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The effectiveness of abdominal compression for motion management in hepatobiliary-pancreatic (HPB) radiotherapy has not been systematically evaluated. A systematic review was carried out using PubMed/Medline, Cochrane Library, Web of Science, and CINAHL databases up to 1 July 2021. No date restrictions were applied. Additional searches were carried out using the University of Manchester digital library, Google Scholar and of retrieved papers' reference lists. Studies conducted evaluating respiratory motion utilising imaging with and without abdominal compression in the same patients available in English were included. Studies conducted in healthy volunteers or majority non-HPB sites, not providing descriptive motion statistics or patient characteristics before and after compression in the same patients or published without peer-review were excluded. A narrative synthesis was employed by tabulating retrieved studies and organising chronologically by abdominal compression device type to help identify patterns in the evidence. The inclusion criteria were met by 6 studies with a total of 152 patients. Designs were a mix of retrospective and prospective quantitative designs with chronological, non-randomised recruitment. Abdominal compression reduced craniocaudal respiratory motion in the majority of patients, although in four studies there were increases seen in at least one direction. The influence of patient comorbidities on effectiveness of compression, and/or comfort with compression was not evaluated in any study. Abdominal compression may not be appropriate for all patients, and benefit should be weighed with potential increase in motion or discomfort in patients with small initial motion (<5 mm). Patient factors including male sex, and high body mass index (BMI) were found to impact the effectiveness of compression, however with limited evidence. High-quality studies are warranted to fully assess the clinical impact of abdominal compression on treatment outcomes and toxicity prospective in comparison to other motion management strategies. [ABSTRACT FROM AUTHOR]

Background. Intraoperative radiotherapy (IORT) has been given for primary and locally recurrent rectal cancer for 30 years. Still, its effect is not clear. Material and methods. PubMed and EMBASE search for papers after 1989 on surgical treatment and external beam radiotherapy (EBRT) for primary advanced and locally recurrent rectal cancer, with and without IORT. From each center the most recent paper was generally selected. Survival and local recurrence at five years was tabulated for the total groups and separate R-stages. Also, the technique for IORT, use of EBRT and chemotherapy as well as surgical approach was registered. Results. In primary cancer 18 papers from 14 centers were tabulated, including one randomized and five internally comparing studies, as well as seven studies without IORT. In locally recurrent cancer 18 papers from 13 centers were tabulated, including four internally comparing studies and also five without IORT. Overall survival (OS) and local recurrence rate (LRR) were higher for primary cancer compared to recurrent cancer. Patients with R0 resections had better outcome than patients with R1 or R2 resections. For primary cancer OS and LR rate of the total groups and R0 stages was not influenced by IORT. An effect on R1/R2 stages cannot be excluded. The only randomized study (primary cancer) did not show any effect of IORT. Conclusion. IORT does not convincingly improve OS and LR rate for primary and locally recurrent rectal cancer. If there is an effect of IORT, it is small and cannot be shown outside randomized studies analyzing the separate R stages. [ABSTRACT FROM AUTHOR]

Background. Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds. Methods. After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers. Results. Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02). Conclusions. Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined. [ABSTRACT FROM AUTHOR]

Background and purpose — There is ongoing debate as to whether commercial funding influences reporting of medical studies. We asked: Is there a difference in reported tones between abstracts, introductions, and discussions of orthopedic journal studies that were commercially funded and those that were not commercially funded? Methods — We conducted a systematic PubMed search to identify commercially funded studies published in 20 orthopedic journals between January 1, 2000 and December 1, 2019. We identified commercial funding of studies by including in our search the names of 10 medical device companies with the largest revenue in 2019. Commercial funding was designated when either the study or 1 or more of the authors received funding from a medical device company directly related to the content of the study. We matched 138 commercially funded articles 1 to 1 with 138 non-commercially funded articles with the same study design, published in the same journal, within a time range of 5 years. The IBM Watson Tone Analyzer was used to determine emotional tones (anger, fear, joy, and sadness) and language style (analytical, confident, and tentative). Results — For abstract and introduction sections, we found no differences in reported tones between commercially funded and non-commercially funded studies. Fear tones (non-commercially funded studies 5.1%, commercially funded studies 0.7%, p = 0.04), and analytical tones (non-commercially funded studies 95%, commercially funded studies 88%, p = 0.03) were more common in discussions of studies that were not commercially funded. Interpretation — Commercially funded studies have comparable tones to non-commercially funded studies in the abstract and introduction. In contrast, the discussion of non-commercially funded studies demonstrated more fear and analytical tones, suggesting them to be more tentative, accepting of uncertainty, and dispassionate. As text analysis tools become more sophisticated and mainstream, it might help to discern commercial bias in scientific reports. [ABSTRACT FROM AUTHOR]

Background: Supporting unemployed or work-disabled cancer survivors in their work participation can have extensive individual and societal benefits. We aimed to identify and summarise interventions for work participation of unemployed or work-disabled cancer survivors. Methods: Five databases (Medline, Embase, PsycINFO, CINAHL and Cochrane Library) were systematically searched for quantitative studies on interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors. Work participation refers to participation in the workforce, fulfilling one's work role. Manual and automatic screening (with ASReview software) were performed on titles and abstracts, followed by manual full-text screening. Data were extracted regarding study, patient and intervention characteristics, and work participation outcomes. Risk of bias (RoB) was assessed using the Cochrane RoB2 and QUIPS tools. Results: We identified 10,771 articles, of which we included two randomised controlled trials (RCTs), of which one feasibility RCT, and three cohort studies. In total, 1862 cancer survivors were included, with predominantly breast cancer. Work participation was mainly measured as time to return to work (RTW) and RTW rate. Interventions included components of coaching (e.g., psychological or rehabilitation), training (e.g., building confidence and managing fatigue) and self-management. Two RCTs with unclear RoB did not show an effect of multicomponent interventions compared to care as usual. One cohort study found a significant effect of a psycho-educational intervention on RTW rates, with moderate RoB. The other two cohort studies, with moderate RoB, reported significant associations between components including job search and placement assistance, and work participation. Discussion: Only few interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors, have been evaluated. In two cohort studies, promising components for future multicomponent interventions were identified. However, findings suggest that more evidence is necessary on such multicomponent interventions, in which elements explicitly directed at work and including the workplace should be included. [ABSTRACT FROM AUTHOR]

Insulin resistance is a critical cause of metabolic dysfunctions. Metabolic dysfunction is common in patients with cancer and is associated with higher cancer recurrence rates and reduced overall survival. Yet, insulin resistance is rarely considered in the clinic and thus it is uncertain how frequently this condition occurs in patients with cancer. To address this knowledge gap, we performed a systematic review and a meta-analysis guided by the Preferred Items for Systematic Review and Meta-Analyses (PRISMA) statement. We included studies assessing insulin resistance in patients with various cancer diagnoses, using the gold-standard hyperinsulinemic–euglycemic clamp method. Studies eligible for inclusion were as follows: (1) included cancer patients older than 18 years of age; (2) included an age-matched control group consisting of individuals without cancer or other types of neoplasms; (3) measured insulin sensitivity using the hyperinsulinemic–euglycemic clamp method. We searched the databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published from database inception through March 2023 with no language restriction, supplemented by backward and forward citation searching. Bias was assessed using funnel plot. Fifteen studies satisfied the criteria. The mean insulin-stimulated rate of glucose disposal (Rd) was 7.5 mg/kg/min in control subjects (n = 154), and 4.7 mg/kg/min in patients with a cancer diagnosis (n = 187). Thus, the Rd mean difference was −2.61 mg/kg/min [95% confidence interval, −3.04; −2.19], p<.01). Heterogeneity among the included studies was insignificant (p=.24). These findings suggest that patients with a cancer diagnosis are markedly insulin resistant. As metabolic dysfunction in patients with cancer associates with increased recurrence and reduced overall survival, future studies should address if ameliorating insulin resistance in this population can improve these outcomes thereby improving patient care. Metabolic dysfunction increases cancer recurrence rates and reduces survival for patients with cancer. Insulin resistance is a critical cause of metabolic dysfunctions. To date, no comprehensive compilation of research investigating insulin resistance in cancer patients has been produced. In this meta-analysis, we found that patients with various cancers were markedly insulin-resistant. [ABSTRACT FROM AUTHOR]

Background and purpose -- Robotic-assisted total knee arthroplasty (RATKA) is an alternative surgical treatment method to conventional total knee arthroplasty (COTKA) that may deliver better surgical accuracy. However, its impact on patient outcomes is uncertain. The aim of this systematic review of randomized controlled trials (RCTs) is to evaluate whether RATKA could improve functional and radiological outcomes compared with COTKA in adult patients with primary osteoarthritis of the knee. Methods -- We searched Ovid MEDLINE, EMBASE, Scopus, and the Cochrane Library to identify published RCTs comparing RATKA with COTKA. 2 reviewers independently screened eligible studies, reviewed the full texts, assessed risk of bias using the Risk of Bias 2.0 tool, and extracted data. Outcomes were patient-reported outcomes, range of motion, and mechanical alignment (MA) deviation and outliers, and complications. Results -- We included 12 RCTs involving 2,200 patients. RATKA probably results in little to no effect on patient-reported outcomes (mean difference (MD) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of -0.35 (95% confidence interval [CI] -0.78 to 0.07) and range of motion (MD -0.73°; CI -7.5° to 6.0°) compared with COTKA. However, RATKA likely results in a lower degree of MA outliers (risk ratio 0.43; CI 0.27 to 0.67) and less deviation from neutral MA (MD -0.94°; CI -1.1° to -0.73°). There were no differences in revision rate or major adverse effects associated with RATKA. Conclusion -- Although RATKA likely results in higher radiologic accuracy than COTKA, this may not be clinically meaningful. Also, there is probably no clinically important difference in clinical outcomes between RATKA and COTKA, while it is as yet inconclusive regarding the revision and complication rates due to insufficient evidence. [ABSTRACT FROM AUTHOR]

Background and purpose -- We conducted a systematic review and meta-analysis of RSA studies to investigate the early and long-term migration patterns of acetabular cups and the influence of implant factors on cup migration over time. Methods -- We performed a systematic search of PubMed, Embase, and Scopus databases to identify all RSA studies of cup migration following primary total hip replacement (THR). Proximal migration at 3 and 6 months, 1, 2, 5, and 10 years were considered for analysis. Implant factors investigated included fixation type, head size, bearing surface, uncemented coating design, and the decade of RSA introduction. Results -- 47 studies reported the proximal migration of 83 cohorts (2,328 cups). Besides 1 threaded cup design, no implant factor investigated was found to significantly influence proximal migration. The mean pooled 2-year proximal migration of cemented cups (0.14 mm, 95% confidence interval [CI] 0.08-0.20) was not significantly different from uncemented cups (0.12 mm, CI 0.04-0.19). The mean pooled proximal migration at 6 months was 0.11 mm (CI 0.06-0.16) and there was no significant increase between 6 months and 2 years (0.015 mm, CI 0.000-0.030). 27 of 75 cohorts (36%) reported mean proximal migration greater than 0.2 mm at 2 years, which has previously been identified as a predictor of implants at risk of long-term loosening. Conclusion -- Our meta-analysis demonstrated that the majority of cup migration occurs within the first 6 months. With one exception, no implant factors influenced the 2-year proximal migration of acetabular cups. 36% of studies with 2-year migration were considered at risk of long-term loosening. Further investigation and comparison against longterm survivorship data would validate 6-month and/or 1-year proximal migration measurements as an earlier predictor of long-term loosening than the current 2-year threshold. [ABSTRACT FROM AUTHOR]

Background and purpose -- Assessing peri-acetabular bone quality is valuable for optimizing the outcomes of primary total hip arthroplasty (THA) as preservation of good quality bone stock likely affects implant stability. The aim of this study was to perform a meta-analysis of peri-acetabular bone mineral density (BMD) changes over time measured using quantitative computer tomography (CT) and, second, to investigate the influence of age, sex, and fixation on the change in BMD over time. Methods -- A systematic search of Embase, Scopus, Web of Science, and PubMed databases identified 19 studies that measured BMD using CT following THA. The regions of interest (ROI), reporting of BMD results, and scan protocols were extracted. A meta-analysis of BMD was performed on 12 studies that reported measurements immediately postoperatively and at follow-up. Results -- The meta-analysis determined that periacetabular BMD around both cemented and uncemented components decreases over time. The amount of BMD loss increased relative to proximity of the acetabular component. There was a greater decrease in cortical BMD over time in females and cancellous BMD for young patients of any sex. Conclusion -- Peri-acetabular BMD decreases at different rates relative to its proximity to the acetabular component. Cancellous BMD decreases more in young patients and cortical bone decreases more in females. Standardized reporting parameters and suggested ROI to measure peri-acetabular BMD are proposed, to enable comparison between implant and patient variables in the future. [ABSTRACT FROM AUTHOR]

Osimertinib is a recently approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M resistance mutations. The aim of the present meta-analysis was to investigate the efficacy and safety of osimertinib for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Databases were searched for randomized controlled studies that reported the efficacy and safety of osimertinib versus other treatments (chemotherapy, other EGFR-TKIs, etc.) in treating EGFR-mutated NSCLC. The measured effects included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), central nervous system progression-free survival (CNS-PFS), and overall survival (OS). Additional outcome was the incidence of adverse event. Relative risk (RR) for incidence and hazard ratio (HR) for survival outcomes were pooled. Seven studies containing 3335 participants were finally included. Osimertinib tended to improve ORR and DCR (RRs >1) as compared with other treatments. Osimertinib was also a significant protective factor for PFS, CNS-PFS, and OS (HRs <1 and p <.05). Osimertinib showed similar advantages in improving tumor response and patient survival when used as first-line, second-line, and third-line/adjuvant therapy, respectively, as compared with other treatments (RRs >1 for ORR and DCR; HRs <1 for PFS, CNS-PFS, and OS). Osimertinib also had better therapeutic effects as compared with chemotherapy, other EGFR TKIs, docetaxel + bevacizumab, and placebo, respectively. The five most common adverse events with pooled incidence > 20% were diarrhea, rash, nail effects, dry skin, and stomatitis, yet the pooled incidence of serious adverse events was less than 2%. This meta-analysis suggests that osimertinib has a positive effect in disease control and survival for patients with EGFR-mutated NSCLC with acceptable toxicities. [ABSTRACT FROM AUTHOR]

Background and purpose -- After initial clubfoot correction through Ponseti treatment, recurrence rates range from 26% to 48%. Even though various factors have been associated with increased recurrence risk, systematic assessments of the prognostic capacity of recurrence risk factors and their clinical relevance are lacking. Therefore we assessed clinically relevant prognostic factors for recurrent idiopathic clubfoot deformity after initial correction through Ponseti treatment. Methods -- PubMed, Embase, Cinahl, and Web of Science were systematically searched for studies investigating the association between clinically relevant factors and recurrence rates. Prognostic factors were qualitatively assessed and included in the meta-analysis if ≥ 2 studies investigated the same factor and methods were comparable. Results -- 34 articles were included in the qualitative synthesis, of which 22 were also included in the meta-analysis. Meta-analysis revealed that poor evertor muscle activity (OR = 255, 95% CI 30--2,190), brace non-compliance (OR = 10, CI 5--21), no additional stretching (OR = 31, CI 10--101), more casts (OR = 3.5, CI 1.6--7.8), lower education level of parents (OR = 1.8, CI 1.2--2.6), non-marital status of parents (OR = 1.8, CI 1.1--3.0), and higher Dimeglio scores (OR = 1.9, CI 1.2--3.3) were associated with higher recurrence rates. Interpretation -- Brace non-compliance and poor evertor muscle activity have been identified as main recurrence risk factors and are therefore important to be closely monitored during clinical follow-up of clubfoot patients. Adding additional stretching during the bracing protocol might be promising in the quest to prevent relapse, but scientific evidence for clear clinical treatment recommendations is still limited. [ABSTRACT FROM AUTHOR]

Background and purpose — External validation of machine learning (ML) prediction models is an essential step before clinical application. We assessed the proportion, performance, and transparent reporting of externally validated ML prediction models in orthopedic surgery, using the Transparent Reporting for Individual Prognosis or Diagnosis (TRIPOD) guidelines. Material and methods — We performed a systematic search using synonyms for every orthopedic specialty, ML, and external validation. The proportion was determined by using 59 ML prediction models with only internal validation in orthopedic surgical outcome published up until June 18, 2020, previously identified by our group. Model performance was evaluated using discrimination, calibration, and decision-curve analysis. The TRIPOD guidelines assessed transparent reporting. Results — We included 18 studies externally validating 10 different ML prediction models of the 59 available ML models after screening 4,682 studies. All external validations identified in this review retained good discrimination. Other key performance measures were provided in only 3 studies, rendering overall performance evaluation difficult. The overall median TRIPOD completeness was 61% (IQR 43–89), with 6 items being reported in less than 4/18 of the studies. Interpretation — Most current predictive ML models are not externally validated. The 18 available external validation studies were characterized by incomplete reporting of performance measures, limiting a transparent examination of model performance. Further prospective studies are needed to validate or refute the myriad of predictive ML models in orthopedics while adhering to existing guidelines. This ensures clinicians can take full advantage of validated and clinically implementable ML decision tools. [ABSTRACT FROM AUTHOR]

There is currently no FDA or EMA-approved standard of care for metastatic uveal melanoma. A systematic review of all interventional uveal melanoma trials on the ClinicalTrials.gov database and EU Clinical Trials Register was conducted from January 15, 2019 through November 30, 2019. Categorical data analysis and descriptive statistics were generated. A total of 119 trials met inclusion criteria for this systematic review, of which 39 were active. Of all trials, 47% were NIH-funded while 59% of active trials were industry funded. Of all trials, 86% were concerned with treatment of metastasis, 7% with adjuvant therapy, and 8% with treatment of primary tumor. In trials treating metastasis, 62% reported response rates as their primary outcome measure. Non-randomized patient allocation to treatment arms was reported in 73% of trials, and 8% of trials were in phase 3. Pharmaceutical drugs were utilized by 69% of trials. Of the 6 negative randomized trials, all reported no significant effect from intervention compared to a control arm and were usually initiated on preclinical or early phase data. Given decreased NIH funding for uveal melanoma trials, clinicians should consider industry funding partnerships. Standardization of primary outcome measures between trials will also allow for statistical meta-analyses of results in this rare patient population. Finally, clinicians should use single arm studies to establish significant treatment response rates before proceeding with randomized trials. [ABSTRACT FROM AUTHOR]

Background: The α/β values for prostate cancer (PCa) are usually assumed to be low (1.0-1.8 Gy). This study estimated the α/β values of PCa from phase III randomized trials of conventional (CRT) versus hypofractionated (HRT) external beam radiotherapy (RT), reported as isoeffective in terms of their 5-year biochemical (BF) or biochemical and/or clinical failure (BCF) rates. Material and methods: The α/β for each trial was estimated from the equivalent biological effective doses using the linear-quadratic model for each of their HRT and CRT schedules. The cumulative outcomes of these trials were evaluated by meta-analysis for odds ratio (OR), risk ratio (RR) and risk difference (RD). Results: Eight trials from seven studies, randomized 6993 patients between CRT (n¼2941) and HRT (n¼4052). RT treatment varied between the two treatment groups in terms of dose/fraction, total dose, overall treatment time and %patients on androgen deprivation therapy (ADT). Differences in OR, RR, and RD for both BF and BCF were nonsignificant. The computed α/β ranged from 1.3 to 11.1 Gy (4.9± 3.9 Gy; 95% CI: 1.6-8.2). On multivariate regression, %ADT was the sole determinant of computed α/β (model R2: 0.98, p<.001). Conclusions: Clinically estimated α/β for PCa from isoeffective randomized trials using known variables in the linear-quadratic expression ranged between 1.3 and 11.1 Gy. The estimated α/β values were inversely related to %ADT usage, which should be considered when planning future RT dose-fractionation schedules. [ABSTRACT FROM AUTHOR]

Background:Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine. Methods:Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected. Search was done through Medline and the registry of the NIH. Keywords used for searching were ‘pancreas’, ‘pancreatic’, ‘gemcitabine’. Study quality was assessed with MERGE criteria. Findings were depicted in classical Forest plots. Publication bias was evaluated by the construction of funnel plot. Results:Nine studies met the meta-analysis inclusion criteria including 4564 patients. The target therapies were: erlotinib, cetuximab, rigosertib, elpamotide, bevacizumab, aflibercept, axitinib, masitinib and ganitumab. There was no statistically significant heterogeneity among the nine trials (p =0.77). The hazard ratio (HR) of the pooled analysis was 0.998 (CI 95%: 0.932–1.068). Subgroup meta-analysis was also performed in anti-EGFR and anti-angiogenesis trials: the pooled HR were 0.94 (CI 95%: 0.705–1.175) and 1.055 (CI 95%: 0.913–1.197), respectively. Conclusions:The present meta-analysis does not show significant improvements in survival for targeted drugs in advanced pancreatic cancer. The possible reason of these results could be linked to the biology of pancreatic cancer as well as to the absence of predictive factors. [ABSTRACT FROM PUBLISHER]

Background and purpose - There is no consensus on the treatment of proximal humerus fractures in the elderly. Patients and methods - We conducted a systematic search of the medical literature for randomized controlled trials and controlled clinical trials from 1946 to Apr 30, 2014. Predefined PICOS criteria were used to search relevant publications. We included randomized controlled trials involving 2- to 4-part proximal humerus fractures in patients over 60 years of age that compared operative treatment to any operative or nonoperative treatment, with a minimum of 20 patients in each group and a minimum follow-up of 1 year. Outcomes had to be assessed with functional or disability measures, or a quality-of-life score. Results - After 2 independent researchers had read 777 abstracts, 9 publications with 409 patients were accepted for the final analysis. No statistically significant differences were found between nonoperative treatment and operative treatment with a locking plate for any disability, for quality-of-life score, or for pain, in patients with 3- or 4-part fractures. In 4-part fractures, 2 trials found similar shoulder function between hemiarthroplasty and nonoperative treatment. 1 trial found slightly better health-related quality of life (higher EQ-5D scores) at 2-year follow-up after hemiarthroplasty. Complications were common in the operative treatment groups (10-29%). Interpretation - Nonoperative treatment over locking plate systems and tension banding is weakly supported. 2 trials provided weak to moderate evidence that for 4-part fractures, shoulder function is not better with hemiarthroplasty than with nonoperative treatment. 1 of the trials provided limited evidence that health-related quality of life may be better at 2-year follow-up after hemiarthroplasty. There is a high risk of complications after operative treatment. [ABSTRACT FROM AUTHOR]

Strong evidence exists supporting the effect of lack of physical activity on the risk of developing breast cancer. However, studies examining the effects of physical activity on breast cancer outcomes, including survival and prognosis have been inconclusive. Therefore, the aim of the current study was to provide a systematic review and meta-analysis of studies investigating the association between physical activity and breast cancer recurrence and death. Methods. PubMed, EMBASE, and CENTRAL databases were searched up to 18 October 2014. Reference lists of retrieved articles and relevant previous reviews were also searched. Observational studies that reported risk estimates for all-cause and/or breast cancer-related death and/or breast cancer recurrences by levels of physical activity, were included in the review. Random effects models were used to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) and to incorporate variation between studies. The Newcastle-Ottawa scale was used to critically appraise the risk of bias across studies. Results. Twenty-two prospective cohort studies were eligible in this meta-analysis. During average follow-up periods ranging from 4.3 to 12.7 years there were 123 574 participants, 6898 all-cause deaths and 5462 breast cancer outcomes (i.e. breast cancer-related deaths or recurrences). The average Newcastle-Ottawa score was six stars (range 4-8). Compared to those who reported low/no lifetime recreational pre-diagnosis physical activity, participants who reported high lifetime recreational pre-diagnosis physical activity levels had a significantly lower risk of all-cause (HR = 0.82, 95% CI 0.70-0.96, p < 0.05) and breast cancer-related death (HR = 0.73, 95% CI 0.54-0.98, p < 0.05). Significant risk reductions for all-cause and breast cancer-related death was also demonstrated for more recent pre-diagnosis recreational physical activity (HR = 0.73, 95% CI 0.65-0.82, p < 0.001; and HR = 0.84, 95% CI 0.73-0.97, p < 0.05, respectively), post-diagnosis physical activity (HR = 0.52, 95% CI 0.43-0.64, p < 0.01; and HR = 0.59, 95% CI 0.45-0.78, p < 0.05, respectively) and meeting recommended physical activity guidelines (i.e. ≥ 8 MET-h/wk) post-diagnosis (HR = 0.54, 95% CI 0.38-0.76, p < 0.01; and HR = 0.67, 95% CI 0.50-0.90, p < 0.01, respectively). However, there was evidence of heterogeneity across lifetime recreational pre- and post-diagnosis physical activity analyses. Both pre-diagnosis (lifetime and more recent combined) and post-diagnosis physical activity were also associated with reduced risk of breast cancer events (breast cancer progression, new primaries and recurrence combined) (HR = 0.72 95% CI 0.56-0.91, p < 0.01; and HR = 0.79, 95% CI 0.63-0.98, p < 0.05, respectively). Conclusion. There is an inverse relationship between physical activity and all-cause, breast cancer-related death and breast cancer events. The current meta-analysis supports the notion that appropriate physical activity may be an important intervention for reducing death and breast cancer events among breast cancer survivors. [ABSTRACT FROM AUTHOR]

Background and purpose - To retain or to sacrifice the posterior cruciate ligament (PCL) in total knee arthroplasty (TKA) remains a matter of discussion. In this systematic review, we wanted to find differences in functional and clinical outcome between the 2 methods. Methods - We conducted a systematic review and meta-analysis including all randomized controlled trials (RCTs) and quasi-RCTs that have compared PCL retention with PCL sacrifice in TKA with a minimum of 1-year follow-up. Primary outcome was range of motion. Secondary outcomes were knee pain and clinical scoring systems that were preferably validated. Quality of evidence was graded using the GRADE approach. All outcomes available for data pooling were used for meta-analysis. Results - 20 studies involving 1,877 patients and 2,347 knees were included. In meta-analysis, the postoperative flexion angle had a mean difference of 2 degrees (95% CI: 0.23-4.0; p = 0.03) and the KSS functional score was 2.4 points higher in favor of PCL sacrifice (95% CI: 0.41-4.3; p = 0.02). There were no statistically significant differences regarding other measured clinical outcomes such as WOMAC, KSS pain, clinical and overall score, HSS score, SF-12, radiolucencies, femoro-tibial angle, and tibial slope. The quality of the studies varied considerably. Risk of bias in most studies was unclear; 5 were judged to have a low risk of bias and 5 to have a high risk of bias. Interpretation - We found no clinically relevant differences between retention and sacrifice of the PCL in TKA, in terms of functional and clinical outcomes. The quality of the studies ranged from moderate to low. Based on the current evidence, no recommendation can be made as to whether to retain or to sacrifice the PCL. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC). Methods. A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated. Results. Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86). Conclusion. Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation. [ABSTRACT FROM AUTHOR]

Background. Stereotactic radiotherapy is a non-invasive, ablative technique which may be particularly effective in treating metastatic renal cell carcinoma (RCC). The study objective was to analyse outcomes and toxicity of stereotactic radiotherapy in metastatic RCC. Material and methods. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of Medline was performed in March 2013. Exclusion criteria included mixed histology studies and case series. Local control, overall survival and toxicities were analysed. Results. From 148 publications identified, 16 and 10 publications for cranial and extracranial metastatic RCC met inclusion criteria, respectively. There were 810 intracranial patients and 2433 targets. The weighted local control was 92%. Overall survival ranged from 6.7 to 25.6 months. Significant Grade 3-4 toxicity ranged from 0% to 6%. The weighted rate of treatment-related mortality was 0.6%, all secondary to intratumoral haemorrhage. There were 389 extracranial patients and 730 targets. The weighted local control was 89%. Median overall survival ranged from 11.7 to 22 months. Grade 3-4 toxicity ranged from 0% to 4%. Treatment-related mortality was 0.5%. Conclusion. Stereotactic radiotherapy is associated with excellent local control and low rates of toxicity for intracranial and extracranial metastatic RCC. Future randomised studies are required to confirm the additional benefit of Stereotactic Ablative Body Radiotherapy (SABR) above standard conservative or palliative approaches. [ABSTRACT FROM AUTHOR]

Background. Inhibitors of the mammalian target of rapamycin (mTOR) are currently approved for the treatment of several cancers, and their use is associated with serious rash, which affects patient's quality of life and leads to undesirable dose reductions or interruptions. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the overall risk of developing high-grade rash with mTOR inhibitors in cancer patients. Methods. We searched the PubMed database and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings up to December 2013 for relevant studies. Eligible studies included RCTs in which everolimus or temsirolimus was compared to controls in cancer patients. The summary incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included trials. Results. A total of 11 RCTs with 4752 patients (mTORs: 2725, controls: 2027) with a variety of solid tumors were included in the analysis. The incidences of all-grade (grade 1-4) and high-grade rash (grade 3-4) were 27.3% (95% CI 21.0-34.7%) and 1.0% (95% CI 0.6-1.4%), respectively. In comparison with controls, mTOR inhibitors significantly increased the risk for developing all-grade rash (RR = 3.55, 95% CI 3.0-4.20, p < 0.001) and high-grade rash (RR = 4.25, 95% CI 1.63-11.10, p = 0.003). The increased risk of high-grade rash did not vary significantly among different tumors (p = 0.91). There was no significant difference between everolimus and temsirolimus (p = 0.60). There was also no significant difference between mTOR inhibitors alone and in combination with other agents (p = 0.57). Conclusions. Everolimus and temsirolimus significantly increased the risk of high-grade rash in cancer patients. Early recognition and appropriate treatment is recommended. [ABSTRACT FROM AUTHOR]

Background. Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements in pre-operative staging, surgery, and pathological examination. The aim is to review the current risk of recurrence in stage II and III patients and second, to estimate the relative importance of routinely assessed clinico-pathological variables. Methods. The PubMed/MEDLINE and the Cochrane databases were systematically searched for randomized controlled studies and observational studies published after 1 January 2005 with patients included after January 1995 on prognosis in surgically treated stage II and III CC patients. Results. Of 2596 studies identified, 37 met the inclusion criteria and 25 provided data for meta-analysis. The total patient sample size in the 25 studies reporting either disease-free (DFS) or recurrence-free survival was 15 559 in stage II and 18 425 in stage III. Five-year DFS for stage II patients operated without subsequent adjuvant chemotherapy was 81.4% [95% confidence interval (CI) 75.4-87.4; in studies with good/very good quality of reporting 82.7%, (95% CI 80.8-84.6)]. For stage II patients treated with adjuvant chemotherapy, the five-year DFS was 79.3% (95% CI 75.6-83.1). For stage III patients without chemotherapy, five-year DFS was 49.0% (95% CI 23.2-74.8) and for those treated with adjuvant chemotherapy, 63.6% (95% CI 59.3-67.9). The prognostic impact of commonly investigated clinico-pathological parameters, (pT-stage, pN-stage, differentiation, number of lymph nodes studied, MMR-status, and emergency surgery) were confirmed. Conclusions. In this meta-analysis, studies with good quality of reporting show a five-year DFS of 82.7% for stage II CC without adjuvant chemotherapy, whereas the five-year DFS is 63.8% for stage III CC with adjuvant chemotherapy. Due to insufficient reporting on treatment quality the presented DFS is likely an under-estimation of what is achieved at high-quality centers today. [ABSTRACT FROM AUTHOR]

Background. Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism (VTE). We performed a meta-analysis of all randomized controlled trials (RCTs) which evaluated low molecular weight heparin (LMWH) as primary prophylaxis in ambulatory patients with solid malignancies. Methods. A comprehensive search was conducted until October 2013. Primary outcome was symptomatic VTE. Secondary outcomes were pulmonary embolism (PE), any VTE, deep vein thrombosis (DVT), mortality and adverse events. Results. Eleven trials met the inclusion criteria, and evaluated a total of 6942 patients. Primary prophylaxis with LMWH reduced symptomatic VTE (RR 0.46, 95% CI 0.32-0.67) and the rate of PE (RR 0.49, 95% CI 0.29-0.84). In the subgroup analysis of VTE in patients with lung and pancreatic cancers LMWH further reduced VTE [RR 0.42 (95% CI 0.25-0.71); RR 0.31 (95% CI 0.18-0.55), respectively]. Meta-analysis of six trials which reported survival outcomes revealed no statistically significant benefit for LMWH in one-year mortality rates (RR 0.93, 95% CI 0.83-1.04). There was no significant increase in major bleeding events (RR 1.28, 95% CI 0.84-1.95). Conclusions. LMWH reduces the incidence of symptomatic VTE and PE in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. The benefit is most apparent in pancreatic cancer and also lung cancer. VTE prophylaxis should be considered for these specific populations. [ABSTRACT FROM AUTHOR]

Background - Surgeon-dependent factors such as optimal implant alignment are thought to play a significant role in outcome following primary total knee arthroplasty (TKA). Exact definitions and references for optimal alignment are, however, still being debated. This overview of the literature describes different definitions of component alignment following primary TKA for (1) tibiofemoral alignment in the AP plane, (2) tibial and femoral component placement in the AP plane, (3) tibial and femoral component placement in the sagittal plane, and (4) rotational alignment of tibial and femoral components and their role in outcome and implant survival. Methods - We performed a literature search for original and review articles on implant positioning following primary TKA. Definitions for coronal, sagittal, and rotational placement of femoral and tibial components were summarized and the influence of positioning on survival and functional outcome was considered. Results - Many definitions exist when evaluating placement of femoral and tibial components. Implant alignment plays a role in both survival and functional outcome following primary TKA, as component malalignment can lead to increased failure rates, maltracking, and knee pain. Interpretation - Based on currently available evidence, surgeons should aim for optimal alignment of tibial and femoral components when performing TKA. [ABSTRACT FROM AUTHOR]

Background and purpose - Guidelines for standardization of radiostereometry (RSA) of implants were published in 2005 to facilitate comparison of outcomes between various research groups. In this systematic review, we determined how well studies have adhered to these guidelines. Methods - We carried out a literature search to identify all articles published between January 2000 and December 2011 that used RSA in the evaluation of hip or knee prosthesis migration. 2 investigators independently evaluated each of the studies for adherence to the 13 individual guideline items. Since some of the 13 points included more than 1 criterion, studies were assessed on whether each point was fully met, partially met, or not met. Results - 153 studies that met our inclusion criteria were identified. 61 of these were published before the guidelines were introduced (2000-2005) and 92 after the guidelines were introduced (2006-2011). The methodological quality of RSA studies clearly improved from 2000 to 2011. None of the studies fully met all 13 guidelines. Nearly half (43) of the studies published after the guidelines demonstrated a high methodological quality and adhered at least partially to 10 of the 13 guidelines, whereas less than one-fifth (11) of the studies published before the guidelines had the same methodological quality. Commonly unaddressed guideline items were related to imaging methodology, determination of precision from double examinations, and also mean error of rigid-body fitting and condition number cutoff levels. Interpretation - The guidelines have improved methodological reporting in RSA studies, but adherence to these guidelines is still relatively low. There is a need to update and clarify the guidelines for clinical hip and knee arthroplasty RSA studies. [ABSTRACT FROM AUTHOR]

Background and purpose- There is no consensus regarding the clinical relevance of gender-specific prostheses in total knee arthroplasty (TKA). We summarize the current best evidence in a comparison of clinical and radiographic outcomes between gender-specific prostheses and standard unisex prostheses in female patients. Methods- We used the PubMed, Embase, Cochrane, Science Citation Index, and Scopus databases. We included randomized controlled trials published up to January 2013 that compared gender-specific prostheses with standard unisex prostheses in female patients who underwent primary TKAs. Results- 6 trials involving 423 patients with 846 knee joints met the inclusion criteria. No statistically significant differences were observed between the 2 designs regarding pain, range of motion (ROM), knee scores, satisfaction, preference, complications, and radiographic results. The gender-specific design (Gender Solutions; Zimmer Inc, Warsaw, Indiana) reduced the prevalence of overhang. However, it had less overall coverage of the femoral condyles compared to the unisex group. In fact, the femoral prosthesis in the standard unisex group matched better than that in the gender-specific group. Interpretation- Gender-specific prostheses do not appear to confer any benefit in terms of clinician- and patient-reported outcomes for the female knee. [ABSTRACT FROM AUTHOR]

Background. In metastatic colorectal cancer, mutation testing for KRAS exon 2 is widely implemented to select patients with wild-type tumors for treatment with the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment. Methods. In total, 22 studies that include 2395 patients formed the basis for a meta-analysis on alterations in KRAS exons 3 and 4, NRAS, BRAF, and PIK3CA and PTEN and outcome of anti-EGFR treatment. Odds ratios for objective response rate (ORR) and hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated. Results. Mutations in KRAS exons 3 and 4, BRAF, PIK3CA and non-functional PTEN (mutations or loss of protein expression) significantly predicted poor ORR (OR = 0.26, OR = 0.29, OR = 0.39, and OR = 0.41, respectively). Significantly shorter PFS applied to mutations in KRAS exons 3 and 4 (HR = 2.19), NRAS (HR = 2.30) and BRAF (HR = 2.95) and non-functional PTEN (HR = 1.88). Significantly shorter OS applied to mutations in KRAS exons 3 and 4 (HR = 1.78), NRAS (HR = 1.85), BRAF (HR = 2.52), PIK3CA (HR = 1.43) and alterations in PTEN (HR = 2.09). Conclusions. Meta-analysis suggests that mutations in KRAS exons 3 and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Objectives. In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged ≤ 35 years. Methods. Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged ≤ 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified. Results. Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter. Conclusions. There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible. [ABSTRACT FROM AUTHOR]

Aim. The aim of this systematic review is to summarise all available data on the effect of a geriatric evaluation on the multidisciplinary treatment of older cancer patients, focussing on oncologic treatment decisions and the implementation of non-oncologic interventions. Methods. A systematic search in MEDLINE and EMBASE for studies on the effect of a geriatric evaluation on oncologic and non-oncologic treatment for older cancer patients. Results. Literature search identified 1654 reports (624 from Medline and 1030 from Embase), of which 10 studies were included in the review. Three studies used a geriatric consultation while seven used a geriatric assessment performed by a cancer specialist, healthcare worker or (research) nurse. Six studies addressed a change in oncologic treatment, the initial treatment plan was modified in a median of 39% of patients after geriatric evaluation, of which two thirds resulted in less intensive treatment. Seven studies focused on the implementation of non-oncologic interventions based on the results of the geriatric evaluation; all but one reported that interventions were suggested for over 70% of patients, even in studies that did not focus specifically on frail older patients. In the other study, implementation of non-oncologic interventions was left to the cancer specialist's discretion. Conclusion. A geriatric evaluation has significant impact on oncologic and non-oncologic treatment decisions in older cancer patients and deserves consideration in the oncologic work-up for these patients. [ABSTRACT FROM AUTHOR]

Background. It has long been recognized that some human breast cancers are hormone dependent. Preeclampsia is a syndrome of pregnancy defined by the onset of hypertension and proteinuria and characterized by dysfunction of the maternal endothelium. Many hormonal changes occur with preeclampsia, and we hypothesize that these changes may influence the risk of maternal breast cancer. We also analyzed the relation between pregnancy-induced hypertension (PIH) and maternal risk of breast cancer. Methods. Among 13 relevant publications about preeclampsia and six relevant publications about PIH, some studies find preeclampsia associated with a lower risk of breast cancer, but others did not. Therefore, these results are inconclusive. We conducted meta-analysis to evaluate more precisely the relationship between preeclampsia, PIH and maternal risk of breast cancer. Results. The pooled estimate of the hazard ratio (HR) associated with preeclampsia was 0.86 (95% CI 0.73-1.01), and that associated with PIH was 0.83 (0.66-1.06), both based on the random effects model. Conclusion. Some suggestive but not entirely consistent nor conclusive evidence was found on the association between the history of preeclampsia or PIH with the subsequent risk of breast cancer. [ABSTRACT FROM AUTHOR]

Purpose. The angiogenesis inhibitor pazopanib has been approved for the treatment of advanced renal cell cancer (RCC) and soft tissue sarcoma. Severe and fatal hepatotoxicity has been observed in its clinical studies. This analysis was conducted to determine the risk of liver toxicity by a systematic review and meta-analysis of clinical trials. Patients and methods. Databases from PubMed, Web of Science and abstracts presented at ASCO meetings up to January, 2012 were searched to identify relevant studies. Eligible studies included prospective trials of cancer patients treated with pazopanib starting at 800 mg daily. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. Results. A total of 1478 patients from 10 clinical trials were included. The incidences of all-grade aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin elevation were 39.6% (95% CI 31.2-48.6%), 41.4% (95% CI 34.1-49.0%), and 24.8% (95% CI 16.3-35.3%), respectively. The incidences of high-grade (Grade 3 and 4) AST, ALT and bilirubin elevation were 6.9% (95% CI 5.5-8.6%), 9.4% (95% CI 7.8-11.4%), and 3.4% (2.4-5.0%), respectively. In comparison with placebo, pazopanib significantly increased the risk of high-grade AST elevation (RR 6.56, 95% CI 2.04-21.07, p = 0.002) and ALT elevation (RR 4.33, 95% CI 1.88-10.0, p = 0.001). However, the risks of high-grade bilirubin elevation (RR 1.31, 95% CI 0.47-3.64) and fatal hepatotoxicity (RR 2.51, 95% CI 0.12-51.91, p = 0.55) were not significantly elevated. Conclusion. The use of pazopanib was associated with a significantly increased risk of severe non-fatal hepatotoxicity in cancer patients. [ABSTRACT FROM AUTHOR]

Background. The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design. A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85-1.04, p-value = 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72-1.06, p-value = 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93-1.07, p-value = 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion. Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose There is no consensus on the difference in effects of internal fixation (IF) and external fixation (EF) on outcomes for the treatment of distal radius fractures. We performed a meta-analysis of randomized clinical studies. Methods We searched the literature and included studies that compared the effects of IF and EF on the treatment of distal radius fractures. Statistically, we pooled patient data using standard meta-analytic methods. For the continuous variables, the weighted mean difference (WMD) was used. For dichotomous data, the relative risk (RR) was calculated. Results 10 studies were eligible for data extraction. The pooled data showed that compared with EF, IF led to statistically significantly better Disabilities of the Arm, Shoulder, and Hand (DASH) scores at 12 months postoperatively, recovery of forearm supination at 3 months, and restoration of volar tilt and radial inclination. IF using volar locking plates resulted in better DASH scores than EF at 3 and 6 months, but the trend diminished over time; at 12 months postoperatively, the scores were not statistically significant. Compared with EF, IF led to fewer minor surgical complications. Interpretation For surgical treatment of distal radius fractures, IF yields better functional outcomes, forearm supination, restoration of anatomic volar tilt and radial inclination, and fewer minor complications. The patients who received IF using volar locking plates for the treatment of distal radius recovered more quickly than did patients who received EF. [ABSTRACT FROM AUTHOR]

Background. Patient-reported outcomes (PROs) and assessments of treatment-related toxicity provide important information on the effect of palliative chemotherapy and/or radiotherapy. The aim of this study was to review the effect of palliative radiotherapy and/or chemotherapy on symptoms and quality of life assessed by PROs and measurement of toxicity for patients with oesophageal cancer. Methods. The Central, Medline and Embase databases (1990 to November 2011) were systematically searched for prospective studies of palliative chemotherapy and/or radiotherapy in patients with advanced oesophageal cancer with PRO- and/or toxicity outcomes. The risks of bias were assessed. Results. Of 2677 records identified, only 32 included PROs, of which eight were randomised controlled trials. In studies with sufficient standard of PRO (n = 18), either Health Related Quality of Life (HRQL) (n = 14) or patient-reported dysphagia (n = 4), were assessed. Docetaxel added to cisplatin + fluorouracil (CF) improved HRQL compared to CF only, even though toxicity increased. Epirubicin added to CF resulted in longer preserved HRQL than its comparator in two trials, and non-inferiority in one. All phase II chemotherapy studies reported maintained HRQL or improved dysphagia combined with low level of toxicity. Brachytherapy resulted in better HRQL compared to stent placement in two trials, and external radiotherapy relieved dysphagia. The quality of the HRQL methodology and the interpretation and presentation of the PRO results varied, and clinical significance was seldom discussed. Conclusion. PRO endpoints are seldom used and further studies of homogenous patient groups with valid measures and methodology of PROs should be encouraged in the evaluation of palliative treatment. Brachytherapy, external radiotherapy and combination chemotherapy improved HRQL and dysphagia in the few identified studies with sufficient PRO methodology. [ABSTRACT FROM AUTHOR]

Background. The multitargeted tyrosine kinase inhibitor sunitinib is used in various cancers. Clinical studies have reported a substantial variation in the incidence of hypothyroidism associated with sunitinib, without a systemic attempt to synthesize these data. Methods. We searched Medline databases for relevant clinical trials published up to May 2012. Phase II and III trials and expanded access programs of sunitinib in patients with any type of cancer that reported occurrence of hypothyroidism were eligible. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results. Incidence analysis was performed using 6678 sunitinib-treated patients from all 24 eligible trials. The incidence of all- and high-grade hypothyroidism was 9.8% (95% CI 7.3-12.4%) and 0.4% (95% CI 0.3-0.5%), respectively. A meta-analysis of seven randomized trials with 2787 subjects revealed a RR of all- and high-grade hypothyroidism of 13.95 (95% CI 6.91-28.15; p < 0.00001) and 4.78 (95% CI 1.09-20.84; p = 0.04), respectively. Subgroup analysis revealed a significantly higher incidence of all-grade hypothyroidism in patients receiving sunitinib for longer duration than in patients receiving sunitinib for shorter duration (p = 0.02). Conclusions. This meta-analysis of data available from clinical trials demonstrates that sunitinib is associated with a significant risk of developing all- and high-grade hypothyroidism. These data provide further evidence to recommend monitoring for hypothyroidism in patients receiving sunitinib. [ABSTRACT FROM AUTHOR]

The article discusses the decision making process which is used by medical professionals in the surgical treatment of chronic low back pain. A discussion of research which investigated the side effects of lumbar spinal fusion and the performance of prognostic tests used to select patients with low back pain who could be eligible for lumbar spinal fusion is presented.

Significant progress has been made in the field of exercise-oncology research over the past two decades. As the field continues to forge ahead, it is time to reflect on past accomplishments in order to inform and define the critical unanswered questions postulated to have the largest impact on the field and on clinical care. Against this background, we overview the extant literature base together with ongoing/planned studies examining the role of exercise therapy following a cancer diagnosis with a view towards identifying major gaps in the knowledge. Method. We adapted the Physical Exercise Across the Cancer Experience (PEACE) organizational framework to systematically overview published as well as ongoing studies of exercise therapy across the cancer survivorship continuum [i.e. 1) pretreatment; 2) during treatment; and 3) post-treatment]. To overview ongoing studies, we performed a systematic review of all exercise trials in adult cancer patients registered in Clinical Trials.Gov and the International Standard Randomized Controlled Trial Number Register. Results. Data from published studies provides relatively strong evidence that exercise therapy is a well-tolerated and safe adjunct therapy that can mitigate several common treatment-related side effects among cancer patients across the PEACE framework. In addition, observational studies suggest that higher levels of exercise may be associated with improved prognosis in patients with solid tumors. Regarding ongoing studies, a total of 82 independent clinical studies were identified. Consistent with prior work, most ongoing studies are being conducted either during or following adjuvant therapy in women with breast cancer with exercise interventions following standard exercise prescription guidelines. Across all studies, there were a total of approximately 51 different primary endpoints; in two-thirds of studies, quality of life, fatigue, or physical functioning was the primary endpoint. Conclusion. There have been significant leaps in knowledge regarding the role and efficacy of exercise therapy in cancer survivors over the past 25 years. On the platform of this evidence base, it is now time to launch the next generation of research to ensure continued progress in this emergent field. This work will continue to contribute to the ultimate goal of improving both the quantity and quality of life of persons diagnosed with cancer. [ABSTRACT FROM AUTHOR]

Background: Current guidelines are inconclusive regarding intravenous (IV) iron for treatment of chemotherapy-induced anaemia (CIA). Material and methods: Systematic review and meta-analysis of randomised controlled trials comparing IV iron with no iron or oral iron for treatment of chemotherapy induced anaemia (CIA). Primary outcomes: haematopoietic response and red blood cell (RBC) transfusion requirements. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences were calculated. Results: Eleven trials included 1681 patients, the majority examining the addition of IV iron to erythropoiesis stimulating agents (ESA) (1562 patients, 92.9%). IV iron significantly increased haematopoietic response rate [RR 1.28 (95% CI 1.125-1.45), seven trials with ESA] and decreased the rate of blood transfusions both in trials with ESA [RR 0.76 (95% CI 0.61-0.95), seven trials] and without ESA [RR 0.52 (95% CI 0.34-0.80)]. The increase in haematopoietic response rate correlated with total IV iron dose, regardless of baseline iron status. Mortality and safety profile was comparable between groups. Conclusions: IV iron added to ESA results in an increase in haematopoietic response and reduction in the need for RBC transfusions, with no difference in mortality or adverse events. [ABSTRACT FROM AUTHOR]

Background. There are no established treatments for cachexia. Recently it has been suggested that the evidence for non-steroidal anti-inflammatory (NSAID) treatment is sufficient to support its regular clinical use. Primary objective in this systematic review was to assess efficacy and safety of NSAID treatment in improving body weight and muscle mass in patients with cancer cachexia. Secondary objectives were to assess whether this treatment could improve other cachexia domains such as anorexia and food intake, catabolic drive and function. Material and methods. A systematic literature review of PubMed, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Results. Thirteen studies were included; all but two trials showed either improvement or stabilization in weight or lean body mass. Seven studies were without a comparator. Studies are generally small and a few are methodologically flawed, often due to multiple outcomes with excess risk of false positives. Conclusion. NSAIDs may improve weight in cancer patients with cachexia, and there is some evidence on effect on physical performance, self-reported quality of life and inflammatory parameters. Evidence is too frail to recommend NSAID for cachexia outside clinical trials. This is supported by the known side effects of NSAIDs, even though the reviewed literature report almost negligible toxicity. [ABSTRACT FROM AUTHOR]

Background. Dyspnea is commonly encountered by many cancer patients in the terminal stage of their disease and it severely hampers their quality of life. We aimed to evaluate the role of interventions to alleviate dyspnea. Methods. Systematic review and meta-analysis of randomized controlled trials assessing all interventions for dyspnea palliation in cancer patients, and searched the Cochrane Library, MEDLINE, conference proceedings, and references. Results. Our search yielded 18 trials. Eight studies evaluated opioids in any route of administration, seven studies evaluated the use of oxygen, two studies assessed the role of benzodiazepines and two studies evaluated the role of furosemide in alleviating cancer-related dyspnea. Weighted mean difference (WMD) was calculated for continuous variables that were reported on the same scale. For continuous data reported in different scales, standardized mean difference (SMD) was calculated. Meta-analysis of three trials yielded a positive effect for opioid administration, WMD −1.31[95% CI (−2.49)-(− 0.13)]. Meta-analysis of the six studies showed lack of benefit to oxygen to improve dyspnea, SMD −0.3[95% CI −1.06-0.47]. The role of benzodiazepines remains unclear, furosemide was not beneficial. Conclusions. Our systematic review and meta-analysis demonstrate a beneficial effect to opioids in alleviating cancer-related dyspnea, and no advantage for the use of oxygen. [ABSTRACT FROM AUTHOR]

Background. mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials. Material and methods. PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. Results. A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. Conclusions. The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors. [ABSTRACT FROM AUTHOR]

Background. In this modern era of multi-modality treatment there is increasing interest in the possibility of avoiding radical surgery in complete responders after neo-adjuvant long-course chemoradiotherapy (LCPRT). In this article, we present a systematic review of such treatments and discuss their therapeutic applicability for the future. Methods. We searched the PubMed online libraries to identify studies that reported on the long-term surgical and pathological outcomes after local excision together with those that explored the possibility of clinical observation only in patients achieving a complete clinical response after LCPRT. Results. Several retrospective (n == 10), one single-arm prospective, and one small randomised series have reported on the use of local excision after LCPRT and demonstrated acceptably low levels of local recurrence with survival comparable to patients progressing to conventional surgery. One prospective series allocated patients to observation or radical surgery based on histological parameters after local excision (ypT0 and ypT1) and showed no differences in outcomes. Two retrospective series from the same group on a Brazilian cohort of patients reported excellent long-term outcomes after 'wait and watch' in complete clinical responders. However, other reports have shown no direct correlation between clinical and pathological response. Conclusion. Local excision may be an appropriate option for selected patients developing good clinical response after LCPRT. In our opinion, a policy of clinical observation in complete clinical responders after LCPRT may not be a safe strategy, unless we had robust predictive models for accurate identification of pathological complete response. In order to identify patients that may be potentially appropriate for such an approach we propose a clinical algorithm incorporating important clinical, radiological, and pathological parameters. The proposed model will require validation in a prospective study. Finally, we need randomised data for demonstrating the non-inferiority of clinical observation compared to conventional surgery before this can be considered as standard possible therapeutic option. [ABSTRACT FROM AUTHOR]