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The Edmonton Symptom Assessment Scale (ESAS) is a validated tool used in patients with varied cancer diagnoses to measure patient symptoms. The present manuscript will review the literature assessing the ability of the ESAS to predict patient-related outcomes in breast cancer patients. A literature search was conducted of Cochrane Central Register of Controlled Trials databases, Ovid MEDLINE, and Embase for English articles that investigated the use of predictive modelling with the ESAS in the breast cancer population. Study type, publication year, sample size, patient demographics, predicted outcomes, and strongest predictive factors/symptoms were summarized for each study. A total of nine articles were included in this review. Five articles used the ESAS in predictive models to determine patient time to death. ESAS was also used to predict emergency department visits, determine symptoms associated with decreased quality of life, and generate a Health Utility Score. Lack of appetite was the most common ESAS symptom, as it was reported in five studies to be associated with decreased survival. In four of the nine articles, an additional survey investigating physical functioning was used in combination with ESAS to strengthen the predictive models. Included studies support the use of ESAS in predictive models, particularly for predicting survival. Using the ESAS as a predictive tool allows for more accurate time to death predictions, potentially improving symptom management and preventing overtreatment of palliative patients near the end of life.

Radiation dermatitis is a common adverse effect of radiotherapy (RT) in breast cancer patients. Although radiation dermatitis is reported by either the clinician or the patient, previous studies have shown disagreement between clinician-reported outcomes (CROs) and patient-reported outcomes (PROs). This review evaluated the extent of discordance between CROs and PROs for radiation dermatitis. Studies reporting both clinician and patient-reported outcomes for external beam RT were eligible. Nine studies met the inclusion criteria for the systematic review, while 8 of these studies were eligible for inclusion in a meta-analysis of acute and late skin toxicities. We found an overall agreement between CROs and PROs of acute skin colour change, fibrosis and/or retraction, and moist desquamation (p > 0.005). Reporting of late breast pain, breast edema, skin colour change, telangiectasia, fibrosis and/or retraction and induration/fibrosis alone (p > 0.005) were also in agreement between clinicians and patients. Our meta-analysis revealed a greater reporting of acute breast pain by patients (RR = 0.89, 95% CI 0.87–0.92, p, Highlights • Patient- and clinician-reported outcomes generally demonstrated high levels of agreement. • Patients reported more acute breast pain and late breast shrinkage than clinicians. • Clinicians reported more acute breast edema than patients. • The measurement tools and time points at which radiotherapy side effects were assessed varied considerably across studies. • Standardized reporting of radiotherapy side effects by clinicians and patients could impact future symptom management.

Purpose: Several studies have used objective radiologic data to assess the effect of palliative radiotherapy on tumor burden. The purpose of this literature review was to survey the various metrics that have been used to quantify bone tumor response to palliative radiotherapy by radiographical means and to determine whether any of these metrics were associated with clinical palliative outcomes. Methods: In accordance with PRISMA extension for Scoping Reviews guidelines, a literature search Ovid Medline and OldMedline from 1946 to February 6, 2019, Embase Classic/Embase from 1947 to 2019 week 5, and Cochrane Central Register of Controlled Trials February 2019 to extract articles related to quantified radiologic evaluation of bone metastases following palliative radiotherapy. Imaging modality, quantification metric, and association between imaging modality and clinical response were recorded. Results: Fourteen articles selected for full-text review utilized computed tomography (10 studies), fluorodeoxyglucose-positron emission tomography (3 studies), magnetic resonance imaging (1 study), diffusion-weighted magnetic resonance imaging (3 studies), and X-ray (1 study) imaging modalities. Variables assessed included tumor volume regression, bone density, metabolic activity, and signal intensity. Studies differed both in the type of imaging modality used and metric derived to quantify the radiologic findings. Fifty percent of the included studies aimed to identify a relationship between a quantified radiologic metric and clinical palliative response. Of these studies, 86% reported a correlation. Conclusion: Quantified radiologic metrics can provide an objective measure of response to palliative radiotherapy and may be useful in predicting clinical palliative response. More studies are needed to validate these metrics and develop a standardized protocol for radiologic evaluation that can be implemented into a clinical workflow.

Despite having an excellent prognosis, patients with ductal carcinoma in situ (DCIS) report significant anxiety and depression following diagnosis. This study evaluated psychological morbidity using the Edmonton Symptom Assessment Scale (ESAS) in patients with DCIS compared with women with early-stage invasive breast cancer (EIBC) receiving radiotherapy (RT). We identified patients diagnosed with DCIS or EIBC (stage I or II breast cancer) from 2011 to 2017 who had at least one ESAS completed pre- and post-RT. Data on systemic treatment, radiation, patient demographics, and disease stage were extracted from existing databases. Psychological morbidity was evaluated through measurement of depression, anxiety, and overall wellbeing within the ESAS. The Wilcoxon rank-sum test or chi-square test was performed for continuous or categorical variables. This study included 137 women with DCIS and 963 women with EIBC. ESAS was completed on average 28 days before RT (baseline) and 142 days after RT. Baseline ESAS scores showed significantly higher rates of depression among women with EIBC compared with those with DCIS (p = 0.006). Patients with EIBC also reported higher levels of anxiety and lower overall wellbeing than patients with DCIS, but this difference was not statistically significant. Post-RT ESAS scores showed significantly higher anxiety in patients with EIBC compared with DCIS (p = 0.049). Post-RT measures of anxiety and overall wellbeing were higher in patients with EIBC but differences were not statistically significant. Women with DCIS experience relatively less psychological morbidity than women with EIBC, pre- and post-RT.

OBJECTIVE Seasonal effects on patients diagnosed with depression/anxiety-related psychological disorders have varying impacts on symptom severity. Seasonal changes in psychological distress may be due to decreased daylight exposure during the fall/winter seasons. Patients receiving radiation therapy (RT) for early-stage invasive breast cancer (EIBC) are at high risk for developing depressive symptoms. Of interest is whether seasonal factors influence the psychological symptoms of patients being treated for EIBC. METHODS Patients treated with RT for EIBC between January 2011 and June 2017 were identified. Patients who completed at least one Edmonton Symptom Assessment Scale (ESAS-r) pre-RT and post-RT were included in our analysis. Patients receiving RT during the autumn and winter (November-March) were compared with patients receiving RT during the spring and summer (April-August). Psychological distress was evaluated based on patient-reported depression, anxiety, and overall wellbeing on the ESAS-r. Data on systemic treatment and radiation were extracted from existing databases. RESULTS Eight-four patients treated with RT in spring/summer and 102 patients treated with RT in autumn/winter were included. Patients receiving RT during spring/summer had better wellness score prior to RT, compared with those receiving RT during winter/autumn (P = .03). However, patients receiving RT in the spring/summer had worse symptom trajectories across three domains of depression, anxiety, and wellbeing (P = .03, P = .008, and P < .0001, respectively). CONCLUSIONS Seasonality influenced the symptoms reported by patients with EIBC receiving RT. Future studies are needed to understand when during treatment patients are at highest risk for psychological distress and how seasonality may influence high-risk periods.

Background: During recovery from stroke, the contralesional motor cortex (M1) may undergo maladaptive changes that contribute to impaired interhemispheric inhibition (IHI). Transcranial direct current stimulation (tDCS) with the cathode over contralesional M1 may inhibit this maladaptive plasticity, normalize IHI, and enhance motor recovery.Objective: The objective of this systematic review and meta-analysis was to evaluate available evidence to determine whether cathodal tDCS on contralesional M1 enhances motor re-learning or recovery post-stroke more than sham tDCS.Methods: We searched OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials for participants with stroke (>1 week post-onset) with motor impairment and who received cathodal or sham tDCS to contralesional M1 for one or more sessions. The outcomes included a change in any clinically validated assessment of physical function, activity, or participation, or a change in a movement performance variable (e.g., time, accuracy). A meta-analysis was performed by pooling five randomized controlled trials (RCTs) and comparing the change in Fugl–Meyer upper extremity scores between cathodal and sham tDCS groups.Results: Eleven studies met the inclusion criteria. Qualitatively, four out of five cross-over design studies and three out of six RCTs reported a significant effect of cathodal vs. sham tDCS. In the quantitative synthesis, cathodal tDCS (n = 65) did not significantly reduce motor impairment compared to sham tDCS (n = 67; standardized mean difference = 0.33, z = 1.79, p = 0.07) with a little observed heterogeneity (I2 = 5%).Conclusions: The effects of cathodal tDCS to contralesional M1 on motor recovery are small and consistent. There may be sub-populations that may respond to this approach; however, further research with larger cohorts is required.

Introduction The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC. Methods Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model. Results Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty. Conclusion Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg. Supplementary Information The online version contains supplementary material available at 10.1007/s00520-020-05935-7.

This review aimed to assess the quality and efficacy of tools currently used in breast cancer patients to score radiation dermatitis (RD), a common debilitating side effect of radiotherapy (RT). A search was conducted through Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials databases on 14 February 2020. English articles that evaluated an instrument’s use in assessing RD among breast cancer patients receiving external beam RT were included. Studies that reported on the reliability, validity, or concordance of items between assessment tools were included in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria. Twelve studies were included in this review, with a total of 13 skin toxicity assessment tools discussed. Tools that assessed clinician-reported outcomes (CROs) mostly reported moderate correlation with biophysical parameter (BP) measurements and low correlation with patient-reported outcomes (PROs). Traditionally used CRO scoring tools demonstrated moderate inter-rater reliability between clinicians, likely due to the subjective nature of items on the grading scales. Most commonly used tools were found to be either insufficient or indeterminate in their measurement properties. Current standardized tools that measure CROs are subject to clinician interpretation and fail to represent the patient experience. Tools designed to assess PROs are promising in their assessments of the impact of RT on patient quality of life; however, most PRO tools are generic to all skin conditions and require further validation for use in breast cancer. Among tools that measure CROs, PROs, and BPs, there is insufficient evidence on their measurement properties to establish a “gold standard” for the assessment of RD in breast cancer patients.

Background The influence of cigarette smoking on cancer risk has been well-studied. Similarly, exposure to ionizing radiation from radiotherapy (RT) can produce detrimental effects on an individual's health. In patients administered RT, there has been an observed relationship in other primary carcinomas. The purpose of this systematic review was to summarize the influence of cigarette smoking on outcomes post adjuvant RT in breast cancer patients. Methods OVID Medline, Cochrane and Embase were searched and 1893 articles were identified. A total of 71 articles were included in the review. Study type, published year and sample size, age, systemic therapies, RT techniques and treatment side effects were collected if available. Results The review found 198 different outcomes which fell into 7 categories and similar outcomes were recorded. 40% of skin reaction outcomes, 50% of cardiovascular outcomes, 71% of reconstruction outcomes, 29% of pulmonary function outcomes, 33% of mortality outcomes and 42% of secondary recurrence outcomes reported significant differences between smokers and non-smokers. None of the articles reported non-smokers to have a higher risk than smokers. Conclusion Cigarette smoking can pose a higher risk of post-treatment complications that can influence an individual's quality of life, survival rate and/or recurrence risk. This review further assessed the impact of smoking on various patient outcomes and side-effects in the adjuvant breast RT setting. The information provided in this review suggest that smoking cessation programs would help educate patients to understand their risks of being a current or former smoker when undergoing RT.

This report presents the results from the 2016 Association of Biomolecular Resource Facilities Proteome Informatics Research Group (iPRG) study on proteoform inference and false discovery rate (FDR) estimation from bottom-up proteomics data. For this study, 3 replicate Q Exactive Orbitrap liquid chromatography-tandom mass spectrometry datasets were generated from each of 4 Escherichia coli samples spiked with different equimolar mixtures of small recombinant proteins selected to mimic pairs of homologous proteins. Participants were given raw data and a sequence file and asked to identify the proteins and provide estimates on the FDR at the proteoform level. As part of this study, we tested a new submission system with a format validator running on a virtual private server (VPS) and allowed methods to be provided as executable R Markdown or IPython Notebooks. The task was perceived as difficult, and only eight unique submissions were received, although those who participated did well with no one method performing best on all samples. However, none of the submissions included a complete Markdown or Notebook, even though examples were provided. Future iPRG studies need to be more successful in promoting and encouraging participation. The VPS and submission validator easily scale to much larger numbers of participants in these types of studies. The unique "ground-truth" dataset for proteoform identification generated for this study is now available to the research community, as are the server-side scripts for validating and managing submissions.

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. 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. 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. 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.

Despite the prevalence of radiation dermatitis in breast cancer patients, current practice guidelines for its treatment are limited. We aimed to discuss the quality of evidence for the barrier-forming Mepitel Film for prophylaxis of radiation dermatitis, and argue for further investigation into evidence-based management of skin toxicities. Two studies assessing Mepitel Film were critically evaluated. Both reported that Mepitel Film decreased radiation dermatitis; moreover, patient-reported outcomes significantly favoured Mepitel Film. However, there has not been global adoption of barrier-forming films such as Mepitel, in part due to the absence of multi-centred randomised trials and the heterogeneity of study designs.

To investigate the natural history of taxane-associated acute pain syndrome (TAPS) in a docetaxel patient cohort and to examine the long-term manifestation of TAPS. For three consecutive treatment cycles, taxane-naive breast cancer patients completed diaries on days 1–7, 14, and 21 and telephone questionnaires 1, 3, 6, 9, and 12 months following treatment. Questionnaires to assess pain and interference were adapted from the Brief Pain Inventory. To examine the experience of arthralgia and myalgia as one syndrome, information on patient experiences with arthralgia or myalgia was elicited separately in order to determine how closely experiences of each toxicity correlated with each other. A ≥2 point increase from baseline was defined as an arthralgia or myalgia “pain flare,” and only those with “flare” were included in calculations of incidence. A total of 278 patients were accrued. Thirty-eight patients were omitted due to missing information, and 24 patients were omitted due to metastatic disease, for a total of 216 patients overall and 188 in the docetaxel cohort. A total of 74.5% of docetaxel patients experienced joint pain flare, and 78.2% experienced muscle pain flare at some point in the overall course of three treatment cycles. Joint and muscle pain peaked on days 4–5 for each cycle, and median pain severity for both joint and muscle pain was 4/10 during the 21-day period. Median onset of joint pain flare was 3 days for cycle 1 and 4 days for cycles 2 and 3, with an average median duration of 4 days. Median onset of muscle pain flare was 4 days for all three cycles, with a median duration of 4 days for cycles 1 and 2, and 5 days for cycle 3. Both joint and muscle pain persisted 1 year after treatment in approximately half of responding patients. This study documents the significant incidence of TAPS in patients treated with docetaxel chemotherapy and shows a long-term persistence of the syndrome.

Background and purpose Impending or pathological fractures due to bone metastases may require surgical fixation. Postoperative radiation is often recommended to reduce local progression and prevent prosthesis displacement, hence reducing the need for second surgery. The objectives of this study were to investigate the need for second surgery, and to report on rates of re-irradiation, tumor progression and prosthesis displacement following postoperative radiation. Materials and methods Data were collected from 65 patients who received postoperative radiation to 74 sites in the extremities in a palliative radiation clinic between January 2009 and January 2017. Descriptive statistical analyses were performed. Results Only 2 patients required a second surgery (2.7%) at 9 and 10months after postoperative radiation. Increase in pain requiring re-irradiation was reported in 7 patients (9.5%), at a median time of 9.3months after the delivery of radiation. Of the 47 patients who had radiological imaging available post-radiation, local progression of bone metastases was seen in 8 patients (17.0%) and displacement of the prosthesis in 1 patient (2.1%). Conclusion Rates of prosthesis displacement and progression of bone metastases at site of surgery were low after postoperative radiation. There were few incidences of second surgery and re-irradiation observed in the cohort. These findings provide support for the benefit of postoperative radiation.

Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11–1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported “emetic episode/event” measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., “response,” “control,” “success”) that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.

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) , Embase Classic & Embase 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.

Purpose of review Cancer-related cognitive impairment (CRCI) is highly prevalent, and assessment of cognition is crucial in providing optimal cancer care. Neuropsychological assessment (NPA) can be lengthy and expensive. Cognitive screening tools are plenty but validity has not been thoroughly studied for use in cancer patients. Recent findings Our search of the recent literature revealed that the Montreal Cognitive Assessment, Mini-Mental State Examination, and Clock Draw Test were the most frequently studied objective screening tools. The Functional Assessment of Cancer Therapy-Cognitive Function and the Cognitive Symptom Checklist-Work 21 were the most commonly studied subjective measures of perceived cognitive impairment. Evidence supports using the Montreal Cognitive Assessment or the Clock Draw Test over the Mini-Mental State Examination to screen for cognitive impairment within specific patient populations. In addition, adding a subjective measure of cognitive impairment (e.g., Functional Assessment of Cancer Therapy-Cognitive Function) may increase diagnostic sensitivity. Summary These suggest that cognitive screening tools may have a role in screening for CRCI, particularly when full NPA is not feasible. Researchers must continue to conduct high-quality studies to build an evidence to guide best practices in screening for CRCI.

Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Purpose Symptoms experienced by breast cancer patients often cluster together in groups known as “symptom clusters”. The aim was to determine the symptom clusters in women with non-metastatic breast cancer treated by radiation therapy (RT). Methods Edmonton Symptom Assessment Scale (ESAS) scores were taken from breast cancer patients receiving RT before, at completion of RT, and after RT. Exploratory factor analysis (EFA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items at all three time points. Results This study included 1224 patients. The PCA and EFA identified the same two symptom clusters before the start of RT: 1) pain, tiredness, nausea, drowsiness, appetite, and dyspnea; 2) depression, anxiety, and wellbeing. The HCA further split the symptoms into three clusters. Wellbeing, depression, and anxiety consistently clustered together. Among the ESAS scores collected at the end of and after RT, each statistical method identified different symptom clusters. For the symptom clusters experienced at the end of RT, the following symptoms were always in the same cluster: wellbeing, depression, and anxiety; nausea and appetite; drowsiness and dyspnea. Following RT, depression and anxiety consistently clustered together, with nausea and appetite in a second cluster. Conclusion Among the symptom clusters derived before, at the end of RT, and after RT, the following symptoms consistently presented together: depression and anxiety, nausea and appetite, pain and tiredness, and drowsiness, dyspnea, and tiredness. Understanding symptom clusters in this population can improve management of symptoms.

INTRODUCTION: There has been a long-standing debate regarding the efficacy of single fraction radiotherapy (SFRT) compared to multiple fraction radiotherapy (MFRT); many systematic reviews and meta-analyses have been conducted to resolve the debate and suggested SFRT is equally as effective as MFRT. Given the adequate amalgamated sample size that exists, it is difficult to appreciate the need for further RCTs. The aim of this paper was to conduct a cumulative meta-analysis to determine whether further trials will be of value to the meta-conclusion. This paper also assessed publication quality.METHODS: A total of 29 studies were used in our meta-analysis. Comprehensive Meta-Analysis (Version 3) by Biostat was used to conduct a cumulative meta-analysis. The Cochrane Risk of Bias assessment tool was employed to assess study quality of the included RCTs. Funnel plots were generated using Review Manager (RevMan 5.3) by Cochrane IMS, to visually assess for publication bias.RESULTS: All but one endpoint, overall response rates in assessable patients, maintained the same meta-conclusion over publication time; published studies did not change the amalgamated scientific conclusion of existing literature. Additional studies have simply confirmed pre-existing conclusions and refined the point estimate of the efficacy estimate. The majority of included studies have low risk of bias.CONCLUSION: In conclusion, the meta-conclusion has remained consistent over time - SFRT is equally as efficacious as MFRT. Recent studies have had little impact on the overall conclusion, and given the vast amount of resources to execute a randomized trial, future resources should not be used to repeat these studies, and can be better allocated to test other hypotheses.

Introduction The aim is to conduct an updated systematic review comparing palonosetron to other 5-HT3RAs for the prophylaxis of CINV, assess for publication biases, and determine whether further RCTs are required, that could potentially lead to a different meta-conclusion. Methods Random-effects analysis model was used to generate odds ratio (OR), risk differences (RD) and accompanying 95% confidence intervals (CI). Funnel plots to assess for biases and cumulative meta-analyses to assess effect size over time were generated. Results 4145 patients were randomized to palonosetron and 4911 received other 5-HT3RAs. In the majority of efficacy endpoints, the meta-conclusion has not changed over time - recent clinical trials simply narrow CIs the meta-conclusion. Safety profile boasts a stable conclusion over time. No publication biases exist. Conclusion Considering the vast amount of resources needed to conduct RCTs, resources should be dedicated to other prophylactic treatments/settings which have not been as well explored.

Background Breast cancer patients often experience multiple symptoms that negatively affect quality of life (QOL). Patient-reported scores on symptom screening tools are used by health care professionals to manage QOL. We aimed to examine which symptoms from the Edmonton Symptom Assessment Scale (ESAS) were most predictive of overall well-being (QOL) in breast cancer patients over the course of radiotherapy (RT). Patients and Methods ESAS results completed before, at the end of, and after RT were obtained from all nonmetastatic breast cancer patients. Univariate and multivariable (backward stepwise selection) linear regression analyses were applied to select the most significant ESAS symptoms or treatment variables related to overall QOL at all 3 time points. Results A total of 1224 patients were included in the study. Before RT, multivariable analysis identified 5 symptoms that were significantly associated with overall QOL: pain, tiredness, anxiety, depression, and loss of appetite. At the end of RT, pain, tiredness, and anxiety were the most significant predictors of QOL. After RT, 6 symptoms were found to have the strongest correlation with QOL: pain, tiredness, anxiety, depression, loss of appetite, and drowsiness. At each time point, patients with higher scores for the identified significant symptoms were likely to have a worse overall QOL. Conclusion Of the ESAS symptoms identified as significant predictors of QOL, pain, tiredness, and anxiety correlated with overall well-being at all time points. Special attention should be paid to manage symptoms that are most predictive of overall QOL in order to ensure optimal symptom management in breast cancer patients receiving RT.

Purpose Arthralgia and myalgia following taxane chemotherapy has been documented in the literature. However, these two toxicities associated with taxane treatment have not been closely examined in the literature, and data remain inconsistent in terms of the reported incidences of these toxicities. The purpose of this literature review was to provide a more comprehensive understanding of the incidence of taxane-induced arthralgia and myalgia, as well as to document the risk factors and preventative and therapeutic treatments that have been investigated. Methods A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as: “arthralgia,” “myalgia,” “muscle pain,” “joint pain,” “taxane,” “chemotherapy,” “docetaxel,” “paclitaxel.” Results The reported incidences of arthralgia and myalgia were variable. Taxane chemotherapy was found to be associated with greater incidences of arthralgia and myalgia than non-taxane forms of chemotherapy. Moreover, docetaxel and nab-paclitaxel seem to be associated with lower incidences of arthralgia and myalgia than paclitaxel. Finally, the literature on prevention and therapeutic treatment of taxane-induced arthralgia and myalgia is scarce. Conclusion More studies should be done in order to more conclusively identify optimal therapeutic and preventative treatments as well as different risk factors. We recommend that a prospective study be done in order to better understand the true incidence of arthralgia and myalgia in patients being treated with the paclitaxel, docetaxel, and nab-paclitaxel.

Background: Studies have reported that performance status (PS) is a good prognostic indicator in patients with advanced cancer. However, different health care professionals (HCPs) could grade PS differently. The purpose of this review is to investigate the PS scores evaluated by different HCPs as reported in the literature. Methods: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE from 1946 to Present (July 5, 2015), Embase Classic and Embase from 1947 to 2015 Week 26, and Cochrane Central Register of Controlled Trials up to May 2015. Information of interest was whether there was a difference of PS assessment between HCPs. Other statistical information provided to assess the agreement in ratings, such as Cohen’s kappa coefficient, Krippendorff’s alpha coefficient, Spearman Rank Coefficient, and Kendall’s correlation, was noted. Results: Of the fifteen articles, eleven compared PS assessments between HCPs of different disciplines, one between the attending and resident physician, two between similarly-specialized physicians, and one between two unspecified-specialty physicians. Three studies reported a lack of agreement (kappa =0.19–0.26; Krippendorff’s alpha =0.61–0.63), four reported moderate inter-rater reliability (kappa =0.31–0.72), two reported mixed reliability, and six reported strong reliability (kappa =0.91–0.92; Spearman rank correlation =0.6–1.0; Kendall’s correlation =0.75–0.82). Four studies reported that Karnofsky performance status (KPS) had better inter-rater reliability than both the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the palliative performance scale (PPS). Conclusions: The existing literature cites both good and bad inter-rater reliability of PS scores. It is difficult to conclude which HCPs’ PS assessments are more accurate.

Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV. A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases. Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis. Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Background The aim of this review is to describe the challenges and barriers to conducting research in long-term care facilities. Methods A 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. Results Of 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. Conclusions Conducting 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. Electronic supplementary material The online version of this article (10.1186/s12877-018-0934-9) contains supplementary material, which is available to authorized users.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment during chemotherapy. Identifying predictive biomarkers of CIPN would allow physicians to alter treatment given to patients according to a personal risk of developing this condition. The current literature on CIPN biomarkers is reviewed, identifying biomarkers which have been found to be significantly related to CIPN. Three genetic biomarkers are identified (ARHGEF10 rs9657362, CYP2C8 rs11572080/rs10509681 and FGD4 rs10771973) which have been found to act as predictive CIPN biomarkers in multiple studies. Possible mechanisms underlying the relationship between these single nucleotide polymorphisms and CIPN development are explored. The biomarkers identified in this study should be investigated further to generate predictive biomarkers that may be used in a clinical setting.

Purpose To evaluate the prevalence and severity of persistent pain after breast cancer treatment (PPBCT) in patients who received surgery, radiotherapy or a combination of treatments and to explore how different treatments and techniques impact pain. Methods Medline, Embase and Cochrane Central databases were searched for articles which evaluated the prevalence of PPBCT. Search results were limited to studies addressing chronic post-surgical pain (CPSP), persistent post-surgical pain (PPSP), post-mastectomy pain syndrome (PMPS) or radiotherapy (RT) related pain in breast cancer patients and published in the English language. The primary outcome was the incidence or severity of PPBCT. Descriptive analyses were performed. Results A total of 177 studies were included in this review. Overall, pain prevalence was 29.8% amongst 3746 patients (Group 1: 30 studies) post-surgery, 27.3% post-RT (Group 2: 41 studies, n = 15 019), and 21.8% amongst BC survivors who reported on the general prevalence of after receiving various combinations of BC treatment (Group 3: 106 studies, n = 135 437). Conclusion PPBCT remains to be a prevalent and complex clinical issue, despite a variety of different techniques and treatments. Various factors such as varying definitions of pain, inconsistent use of assessment tools and differences in methodology between studies may contribute to discrepancies in reports of PPBCT. A greater understanding of BC treatments and their impact on PPBCT may help identify potential risk factors, prevention and pain management strategies.

Background: Clinician predicted survival (CPS) plays a crucial role in palliative care, informing physicians of appropriate treatment best suited to the patient. The primary objective of this study was to assess the accuracy of CPS of cancer patients referred for palliative radiotherapy. Secondary objectives included an analysis of factors predictive of accurate CPS, comparisons of the accuracy of survival predictions over subsequent clinic visits, and comparisons to the previous study in the Rapid Response Radiotherapy Program (RRRP) in 2005. Methods: CPS was provided by one of four radiation oncologists from August 2014 to March 2017. Karnofsky Performance Status (KPS), primary cancer site, and sites of metastases were recorded. Date of death was retrieved from the Patient Care System (PCS) and Excelicare. Mean difference between actual survival (AS) and CPS was used to determine the accuracy of survival predictions. Results: One-hundred seventy-two patients were included in the final analysis. Survival was largely overestimated (n=135, 78.5%), with CPS being overestimated by 19.0 weeks on average. KPS (P=0.2), primary cancer site (P=0.08), and various sites of metastases were not significantly related to CPS accuracy. Gender was significantly related to CPS accuracy after multivariable analysis (P=0.04), but was no longer significant after excluding prostate and breast cancer patients in multivariable analysis (P=0.2). The mean difference between AS and CPS did not significantly change over subsequent visits (P=0.5) and CPS accuracy decreased significantly compared to the previous RRRP study (P=0.04). Conclusions: The survival estimates provided by radiation oncologists are inaccurately overestimated. Further research should aim to increase the accuracy of CPS in order to improve patient outcomes.

Radiotherapy (RT) for breast cancer improves survival, but poses risk to the heart, resulting from a linear relationship between RT dose and heart disease. This review presents studies worldwide reporting heart doses from whole breast RT after 2014 to update a previous systematic review (Taylor et al, Int J Radiat Oncol Biol Phys, 2015) in order to determine patterns of current heart dosimetry among varying RT regimens. Studies published between January 2014 and September 2017 were included if they reported whole heart dose based on whole breast RT technique or treatment position and had a sample size of ≥ 20 patients. Studies reporting brachytherapy, proton RT only, or boost to tumor bed were excluded. Among 99 studies, whole heart dose was reported by 231 regimens. The mean heart dose for left-sided breast cancer, reported by 84 studies (196 regimens), was 3.6 Gy, compared with a review of those previously reported (5.4 Gy). Regimens employing breathing control in any position had a significantly lower mean heart dose (1.7 Gy) compared with regimens without breathing control (4.5 Gy) (P .0001). The mean heart dose varied significantly between continents (P .0001), with heterogeneity reported among countries within Europe (P = .04) although not within other continents. On average, the mean heart dose steadily decreased between 2014 (4.6 Gy) and 2017 (2.6 Gy) (P = .003). Other heart dose parameters including the mean dose to the left anterior descending artery were reported by 80 left-sided regimens, and the mean left anterior descending artery dose was 12.4 Gy.

Radiation dermatitis is a common side effect of radiotherapy. Radiation dermatitis has been investigated for decades, and many approaches have been proposed to limit its incidence and severity. The purpose of the present systematic review was to summarize the approaches and findings of studies testing various methods for management of radiation dermatitis in breast cancer patients. Medline, Cochrane, and Embase were searched for studies pertaining to radiation-induced skin toxicity in breast cancer patients. The search results were limited to randomized trials of external beam radiotherapy conducted in humans and reported in the English language. The primary outcome was the incidence or severity of radiation dermatitis. Descriptive statistical analyses were performed. A total of 96 studies were included in the present review. These evaluated the effect of different radiotherapy techniques, topical treatments, supplements, skin care regimens, and treatments on radiation dermatitis. Few topical agents and oral supplements demonstrated their effectiveness across the randomized trials; however, various radiotherapy techniques, such as intensity-modulated radiotherapy, hypofractionated radiotherapy, accelerated partial breast irradiation, simultaneous integrated boost, and prone positioning consistently demonstrated decreased rates of radiation dermatitis, despite the limited number of studies in which they were evaluated.

Background Phyllodes tumours are rare and histologically diverse, posing challenges in prognosis and treatment. Due to their rarity, they have seldom been studied. Purpose The purpose was to investigate clinical practices in the management of phyllodes tumours, as well as patient outcomes to contribute to the limited body of knowledge surrounding these tumours. Methods A retrospective review was conducted on all patients with phyllodes tumours at a single institution. Descriptive analyses were conducted on demographic, disease and treatment (breast-conserving surgery, mastectomy, surgical re-excision, adjuvant/palliative radiation, palliative chemotherapy) information. Overall and disease-free survivals were analyzed, and the cumulative incidence of recurrence and metastases was compared. Results 79 patients with phyllodes tumours of the breast were included in the study. Tumours were classified as malignant, borderline, or benign in 67.1%, 21.5%, and 11.4% of patients, respectively. There were no statistically significant differences in overall or disease-free survival between patients with benign, borderline or malignant disease. Only patients with malignant disease developed recurrence or metastases. Those with malignant disease who received mastectomies had a lower 10-year cumulative incidence of recurrence; however this was not statistically significant (p = 0.69). All patients had negative surgical margins due to a re-excision or mastectomy following margin-positive breast conserving surgery. Of all risk factors assessed, necrosis was significantly associated with increased incidence of recurrence (local or distant) in patients with malignant disease (p = 0.03). Conclusion The presence of tumour necrosis is a significant negative prognostic factor. Breast-conserving surgery may be adequate in providing local control, given negative surgical margins.

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.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 study's odds ratios were computed using a random effects model and the Mantel-Haenszel statistic.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.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.

Palliative care aims to improve quality of life (QoL) for patients and families and does so by addressing issues not limited to pathology, but other symptoms that may be debilitating to patient experience and QoL. Despite sexual health being an important aspect of life for many patients, it is often omitted in clinical practice. This review summarizes published primary studies to explore the prevalence and importance of incorporating sexual health in the symptom screening and assessments of palliative patients, to identify current interventions that are implemented to address sexual health issues, and identify the barriers that health care professionals (HCPs) and patients may encounter which may prevent sexual health discussions. A literature review was conducted on Medline and Embase databases using keywords including "cancer", "sexual health", "intimacy", and "palliative care". Eleven papers focusing on the sexual health and intimacy of terminally ill patients in hospice, palliative or terminal care settings were identified for inclusion. Discussions about sexual health, functioning, and intimacy were not common in patient care, despite being a service that both patients and their partners desired. Referrals to sexologists, or discussions with patients and partners about intimacy and sexuality over the course of the disease trajectory were shown to improve QoL as well as alleviate some of the stress of receiving palliative care services. HCPs cited a lack of training, their own life experiences, or discomfort with the topic as barriers to initiating conversations with patients. In conclusion, sexuality and intimacy remain important parts of many people's lives regardless of their health, and should be incorporated into the care of all patients including those in palliative care. There is a need for further research to evaluate different methods or procedures for educating and counselling patients and their partners on sexual health issues. HCPs should have specific training and education in sexual health care to enable them to initiate and direct these discussions.

Background: Pain is reported in approximately 50–70% of cancer patients. Studies on gender differences in perceived pain generally report lower pain thresholds and increased pain prevalence in women, which may be attributed to gender-specific behaviors, stereotypes, and unknown etiological factors. There are sparse and inconclusive results on gender differences in self-perceived pain in the cancer setting. The aim of this article was to examine the effect of gender on baseline perceived pain intensity in cancer patients through a meta-analysis. Methods: A literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1947–2016] to identify observational studies and controlled trials that reported on gender-specific pain intensity in cancer patients. Using random-effects modeling, weighted mean differences and 95% confidence intervals (CI) were used to estimate the effect of gender on pain severity in cancer patients. A P value of less than 0.05 was considered statistically significant. Results: Of the 1,911 search results reviewed, 13 studies were included. The weighted mean difference (95% CI) in pain intensity was as follows: −0.26 (95% CI: −0.57 to 0.04, P=0.09) for the 0–10 Numerical Rating Scale (NRS) group (n=3,752, 9 studies). When restricted to only patients with advanced cancer, the weighted mean difference was −0.08 (95% CI: −0.36 to 0.20, P=0.58) (n=2,762, 4 studies). The weighted mean difference in the Brief Pain Inventory scores between males and females was 0.03 (95% CI: −1.23 to 1.29, P=0.96) (n=521, 4 studies). Conclusions: Baseline perceived pain intensity in cancer patients did not significantly differ based on gender.

Background and purpose Single fraction radiation treatment (SFRT) is recommended for its equivalence to multiple-fraction (MF) RT in the palliation of uncomplicated bone metastases (BM). However, adoption of SFRT has been slow. Materials and methods Literature searches for studies published following 2014 were conducted using online repositories of gray literature, Ovid MEDLINE, Embase and Embase Classic, and the Cochrane Central Register of Controlled Trials databases. Results A total of 32 articles detailing patterns of practice and clinical practice guidelines were included for final synthesis. The majority of organizations have released high level recommendations for SFRT use in treatment of uncomplicated BM, based on evidence of non-inferiority to MFRT. There are key differences between guidelines, such as varying strengths of recommendation for SFRT use over MFRT; contraindication in vertebral sites for SFRT; and risk estimation of pathologic fractures after SFRT. Differences in guidelines may be influenced by committee composition and organization mandate. Differences in patterns of practice may be influenced by individual center policies, payment modalities and consideration of patient factors such as age, prognosis, and performance status. Conclusion Although there is some variation between groups, the majority of guidelines recommend use of SFRT and others consider it to be a reasonable alternative to MFRT.

Aim: The aim of this review is to document pain assessment tools used primarily for older adults in long-term care facilities and compare self-report and observer-rated tools. Methods: A literature search was conducted in Ovid MEDLINE®, Embase, Cochrane and PsycINFO. Keywords included ‘dementia’, ‘pain management’ and ‘managing pain’. Results: Of 1033 references, 23 articles were selected for inclusion. Six tools were self-rated and 18 tools were administered by an observer. 13 studies evaluated the reliability/validity of their scales; four studies compared different scales against each other. Conclusion: Self-report should be the first-line approach when possible, with observational assessment used as a supplementary tool. Reliable observational tools have been shortened, and shown to maintain high reliability/validity, and positive psychometric properties.

Background: Single fraction radiotherapy (SFRT) and multiple fraction radiotherapy (MFRT) are effective for painful uncomplicated bone metastases and have been shown to be of similar efficacy. The optimal conventional external beam SFRT dose for maximum pain relief remains uncertain. The aim of this systematic review was to comprehensively review and synthesize overall pain response rates by dose. Methods: A literature search was conducted in Ovid MEDLINE(R) (1946 to June 2016 week 3), Embase Classic & Embase (1947 to 2016 week 26) and Cochrane Central Register of Controlled Trials (May 2016) using keywords such as bone metastases, radiotherapy and single fraction (SF). Results: The 635 results from the search were screened, and ultimately 27 were included for quantitative synthesis. The review indicated that 10 and 6 Gy may produce superior overall response (OR) and complete response (CR) rates compared to 8 Gy, and 6 Gy may result in better partial response (PR) than 8 Gy. However, only a few studies documented doses other than 8 Gy. In trials that directly compared 8 Gy to 4 Gy or 6 Gy, 8 Gy was deemed statistically superior. Conclusions: 8 Gy SFRT was the most commonly administered dose for palliation of bone metastases supporting its efficacy and safety. Future studies should explore the efficacy of 10 Gy while minimizing its side effects.

Background: The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV). Methods: A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases. Secondary endpoints included use of rescue medication, quality of life (QoL) and incidence of adverse events. Results: Seventeen RCTs were identified. Among patients receiving radiotherapy to abdomen/pelvis, our meta-analysis showed that prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA) was significantly more efficacious than placebo and dopamine receptor antagonists in both complete control of vomiting [OR 0.49; 95% confidence interval (CI): 0.33–0.72 and OR 0.17; 95% CI: 0.05–0.58 respectively] and complete control of nausea (OR 0.43; 95% CI: 0.26–0.70 and OR 0.46; 95% CI: 0.24–0.88 respectively). 5HT3 RAs were also more efficacious than rescue therapy and dopamine receptor antagonists plus dexamethasone. The addition of dexamethasone to 5HT3 RA compared to 5HT3 RA alone provides a modest improvement in prophylaxis of RINV. Among patients receiving TBI, 5HT3 RA was more effective than other agents (placebo, combination of metoclopramide, dexamethasone and lorazepam). Conclusions: 5HT3 RAs are more effective than other antiemetics for prophylaxis of RINV in patients receiving radiotherapy to abdomen/pelvis and TBI. Future RCTs should investigate the efficacy of newer agents such as substance P neurokinin 1 receptor antagonists in addition to 5HT3 RAs in prophylaxis of RINV during both acute and delayed phases.

Pain is one of the most prominent symptoms faced by cancer patients. It is known that patient and caregiver-targeted educational interventions addressing the proper use of pain management may provide significant clinical value. This review examines the literature surrounding the use of multimedia interventions for patient and caregiver education (PCE) on pain management compared to traditional educational interventions. A literature search was conducted in Ovid MEDLINE (1946-July Week 2, 2016), Ovid Embase (1947-2016 Week 29), and Ovid Cochrane Central Register of Controlled Trials (up to June 2016). Paired reviewers conducted title and abstract screening and full-text screening to identify experimental, quasi-experimental and cohort studies evaluating one or more multimedia-based PCE interventions focused on cancer pain and pain management and targeting patients and/or caregivers. Findings were extracted by paired reviewers and synthesized qualitatively. Of the 68 full-text papers assessed, 7 were deemed relevant, of which 5 were RCTs and 2 were observational studies. We found limited but convincing quantitative data to suggest that the use of multimedia use in pain management education for patients/caregivers has greater value-added benefit compared to standard education. While there is evidence suggesting a positive effect on pain-related outcomes with the use of multimedia-based patient and caregiver-targeted interventions, it is limited to a small number of lower-quality studies. More robust and large-scale studies are needed to supplement existing evidence and provide more insight regarding the usability and user-friendliness of these tools in practice.

Background: Whole brain radiotherapy (WBRT) is commonly used to treat brain metastases. Previous studies have explored how radiotherapy treatment time can affect response. The present study evaluated the influence of treatment time on overall survival (OS) for cancer patients receiving WBRT. Methods: Patients who received WBRT from 2004 to 2016 were included. Demographic information including age, performance status, primary site, dose, fraction, treatment time, and date of death were collected. Based on different percentages of treatment times falling into one time frame (i.e., 100%, ≥80%, ≥70%, or ≥60%), patients were allocated to three cohorts (8:00–11:00 AM, 11:01 AM–2:00 PM, 2:01–5:00 PM). Demographics were compared among cohorts using the Kruskal-Wallis nonparametric test and Fisher exact test. To control the multiple comparisons on select demographic variables a Bonferroni adjusted P value was considered statistically significant. Kaplan-Meier curves were created for OS. Univariate and multivariate Cox proportional hazard (PH) model were used to find predictive factors of OS in all patients, females and males. Results: A total of 755 patients were included with a median age of 66 years. The actuarial median OS was 2.37 months. Treatment time was not associated with OS for all patients or males only. In elderly female patients (>65 years), a significant difference in OS was found among treatment cohorts (P=0.02). Treatment time (when ≥80% or ≥70% of treatment times were in one time frame), age, and Karnofsky performance status (KPS) were significant predictive factors of OS in univariate analysis for females. Only age and KPS remained significant in multivariate analysis. Conclusions: Time of WBRT delivery for brain metastases was significantly related to OS upon univariate analyses in females only. Future investigations should be conducted prospectively with homogenous patient groups to elucidate the effect of chronotherapy in palliative brain metastases patients as time of WBRT administration may affect OS in specific subsets of patients.

Previous studies have observed how the time of radiotherapy delivery can impact toxicities and outcomes. The goal of this study was to determine whether treatment time influenced radiotherapy response for bone metastases.Patients who received radiation treatment to painful bone metastases from January 2000 to December 2010 were included in our analysis. Demographic and treatment information including performance status, primary site, treatment dose and fraction, and response were collected prospectively. Treatment times were extracted from patient medical records. Patients were allocated to 8:00 AM-11:00 AM, 11:01 AM-2:00 PM, or 2:01 PM-5:00 PM cohorts based on their treatment times. To compare treatment response between the three cohorts, the Fisher exact test was used. A two-sided P value of0.05 was considered statistically significant. Analysis was repeated with males and females separately.A total of 194 patients were included. The median age was 68 years and 55.5% of patients responded to treatment. The dose and fraction of radiation received differed significantly between treatment cohorts using all allocation methods. Females in the 11:01 AM-2:00 PM cohort exhibited a significantly higher response rate (P=0.02) and differing proportions of response types (P=0.03) compared to the 8:00 AM- 11:00 AM and 2:01 PM-5:00 PM cohorts when allocated using all treatment times. No significant differences in response were seen between cohorts when all patients were analysed together or analysed for males only.Treatment time may affect response in female patients receiving radiotherapy for painful bone metastases. Subsequent chronotherapy studies in radiation should investigate these gender differences.

The purpose of this review was to compare the development, characteristics, validity, and reliability of three widely used quality of life (QOL) assessment tools used in colorectal cancer (CRC) patients: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), the European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Quality of Life Questionnaire Colorectal Cancer Module (QLQ-CR38) and its successor, the QLQ-CR29. A literature search was conducted using Ovid EMBASE and EMBASE Classic (1996–2015 Week 39), Ovid MEDLINE and OLDMEDLINE (1996 September Week 4 2015), and the Cochrane Central Register of Controlled Trials (up to August 2015) to identify studies that discussed the FACT-C, EORTC QLQ-CR38, and QLQ-CR29 including, but not limited to, their development, characteristics, validity, and reliability. The FACT-C consists of 36 items, presented on a 5-point Likert scale, in four domains of well-being (physical, emotional, social, and functional), and the Colorectal Cancer Subscale (CCS). The physical and social well-being scales showed reasonable internal consistency (Cronbach’s alpha coefficient > 60) in all studied populations. The EORTC QLQ-CR38 (38 items) and the QLQ-CR29 (29 items) are implemented in conjunction with the core QLQ-C30 (30 items); all are presented in 4-point Likert scales. Seven scales in the QLQ-CR38 demonstrated good internal consistency (Cronbach’s alpha coefficient > 0.70). In the QLQ-CR29, three scales had a Cronbach’s alpha coefficient of less than 0.70. The FACT-C, QLQ-CR38, and QLQ-CR29 have been extensively validated. However, analysis of their characteristics, validity, and reliability suggest differing suitability in assessing QOL in specific clinical situations.

The purpose of this study was to assess which pain intensity dimension scale (worst, least, average, or current pain) from the Brief Pain Inventory (BPI) correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia. Breast cancer patients scheduled to receive docetaxel, paclitaxel, or albumin-bound paclitaxel (nab-paclitaxel) were enrolled in the study. Patients completed an initial baseline questionnaire and subsequently filled out a diary based on the BPI on days 1–7, 14, and 21 for three consecutive treatment cycles. Pain scores for worst, least, average, and current pain intensity dimensions as well as pain interference scores were recorded in the diaries and questionnaires using the BPI. Worst, least, average, and current pain scores were correlated with functional pain interference scores using Spearman’s rank correlation coefficients. A general linear mixed model of each functional interference measure was performed over time for cycles 1–3 with each pain intensity dimension scale. Among worst, average, least, and current joint pain dimensions, average joint pain scores correlated best with all BPI interference responses while average muscle pain scores correlated best with all BPI interference responses except for sleeping probability and normal work. We recommend the BPI scale measuring average pain for future studies evaluating pain scores in patients experiencing taxane-induced arthralgia and myalgia.

Olanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV. A literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory. Across the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8 % for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5 %, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6 % for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4 %, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects. Olanzapine is efficacious and safe when used as a prophylaxis for CINV.

Alternative level metrics (Altmetrics) are a new method to assess the sharing and spread of scientific knowledge. The primary objective of this study was to describe the traditional metrics and Altmetric scores of the fifty most frequently cited articles published in emergency medicine (EM) journals. Since many articles related to EM are published in other journals, the secondary aim of this study was to describe the Altmetric scores of the most frequently cited articles relevant to EM in other biomedical journals. A structured search of the Institute for Scientific Information (ISI) Web of Science version of the Science Citation Index Expanded was conducted. The 200 most frequently cited articles in the top ten EM journals (2011 Journal Citation Report) were identified. The 200 most frequently cited articles from the rest of the medical literature, matching a pre-defined list of keywords relevant to the specialty of EM, were identified. Two authors reviewed the lists of citations for relevance to EM and a consensus approach was used to arrive at the final lists of the top 50 cited articles. The Altmetric scores for the top fifty cited articles in EM and other journals were determined. Descriptive statistics and Spearman correlation were performed. The highest Altmetric score for EM articles was 25.0, the mean was 1.9 [SD=5.0]. The EM journal with the highest average article Altmetric score was Resuscitation. The main clinical areas shared for articles from EM articles were trauma (mean 11.0, median 11.0 [SD=15.6]) and cardiac arrest (mean 2.7, median 0 [SD=5.8]). The highest Altmetric score for other journals was 176.0, mean 23.3 [SD=40.8]. The other journal with the highest average article Altmetric score was the New England Journal of Medicine. The main clinical areas shared for articles were critical care (mean score 36.5, median 36.5 [SD= 47.4], sepsis (mean 24.6, median 12.0 [SD=48.8]), cardiology (mean 19.2, median 7.0 [SD=35.6]) and infectious diseases (mean 17.0, median 17.0 [SD=12.7]). Spearman correlation demonstrated weakly positive correlation between citation counts and Altmetric scores for EM articles, and other journals. This study is the first analysis of Altmetric scores for the top cited articles in emergency medicine. We demonstrated that there is a mild correlation between citation counts and Altmetric scores for the top papers in emergency medicine and other biomedical journals. We also demonstrated that there is a gap between the sharing of the top articles in emergency medicine journals and those related to emergency medicine in other biomedical journals. Future research to explore this relationship and its temporal trends will benefit the understanding of the reach and dissemination of emergency medicine research within the scientific community and society in general. This article is protected by copyright. All rights reserved.

Objective The purpose of this study was to determine whether serum antibody response to the three versions of chlamydial heat shock protein 60 is associated with an increased risk for cervical cancer. Study design Women with cervical carcinoma were identified by linking the data files of three Nordic serum banks with cancer registries. Overall, 178 women with invasive cervical carcinoma were identified. For each case, the earliest prediagnostic serum sample was chosen, and three matched control subjects who were free of cancer at the time of the case diagnosis were selected randomly. Serum antibodies to the chlamydial heat shock protein 60 were measured by enzyme-linked immunosorbent assay and correlated with the risk of the subsequent development of cervical cancer. Results Antibodies to chlamydial heat shock protein 60–1 were associated with cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds ratio, 2.4; 95% CI, 1.1–5.1). Antibodies to chlamydial heat shock protein 60–2 or chlamydial heat shock protein 60–3 were not associated with cervical cancer risk. Conclusions The finding that chlamydial heat shock protein 60–1 antibodies are associated with an increased cervical cancer risk suggests that persistent Chlamydia trachomatis infection may contribute to cervical neoplasia.

Purpose To determine the optimal dose of single fraction conventional palliative radiation therapy for the relief of pain caused by bone metastases. Material and methods Ovid version of EMBASE and EMBASE Classic, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched for relevant randomised controlled trials. Pain response data were standardised according to the clinical trial endpoints recommended by the International Bone Metastases Consensus Working Party. Results From 2696 references we selected 26 articles for review. These described 24 trials that cumulatively randomised 3233 patients to 28 single fraction arms: two arms received 4Gy, one 5Gy, one 6Gy, twenty-two 8Gy, one 10Gy and one 8–15Gy. Eighty-four percent of all patients received 8Gy and this imbalance precluded formal modelling analyses for different doses. Efficacy endpoints and pain assessment times varied. In general, higher doses produced better pain response rates. The overall (OR) and complete (CR) pain response rates for different doses according to available intention-to-treat (ITT) and assessable patient (A) figures were: 4Gy [OR(ITT)=23–47%, OR(A)=44–47%, CR(ITT)=15–18%, CR(A)=15–26%], 5Gy [OR(A)=72%, CR(A)=55%], 6Gy [OR(ITT&A)=65%, CR(ITT&A)=21%], 8Gy [OR(ITT)=21–81%, OR(A)=31–93%, CR(ITT)=9–52%, CR(A)=14–57%], 10Gy [OR(A)=84%, CR(A)=39%]. In trials that directly compared different single fraction doses, 8Gy was statistically superior to 4Gy. Conclusions 8Gy was by far the most commonly administered single fraction dose within 24 randomised trials of conventional radiation therapy for the palliation of bone metastases. 8Gy should be the standard dose against which future treatments are compared due to its reproducible pain response rate and its established safe profile. The optimal dose for the relief of pain remains an open question, however, 8Gy produced statistically superior pain response rates compared to 4Gy in trials directly comparing those doses, and in general across all trials doses of 8Gy or more produced numerically superior pain response rates compared to doses less than 8Gy.