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.

The effectiveness of the Ivan H. Smith Memorial Studentships program on encouraging medical students to pursue a career in radiation oncology.

BACKGROUND: Founded in 1963, the Ivan H. Smith Memorial Studentship (ISMS) is a summer program that familiarizes students with the work of several cancer centers and aims to attract medical students into oncology. METHODS: In this study, we attempted to evaluate the impact of the ISMS Program on career choice in radiation oncology (RO). RESULTS: There were 5.9 times as many ISMS recipients from 1971 to 1981 who completed training in RO compared to the number of graduates exiting post-MD training in RO in 1989. CONCLUSION: Although few former ISMS students entered RO, the ISMS encourages medical students into this field.

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.

Medicine's moment of misrule: the medical student show.

Medical student shows are a prominent feature of medical student life around the world. Following a traditional vaudeville format of skits and songs, the shows are notorious for their exuberance, bawdiness, and lack of political correctness. Despite their widespread prevalence and sometimes hostile reactions, there has been no previous study of these shows. Based on research of scripts, programs, reviews, and oral history, this article explores their history and content and argues that, far from being irrelevant frivolities, these shows serve several important functions. These include the fostering of communal spirit, the development of skills in teamwork, and the collective ventilation of emotional reactions to the process of becoming a doctor. They are one offshoot of the ancient and important tradition of misrule in Western society.

Accuracy of survival prediction by palliative radiation oncologists.

PURPOSE: To examine the accuracy of survival prediction by palliative radiation oncologists. METHODS AND MATERIALS: After consultation of cancer patients with metastatic disease for referral of palliative radiotherapy, radiation oncologists estimated the survival of the patients. These were compared with the actual dates of death obtained from the Cancer Death Registry. The time to death from all causes was the outcome. The survival times were measured from the date of the first consultation at the palliative radiotherapy clinics. RESULTS: Six radiation oncologists provided estimates for 739 patients. Of the 739 patients, 396 were men and 343 were women (median age, 69 years). The median survival of all patients was 15.9 weeks. The mean difference between the actual survival (AS) and the clinician predicted survival (i.e., actual survival minus clinician predicted survival) was -12.3 weeks (95% confidence interval, -15.0 to -9.5) for the entire population. The mean difference was -21.9 weeks when the actual survival was < or =12 weeks, -19.2 weeks when the AS was 13-26 weeks, -9.7 weeks when the AS was 27-52 weeks, and +23.0 weeks when the AS was >52 weeks. CONCLUSION: In this study, the prediction of survival by radiation oncologists was inaccurate and tended to be overly optimistic.

Treatment of bone metastases with palliative radiotherapy: patients' treatment preferences.

PURPOSE: To determine the proportion of patients undergoing palliative radiotherapy (RT) for bone pain who would like to participate in the decision-making process, and to determine their choice of palliative RT regimen (2000 cGy in five fractions vs. 800 cGy in one fraction) for painful bone metastases. METHODS AND MATERIALS: Eligible patients were approached and all patients agreeing to participate provided written informed consent. Patients' decisional preferences were studied using a five-statement preference instrument. A decision board was used to help patients decide their preferred palliative RT regimen. Factors influencing patients' choices were studied using a visual analog scale. RESULTS: A total of 101 patients were enrolled in the study (55 women and 46 men). The preferences for decision-making were as follows: 30 active, 47 collaborative, and 24 passive. Most (55 [76%] of 72) patients favored one fraction of palliative RT (95% confidence interval, 65-86%). Patients were more likely to select the 800 cGy in one fraction because of the convenience of the treatment plan (odds ratio, 1.024; 95% confidence interval, 1.004-1044) but were less likely to choose it because of the chance of bone fracture (odds ratio, 0.973; 95% confidence interval, 0.947-1.000) compared with 2000 cGy in five fractions. CONCLUSION: Most participating patients preferred to decide either by themselves or with the radiation oncologists which treatment option they preferred. An 800-cGy-in-one-fraction regimen was favored, independent of the treated site. The convenience of the treatment plan and the likelihood of bone fracture were the most important factors influencing patients' choice.

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.

Fractionated stereotactic radiotherapy for the treatment of vestibular schwannomas: combined experience of the Toronto-Sunnybrook Regional Cancer Centre and the Princess Margaret Hospital.

PURPOSE: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for vestibular schwannomas in patients treated at two university-affiliated hospitals. METHODS AND MATERIALS: Thirty-nine patients were treated between April 1996 and September 2000. The median age was 56 years (range: 29-80), and median maximal tumor diameter was 20 mm (range: 9-40). A total of 11 patients had fifth and/or seventh cranial nerve dysfunction before irradiation; 2 patients had only facial weakness, 5 patients had only facial numbness, and 4 patients had both facial weakness and numbness. Thirty-three patients were treated with primary FSRT, and 6 patients were treated for recurrent or persistent disease after previous surgery. All patients were treated with 6-MV photons using a stereotactic system with a relocatable frame. The 39 patients received 50 Gy in 25 fractions over 5 weeks. Median follow-up was 21.8 months (range: 4.4-49.6). RESULTS: Local control was achieved in 37 patients (95%). Two patients experienced deterioration of their symptoms at 3 and 20 months as a result of clinical progression in one case and tumor progression in the other and underwent surgery post FSRT. A total of 19/28 (67.9%) patients preserved serviceable hearing after FSRT. Deterioration of the facial and trigeminal nerves was observed in only 2 patients who were treated with surgery post FSRT. CONCLUSION: FSRT provided excellent tumor control with minimal morbidity and good hearing preservation in this cohort of patients. Longer follow-up is required to confirm long-term control rates.

Computed tomography (CT) evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy--a feasibility study.

Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8Gy, 20Gy/5#, 30Gy/10# were: 128 (range 98-255), 141 (79-342), and 145 (65-235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy.

Priapism as a possible acute side effect of radical radiotherapy for prostate cancer.

We report a case of a 73 year-old male diagnosed with T1 N0 M0 prostate cancer, Gleason score 7, undergoing a course of radical radiotherapy using 7600 cGY delivered in 38 fractions. Several hours after receiving his 27th fraction, he reported experiencing a painful penile erection lasting more than 6 hours. A history and several investigations were conducted to determine the etiology of this adverse event. Although several possible etiologies were considered, the two most likely possibilities were direct prostate-irradiation and/or his use of alfuzosin, a novel alpha 1-adrenergic antagonist. A literature search revealed one case of priapism secondary to radiotherapy as well as reports of priapism associated with drugs similar to alfuzosin.

Tarnished adornment: The troubled history of Québec's institut du radium.

In 1922 the Québec government appropriated $100,000 for the purchase of radium to found an Institut du Radium at the University of Montreal. Opened largely through the initiative and drive of Dr. Joseph-Ernest Gendreau, the institut was the first organization devoted to radium therapy and cancer treatment in Canada. This paper describes the background, origins and development of the Institut with a focus on the medical, political, and cultural factors which led to its establishment. From the point of view of the Québec government, the Institut was a way of showing its commitment to health care, of strengthening cultural bonds with France, and of demonstrating the province's emerging technological prowess. Radium was to be an adornment which showed off the scientific advancement of 20th century Québec. Unfortunately, the Institut never achieved the scientific or cultural stature promised by the rhetoric. Which surrounded its opening, and this paper will examine the factors which led to its instability and eventual demise. In addition to an overwhelming clinical workload, chronic underfunding and geographic isolation, the Institut fell victim to medical politics. Its success was undermined by opposition from medical groups and competition from hospitals which led to the establishment of multiple radium centres in Montreal. A fundamental problem was confusion over whether its role should be a research institute, a general medical clinic, or a specialized cancer centre. Despite numerous financial and administrative crises and the severing of its academic affiliation in 1945, the Institut survived until 1967. Despite its troubled history, the Institut made an important contribution to Canadian medicine through its ground braking role in the establishment of radiotherapy and cancer treatment. In addition, the lessons learned from its difficulties proved useful to other provinces planning their own cancer programs.

Reasons for poor accrual in palliative radiation therapy research studies.

BACKGROUND: Patients with advanced-stage cancer commonly have multiple symptoms, poor performance status, and limited life expectancies. Despite the need for evidence-based practice and guidelines for palliative radiation therapy (RT), conducting clinical palliative research has proven to be a challenge in the past because of low accrual rates and high patient attrition. We explore the change in accrual rates, reasons for nonparticipation in palliative RT clinical research trials, and factors that contributed to the increase in accrual over a 3-year period. PATIENTS AND METHODS: A record was kept for all patients seen at the Rapid Response Radiotherapy Program between 2002 and 2005, including information on patient demographics, disease characteristics, and whether patients were accrued into >/=1 palliative research study at the time of clinic visit. If a patient did not participate in a study, the reason for nonaccrual was recorded. RESULTS: Despite previous difficulties, changes to the methods of conducting palliative research and study design have resulted in an increase in patient accrual, from 14% to an average of approximately 60%. The implementation of a full-time clinical research assistant and a simple study design with realistic eligibility criteria contributed to the increase in patient participation. CONCLUSION: Difficulties in conducting palliative clinical research trials were improved through changes in study design and research administration. Future clinics should use a dedicated clinical research assistant responsible for patient recruitment and study management. Studies should be designed specifically for the patient population receiving palliative care and should involve clearly defined and realistic eligibility criteria and brief assessments.

A phase II trial of palliative radiotherapy for metastatic renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) has previously been described as being less responsive to radiotherapy (RT) than other tumor types. The authors conducted a prospective study to assess the effect of RT on symptoms and quality of life (QOL) in patients with metastatic RCC. METHODS: Between 1996 and 2002, patients with symptomatic metastatic RCC were entered into a prospective study in two cancer centers. Symptomatic sites of disease were treated with 30 grays (Gy) in 10 fractions. Patients reported pain, analgesic use, symptoms, and QOL using validated questionnaires before RT, 1 month and 3 months after treatment, and every 3 months to 1 year thereafter. RESULTS: Thirty-one patients (19 males and 12 females) were entered into the trial. The median age of the patients was 61 years (range, 35-81 yrs). The most common indication for RT was bone pain (n = 24). The median duration of follow-up was 4.3 months (range, 1-15 mos). Of 23 evaluable patients treated for pain, 83% (n = 19) experienced site-specific pain relief after RT, and 48% (n = 11) did not have an associated increase in analgesic medication use. The median duration of site-specific pain response was 3 months (range, 1-15 mos). The global pain response rate was only 15% (n = 3) because many patients developed other painful metastases. Global QOL was found to improve in 33% (n = 8) of the evaluable patients. CONCLUSIONS: A palliative radiotherapy dose of 30 Gy in 10 fractions can result in a significant response rate and the relief of local symptoms in patients with bone metastases from RCC. Improvements in global pain and QOL appear to be limited by the effects of progressive systemic disease.

Seeds of discord: the politics of radon therapy in Canada in the 1930s.

In the early twentieth century, the therapeutic use of radon gas became an accepted medical practice. "Radium emanation" plants were established in many parts of North America to supply radon seeds to physicians. In Canada, these plants were usually established as part of state-supported cancer programs, creating concern among the medical profession, which had hitherto directed cancer treatment. This article explores how issues surrounding the ownership and distribution of radon played out in two Canadian provinces, Manitoba and Ontario. The main focus is an analysis of a computerized database created from more than two thousand radon order forms, dating from 1933 to 1940, preserved in the Archives of Ontario, which reveals interesting information about patients and the uses of radon in the 1930s, as well as discrepancies between policy and practice that illuminate the medical politics of the era. Although the radon seeds were intended for use in the government-supported central cancer clinics, they were widely distributed to practitioners throughout Ontario, and many patients received treatment for noncancerous conditions. These discrepancies are explored in the context of the struggles over cancer policy between the government and the Ontario medical profession. The article also shows how similar conflicts evolved in Manitoba. Finally, the distribution of radon is linked to the public acceptance of medical radiation despite contemporary reports of harm.

The role of knowledge translation for cancer control in Canada.

The definition and scope of cancer control has been evolving since its inception. The most recent model of cancer control in Canada has acknowledged the importance of knowledge translation to ensure that research results are implemented in practice and will be used to inform policy. However, without effort, the process of translation does not happen on a consistent basis. Knowledge translation focusses on improving the adoption of an innovation, e.g., research results. A number of health organizations in Canada have identified knowledge translation as an important activity and have begun to develop departments or initiatives dedicated to its achievement. As the emphasis in cancer control is on the application of knowledge, knowledge translation has a role to play in attaining the objectives of cancer control in Canada. It is an ideal time for the Canadian Strategy for Cancer Control and other Canadian cancer control initiatives to determine where they will locate knowledge translation in relation to their objectives.

Better knowledge translation for effective cancer control: a priority for action.

Increasing cancer rates are a world wide problem. Efforts towards controlling cancer are most effectively implemented through national cancer control programs. The literature has emphasized prevention and screening as main starting points; by applying what we know a substantial amount of cancer could be prevented. As well, in the areas of access to care, treatment and palliation, there are also many gains to be made. However, despite advances in fundamental and applied research across the cancer continuum, there continue to be delays between research discovery and application. Translation of research knowledge has focused on means traditionally part of the research process such as publication in journals. While knowledge may be disseminated via these methods, they appear to have little impact on implementation of new approaches in practice or policy. Research in the area of knowledge translation identifies important elements and strategies most effective in the translation of research findings. Adding a knowledge translation component to national cancer control programs can help ensure that even small efforts directed at cancer control can have maximum impact.

Multidisciplinary radiation oncology palliative care rounds as a continuing educational activity implementing the rapid response radiotherapy program at the toronto sunnybrook regional cancer centre.

BACKGROUND: This paper describes the development of the Rapid Response Radiotherapy Program and evaluates the continuing medical education (CME) series, in the form of multidisciplinary monthly Radiation Oncology Palliative Care Rounds at the Toronto Sunnybrook Regional Cancer Centre. METHODS: Palliative care rounds were initiated by the multidisciplinary committee in September, 1998. From January, 2000, to June, 2002, attendees used a standard 5- point Likert rating scale to conduct formal evaluations. RESULTS: A total of 203 evaluation forms examining 20 rounds have been collected. Findings indicated that 86.8, 96.0, 87.1, and 90.8% of participants thought the material of the presentation was relevant to their practice, interesting, and instructional. Overall 90.1% of the respondents highly rated the grand rounds (rating of 4 or 5). CONCLUSION: The grand rounds are an effective CME activity at our hospital.