Long-term Toxicity and Health-related Quality of Life after Single-fraction High Dose Rate Brachytherapy Boost and Hypofractionated External Beam Radiotherapy for Intermediate-risk Prostate Cancer.

AIMS: To report health-related quality of life (HRQOL) and toxicity in prostate cancer patients treated with single-fraction high dose rate (HDR) brachytherapy boost and external beam radiotherapy (EBRT). MATERIALS AND METHODS: Patients with intermediate-risk prostate cancer were accrued to a phase II clinical trial of 15 Gy HDR boost and EBRT to a dose of 37.5 Gy in 15 fractions. HRQOL (Expanded Prostate Cancer Index Composite [EPIC]), urinary symptoms (International Prostate Symptom Score [IPSS]), erectile function (International Index of Erectile Function [IIEF]) and toxicity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were monitored prospectively. Univariate and multivariate logistic regression analysis was used to investigate associations between HRQOL/toxicity and baseline covariates. RESULTS: The median follow-up time was 5.2 years. The change in the median EPIC scores from baseline to year 5 in the urinary domain was from 91 to 85 (P = 0.0028), in the bowel domain was from 98 to 96 (P = 0.03), in the sexual domain was from 63 to 35 (P < 0.0001) and the hormonal domain remained unchanged at 95 (P = 0.93). Fifty-nine per cent and 46% of the patients with normal erectile function at baseline remained potent at year 1 and year 5, respectively. Late genitourinary toxicity grade 1, 2 and ≥3 occurred in 29, 59 and 4% of patients, respectively. The rates of late gastrointestinal toxicity grade 1, 2 and ≥3 were documented as 45, 19 and 0%, respectively. On multivariate logistic regression analysis, patients with larger prostates were more likely to develop a urinary late toxicity grade ≥2 (P = 0.01). The dose to 10% of the urethra was the only factor associated with a decline in the EPIC urinary domain score (P = 0.012). Prostate volume >43 ml was associated with higher late genitourinary toxicity grade ≥2. CONCLUSIONS: Single 15 Gy HDR brachytherapy with EBRT has a low rate of late genitourinary and gastrointestinal toxicities. Late urinary morbidity may be minimised by limiting the dose to the urethra, particularly for patients with larger prostates.

Does the Time of Radiotherapy Affect Treatment Outcomes? A Review of the Literature.

Circadian rhythm-dependent cell cycle progression produces daily variations in radiosensitivity. This literature review aims to summarise the data on whether radiotherapy outcomes differ depending on administration time. A literature search was conducted on Ovid Medline, Embase, Cochrane Central Register of Controlled Trials and PubMed using key words such as 'radiotherapy', 'circadian rhythm', 'treatment outcome' and 'survival'. Articles evaluating the correlation between radiotherapy time and outcomes in cancer patients were included and relevant information was extracted. Nine studies met the inclusion criteria. Four investigated lung cancer patients undergoing stereotactic radiosurgery for brain metastases, with one study observing improved local control and survival in patients treated in the morning. Another two studies with breast and cervical cancer patients observed that the prevalence of toxicities was higher in afternoon and morning cohorts, respectively. Two studies in head and neck cancer patients found trends indicating morning patients experienced less oral mucositis. Increased toxicities and biochemical failure rates were associated with evening treatment in prostate cancer patients. As inconsistencies in the literature exist regarding the time dependency of radiotherapy outcomes, further investigation is warranted.

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

Aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting after moderately emetogenic radiotherapy for bone metastases: a prospective pilot study.

PURPOSE: We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (rinv) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases. METHODS: In this single-centre two-arm nonrandomized prospective pilot study, patients undergoing single-fraction radiotherapy (8 Gy) received aprepitant 125 mg and granisetron 2 mg on the day of radiotherapy and aprepitant 80 mg on each of the first 2 days after the day of radiotherapy. Patients undergoing multiple-fraction radiotherapy (20 Gy in 5 fractions) received aprepitant 125 mg on day 1 of radiotherapy, aprepitant 80 mg on days 3 and 5 of radiotherapy, and granisetron 2 mg on every day of radiotherapy. Symptoms and total medication intake were recorded daily during the acute phase (day 1 of radiotherapy until the first day after the last day of radiotherapy), and the delayed phase (days 2-10 after the last day of radiotherapy). Control of vomiting, retching, and nausea was defined as no symptoms and no use of rescue medication. RESULTS: Control rates for single-fraction patients (n = 13) were 100% for acute nausea, 62% for delayed nausea, 100% for acute vomiting and retching, and 85% for delayed vomiting and retching. Control rates for multiple-fraction patients (n = 6) were 67% for acute nausea, 83% for delayed nausea, 67% for acute vomiting and retching, and 83% for delayed vomiting and retching. No grade 3 or 4 toxicities attributable to the study intervention were observed. CONCLUSIONS: The combination of aprepitant and granisetron was safe and efficacious for the prophylaxis of rinv after both single- and multiple-fraction moderately emetogenic radiotherapy for thoracolumbar bone metastases. Our results require confirmation in a larger population.

Patterns of practice in the prescription of palliative radiotherapy for the treatment of bone metastases at the Rapid Response Radiotherapy Program between 2005 and 2012.

OBJECTIVE: We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (rrrp). METHODS: After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose-fractionation schedule. RESULTS: During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. CONCLUSIONS: For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency.

Continued success in providing timely palliative radiation therapy at the Rapid Response Radiotherapy Program: a review of 2008-2012.

OBJECTIVE: We set out to review the Rapid Response Radiotherapy Program (rrrp). METHODS: We retrospectively reviewed a prospective database of patients referred to the rrrp between August 1, 2008, and June 30, 2012, extracting patient demographics, case dispositions, and wait times in days from referral to consultation and from consultation to treatment. RESULTS: Of 2742 patients referred to the rrrp, 1458 (53%) were men, and 1284 (47%) were women. Median age was 64 years. The most prevalent primary cancer sites were lung (33%), breast (21%), and prostate (17%). The most common reasons for referral were bone metastases (53%) and brain metastases (21%). Palliative radiation therapy was given to 1890 patients. The median wait time from referral to consultation was 3 days. Among treated patients, 60% were treated on the day of their consultation, and 33%, within 1-6 days. CONCLUSIONS: The rrrp continues to deliver timely palliative radiation therapy to patients, comparable to earlier reviews. The continued success of the rrrp will remain a model for future rapid-access palliative radiation therapy clinics.

A survey of expectations and understanding of palliative radiotherapy from patients with advanced cancer.

AIMS: To assess patients' understanding of their illness and expectations of palliative radiotherapy for symptomatic metastases before and after consultation and to explore the relationship between response and demographics/Edmonton Symptom Assessment Scale (ESAS) scores. MATERIALS AND METHODS: In total, 100 participants completed a survey before and after consultation from March to October 2009. Descriptive statistics and statistical analyses were conducted to compare responses and to determine any relationship between responses and demographics or ESAS variables. RESULTS: Up to 25% believed their cancer was curable; there was no change in belief that radiotherapy would cure their cancer (17% before and 15% after) or prolong their life (40% before and 45% after). There were significant differences in radiotherapy expectation for symptom relief (P=0.0094) and for patients who did not know the role of radiotherapy (P=0.0025). Patient anxiety was reduced after consultation on questions about radiotherapy (P<0.001), concerns on effectiveness (P<0.0001) and side-effects of treatment (P<0.0001); 96, 24 and 46% said after consultation that they were satisfied with information from the team, better understood their diagnosis of cancer and the role of radiotherapy, respectively. CONCLUSION: A significant proportion of patients with advanced disease believe their cancer is curable, expect that radiotherapy will cure their cancer and prolong their life despite understanding the intent of radiotherapy is for symptom relief. After consultation, patients say they have a better understanding of their cancer and feel more confident about treatment. More work is needed to improve patients' understanding of their illness and expectations of the role of palliative radiotherapy.

Assessment of health-related quality of life with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL after palliative radiotherapy of bone metastases.

AIMS: To assess health-related quality of life (HRQOL) after palliative radiotherapy for painful bone metastases using a palliative questionnaire (European Organization for Research and Treatment of Cancer QLQ-C15-PAL). MATERIALS AND METHODS: Patients scheduled to receive palliative radiotherapy for painful bone metastases (n=178) completed the QLQ-C15-PAL questionnaire before treatment and at week 1, week 2, month 1 and month 2 after the first day of radiotherapy. A partial response (PR) or a complete response (CR) to radiotherapy was defined according to the International Consensus criteria. General linear regression was used to analyse changes in QOL in the entire cohort and within responders and non-responders to radiotherapy at all follow-up periods. RESULTS: The overall radiotherapy response was 45% at week 1 (n=21) (41% PR, 4% CR), 62% at week 2 (n=28) (58% PR, 4% CR), 62% at month 1 (n=58) (60% PR, 2% CR) and 65% at month 2 (n=38) (60% PR, 5% CR). In general, a significant decrease in pain (P<0.0001), insomnia (P<0.0001) and constipation (P=0.004) was seen by month 1 after radiotherapy. In patients who responded to radiotherapy, overall QOL significantly improved by month 2 after radiotherapy (P=0.002). Radiotherapy responders also reported an improvement in emotional functioning together with a decrease in symptoms such as insomnia and constipation at month 1. No improvements were seen in any of the QLQ-C15-PAL scores for patients whose pain did not respond to radiotherapy. CONCLUSION: Radiotherapy responders showed not only an improvement in pain, but also in HRQOL as assessed by QLQ-C15-PAL. As early as 1 week after radiotherapy for bone metastases, a pain relief response was reported by patients.

Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile?

AIMS: To determine the efficacy of radiotherapy for the palliation of pain from bone metastases among patients in their last 3 months of life. MATERIALS AND METHODS: Mutually exclusive, prospectively gathered Edmonton Symptom Assessment System and Brief Pain Inventory databases compiled from patients with bone metastases receiving palliative radiotherapy were reviewed. Demographic information and response rates from patients dying within 3 months of beginning radiotherapy were analysed. RESULTS: From a total of 918 patients, 232 dying within 3 months of beginning treatment were identified. There were 148 men and 84 women. Their median age was 69 years and their median Karnofsky Performance Status was 60. The three most common primary cancers were lung (34%), prostate (18%) and gastrointestinal (14%). Fifty-eight percent of patients received single fraction treatment. A pain response was evaluable for the 109 (47%) patients with available follow-up information. The overall response rates were 70% at 1 month and 63% at 2 months, which included complete and partial responses in accordance with the International Bone Metastases Consensus definitions. CONCLUSIONS: Despite their limited lifespan, patients reported pain relief after palliative radiotherapy. Patients suffering from painful bone metastases with an estimated survival of 3 months should still be considered for palliative radiotherapy.

Palliative response and functional interference outcomes using the Brief Pain Inventory for spinal bony metastases treated with conventional radiotherapy.

AIMS: To report pain and functional interference responses in patients radiated for painful spinal metastases, and to determine if location within the vertebral column or dose fractionation are associated with response. MATERIALS AND METHODS: Patients treated with palliative radiotherapy for symptomatic spinal metastases from May 2003 to June 2005 were analysed. All patients completed the Brief Pain Inventory (BPI) assessment tool at 1, 2 and 3 months after radiotherapy. The pain response was determined using the International Bone Metastases Consensus response definitions. Given seven BPI functional interference items, a Bonferroni adjusted P value of less than 0.007 was considered significant. RESULTS: One hundred and nine treated patients were assessed. About 50% of patients were treated with a single fraction of 8Gy. All pain scores and functional interference scores significantly decreased over time after radiotherapy. At 3 months, 64% of patients achieved a response. Mood was significantly improved for responders (P=0.003) and a trend in improvement was observed for general activity (P=0.01) and normal work (P=0.04). Breast and prostate primaries were more likely to achieve an early response as compared with a lung primary. Neither location within the vertebral column or radiotherapy dose fractionation independently predicted for pain or functional interference responses. CONCLUSION: Conventional radiotherapy with 8Gy in a single fraction for spine metastases resulted in effective palliation of pain at 3 months and had a positive effect on a patient's mood. Location within the spine was not a predictive factor.

Radiotherapy for oncologic emergencies on weekends: examining reasons for treatment and patterns of practice at a Canadian cancer centre.

PURPOSE: Radiotherapy for oncologic emergencies is an important aspect of the management of cancer patients. These emergencies-which include malignant spinal cord compression, brain metastases, superior vena cava obstruction, and uncontrolled tumour hemorrhage -may require treatment outside of hospital hours, particularly on weekends and hospital holidays. To date, there remains no consensus among radiation oncologists regarding the indications and appropriateness of radiotherapy treatment on weekends, and treatment decisions remain largely subjective. The main aim of the present study was to document the incidence and indications for patients receiving emergency treatment on weekends or scheduled hospital holidays at a single institution. The secondary aim was to investigate the compliance of such treatment with the institution's quality assurance policies, both local and provincial. METHODS: From September 1, 2002, to September 30, 2004, patients being treated over weekends (defined as commencing at 6 pm on a Friday and concluding at 8 am of the next scheduled workday) and hospital holidays were retrospectively identified using the Oncology Patient Information System scheduling module. Relevant patient data-including patient age, sex, primary cancer site, specific radiation field, rationale for treatment, referring hospital, total treatment dose, radiation dose fractionation, inpatient or outpatient status, and duration of treatment-were collected and subsequently analyzed. Comparison to local policy was performed subjectively. RESULTS: Over the 2-year period, 161 patients were prescribed urgent radiotherapy over a weekend or on a hospital holiday. Of this cohort, 68% were treated on both Saturday and Sunday, 22% on Saturday alone, and 10% on Sunday alone. Most patients presented with lung (31%), prostate (18%), and breast cancer (17%). The top reasons for referral for emergency weekend treatment included spinal cord compression (56%), brain metastases (15%), and superior vena cava obstruction (6%). Most of the indications for treatment generally followed the quality assurance policies implemented both locally and provincially. CONCLUSIONS: Patients treated over a weekend or on a hospital holiday were generally found to be treated with appropriate intent. Most treatment indications within this study both complied with provincial policy and showed a pattern of care similar to that seen in other studies in the literature. Local policy appears to be robust; however, policy improvements may allow for more cohesiveness across radiation oncologists in patterns of care in this important group of patients. Comparisons with practice at other institutions would be valuable and also a key step in developing sound guidelines for all members of the radiotherapy community to follow.

Change in urinary markers of osteoclast activity following palliative radiotherapy for bone metastases.

AIMS: To examine the effect of radiotherapy for bone metastases on urinary markers of osteoclast activity. MATERIALS AND METHODS: Patients with radiological evidence of bone metastases planned for palliative radiotherapy were eligible for the study. A urine specimen was collected before and 1 month after radiotherapy to assess levels of calcium, creatinine, magnesium, phosphate, N-telopeptide and pyridinoline. The Brief Pain Inventory was completed in person at baseline and by telephone follow-up at 1 month after radiotherapy. Patients were classified as responders (complete or partial pain response) or non-responders (stable or progressive pain) to radiotherapy based on the International Bone Metastases Consensus Criteria for end point measurements. Absolute values of urine markers were compared between responders and non-responders, or between responders and patients with progression. RESULTS: Our study population consisted of 74 men and 51 women. A single 8 Gy or 20 Gy in five daily fractions were commonly employed. At the 1 month follow-up, all Brief Pain Inventory functional interference scores showed a highly significant decrease from baseline (P<0.01). From our study population, 58 (64%) were classified as responders and 57 (46%) as non-responders to radiotherapy. We compared the urinary markers between the responders and the non-responders. There were no statistically significant differences between the two groups either in terms of baseline markers or in terms of month 1 follow-up markers. There was no significant change from baseline to the 1 month follow-up in responders or in non-responders to radiotherapy. CONCLUSION: Baseline levels of urinary markers could not predict which patient would benefit from palliative radiotherapy.

Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study.

AIMS: Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS: Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS: Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION: Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

Two cases of acrometastasis to the hands and review of the literature.

This paper reports two cases of acrometastasis to the hands. The first case involved a 78-year-old woman with a permeative osteolytic lesion in her proximal second metacarpal. A biopsy of this lesion suggested a diagnosis of non-small-cell lung carcinoma with secondary osseous metastasis. This was the first presentation of the woman's primary diagnosis. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's left hand. The treatment proved successful: the woman soon experienced pain relief and regained the use of her hand. The second case involved a 69-year-old woman with extensive lytic destruction involving the proximal two thirds of her third metacarpal. This patient had been diagnosed with carcinoma of the breast in 1990. She also received a single 8-Gy fraction of radiation, which improved both her pain and her hand mobility.An extensive review of the literature uncovered 257 previously reported cases of acrometastasis. Articles were analyzed based on age and sex of the patient, site of the primary carcinoma, metastatic locations within the hand and affected appendage or appendages, the treatment given, and the patient's length of survival. Men were almost twice as likely to experience acrometastasis as women, and the median age of the patients overall was 58 years (range: 18 months-91 years). Lung, kidney, and breast carcinoma were the three most prevalent primary diagnoses reported in the literature. Cancers of the colon, stomach, liver, prostate, and rectum affected the remainder of the population.Overall, the right hand was more often host to the metastatic lesions. In addition, almost 10% of the patients experienced lesions in both hands. The third finger was the digit most affected by osseous metastases reported in the literature. Lesions of the thumb, fourth finger, second finger, and fifth finger were less commonly reported. The region of the digit most often affected within the patient population was the distal phalanx. The metacarpal bones, proximal phalanges, and middle phalanges comprised the remainder of the four most frequent acrometastatic sites. In the literature, single lesions were more prevalent than multiple bony lesions.Based on the reported cases, amputation appeared to be the preferred method of treatment. Radiation, excision, and systemic therapy were the next most frequently used treatments. Patient survival was not well documented within the literature. However, the median survival of patients in the reported cases was 6 months. Thus, our review suggested that a diagnosis of hand metastasis is an indication of poor prognosis.This report serves to emphasize the importance of properly diagnosing acrometastases. Identifying and effectively treating these metastases in a timely manner can lead to a dramatic improvement in a patient's quality of life.

Did the pattern of practice in the prescription of palliative radiotherapy for the treatment of uncomplicated bone metastases change between 1999 and 2005 at the rapid response radiotherapy program?

AIMS: Since 1999, randomised clinical trials and meta-analyses have reported equal efficacy of pain relief from single- and multiple-fraction radiotherapy for bone metastases. A number of factors, including limited radiotherapy resources, waiting times, and patient convenience, suggest single fraction to be the treatment of choice for patients. However, international patterns of practice indicate that multiple fractions are still commonly used. This study examined whether dose-fractionation schemes used for the treatment of bone metastases at the Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Centre have changed since 1999. MATERIALS AND METHODS: A retrospective review of the prospective RRRP database and hospital records were conducted for all patients treated with palliative radiotherapy for uncomplicated bone metastases at the RRRP in 1999 (or baseline), 2001, 2004 and from 1 January to 31 July 2005. Data were collected on patient demographics and clinical characteristics. RESULTS: Of the 693 patients, 65 and 35% were prescribed single fraction (predominantly single 8 Gy) and multiple fractions (predominantly 20 Gy/five fractions), respectively. The administration of single treatments generally increased over time, from 51% in 1999 to 66% in 2005 (P=0.0001). On the basis of multiple logistic regression analyses, patients were more likely to be prescribed single-fraction radiotherapy if they had prostate cancer, had a poorer performance status, were treated to the limbs, hips, shoulders, pelvis, ribs, scapula, sternum, or clavicle (compared with the spine), were treated by a radiation oncologist who had been trained in earlier years, and who were treated after 1999. CONCLUSIONS: Between 1999 and 2005, the use of single-fraction radiotherapy increased, corresponding to publications showing equal efficacy of pain relief between single and multiple fractions in the management of uncomplicated bone metastases. However, about a third of patients still received multiple fractions.

How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4-7, clinically localized prostate cancer?

OBJECTIVE: To compare histologic grades between an initial biopsy and a follow-up biopsy in untreated, Gleason score (GS) 4-7, clinically localized prostate cancer. METHODS AND MATERIALS: In a prospective single-arm cohort study, clinically localized, GS 4-7, prostate cancer was managed with active surveillance alone, provided that a pre-defined definition of disease progression was not met. One hundred five (63%) of a total of 168 eligible patients underwent a follow-up prostate biopsy during surveillance. Median time to a follow-up biopsy was 22 months (range: 7-81). Histologic grades between these two biopsies were compared to evaluate the extent of histologic grade change. RESULTS: On the follow-up biopsy, GS was unchanged in 33 patients (31%), upgraded in 37 (35%), and downgraded in 34 (32%). Eleven (10%) had upgrading by 2 Gleason points or more. Eight (8%) had upgrading to GS 8 (none to GS 9 or 10); of these, six were among those with upgrading by 2 Gleason points or more. Twenty-seven (26%) had no malignancy on the follow-up biopsy. Negative follow-up biopsy was more prevalent in patients with a small volume of malignancy in the initial biopsy and a low baseline PSA. CONCLUSIONS: No consistent change in histologic grade was observed on the follow-up biopsy at a median of 22 months in untreated, GS 4-7, clinically localized prostate cancer. Upgrading to GS > or =8 or by 2 Gleason points or more was relatively uncommon.

New multidisciplinary prostate bone metastases clinic: first of its kind in Canada.

Prostate cancer is the most common non-skin malignancy in men. Almost all men who die from prostate cancer have hormone-refractory prostate cancer with metastasis to bone. Emerging supportive treatments-including chemotherapy, bisphosphonates, and surgery-require integration that is optimized in a multidisciplinary setting. A multidisciplinary clinic for bone metastases has been in place at Toronto-Sunnybrook Regional Cancer Centre since 1999, combining orthopedic surgery, radiation oncology, interventional radiology, and palliative medicine for all patients with bone metastases. The addition of a prostate-focused multidisciplinary clinic integrates these services for patients with advanced prostate cancer.

Rise in prostate-specific antigen in men with untreated low-grade prostate cancer is slower during spring-summer.

To test the hypothesis that the rate of rise in prostate-specific antigen (PSA) is slower during the spring-summer than during the rest of the year, we used PSA data from a prospective single-arm cohort study of men who had been followed to characterize a watchful observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The rate of PSA increase was calculated as the visit-to-visit slope of log (PSA) against time, from 1 calendar-quarter visit to the next. The nonparametric Friedman test confirmed differences in rate of PSA rise among the calendar quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2 was significantly slower than in each one of the other calendar quarters (Q1 versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no differences among quarters Q1, Q3, and Q4. These results are consistent with the vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with spring and summer have a desirable effect on prostate biology. The therapeutic implication is that vitamin D supplementation in the range of 2000 IU/d, a dose comparable to the effect of summer, can benefit men monitored for rising PSA.

An innovative rapid response radiotherapy program to reduce waiting time for palliative radiotherapy.

BACKGROUND: Waiting for radiation therapy (RT) in Ontario has been a major problem for the past decade. In 1996, the Toronto-Sunnybrook Regional Cancer Centre (TSRCC) initiated a Rapid Response Radiotherapy Program (RRRP) to provide timely palliative RT for symptom relief of patients with terminal cancer. PURPOSE: This study reviews the clinical activity of the RRRP over the past 8 years to evaluate if we are meeting the objectives of the program. MATERIALS AND METHODS: From the TSRCC oncology patient information system (OPIS) database, we retrieved the number of patients referred to the RRRP, their demographics, diagnosis and treatment for the calendar years 1996 to 2003 inclusive. We calculated the time interval between referral to consultation, consultation to simulation and the percentage of cases who started RT on their initial consultation for all new cases referred to the RRRP. RESULTS: From 1996 to 2003, the number of cases seen in consultation increased from just over 200 cases annually in the first 2 years to about 500 cases per year in the last 4 years, for a total of 3,290. There were 1,792 (54%) men and 1,498 (46%) women; median age was 69 years (range, 21-95 years). Breast, lung, genitourinary and gastrointestinal primaries accounted for over 80% of all referrals. The majority was referred for palliative treatment of symptomatic bone (70%) or brain (14%) metastases. The dose fractionation for bone metastases was a single 8-Gy fraction in 45%, 20 Gy in five fractions in 42%, 30 Gy in ten fractions in 4% and other dose fractionations in 9%. Nearly 90% were seen within 2 weeks of referral (38% within 1 week). Eighty-five percent were simulated on the day of their initial consultation. Sixty percent started their RT treatment on the day of their consultation visit. The overall median interval from referral to treatment was 8 days. CONCLUSION: Over the past 8 years, the annual number of new cases referred to the RRRP has doubled. The overall median interval from referral to consultation was 8 days. Sixty percent were simulated, planned and started treatment on the day of their initial consultation. We therefore are meeting our goal of providing rapid access to palliative RT for symptomatic cancer patients.

The do-not-resuscitate order: incidence of documentation in the medical records of cancer patients referred for palliative radiotherapy.

Patients with symptomatic metastases referred for outpatient palliative radiotherapy for symptom control at the Rapid Response Radiotherapy Program (RRRP) and the Bone Metastases Clinic (BMC) at the Toronto-Sunnybrook Regional Cancer Centre have a limited life expectancy. Relevant medical information is missing from the files of many referred patients when they arrive at the clinics, potentially causing delayed treatment and ambiguity in the best management of their needs in situations of worsening condition. Clear documentation of the do-not-resuscitate (DNR) order is imperative to avoid panic and the taking of unnecessarily aggressive measures in situations in which cardiopulmonary resuscitation (CPR) has no benefit or is not desired. Here, we report the current practices of CPR code status documentation for patients referred to the RRRP and the BMC for out-patient palliative radiotherapy.We reviewed referral notes and accompanying medical records for 209 consecutive patients seen in the RRRP and the bmc during May-August 2004 for documentation of CPR-related advance directives. Patient demographics and cancer history were also recorded.Only 13 (6.2%) of the 209 patients had any documented reference to CPR code status. Of these 13 patients, 8 were DNR-coded, and 5 were full code. As compared with patients having no documented cpr code status, patients with documented status were significantly older (median age: 77 years; p = 0.0347), had poorer performance status (median Karnofsky performance status score: 40; p = 0.0001), and were more likely to be referred hospital inpatients (69%, p = 0.0004).Only a small proportion of symptomatic advanced cancer patients had any documentation of CPR code status upon referral for outpatient palliative radiotherapy. In future, our clinics plan to request information about CPR code status on our referral form.