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%). CONCLUSION: Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.

Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate.

PURPOSE: To determine if iridium implant (IM) and external-beam radiation therapy (EBRT) is better than standard EBRT in locally advanced prostate cancer. METHODS: Patients with T2 and T3 prostate cancer with no evidence of metastatic disease were randomly assigned to EBRT of 66 Gy in 33 fractions during 6.5 weeks or to IM of 35 Gy delivered to the prostate during 48 hours plus EBRT of 40 Gy in 20 fractions during 4 weeks. The primary outcome consisted of biochemical or clinical failure (BCF). BCF was defined by biochemical failure, clinical failure, or death as a result of prostate cancer. Secondary outcomes included 2-year postradiation biopsy positivity, toxicity, and survival. RESULTS: Between 1992 and 1997, 51 patients were randomly assigned to receive IM plus EBRT, and 53 patients were randomly assigned to receive EBRT alone. The median follow-up was 8.2 years. In the IM plus EBRT arm, 17 patients (29%) experienced BCF compared with 33 patients (61%) in the EBRT arm (hazard ratio, 0.42; P = .0024). Eighty-seven patients (84%) had a postradiation biopsy; 10 (24%) of 42 in the IM plus EBRT arm had biopsy positivity compared with 23 (51%) of 45 in the EBRT arm (odds ratio, 0.30; P = .015). Overall survival was 94% in the IM plus EBRT arm versus 92% in the EBRT arm. CONCLUSION: The combination of IM plus EBRT was superior to EBRT alone for BCF and postradiation biopsy. This trial provides evidence that higher doses of radiation delivered in a shorter duration result in better local as well as biochemical control in locally advanced prostrate cancer.

Contemporary management of prostate cancer: a practice survey of Ontario genitourinary radiation oncologists.

OBJECTIVE: To survey radiation oncology practice in the utilization of hormonal and radiation therapy in the primary, adjuvant and salvage treatment of localized prostate cancer. MATERIALS AND METHODS: Genitourinary radiation oncologists practicing in Ontario were invited to participate in a practice survey examining staging, hormonal and radiation management, and radiation technique for a variety of common clinical scenarios. Background demographic information was collected on all respondents. The survey consisted of three cases relating to the hormonal/radiation management of low-, intermediate-, and high-risk prostate cancer as well as two adjuvant and one salvage post-prostatectomy scenarios. The survey response rate was 70% (26/37). RESULTS: Clinicians were more likely to utilize laboratory and imaging studies for staging as the risk categorization increased. Low-risk disease was managed with radiation alone in 26/26 (70 Gy in 65%, 74-79.8 Gy in 35%). Intermediate-risk disease was managed with radiation (70 Gy in 46%, 74-79.8 Gy in 54%) with neoadjuvant hormones in 58%. All respondents managed high-risk disease with adjuvant hormones in addition to radiation therapy (70-71 Gy in 85%, and 76 Gy in 15%). In the pT3a, margin negative (PSA undetectable) scenario, most individuals would not recommend adjuvant radiation (73%). If margins were positive, 30% would still not recommend adjuvant radiation. In the salvage scenario (slowly rising PSA 4 years post-prostatectomy for pT2a close margin disease), all respondents would manage with radiation therapy. Hormones were not routinely recommended in the initial management of the adjuvant and salvage scenarios. Radiation doses utilized for both adjuvant and salvage treatment ranged from 60-70 Gy (median 66 Gy). CONCLUSIONS: General agreement exists for the management of low- and high-risk disease and in the post-prostatectomy salvage setting. Use of dose-escalation and neoadjuvant hormones in the intermediate-risk setting and use of post-prostatectomy adjuvant radiation in the pT3a scenarios varied among radiation oncologists. Current clinical practice in localized prostate cancer reflects the evolving information in the published medical literature.