Symptom correlates of dyspnea in advanced cancer patients using the Edmonton Symptom Assessment System.

PURPOSE: Dyspnea is frequently experienced in advanced cancer patients and is associated with poor prognosis and functional decline. This study used the Edmonton Symptom Assessment System (ESAS) to characterize the relationship between dyspnea and concurrent symptoms experienced by advanced cancer patients. METHODS: A prospective database was collected and analyzed to extract patient demographics and ESAS scores. Logistic regression analysis and generalized estimating equations (GEE) identified correlations of other ESAS symptoms in three categories: severity of dyspnea (none, mild, moderate, severe), moderate/severe dyspnea (ESAS ≥ 4), and presence of dyspnea (ESAS ≥ 1), at patients' first visit and over time, respectively. RESULTS: Multivariable analysis revealed drowsiness (p = 0.001), and anxiety (p = 0.01) and appetite loss (p = 0.02) were associated with increased severity of dyspnea at first visit. Over time, tiredness (p = 0.02), drowsiness (p = 0.04), nausea (p = 0.02), and anxiety (p = 0.0006) were more likely to experience increased dyspnea severity. Tiredness (p = 0.0003), depression (p = 0.03), and appetite loss (p = 0.003) were significant for moderate/severe dyspnea at first visit. Over multiple visits, tiredness (p < 0.0001), anxiety (p = 0.0008), and appetite loss (p = 0.0008) had higher probabilities of moderate/severe dyspnea. For the presence of dyspnea at the first visit, anxiety (p = 0.03) and drowsiness (p = 0.002) were significantly correlated with an increased frequency of dyspnea. Over time, anxiety (p < 0.0001) and drowsiness (p < 0.0001) remained significant with the addition of nausea (p = 0.0007). CONCLUSIONS: The highly interactive relationship between dyspnea and other common cancer symptoms necessitates the development of comprehensive symptom assessments and utilization of multimodal management approaches that consider concurrent symptoms for improved identification and treatment of dyspnea.

External beam radiation dose escalation for high grade glioma.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells of the nervous system, with several subtypes such as glioblastoma (grade IV astrocytoma), anaplastic (grade III) astrocytoma and anaplastic (grade III) oligodendroglioma. Studies have investigated the best strategy to give radiation to people with HGG. Conventional fractionated radiotherapy involves giving a daily radiation dose (called a fraction) of 180 cGy to 200 cGy. Hypofractionated radiotherapy uses higher daily doses, which reduces the overall number of fractions and treatment time. Hyperfractionated radiotherapy which uses a lower daily dose with a greater number of fractions and multiple fractions per day to deliver a total dose at least equivalent to external beam daily conventionally fractionated radiotherapy in the same time frame. The aim is to reduce the potential for late toxicity. Accelerated radiotherapy (dose escalation) refers to the delivery of multiple fractions per day using daily doses of radiation consistent with external beam daily conventionally fractionated radiotherapy doses. The aim is to reduce the overall treatment time; typically, two or three fractions per day may be delivered with a six to eight hour gap between fractions. OBJECTIVES: To assess the effects of postoperative external beam radiation dose escalation in adults with HGG. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid and Embase Ovid to August 2019 for relevant randomised phase III trials. SELECTION CRITERIA: We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens: daily conventionally fractionated radiotherapy versus no radiotherapy; hypofractionated radiotherapy versus daily conventionally fractionated radiotherapy; hyperfractionated radiotherapy versus daily conventionally fractionated radiotherapy or accelerated radiotherapy versus daily conventionally fractionated radiotherapy. DATA COLLECTION AND ANALYSIS: The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Since the last version of this review, we identified no new relevant trials for inclusion. We included 11 randomised controlled trials (RCTs) with 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for people with HGG receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 favouring postoperative radiotherapy (95% confidence interval (CI) 1.58 to 2.55; P < 0.00001; moderate-certainty evidence). Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17; P = 0.63; very low-certainty evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one participant in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in the subset of two trials (293 participants) which included participants aged 60 years and older with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46; P = 0.21; high-certainty evidence). There were two trials which compared hyperfractionated radiotherapy versus conventional radiation and one trial which compared accelerated radiotherapy versus conventional radiation. However, the results could not be pooled. The conventionally fractionated radiotherapy regimens were 4500 cGy to 6000 cGy given in 180 cGy to 200 cGy daily fractions, over five to six weeks. All trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher. The risk of selection bias was generally low among these RCTs. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life. AUTHORS' CONCLUSIONS: Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.

A review of the Rapid Response Radiotherapy Program in patients with advanced cancer referred for palliative radiotherapy over two decades.

INTRODUCTION: The Rapid Response Radiotherapy Program (RRRP) is an outpatient radiotherapy clinic for palliative cancer patients where consultation, planning, and radiation treatment can take place in 1 day, allowing for rapid access to care. The objective of this study was to compare the patient population and overall survival of patients seen in the RRRP from 2014 to 2017 to that of patients seen in 1999. METHOD: Patient characteristics including sex, primary cancer site, sites of metastases, and Karnofsky Performance Status (KPS) were recorded at each clinic visit. Date of death (DOD) was retrieved from the Patient Care System (PCS) and Excelicare. To show overall survival from the first clinic visit, a Kaplan-Meier overall survival curve was generated in all patients from 2014 to 2017. RESULTS: Five hundred ninety-six patients were included in the final analysis. Most patients were male (n = 347) with a primary cancer site of the lung (n = 165) and metastases to the bone (n = 475). Actuarial median overall survival was 15.3 months. In 1999, 395 patients were analyzed, in which a primary of the lung (n = 143) and metastases to the bone (n = 277) were the most prevalent. An additional 72 patients in this population had brain metastases. The actuarial median survival of the 1999 population was 4.5 months. CONCLUSION: The changing patient population in the RRRP has resulted in visible changes in survival. This may reflect differences in the proportion of patients with specific primaries and sites of metastases, as well as improvements in the availability of palliative radiation over the last two decades.

Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints-complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. RESULTS: A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint-emesis in the overall phase-had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. CONCLUSIONS: Palonosetron seems to be more efficacious and safe than other 5-HT3RAs-statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

Impact of radiation-induced nausea and vomiting on quality of life.

PURPOSE: Radiotherapy-induced nausea and vomiting is a common side effect of radiotherapy. It is well-established that nausea and vomiting have a negative impact on quality of life, but the relative influence of each of symptom is infrequently reported. This study aimed to compare the effects of nausea and vomiting on quality of life in cancer patients receiving palliative radiotherapy. METHODS: The Functional Living Index-Emesis (FLIE) is a quality of life questionnaire developed in the chemotherapy-induced nausea and vomiting setting. The FLIE consists of 18 questions, half of which address nausea and half of which address vomiting. Three prospective studies on the efficacy of various anti-emetic medications conducted at our center used the FLIE to assess radiotherapy-induced nausea and vomiting at various time points during and after palliative radiotherapy. FLIE data from these three studies were combined for the present analysis. Univariate and multivariate analyses were conducted to assess the relationships between nausea and vomiting, time of FLIE completion, and patient-reported quality of life. RESULTS: Nausea and vomiting scores both decreased patients' quality of life. Multivariate modeling showed that both symptoms significantly influenced patients' ability to enjoy meals. Nausea was also associated with increased hardship for the patient, while vomiting imposed more difficulty on the patients' loved ones. CONCLUSIONS: Nausea and vomiting both significantly influence quality of life. Nausea seems to impact the patient more directly, whereas vomiting affects those closest to the patient.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

BACKGROUND: This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. SELECTION CRITERIA: We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. MAIN RESULTS: We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. AUTHORS' CONCLUSIONS: None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

To frame or not to frame? Cone-beam CT-based analysis of head immobilization devices specific to linac-based stereotactic radiosurgery and radiotherapy.

PURPOSE: Noninvasive frameless systems are increasingly being utilized for head immobilization in stereotactic radiosurgery (SRS). Knowing the head positioning reproducibility of frameless systems and their respective ability to limit intrafractional head motion is important in order to safely perform SRS. The purpose of this study was to evaluate and compare the intrafractional head motion of an invasive frame and a series of frameless systems for single fraction SRS and fractionated/hypofractionated stereotactic radiotherapy (FSRT/HF-SRT). METHODS: The noninvasive PinPoint system was used on 15 HF-SRT and 21 SRS patients. Intrafractional motion for these patients was compared to 15 SRS patients immobilized with Cosman-Roberts-Wells (CRW) frame, and a FSRT population that respectively included 23, 32, and 15 patients immobilized using Gill-Thomas-Cosman (GTC) frame, Uniframe, and Orfit. All HF-SRT and FSRT patients were treated using intensity-modulated radiation therapy on a linear accelerator equipped with cone-beam CT (CBCT) and a robotic couch. SRS patients were treated using gantry-mounted stereotactic cones. The CBCT image-guidance protocol included initial setup, pretreatment and post-treatment verification images. The residual error determined from the post-treatment CBCT was used as a surrogate for intrafractional head motion during treatment. RESULTS: The mean intrafractional motion over all fractions with PinPoint was 0.62 ± 0.33 mm and 0.45 ± 0.33 mm, respectively, for the HF-SRT and SRS cohort of patients (P-value = 0.266). For CRW, GTC, Orfit, and Uniframe, the mean intrafractional motions were 0.30 ± 0.21 mm, 0.54 ± 0.76 mm, 0.73 ± 0.49 mm, and 0.76 ± 0.51 mm, respectively. For CRW, PinPoint, GTC, Orfit, and Uniframe, intrafractional motion exceeded 1.5 mm in 0%, 0%, 5%, 6%, and 8% of all fractions treated, respectively. CONCLUSIONS: The noninvasive PinPoint system and the invasive CRW frame stringently limit cranial intrafractional motion, while the latter provides superior immobilization. Based on the results of this study, our clinical practice for malignant tumors has evolved to apply an invasive CRW frame only for metastases in eloquent locations to minimize normal tissue exposure.

Impact of dyspnea on advanced cancer patients referred to a palliative radiotherapy clinic.

PURPOSE: Dyspnea is a debilitating symptom commonly experienced by advanced cancer patients that can lead to negative effects on function and quality of life (QOL). The present study aims to determine the relationship between dyspnea and other Edmonton Symptom Assessment System (ESAS) symptoms in palliative cancer patients referred to a radiotherapy clinic. METHODS: The presence and severity of dyspnea was measured using the ESAS. All patients that visited a palliative radiotherapy clinic between 1999 to 2002 and 2006 to 2009 and completed the ESAS were included. ESAS scores and other demographic and clinical information were extracted from a prospectively collected database. Statistical tests including chi-squared tests, Spearman correlations, and multivariate analysis were conducted to explore the relationship between dyspnea, other ESAS items, and other demographic factors. Kaplan-Meier overall survival curves were generated based on dyspnea severity. RESULTS: One thousand three hundred forty-four patients were included in the dyspnea analysis; reported moderate or severe dyspnea. Dyspnea severity was significantly associated with eight other ESAS interference severities (p < 0.001). Upon multivariate analysis, greater severity of dyspnea was significantly related to higher ESAS scores for tiredness, nausea, depression, anxious, drowsiness, and poor appetite (p < 0.05). The actuarial median survival time was 6.57 months (95% CI 5.91-7.29 months). There were highly significant differences in overall survival between those with none, mild, and moderate dyspnea (p < 0.0001). CONCLUSION: Cancer patients often experience dyspnea along with a multitude of other symptoms. Moderate and severe dyspnea should be assessed and optimally managed to reduce functional and QOL debilitations. As presence of increased dyspnea severity is associated with worse overall survival, interventions should occur at the end of life to reduce symptom burden in palliative patients.

An update in symptom clusters using the Edmonton Symptom Assessment System in a palliative radiotherapy clinic.

PURPOSE: To identify symptom clusters in advanced cancer patients attending a palliative radiotherapy clinic using the Edmonton Symptom Assessment System (ESAS). METHODS: Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items using scores from each patient's first visit. RESULTS: ESAS scores from 182 patients were analyzed. The PCA identified three symptom clusters (cluster 1: depression-anxiety-well-being, cluster 2: pain-tiredness-drowsiness, cluster 3: nausea-dyspnea-loss of appetite). The EFA identified two clusters (cluster 1: tiredness-drowsiness-loss of appetite-well-being-pain-nausea-dyspnea, cluster 2: depression-anxiety). The HCA identified three clusters similar to the PCA with an exception of the loss of appetite item being classified under cluster 1 rather than 3. Two to three symptom clusters were identified using three analytical methods, with similar patterns reported in the literature. Particular groups of items co-occurred consistently across all three analyses: depression and anxiety; nausea and dyspnea; as well as pain, tiredness, and drowsiness. CONCLUSION: Three similar symptom clusters were identified in our patient population using the PCA and HCA; whereas, the EFA produced two clusters: one physical and one psychological cluster. Given the implications of symptom clusters in the management of quality of life, clinicians should be aware of these clusters to aid in the palliative treatment of patients.

Inadequate pain management in cancer patients attending an outpatient palliative radiotherapy clinic.

PURPOSE: The aim of this study is to assess the prevalence of undertreated cancer pain in an outpatient palliative radiotherapy clinic using the Pain Management Index (PMI). METHODS: A retrospective analysis of a prospective database to assess pain management was done on patients with cancer pain enrolled from January 2009 to March 2015 using recorded pain intensity (0-10) and baseline pain medications. The pain intensities were categorized into no pain (0), mild pain (1), moderate pain (2), and severe pain (3), and an analgesic score was assigned to the most potent pain medication the patient was taking during the time of data collection. "0" was assigned to no analgesics, "1" to non-opioids, "2" to weak opioids, and "3" for strong opioids based on the WHO guidelines. The PMI was calculated for each patient by subtracting the pain score from the analgesic score. A negative value indicated undertreatment, and a value of 0 or greater corresponded to adequate pain management. RESULTS: Three hundred fifty-four patients were included in the study. The incidence of inadequate pain management was 33.3 %, similar to that reported in our previous studies. Additionally, 106 patients were taking strong opioids and reporting severe pain despite being the PMI reporting adequately treated. CONCLUSION: The rate of undertreatment is similar to that reported in past studies; however, the rates have shown a slight increase in our palliative radiotherapy clinic since the last assessment. Inadequate management of cancer pain continues to be a problem.

Symptoms and quality of life in patients with brain metastases receiving whole-brain radiation therapy.

PURPOSE: Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT. METHODS: A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman's correlations were applied to determine the relationship between symptom scores and QOL. RESULTS: Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1-month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes. CONCLUSIONS: Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time.

External beam radiation dose escalation for high grade glioma.

BACKGROUND: The incidence of high grade glioma (HGG) is approximately 5 per 100,000 person-years in Europe and North America. OBJECTIVES: To assess the effects of postoperative external beam radiation dose escalation in adults with HGG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE (1977 to October 2015) and Embase (1980 to end October 2015) for relevant randomised phase III trials. SELECTION CRITERIA: We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens.1. Daily conventionally fractionated radiation therapy versus no radiation therapy.2. Hypofractionated radiation therapy versus daily conventionally fractionated radiation therapy.3. Hyperfractionated radiation therapy versus daily conventionally fractionated radiation therapy.4. Accelerated radiation therapy versus daily conventionally fractionated radiation therapy. DATA COLLECTION AND ANALYSIS: The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression-free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We used the GRADE approach, as outlined by Cochrane, to interpret the overall quality of the evidence from included studies. MAIN RESULTS: We included 11 randomised controlled trials (RCTs) with a total of 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for HGG participants receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 (95% confidence interval (CI) 1.58 to 2.55, P < 0.00001), moderate GRADE quality evidence favouring postoperative radiotherapy. Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data.Overall survival was similar between hypofractionated versus conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17, P = 0.63), very low GRADE quality evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one patient in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data.Overall survival was also similar between hypofractionated versus conventional radiotherapy in the subset of two trials (293 participants) which included 60 years and older participants with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46, P = 0.21), high GRADE quality evidence.There were two trials which compared hyperfractionated radiation therapy versus conventional radiation and one trial which compared accelerated radiation therapy versus conventional radiation. However, the results could not be pooled.The conventionally fractionated radiation therapy regimens were 4500 to 6000 cGy given in 180 to 200 cGy daily fractions, over 5 to 6 weeks.All these trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher.The risk of selection bias was generally low among these randomized trials. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life. AUTHORS' CONCLUSIONS: Postoperative conventional daily radiotherapy improves survival for adults with good performance status and HGG as compared to no postoperative radiotherapy.Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.There is insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy).There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These poor prognosis HGG individuals have generally been excluded from the randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these poor prognosis patients.

Fatigue scores in patients receiving palliative radiotherapy for painful bone metastases.

INTRODUCTION: The purpose of this study was to examine changes in fatigue scores for patients receiving radiation therapy for bone metastases and its impact on quality of life (QOL). METHODS: Fatigue and QOL scores were prospectively collected in patients for up to 3 months following radiation therapy for bone metastases using three questionnaires: group 1, Edmonton Symptom Assessment System (ESAS) (0-10); group 2, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30); and Core 15 Palliative (EORTC QLQ-C15-PAL) (1-4). RESULTS: Average fatigue score in group 1 (399 patients) was 4.72 at baseline, 5.08 at month 1, 5.01 at month 2, and 4.95 at month 3, and was 2.40, 2.39, 2.56, and 2.70 in group 2 (482 patients), respectively. Thirty-five percent of patients in group 1 had fatigue score increase ≥2 points at month 1, 36% at month 2, and 36% at month 3. Twenty-one percent of patients in group 2 had fatigue score increase ≥1 at month 1, 27% at month 2, and 40% at month 3. There was a statistically significant increase in fatigue score from baseline to all 3 months in group 1 only. In both groups, there was a highly significant negative correlation between fatigue and overall QOL scores at baseline and any follow-up month. CONCLUSIONS: There was a statistically significant worsening in fatigue in group 1 only. Up to one third had increased fatigue of clinical significance. Patients with less fatigue symptoms reported better overall QOL.

Minimal clinically important differences in the EORTC QLQ-BN20 in patients with brain metastases.

INTRODUCTION: Quality of life (QOL) is an important treatment endpoint in advanced cancer patients with brain metastases. In clinical trials, statistically significant changes can be reached in a large enough population; however, these changes may not be clinically relevant. OBJECTIVE: The objective of this study was to determine the minimal clinically important difference (MCID) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire brain module (EORTC QLQ-BN20) in patients with brain metastases. METHODS: Patients undergoing radiotherapy for brain metastases completed the EORTC QLQ-BN20 and QLQ-C30/C15-PAL at baseline and 1-month follow-up. MCIDs were calculated for both improvement and deterioration using anchor- and distribution-based approaches. The anchor of overall QOL (as assessed by question 30 or question 15 on the QLQ-C30 and QLQ-C15-PAL, respectively) was used to determine meaningful change. RESULTS: A total of 99 patients were included. The average age was 61 years, and the most common primary cancer sites were the lung and breast. Statistically significant meaningful differences were seen on two scales. A decrease of 6.1 (95 % confidence interval (CI) 0.8 to 11.4) units and 13.8 (0.2 to 27.4) units was required to represent clinically relevant deterioration of seizures and weakness of legs, respectively. Distribution-based MCID estimates tended to be closer to 0.5 SD on the EORTC QLQ-BN20. CONCLUSION: Understanding MCIDs allows physicians to determine the impact of treatment on patients' QOL and allows for determination of sample sizes for clinical trials. Future studies should be conducted to validate our findings in a larger population of patients with brain metastases.

Student Accomplishments in the Rapid Response Radiotherapy Program: A 10-Year Review.

In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students.

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT(3)RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT(3)RAs in CINV prophylaxis. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT(3)RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT(3)RA-related adverse events. RESULTS: Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT(3)RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints. CONCLUSIONS: Palonosetron is safer and more efficacious than other 5-HT(3)RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

Psychometric validation of the functional assessment of cancer therapy--brain (FACT-Br) for assessing quality of life in patients with brain metastases.

OBJECTIVE: This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT-Br) in patients with brain metastases. METHODS: Patients with brain metastases were interviewed using the FACT-Br (including the FACT-general) 1 week prior to treatment. All patients completed a follow-up assessment 1 month post-treatment. Patients with a good performance status and receiving stereotactic radiosurgery completed an additional 1 week follow-up assessment after the initial baseline interview to assess test-retest reliability. RESULTS: Forty patients had complete 1 month follow-up data. Ten of these patients also completed the 1 week follow-up assessment from baseline. The median Karnofsky performance status of patients was 80 and the median age was 64 years. All subscales of the FACT-Br were found to be conceptually related (except for two correlations) using the following subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent reliability, except for the SWB scale which revealed good reliability. The FACT-Br scores showed no significant change in the quality of life (QoL) of patients from baseline to 1 month follow-up. CONCLUSION: The use of the combined FACT-G and FACT-Br Subscale to assess QoL specifically in patients with brain metastases has successfully undergone psychometric validation. Future clinical trials should use the FACT-G and FACT-Br Subscale to assess QoL in this patient population.