Ronald Chow

Quality of life in patients with primary and metastatic brain cancer as reported in the literature using the EORTC QLQ-BN20 and QLQ-C30

The objective of this study is to compare the differences in quality of life (QoL) as assessed by the QLQ-BN20 and QLQ-C30 in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted over the OvidSP platform in MEDLINE (1980–2012) and EMBASE (1980–2012). Studies in which the QLQ-BN20 was used as a QoL assessment for patients with malignant brain tumors (either metastatic or primary) were included in the study. Articles were included if they reported scores of at least one subscale of the QLQ-C30 or QLQ-BN20. The weighted means of the QLQ-BN20 and QLQ-C30 subscales were calculated based on sample size for included studies. Weighted analysis of variance was conducted to compare these scores in primary and metastatic brain patients. A p-value of < 0.05 was considered statistically significant. A total of 14 studies (16 arms: three brain metastases and 13 primary brain tumors) were identified and included in the data analysis. Fifteen of the 16 arms included QLQ-C30 scores along with QLQ-BN20 scores. Performance status of patients in both cohorts was similar. Patients with primary brain tumors and brain metastases had the following findings: physical functioning (weighted mean: 79.18 vs 74.93), global QoL (61.88 vs 59.44), role functioning (67.37 vs 75.00) and emotional functioning (70.44 vs 71.86); but none of them were statistically significantly different. Only cognitive functioning from the QLQ-C30 was significantly worse in patients with primary brain tumors (p-value = 0.0199). Despite cognitive function being significantly worse in patients with primary brain tumors, patients with metastatic brain tumors and patients with primary brain tumors have very similar QoL profiles. The study is limited by the large discrepancy in cohort sizes (1260 patients with primary brain cancer vs 183 patients with brain metastases) and the lack of clinical data.

Efficacy of multiple fraction conventional radiation therapy for painful uncomplicated bone metastases: A systematic review

BACKGROUND Radiation therapy is effective for painful uncomplicated bone metastases, with multiple fraction radiation therapy (MFRT) administered frequently. The optimal dose for MFRT to yield maximum pain relief remains unclear. The aim of this systematic review was to determine pain response across MFRT doses. METHODS A literature search was conducted in Ovid MEDLINE(R) <1946 to July Week 3 2016>, Embase Classic & Embase <1947 to 2016Week 30> and Cochrane Central Register of Controlled Trials . Pain response rates and the side effects for MFRT doses were extracted. RESULTS From the 3719 articles identified from the search, 17 were included for quantitative synthesis. 22.5Gy/5 had the highest overall response (OR) rate, 30Gy/15 had better complete response (CR) rate and 20Gy/2 had better partial response (PR) rate. Only 4 of the 17 included studies directly compared MFRT doses with each other - one reported marginally-better OR for 24Gy/6 over 20Gy/2; another found 20Gy/10 to be slightly more efficacious than 30Gy/15 and 22.5Gy/5 for OR. Two randomized trials compared 20Gy/5 and 30Gy/10 - one favored 20Gy/5 while the other concluded 30Gy/10 to be the better option. The overall rate of GI toxicities, nausea, and vomiting did not differ greatly between MFRT doses. CONCLUSION No major difference exists between the schedules and toxic events studied in these trials. This is consistent with the wealth of randomized data which show no dose response for pain relief after radiotherapy for metastatic bone pain.

The incidence of neuropathic pain in bone metastases patients referred for palliative radiotherapy

BACKGROUND AND PURPOSE To estimate the prevalence of neuropathic pain in patients with symptomatic bone metastases referred for palliative radiotherapy. MATERIAL AND METHODS A prospective study of patients with symptomatic bone metastases was conducted. Patients referred for palliative radiotherapy completed the Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire to assess for neuropathic pain. Patient demographics, medication use, and radiotherapy prescribed were collected. Statistical approaches to identify relationships between the presence of neuropathic and other patient factors were conducted. RESULTS 62 patients completed the S-LANSS and 16 (25.8%) patients had a score suggesting neuropathic pain. Fifty-nine (95.2%) patients received radiotherapy with total of 81 sites treated, the most common sites were spine and pelvis. No statistically significant difference in fractionation was found between patients with and without neuropathic pain. Of the 16 patients with neuropathic pain, only 2 were receiving a neuropathic specific analgesic. No significant difference between demographic factors or radiation treatments between patients with and without neuropathic pain was found. There was no significant difference in worst pain score between these two groups. CONCLUSIONS Pain with neuropathic features remains prevalent in a population of patients referred for palliative radiotherapy. More frequent prescription of pain medications targeting neuropathic pain may be warranted in this patient population.

Update of the systematic review of palliative radiation therapy fractionation for bone metastases

PURPOSE Radiation therapy is an effective modality for pain management of symptomatic bone metastases. We update the previous meta-analyses of randomized trials comparing single fraction to multiple fractions of radiation therapy in patients with uncomplicated bone metastases. METHODS A literature search was conducted in Ovid Medline, Embase, and Cochrane Central Register. Ten new randomized trials were identified since 2010, five with adequate and appropriate data for inclusion, resulting in a total of 29 trials that were analyzed. Forest plots based on each studys odds ratios were computed using a random effects model and the Mantel-Haenszel statistic. RESULTS In intention-to-treat analysis, the overall response rate was similar in patients for single fraction treatments (61%; 1867/3059) and those for multiple fraction treatments (62%; 1890/3040). Similarly, complete response rates were nearly identical in both groups (23% vs 24%, respectively). Re-treatment was significantly more frequent in the single fraction treatment arm, with 20% receiving additional treatment to the same site versus 8% in the multiple fraction treatment arm (p < 0.01). No significant difference was seen in the risk of pathological fracture at the treatment site, rate of spinal cord compression at the index site, or in the rate of acute toxicity. CONCLUSION Single fraction and multiple fraction radiation treatment regimens continue to demonstrate similar outcomes in pain control and toxicities, but re-treatment is more common for single fraction treatment patients.

Pain control with palliative radiotherapy in patients with bone metastases

Abstract Bone metastases remain the most common cause of cancer-related pain. Multiple treatment approaches are currently available for alleviating pain from bone metastases. Among them, radiotherapy is both efficacious and cost-effective. In the bone metastases setting, radiotherapy is frequently employed with palliative intent in order to minimize tumor-related symptoms. Evidence continues to mount in support of the efficacy of single fraction radiation schedule in treating patients with uncomplicated bone metastases. Pain flare and radiotherapy-induced nausea and vomiting can be distressing side effects in patients receiving radiotherapy; investigations into the incidence and timing of symptoms, as well as into effective therapies, have recently been published. Complications of bone metastases, including pathologic fracture and spinal cord compression, are commonly encountered in the clinic. Comparative cost-effectiveness, re-irradiation, quality of life assessment and integration of palliative radiotherapy with other modalities are areas of active research. Due to the increasing number of effective modalities for relief of pain secondary to bone metastases, a multidisciplinary approach to patient assessment has never been more important. In addition, there is an urgent need for more randomized controlled trials in the radiotherapy of complicated bone metastases, such as in the settings of neuropathic pain and impending fracture.

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

PurposeChemotherapy-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.MethodsA 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.ResultsA 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.ConclusionsPalonosetron 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.

National Dementia Strategies: What Should Canada Learn?

Background In order to provide appropriate care for the aging population, many countries are adopting a National Dementia Strategy (NDS). On June 22, 2017, Canada announced it will become the 30th country to launch a NDS. In light of this announcement and as Canada prepares to develop its own NDS, we conducted this review to examine and compare the NDSs of the other previous 29 countries with Canadian government’s policies to date. Methods NDSs were compared according to their major priorities. The primary endpoints were the framework conditions and key actions outlined in the strategies. Secondary endpoints included the years active, involvement of stakeholders, funding, and implementation. Results We were able to review and compare 25 of the 29 published NDSs. While the NDSs of each country varied, several major priorities were common among the strategies—increasing awareness of dementia, reducing its stigma, identifying support services, improving the quality of care, as well as improving training and education and promoting research. Conclusions This review comprehensively lists and compares the NDSs of different countries. The results should be of great interest to policy-makers, health-care professionals and other key stakeholders involved in developing Canada’s forthcoming NDS. We hope that policy-makers in Canada can review other NDSs, learn from their example, and develop an effective NDS for our country.

Challenges of conducting research in long-term care facilities: a systematic review

BackgroundThe aim of this review is to describe the challenges and barriers to conducting research in long-term care facilities.MethodsA literature search was conducted in Ovid MEDLINE, Embase, Cochrane Central, PsycINFO and CINAHL. Keywords used included “long term care”, “nursing home”, “research”, “trial”, “challenge” and “barrier”, etc. Resulting references were screened in order to identify relevant studies that reported on challenges derived from first-hand experience of empirical research studies. Challenges were summarized and synthesized.ResultsOf 1723 references, 39 articles were selected for inclusion. To facilitate understanding we proposed a classification framework of 8 main themes to categorize the research challenges presented in the 39 studies, relating to the characteristics of facility/owner/administrator, resident, staff caregiver, family caregiver, investigator, ethical or legal concerns, methodology, and budgetary considerations.ConclusionsConducting research in long-term care facilities is full of challenges which can be categorized into 8 main themes. Investigators should be aware of all these challenges and specifically address them when planning their studies. Stakeholders should be involved from an early stage and flexibility should be built into both the methodology and research budget.

Skeletal morbidity rates over time in patients with bone metastases from solid tumors reported in bone modifying agents randomised trials.

Objective Skeletal related events (SREs) are common in patients with bone metastases and lead to decreased quality of life and functional status. The definition of an SRE has evolved over the years and now excludes hypercalcemia of malignancy due to its low incidence. The purpose of this review was to investigate if advances in bone-targeted therapies have decreased skeletal morbidity rates (SMR) over time. Methods A literature search was conducted in several databases to identify phase III results from bone-targeted therapy trials from 1980 through September 2011. Graphs were created to document the trends of the natural log of SMR over the mean time of enrolment for all placebo and intervention arms. Statistical hypothesis testing was employed to account for confounding factors. Results A total of 14 studies were identified which reported the SMR from phase III trials from 1990 to 2007. A statistically significant downward trend was observed in the placebo arms of trials over time; a similar trend was seen in all intervention arms. In a direct comparison of intervention against placebo arms, it was found that there was a significant decreasing time trend (p<0.0001) and a significant departure in SMR from placebo to intervention arms (p=0.0348). These results were seen even after accounting for the confounding factors of histology and differences in drugs. Conclusion The decrease in SMR over time may not only be a result of advancements with bone targeted agents, but also due to better management and awareness of events associated with bone metastases.