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Aims: Higher mean lung dose (MLD) in breast cancer patients has been associated with pneumonitis, pulmonary fibrosis and secondary lung cancer primaries. This study examined MLD in a single institution from 2014 to 18 to assess trends in median MLD (Gy) over time and factors associated with higher MLD to determine best practices for limiting lung toxicity., Materials and Methods: General linear regressions were analysed to determine significant change in median MLD over time in patients receiving conventional or hypofractionated schedules for whole breast/chest wall (WB) radiotherapy with or without sequential boost or simultaneous integrated boost, WB tangential radiotherapy only and WB locoregional radiotherapy. Univariate and multivariable linear regression analysed identified factors associated with MLD., Results: In total, 3894 patients were included in the analysis. The total median MLD across all years was 6.8 Gy in patients treated with conventional fractionation and 3.4 Gy in patients treated with hypofractionation. A significant increase in MLD was observed between 2014 and 2018 in patients receiving conventional or hypofractionation, conventional WB treatment with locoregional radiotherapy, conventional WB radiotherapy with simultaneous integrated boost and hypofractionated WB radiotherapy with sequential boost. Increased MLD was significantly correlated with lower lung volume and larger treatment volume due to locoregional radiotherapy, inclusion of a boost, chest wall treatment and reverse decubitus or supine positioning (P < 0.0001)., Conclusion: A significant increase in MLD was observed over the years in patients receiving conventional and hypofractionated radiotherapy. Techniques such as prone positioning should be considered to lower MLD, particularly for patients with predisposing pulmonary risk., (Copyright © 2020 The Royal College of Radiologists. All rights reserved.)

Aims: Male breast cancer is a rare disease with limited evidence-based guidelines for treatment. This study aimed to identify demographic, pathological and clinical factors associated with its prognosis., Materials and Methods: A retrospective review of 161 male breast cancer patients diagnosed at a single institution from 1987 to June 2017 was conducted. Patient demographics, disease characteristics, treatment and outcome were extracted and included in competing-risk analysis and the univariate Cox proportional hazard model for univariate analysis. Factors with P < 0.10 were included in multivariable analysis., Results: The mean age at diagnosis was 67 years (standard deviation = 11.2) and the median follow-up duration was 5.3 years (range 0-25 years). There were 48 deaths, including 23 cancer-specific deaths. The actuarial median survival was 19.9 years. In multivariable analysis, factors associated with overall survival were size of tumours (hazard ratio 2.0; 95% confidence interval 1.4-2.7, P < 0.0001) and diagnosis of metastatic disease (hazard ratio 8.7; 95% confidence interval 1.9-40.6; P = 0.006). Of 138 patients without metastases at diagnoses, 11 had local-regional recurrence and 26 had distant metastases. In the multivariable model for local-regional recurrence, a more recent year of diagnosis was associated with reduced risk (hazard ratio 0.9, 95% confidence interval 0.8-1.0, P = 0.008), whereas more positive lymph nodes was associated with higher risk (hazard ratio 2.2, 95% confidence interval 1.2-4.0, P = 0.01). A higher risk of metastases was associated with more positive lymph nodes (hazard ratio 1.9; 95% confidence interval 1.1-3.3; P = 0.03) and tumour size (hazard ratio 1.8; 95% confidence interval 1.1-2.9; P = 0.01). A higher risk of any recurrence or metastases was associated with the number of positive nodes (hazard ratio 1.9; 95% confidence interval 1.2-3.0; P = 0.005) and tumour size (hazard ratio 1.6; 95% confidence interval 1.1-2.2; P = 0.01)., Conclusion: In general, tumour size and more positive lymph nodes were associated with worse prognosis. Larger powered studies are needed to identify prognostic factors with smaller effect sizes., (Copyright © 2018 The Royal College of Radiologists. All rights reserved.)

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., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Skeletal-related events (SREs) in patients with bone metastases decrease a patient's quality of life and functional status. Although bone-modifying agents have been found to reduce the time to first on-trial SRE and decrease the total incidence of SREs in randomised clinical trials, standard practice in the management of bone metastases has changed concurrently. The purpose of this study was to investigate if advances in bone-targeted therapies have decreased the incidence of individual types of SREs and to delineate the trend of SREs., Materials and Methods: A literature review was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify phase III, randomised bisphosphonate and other bone-targeted therapy trials from 1980 to September 2011. For all studies, a mean year of enrolment ([start of enrolment + end of enrolment]/2) was calculated. The incidences of SREs were tabulated and expressed as percentages of on-trial patients. Generalised linear mixed models were used to search for the trends of SREs over time for all placebo and intervention arms. Regression coefficients were interpreted as the odds ratio, which was calculated using the exponential of the slope. Ninety-five per cent confidence intervals were also calculated., Results: In total, 20 eligible studies were identified that reported SRE data from phase III trials, of which 11 were suitable for the quantitative analysis. Most of the articles included patients with breast cancer and the remaining involved patients with prostate, renal cell, bladder and lung cancer or other solid tumours. Enrolment periods for all included data ranged from 1990 to 2009. Statistically significant overall downward trends in pathological fractures and the need for surgery were seen over time. Also significant differences between intervention and placebo were seen with all SREs., Conclusion: The decrease in SREs over time may not only be a result of the development of new generation bone-targeted agents, but also due to better systemic management and awareness of events associated with bone metastases., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Most cancers occur in those older than the age of 65 years. As the population of the world ages and life expectancies continue to increase, it is important to address treatment challenges for elderly patients. This narrative review details the challenges of palliative radiotherapy treatment for elderly patients with bone metastases. We begin with the definition of elderly and its appropriateness, outlining recent demographic data of patients with cancer. The current status of elderly participation in clinical trials is discussed by reviewing the recent literature and clinical trial data. Factors affecting enrolment of the elderly are assessed, with a focus on palliative radiotherapy trials, and what we can do to improve accrual in this data-driven setting. At present, there is a lack of level 1 evidence that evaluates the optimal treatment for elderly patients with bone metastases. Therefore, a review of safety and efficacy is given based on previously published reports. Palliative radiotherapy for elderly patients is a worthwhile treatment and should be recommended regardless of age, as supported by available evidence. Patient, family and physician concerns about physical burden may be reduced as single treatments (that often can be done in a single visit) are as beneficial as multiple treatments for painful bone metastases. In elderly patients, radiotherapy may even be the best treatment for these cases as opioid-related adverse events are amplified in this group and often dosages are more difficult to titrate. Clinicians should continue to encourage the enrolment of elderly patients on to clinical trials as these data form the basis of optimal treatment guidelines. Radiation oncologists are encouraged to reduce the physical burden for elderly patients by offering single treatments where appropriate and completing consultation, treatment simulation and treatment in a single clinical visit., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: Well-being falls within a broad category of quality of life indicators and encompasses both physical and emotional factors. Identification of the most important factors affecting overall well-being may allow health care practitioners to target these symptoms and improve patients' quality of life. The purpose of this study was to determine factors most predictive of well-being in advanced cancer patients., Materials and Methods: Patients referred to the Rapid Response Radiotherapy Program completed the Edmonton Symptom Assessment System (ESAS) at consultation. ESAS scores and demographics were analysed for their predictive ability for well-being via regression analysis of the raw and categorical scores., Results: In total, 1439 ESAS assessments were analysed; the median age was 69 years (range 21-95). The most common primary cancers were of the lung (36%), breast (21%) and prostate (18%). Greater distress in all ESAS items, lower Karnofsky performance status (KPS) and referral for bone metastases significantly predicted for worse well-being (all P < 0.0001). However, referral for brain metastases predicted for better well-being. In multivariate analysis, the most predictive factors for worse well-being were lower KPS (P = 0.003) and greater distress in drowsiness (P = 0.01), pain (P < 0.0001), fatigue (P < 0.0001), depression (P < 0.0001) and appetite loss (P < 0.0001). Repeated analyses with categorical scores led to similar results., Conclusion: Greater distress in physical and emotional symptoms assessed by ESAS contributes significantly to poorer well-being. Management for patients with advanced cancer should be directed towards these symptoms, as they form the basis for well-being. Although emotional symptoms may be scored lower than physical symptoms by patients, both significantly affect well-being., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: To update previous meta-analyses of randomised palliative radiotherapy trials comparing single fractions versus multiple fractions., Materials and Methods: All published randomised controlled trials comparing single fraction versus multiple fraction schedules for the palliation of uncomplicated bone metastases were included in this analysis. Odds ratios and 95% confidence intervals were calculated for each trial. Forest plots were created using a random effects model and the Mantel-Haenszel statistic., Results: In total, 25 randomised controlled trials were identified. For intention-to-treat patients, the overall response rate was similar in patients receiving single fractions (1696 of 2818; 60%) and multiple fractions (1711 of 2799; 61%). Complete response rates were 620 of 2641 (23%) in the single fraction arm and 634 of 2622 (24%) in the multiple fraction arm. No significant difference was seen in overall or complete response rates. Pathological fracture did not favour either arm, but spinal cord compression trended towards favouring multiple fractions; however, neither was statistically significant (P = 0.72 and P = 0.13, respectively). Retreatment rates favoured patients in the multiple fraction arm, where the likelihood of requiring re-irradiation was 2.6-fold greater in the single fraction arm (95% confidence interval: 1.92-3.47; P < 0.00001). Repeated analyses excluding drop-out patients did not alter these findings. In general, no significant differences in acute toxicities were seen., Conclusion: Overall and complete response rates were similar in both intention-to-treat and assessable patients. Single and multiple fraction regimens provided equal pain relief; however, significantly higher retreatment rates occurred in those receiving single fractions., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: The prevalence of anxiety and depression in patients with advanced cancer has been reported to be on average 25% and to significantly affect patients' quality of life. Despite high prevalence rates, these disorders remain underdiagnosed and undertreated. The purpose of our study was to examine the self-report rates of anxiety and depression with the Edmonton Symptom Assessment System (ESAS) and to assess the predictive factors for these reports in cancer patients with metastatic disease., Materials and Methods: Consecutive patients who attended the Rapid Response Radiotherapy Program (RRRP) completed the ESAS as well as baseline demographic information. Ordinal logistic regression analysis was used to determine factors that significantly predicted anxiety and/or depression. Pearson χ(2) was used to test goodness-of-fit for categorical variables and established whether or not an observed frequency distribution differed from a predicted frequency distribution. A univariate analysis was conducted first and those variables with a P value<0.100 were included in a multivariate analysis. A score test was used to test the proportional odds assumption., Results: In total, 1439 patients seen in the RRRP between January 1999 and October 2009 completed ESAS questionnaires. Fifty-five per cent of patients reported at least mild symptoms of depression and 65% reported at least mild anxiety. In the univariate analysis, patients who were female, who had a lower performance status score, or primary lung cancer were more likely to report depressed and anxious feelings. Primary prostate cancer patients were significantly less likely to report depression and anxiety. Patients referred for spinal cord compression were significantly less depressed. The multivariate models showed that younger patients were significantly more anxious than older patients and females reported more anxiety than males. Patients who reported higher feelings of nausea, tiredness, drowsiness, dyspnoea, and worse appetite and overall well-being on the ESAS tool were more likely to report feelings of depression. Patients who reported higher nausea, drowsiness, dyspnoea and worse overall well-being more often reported higher feelings of anxiety., Conclusion: The self-report rates of anxiety and depression were consistent with published prevalence rates. However, the explained variance based on factors included in the model remains low. Additional predictive factors should be examined in future studies in this population. The ESAS tool seems to be an efficient screening tool for anxiety and depression; however, future studies should examine its correlative properties with other known screening tools in the advanced cancer population. A prospective study should be conducted to assess the severity cut-off point in which the ESAS scores most frequently lead to a further diagnosis of an anxiety or depressive disorder in the advance cancer population., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Radiotherapy has been proven to be an effective treatment for the palliation of symptomatic bone metastases. Despite its widespread use and long history, there remains considerable debate over whether a single 8 Gy fraction or multiple fraction schemes are more effective at alleviating bone pain. Recent meta-analyses have shown equal efficacy between the different treatment regimens. One of the reasons supporting multiple fraction use is a lower re-irradiation rate. Recent research has explored many issues associated with retreatment, including timing, appropriate patient selection and concerns of toxicities. However, there are notable side-effects due to radiotherapy, perhaps one of the most significant being 'pain flare', which is a temporary increase in bone pain immediately after treatment. It has a reported incidence of up to 44% in patients. Despite possible side-effects like 'pain flare', radiotherapy can improve pain and also quality of life for patients. One of the quality of life tools that has become useful for assessing the effectiveness of palliative radiotherapy on physical, psychosocial and functional issues is the EORTC-QLQ-BM22. In addition to tracking quality of life changes in patients, analysing symptom clusters can be used to better understand the symptomatology of advanced cancer, and how radiotherapy can affect pain and other symptoms that cancer patients commonly experience., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims: Post-lumpectomy breast radiation is the standard of care for all patient subgroups. However, elderly women with stage I breast cancer on adjuvant tamoxifen therapy have a 4% risk of local recurrence after lumpectomy without adjuvant breast radiation. The purpose of this study was to explore the attitudes of Canadian radiation oncologists who treat breast cancer with respect to their use of adjuvant post-lumpectomy radiotherapy, and their willingness to implement a decision aid for this patient population., Materials and Methods: The questionnaire was mailed to 141 Canadian radiation oncologists who treat breast cancer. The respondents were asked to complete an online survey consisting of four parts: (1) demographic information; (2) factors determining post-lumpectomy radiation treatment decisions; (3) hypothetical case scenarios; (4) interest in using a decision aid in their practice., Results: Among the 61 (43%) physicians who completed the survey, there was substantial response variation. After contraindications to radiotherapy, patient overall health and patient preference had the greatest influence on their decision to offer radiotherapy to this patient subgroup. Margin status and use of hormonal therapy were given less importance. For each of the case scenarios, 60-83% of physicians (depending on the case scenario) would offer the patient a choice; far fewer (12-57%) would be comfortable not irradiating. Sixty-four per cent of respondents welcomed the concept of a decision aid for this population., Conclusions: Although there is significant variation in practice patterns and attitudes among radiation oncologists regarding post-lumpectomy radiotherapy for elderly, low-risk breast cancer patients, the vast majority value patient choice and would be willing to use a decision aid designed for this population in their practice., (2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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.

Aims: It is well established that palliative radiotherapy provides effective pain relief for symptomatic bone metastases, but controversy remains regarding the optimal dose fractionation. Several meta-analyses and systematic reviews of trials comparing the efficacy of single vs multiple fractionated radiotherapy schedules noted that it is difficult to reach a consensus when inconsistent response end point definitions are used. The purpose of this study was to determine when the most appropriate time to evaluate a response is., Materials and Methods: Patients with symptomatic bone metastases treated with palliative radiotherapy between May 2003 and June 2005 were enrolled in the study. They were assessed with the Brief Pain Inventory at baseline, 1, 2 and 3 months after radiotherapy. Analgesic consumption during the preceding 24h was recorded and converted into an equivalent total daily dose of oral morphine. The response to radiotherapy was assessed using the International Bone Metastases Consensus end point definitions at 1, 2 and 3 months of follow-up., Results: One hundred and ninety-nine patients were treated with palliative radiotherapy. All pain scores and functional interference items improved after radiotherapy. The proportion of evaluable patients with a complete response or a partial response increased between 1 month (58%) and 3 months of follow-up (67%). However, when considering intention-to-treat percentages, which take attrition into consideration, overall response rates dropped from 35% at 1 month, to 32% at 2 months, and finally 24% at 3 months., Conclusion: We conclude that 2 months after radiotherapy is the most appropriate time point to measure response rates for two reasons: (i) the maximum pain relief for some patients may take more than 4 weeks to achieve and (ii) attrition poses a major problem when response rates are measured at a later date. Future trials should use standardised criteria for end points to facilitate comparison and analysis across clinical trials. Given the limitations of this study, however, further investigations are needed to confirm the response time points for palliative cancer patients.

Aim: To explore the presence of symptom clusters in patients with brain metastases., Materials and Methods: Patients with brain metastases referred to an outpatient palliative radiotherapy clinic were asked to rate their symptom distress using the Edmonton Symptom Assessment Scale (ESAS). Baseline demographic data were obtained. To determine interrelationships between symptoms, a principal component analysis with 'varimax rotation' was carried out on the nine ESAS items. Follow-up was carried out by telephone 1, 2, 4, 8 and 12 weeks after radiation., Results: Between January 1999 and January 2002, 170 patients with brain metastases provided complete baseline data on the ESAS. The most common primary cancer sites were lung, breast and gastrointestinal. Fatigue was the highest scored symptom, followed by a poor sense of well-being, anxiety, drowsiness and poor appetite. The four most prevalent symptoms were fatigue (91.7%), a poor sense of well-being (88.1%), drowsiness (82.2%) and anxiety (82.1%). Three symptom clusters were found at baseline. Cluster 1 included fatigue, drowsiness, shortness of breath and pain. Cluster 2 included anxiety and depression. Cluster 3 included poor appetite, nausea and a poor sense of well-being. Fatigue, nausea, drowsiness and poor appetite showed an overall increase in symptom severity over time; whereas fatigue, drowsiness and poor appetite were experienced to some extent by a greater proportion of patients at week 12 compared with baseline. Symptom clusters emerged in all weeks of follow-up, but consisted of different symptoms in each week., Conclusion: Symptom clusters seemed to exist in patients with brain metastases before and after whole brain radiotherapy. However, different symptoms clustered at various time points. The effectiveness of whole brain radiotherapy in providing palliative relief to patients with brain metastases needs to be explored with regards to symptom clusters.

Aims: To determine which pain intensity scale in the Brief Pain Inventory correlates best with functional interference and should be used to calculate the response to palliative radiotherapy. To determine the differences in functional interference scores for patients classified as responders and non-responders to palliative radiotherapy., Patients and Methods: All patients referred to the Rapid Response Radiotherapy Program for palliative radiotherapy of symptomatic bone metastases were considered for the study. Patients rated the intensity and functional interference of their pain at the irradiated sites according to the Brief Pain Inventory before and 2 months after radiotherapy. Worst, average and current pain scores were correlated with functional interference scores using Spearman rank coefficients. Responders and non-responders to palliative radiotherapy were defined for each pain intensity scale according to the end points specified by the International Bone Metastases Consensus Working Party. Average differences between responders and non-responders were compared using a Wilcoxon rank sum test., Results: Between May 2003 and June 2005, 199 patients enrolled in the study (102 men and 97 women). Ninety-five patients returned complete questionnaires at 2 months of follow-up. All pain intensity and interference scores for evaluable patients were significantly lower at 2 months (P<0.0021). Response rates differed depending on the definition of pain intensity. An overall response rate was observed in 66, 58 and 54% of patients for worst, average and current pain, respectively. Worst pain showed the best correlation with functional interference. Responders reported significantly larger decreases in functional interference scores at follow-up in general activity, normal work, enjoyment of life and average functional interference., Conclusion: Worst pain intensity had higher correlations with all functional interference scores except relationships with others. Therefore, we recommend an 11-point scale measuring worst pain to evaluate response rates in future radiotherapy trials. The mean difference from baseline to follow-up in functional interference scores was significantly larger in patients who responded to radiotherapy treatment.

Aims: Whole-brain radiotherapy (WBRT) is a standard treatment recommendation for patients with brain metastases. The goal of treatment is symptom control, which in the short run can be often achieved by steroids. Patients with a short life expectancy may not derive benefit from the addition of radiation. The ability to identify this group would aid the decision of whether to recommend WBRT., Materials and Methods: Data on all patients referred for WBRT to palliative radiotherapy teams at two comprehensive cancer centres were prospectively collected over a 2-year period. The most frequent radiation dose and fractionation was 2000 cGy in 5 fractions over 1 week. Multivariate logistic regression analysis using forward stepwise selection process was used to develop a prediction model for early death (before 8 weeks). The variables considered were sex, performance status, primary disease, weight loss, age, time from primary diagnosis to brain metastases diagnosis, number of metastatic sites and Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) status., Results: Two hundred and seventy-five patients with brain metastases were assessed. The median follow-up was 19 weeks, and estimated median overall survival was 5.3 months. Multivariate regression revealed Eastern Cooperative Oncology Group (ECOG) performance status and number of metastatic sites to be significant predictors of early death. The odds ratios were 2.38 (95% confidence interval [CI] 1.77-3.19) and 1.39 (95% CI 1.07-1.81), respectively. Sixty-eight per cent of patients could be correctly classified; however, 55% would have been incorrectly predicted to die early., Conclusions: Poor performance status and number of metastatic sites are useful predictors of early death. A regression model was highly predictive overall, but this was primarily due to a high negative predictive value of 86%. The ability to predict patients who would die early (positive predictive value) was only 45%. Thus, despite the understanding that we are over-treating a subset of patients, further research is required to identify patients who do not require radiotherapy.

Objectives: To compare and contrast the definitions of primary treatment endpoints in randomized studies of dose-fractionation schedules for treating bone metastases and to identify basic characteristics of treatment endpoint that may require consensus among investigators., Methods: Randomized controlled trials (RCTs) of various dose-fractionation schedules for painful bone metastases, published between 1980 and 1999, and on-going trials whose protocols were available, were systematically reviewed based on the following features of the primary treatment endpoint: (i) degree of pain relief; (ii) timing of the pain response assessment; (iii) effect of co-interventions on pain relief; (iv) the reduction of analgesic as a treatment response; and (v) quantification of response duration., Results: Ten published RCTs (each sampled over 100 patients), plus two current trial protocols were reviewed. Five of the 12 studies defined any reduction in pain score as the primary endpoint. Three trials defined response at pre-determined time points, whereas eight studies attributed pain improvement at any time during follow-up to the effect of radiotherapy. No trial incorporated effect of systemic treatments on response. Only two trials incorporated analgesic scores into the primary endpoint criteria, although several trials reported results of combined pain and analgesic relief. Eight trials reported duration of response. Three provided some estimation of duration with respect to survival: two of them employing actuarial time to pain progression, and one calculated the ratio of pain response to median survival duration (percent net relief). Quality of life was measured in four of 12 studies, as secondary endpoint., Conclusion: Although available data suggest similarity in pain relief among various dose-fractionation schedules, accurate and consistent description of the degree of benefit from radiotherapy is lacking. While pain relief is a consistent primary treatment goal among randomized trials, a consensus on several important features of treatment endpoint is needed in order to establish common grounds for future trials in palliative radiotherapy.

We conducted a pilot study to examine patients' understanding of their illness and their expectations for palliative radiotherapy for symptomatic metastases. Participants were asked to complete a survey consisting of seven questions prior to the initial consultation. Demographic details and information on extent of disease were collected. Patients were asked to score their symptom distress using the modified Edmonton Symptom Assessment System. Sixty patients participated in the pilot study between January and April 1999. Their median age was 68 years (range 46-90). The most common primary tumours were lung, prostate and breast. Twenty-one patients (35%) believed that their cancer was curable. Twelve (20%) expected that palliative radiotherapy would cure their advanced cancer and 23 (38%) believed that palliative radiotherapy would prolong their lives. Twenty-one patients (35%) had concerns about the effectiveness of radiation therapy and twenty (33%) had concerns about the side-effects of radiotherapy. Fifty-two (87%) were not familiar with the concept of radiation treatment. Forty-seven patients (78%) reported that they were not given information about the radiation treatment; 51 (85%) were not satisfied with the information that their own doctors had provided regarding radiation treatment prior to the consultation at our clinic. A significant proportion of the patients in this pilot study had misconceptions regarding their illness and unrealistic expectations from palliative radiotherapy. We plan to provide educational pamphlets for use in referring doctors' surgeries and clinics in order to inform patients of the nature, rationale and anticipated benefits and side-effects of palliative radiotherapy.

The purpose of this review was to examine the accuracy of physicians' clinical predictions of survival and the available prognostic tools in estimating survival times in terminally ill cancer patients. A MEDLINE search for English language articles published between 1966 and March 2000 was performed using the following keywords: forecasting/clinical prediction, prognosis/prognostic factors, survival and neoplasm metastasis. Searches in CancerLit, EMBASE, PubMed, the Cochrane Library and reference sections of articles were performed. Studies were included if they concerned adult patients with various cancer histological diagnoses and employed clinical prediction and the readily available clinical parameters. Biochemical and molecular markers were excluded. Grading of the evidence and recommendations was performed. Twelve articles on clinical prediction and 19 on prognostic factors met the inclusion criteria. Clinical prediction tends to be incorrect in the optimistic direction but improves with repeated measurements. Performance status has been found to be most strongly correlated with the duration of survival, followed by the 'terminal syndrome', which includes anorexia, weight loss and dysphagia. Cognitive failure and confusion have also been associated with a shorter life span. Performance status combined with clinical symptoms and the clinician's estimate helps to guide an accurate prediction, as reviewed in an Italian series. There is fair evidence to support using performance status, and clinical and biochemical parameters, in addition to clinicians' judgement to aid survival prediction. However, there is weak evidence to support that clinicians' estimates alone could be specifically employed for survival prediction.