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Given the potentially fatal consequences of inadequate adherence with oral anticancer treatment in persons with cancer, understanding the determinants of adherence is vital. This paper aims at identifying psychosocial determinants of adherence to oral anticancer treatment. We reviewed the literature on psychosocial determinants of adherence with oral anticancer treatment, based on published literature in English, from 2015 to present. Literature searches were performed in PubMed, Embase, Web of Science, Cochrane library, Emcare, and PsychINFO, with 'cancer', 'medication adherence', 'psychology', and 'oral anticancer treatment' as search terms. The obtained 608 papers were screened by two independent reviewers. In the 25 studies identified, illness perceptions, medication beliefs, health beliefs, and depression were found to be the major psychosocial determinants of adherence to oral anticancer treatment; sociodemographic and clinical characteristics were found to be of no major importance. The quality of the identified studies as assessed by two independent reviewers was found to be acceptable overall. The majority of papers were from North America and focused on patients with breast cancer; sample size varied from 13 to 1371; adherence was assessed with questionnaires derived from various theoretical models, pill counts and electronic pharmacy records; illness perceptions reflecting adaptive coping, and medication beliefs reflecting high necessity and low concerns were found to be associated with adherence. Psychosocial concepts are major determinants of adherence with oral anticancer treatment. 'Beliefs about medicines' and 'illness perceptions' in particular determine adherence with this treatment. Studies aiming at impacting adherence would benefit from interventions with a solid basis in behavioral theory in order to help health care providers explore and address illness perceptions and medication beliefs. Pre-consultation screening of adherence behavior may be a helpful supportive approach to improve adherence. Blaming the victim ('patients should be educated about the importance of adherence') is better replaced by encouraging health professionals to identify and address maladaptive psychosocial determinants of adherence. [ABSTRACT FROM AUTHOR]

Background. Evidence for the safety and benefits of exercise training as a therapeutic and rehabilitative intervention for cancer survivors is accumulating. However, whereas the evidence for the efficacy of exercise training has been established in several meta-analyses, synthesis of qualitative research is lacking. In order to extend healthcare professionals' understanding of the meaningfulness of exercise in cancer survivorship care, this paper aims to identify, appraise and synthesize qualitative studies on cancer survivors' experience of participation in exercise-based rehabilitation. Material and methods. Five electronic databases (PubMed, PsychINFO, EMBASE, Cinahl and Scopus) were searched systematically for articles published up to May 2014 using keywords and MeSH terms. To be included, studies had to contain primary data pertaining to patient experiences from participation in supervised, structured moderate to vigorous-intensity exercise. Results. In total 2447 abstracts were screened and 37 papers were read in full. Of these, 19 studies (n = 390) were selected for inclusion and critically appraised. Synthesis of data extracted from eight studies including in total 174 patients (77% women, age 28-76 years) exclusively reporting experiences of participation in structured, supervised exercise training resulted in nine themes condensed into three categories: 1) emergence of continuity; 2) preservation of health; and 3) reclaiming the body reflecting the benefits of exercise-based rehabilitation according to cancer survivors. Accordingly, the potential of rebuilding structure in everyday life, creating a normal context and enabling the individual to re-establish confidentiality and trust in their own body and physical potential constitute substantial qualities fundamental to the understanding of the meaningfulness of exercise-based rehabilitation from the perspective of patients. Conclusions. In addition to the accumulating evidence for the efficacy of exercise training in cancer rehabilitation, it is incumbent upon clinicians and policy-makers to acknowledge and promote the meaningfulness of exercise for the individual, and to use this knowledge to provide new solutions to current problems related to recruitment of underserved populations, long-term adherence and implementation. [ABSTRACT FROM AUTHOR]

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: Cancer-related cognitive impairment (CRCI) is a commonly reported complaint among non-CNS cancer patients. Even subtle CRCI may have detrimental effects on quality of life and identifying patients at increased risk for CRCI to improve survivorship care is important. In the present paper, we systematically reviewed available studies of possible genetic risk factors for developing CRCI. Methods: Keyword-based systematic searches were undertaken on 24 July 2018 in PubMed, Web of Science, The Cochrane Library, and CINAHL. Three authors independently evaluated full-texts of identified papers and excluded studies with registration of reasons. Seventeen studies reporting results from 14 independent samples were included for review. Two authors independently quality assessed the included studies. The review was preregistered with PROSPERO (CRD42018107689). Results: Ten studies investigated apolipoprotein E (APOE), with four studies reporting that carrying at least one risk allele (APOE4 (ε4)) was associated with CRCI, while six studies found no association. The remaining identified genetic risk variants associated with CRCI located in: COMT, four DNA repair genes, five oxidative stress genes, 22 genes related to breast cancer phenotype, and GNB3. No associations were found between CRCI and genes coding for interleukin-6 (IL6), tumor necrosis factor alpha (TNF), interleukin 1 beta (IL1B), and brain-derived neurotropic factor (BDNF). With the exception of APOE, the genetic risk factors had only been investigated in one or two studies each. Conclusions: Overall, the available evidence of possible genetic risk factors for CRCI is limited. While some research suggests a role for the ε4 allele, the literature is generally inconsistent, and the currently available evidence does not allow clear-cut conclusions regarding the role of genetic factors in the development of CRCI. Larger genetic studies and studies investigating additional genetic variants are needed to uncover genetic risk factors for CRCI. [ABSTRACT FROM AUTHOR]

Introdution: Variation in shape, position and treatment response of both tumor and organs at risk are major challenges for accurate dose delivery in radiotherapy. Adaptive radiotherapy (ART) has been proposed to customize the treatment to these motion/response patterns of the individual patients, but increases workload and thereby challenges clinical implementation. This paper reviews strategies and workflows for clinical and in silico implemented ART for prostate, bladder, gynecological (gyne) and ano-rectal cancers.Material and methods: Initial identification of papers was based on searches in PubMed. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review.Results: The review consisted of 43 clinical studies and 51 in silico studies. For prostate, 1219 patients were treated with offline re-planning, mainly to adapt prostate motion relative to bony anatomy. For gyne 1155 patients were treated with online brachytherapy re-planning while 25 ano-rectal cancer patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape variations. The studies reported sparing of rectum (prostate and bladder cancer), bladder (ano-rectal cancer) and bowel cavity (gyne and bladder cancer) as compared to non-ART.Conclusion: Implementations of ART were dominated by offline re-planning and online brachytherapy re-planning strategies, although recently online plan selection workflows have increased with the availability of cone-beam CT. Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review. Despite this, clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows. [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 and purpose — Adequate staging of chondroid tumors at diagnosis is important as it determines both treatment and outcome. This systematic review provides an overview of MRI criteria used to differentiate between atypical cartilaginous tumors (ACT) and high-grade chondrosarcoma (HGCS). Patients and methods — For this systematic review PubMed and Embase were searched, from inception of the databases to July 12, 2018. All original articles describing MRI characteristics of pathologically proven primary central chondrosarcoma and ACT were included. A quality appraisal of the included papers was performed. Data on MRI characteristics and histological grade were extracted by 2 reviewers. Meta-analysis was performed if possible. The study is registered with PROSPERO, CRD42018067959. Results — Our search identified 2,132 unique records, of which 14 studies were included. 239 ACT and 140 HGCS were identified. The quality assessment showed great variability in consensus criteria used for both pathologic and radiologic diagnosis. Due to substantial heterogeneity we refrained from pooling the results in a meta-analysis and reported non-statistical syntheses. Loss of entrapped fatty marrow, cortical breakthrough, and extraosseous soft tissue expansion appeared to be present more often in HGCS compared with ACT. Interpretation — This systematic review provides an overview of MRI characteristics used to differentiate between ACT and HGCS. Future studies are needed to develop and assess more reliable imaging methods and/or features to differentiate ACT from HGCS. [ABSTRACT FROM AUTHOR]

Background: The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. Patients and methods: The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS6m) and mean OS time restricted to one year (OS1y). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Results: Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS6m was 2.9 months (95% CI 2.6 to 3.1 months) and OS1y was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS1y is inferior to both the phase II trial and TERRA. Conclusion: This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA. [ABSTRACT FROM AUTHOR]

Background: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments. Methods: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous. Conclusions: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings. [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:The introduction of adjuvant chemotherapy following surgery for early breast cancer (BC) and its integration into routine clinical practice has consistently improved clinical outcomes. Since the addition of other agents to the contemporary standard of care containing an anthracycline, cyclophosphamide and a taxane has not lead to further prolongation of survival, subsequent efforts concentrated on escalating the administered doses and reducing the time interval between chemotherapy cycles. These strategies have been extensively evaluated in randomized trials and dose dense chemotherapy is now recommended by clinical practice guidelines. Method:Eligible trials were identified by searching the EMBASE, Pubmed, Scopus and Cochrane Library databases, as well as conference papers. The findings, shortcomings and impact of these studies are presented and critically discussed. Results:Although a large number of randomized trials has established the value of adjuvant chemotherapy, important questions remain unanswered. Ongoing research focuses on omitting treatment in good risk patients, identifying patients most likely to benefit from a dose dense approach and on administering personalized doses such as in tailored dose chemotherapy. Conclusions:Adjuvant chemotherapy for early BC is an evolving art. Further optimizations could potentially improve outcomes for a patient subset and spare others from unnecessary treatment-related toxicity. [ABSTRACT FROM PUBLISHER]

BackgroundTreatment of cancer with chemotherapy decreases endurance capacity and muscle strength. Training during chemotherapy might prevent this. There are no clear guidelines concerning which type of training and which training dose are effective. This review aims to gain insight into the different training modalities during chemotherapy and the effects of such training to improve endurance capacity and muscle strength in order to obtain the knowledge to compose a future training program which trains cancer patients in the most effective way.Material and methodsA systematic search of PubMed was carried out. In total, 809 studies of randomized controlled trials studying the effects of training during chemotherapy on endurance capacity and muscle strength were considered. Only 14 studies met all the inclusion criteria. The studies were assessed on methodological quality by using Cochrane criteria for randomized controlled trials.ResultsThe quality of the studies was generally poor and the study populations varied considerably as the training programs were very heterogeneous. Variables of endurance capacity reported beneficial effects in 10 groups (59%). Increases due to training ranged from 8% to 31%. Endurance capacity decreased in nine of 13 control groups (69%), which ranged from 1% to 32%. Muscle strength improved significantly in 17 of 18 intervention groups (94%), ranging from 2% to 38%. Muscle strength also improved in 11 of 14 control groups (79%), but this increase was only minimal, ranging from 1.3% to 6.5%.ConclusionsThis review indicates that training during chemotherapy may help in preventing the decrease in muscle strength and endurance capacity. It is important to know which training intensity and duration is the most effective in training cancer patients, to provide a training program suitable for every cancer patient. Training should be based on good research and should be implemented into international guidelines and daily practice. More research is needed. [ABSTRACT FROM PUBLISHER]

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]

Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML. Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment. Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25–2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75–2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53–2.90]), bosutinib (1.41 [1.07–1.86]), and radotinib (1.87 [1.33–2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) patients' anatomy may undergo significant changes during radiotherapy (RT). This potentially affects dose distribution and compromises conformity between planned and delivered dose. Adaptive radiotherapy (ART) is a promising technique to overcome this problem but requires a significant workload. This systematic review aims to estimate the clinical and dosimetric benefits of ART using prospective data. A search on PubMed and Web of Science according to the PRISMA guidelines was made on Feb 6, 2023. Search string used was: 'adaptive radiotherapy head neck cancer'. English language filter was applied. All studies were screened for inclusion on title and abstract, and the full text was read and discussed in the research group in case of uncertainty. Inclusion criteria were a prospective ART strategy for HNC investigating clinical or dosimetric outcomes. A total of 1251 articles were identified of which 15 met inclusion criteria. All included studies were published between 2010 and 2023 with a substantial diversity in design, endpoints, and nomenclature. The number of patients treated with ART was small with a median of 20 patients per study (range 4 to 86), undergoing 1-2 replannings. Mean dose to the parotid glands was reduced by 0.4-7.1 Gy. Maximum dose to the spinal cord was reduced by 0.5-4.6 Gy. Only five studies reported clinical outcome and disease control was excellent. Data on toxicity were ambiguous with some studies indicating reduced acute toxicity and xerostomia, while others found reduced quality of life in patients treated with ART. The literature on clinical ART in HNC is limited. ART is associated with small reductions in doses to organs at risk, but the influence on toxicity and disease control is uncertain. There is a clear need for larger, prospective trials with a well-defined control group. [ABSTRACT FROM AUTHOR]

Cancer treatment frequently results in chemotherapy-induced peripheral neuropathy (CIPN), which is a side effect that is now neither properly preventable nor treatable. Physical therapy has been studied in this patient population and is frequently utilised for neurological rehabilitation after damage. This study set out to thoroughly review randomised controlled trials (RCTs) examining the efficacy of physical therapy for patients with chemotherapy-induced peripheral neuropathy. From their beginning in January 2017 to January 2023, EMBASE, PubMed, Medline, PEDro, and the Cochrane Library were searched for pertinent RCTs. Additionally, manual search techniques were applied. On the basis of the inclusion criteria, two reviewers independently determined the study's eligibility. Reviewers evaluated the quality of the studies and took note of their methodologies, designs, interventions, outcomes, and conclusions. Ten RCTs met all inclusion criteria. Overall results are constrained by the variety of interventions and the small sample sizes of the included studies, which also indicate the need for more studies. Physical therapy has additional benefits for enhancing the quality of life of patients with peripheral neuropathy brought on by chemotherapy. [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]

Electrochemotherapy (ECT) is an established treatment for primary and secondary cutaneous tumours. The method combines chemotherapy with electroporation, thus increasing the cytotoxic effect of the chemotherapeutic drug. Bleomycin is the drug of choice for ECT, as it is already well established as a treatment for several cancer types and has the largest increase in efficacy after electroporation, enhancing the cytotoxic effect several hundred fold. The response rates of ECT have over the past 30 years been high and consistent. Case based reports point out that the efficacy possibly can be maintained even when the dose of bleomycin is reduced. Consequently in 2018, studies began investigating reducing the bleomycin dose. The purpose of this review is to summarise all data published using intravenous bleomycin for cutaneous malignancies and is to our knowledge the first review to examine the use of a reduced bleomycin dose in ECT. This study is a systematic review. Fifty-five clinical studies investigating ECT with intravenous bleomycin for patients with cutaneous malignancies were included. Studies published from 1993 to 2021 investigating the effect of ECT include 3729 patients and indicate a consistent and high response with a mean objective response rate (ORR) of 81.5%. Interestingly, studies using lower doses of bleomycin observe a similar ORR (85.5%), opening the possibility that a lower dose may not be inferior. This study gives an overview of published studies on ECT with intravenous bleomycin for patients with cutaneous malignancies, including the use of a reduced bleomycin dose, as preparation for a randomised study. [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 and purpose The validity of various data sources for the assessment of the outcome quality of medical devices was investigated by comparative analysis of the published data sources available for a sample of implants. It was the aim of the study to determine the performance of this implant and to identify potential bias factors inherent to the various datasets. Methods A comprehensive literature search was carried out from English-language, peer-reviewed journals and worldwide reports from national arthroplasty registers. Publications from Medline-listed journals were included. The main parameter was revision rate, calculated as ''revisions per 100 observed component years'' to allow adjusted direct comparison of different datasets. Results Of 16 clinical studies that met the inclusion criteria, 9 originated from the implant developer's hospital. In the clinical studies category, publications from the developer's hospital suggested considerably lower revision rates than the other datasets. In fact, the values quoted were 5.5 times below the average of all other studies, and 9.51 times lower than in the Australian arthroplasty register. These differences are statistically significant. Interpretation The cementless Taperloc stem is an implant that shows good performance regarding revision rates in registry data and in clinical studies. However, the excellent results published by the developer's clinic are generally not reproducible by other surgeons. In terms of reference data, registry data are able to make an important contribution to the assessment of clinical sample-based studies, particularly regarding evaluation of the extent to which published results are reproducible in daily routine. [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]

Cancer-related fatigue is one of the most prevalent and distressing symptoms among cancer patients, resulting in a great cancer research challenge. Numerous systematic reviews of physical training interventions have been conducted to find the most effective approach. However, evidence remains fragmented, and in which cancer population physical training is more effective than other populations is still unclear. Thus, this study critically appraised systematic reviews and meta-analyses on physical training to reduce adults' cancer-related fatigue. A systematic review of systematic reviews and meta-analysis (PROSPERO: CRD42020189049), assessing the efficacy of exercise training for reducing cancer-related fatigue in adults, was conducted in PubMed, CINAHL, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects, and Pedro. The selected studies (standardized mean difference, SMD; 95%CI), was quantitatively pooled using a random-effects model. Heterogeneity was tested using chi-squared (Q) and I-square statistics (I2). Of 1438 identified articles, 11 met the inclusion criteria, and ten were meta-analyzed. The results yielded a positive effect of physical training on fatigue in all cancer populations, SMD = −0.33 (−0.43, −0.23). Subgroup analysis based on tumor localization showed a slightly higher physical training effect on fatigue in adults with breast cancer, SMD = −0.36 (−0.57, −0.15), and prostate cancer SMD = −0.34 (−0.45, −.0.22). Our analysis demonstrated some potential improvement in cancer-related fatigue in adult patients undergoing physical training during and after cancer treatments, particularly in patients with breast or prostate cancer. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is an established prognostic marker in oropharyngeal squamous cell carcinoma. Currently, the role of HPV in sinonasal carcinoma is being explored. This systematic review addresses the role of HPV in sinonasal cancer, establishing the occurrence of HPV-positive cancers and the influence of HPV-positivity on prognosis in sinonasal cancer as well as the utility of the putative surrogate marker of HPV (p16) in sinonasal cancer. Studies were identified with searches of Medline via PubMed and Embase via OVID (4 May 2020). Articles on original research concerning sinonasal cancer and HPV in humans written in English were included. Case reports with less than five cases were excluded. Initially, 545 articles were identified; 190 duplicate articles were removed leaving 355 articles for title/abstract screening. Title/abstract screening excluded 243 articles, leaving 112 studies assessed for eligibility. After full-text screening, 57 studies were included. All articles investigated the significance of HPV in sinonasal carcinomas. HPV was reported in approximately 30% of sinonasal squamous cell carcinoma (SNSCC), where it was associated with a better prognosis. In sinonasal cancer, p16 is associated with diagnostic pitfalls and a putative utility of p16 in SNSCC has yet to be established. HPV was not frequently reported in other types of sinonasal carcinomas, besides the recently described subtype, HPV-dependent Multiphenotypic Sinonasal Carcinoma. In other types of sinonasal carcinoma, HPV is not frequently found. Approximately 30% of SNSCC are HPV-positive. HPV-positivity in SNSCC is associated with improved survival. HPV occurs only rarely in other sinonasal cancers. There is currently not sufficient evidence for p16 as a surrogate marker of HPV in SNSCC. [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]

Background and purpose — In recent years motorized intramedullary lengthening nails have become increasingly popular. Complications are heterogeneously reported in small case series and therefore we made a systematic review of complications occurring in lower limb lengthening with externally controlled motorized intramedullary bone lengthening nails. Methods — We performed a systematic search in PubMed, EMBASE, and the Cochrane Library with medical subject headings: Bone Nails, Bone Lengthening, and PRECICE and FITBONE nails. Complications were graded on severity and origin. Results — The search identified 952 articles; 116 were full text screened, and 41 were included in the final analysis. 983 segments were lengthened in 782 patients (age 8–74 years). The distribution of nails was: 214 FITBONE, 747 PRECICE, 22 either FITBONE or PRECICE. Indications for lengthening were: 208 congenital shortening, 305 acquired limb shortening, 111 short stature, 158 with unidentified etiology. We identified 332 complications (34% of segments): Type I (minimal intervention) in 11% of segments; Type II (substantial change in treatment plan) in 15% of segments; Type IIIA (failure to achieve goal) in 5% of segments; and Type IIIB (new pathology or permanent sequelae) in 3% of segments. Device and bone complications were the most frequent. Interpretation — The overall risk of complications was 1 complication for every 3 segments lengthened. In 1 of every 4 segments, complications had a major impact leading to substantial change in treatment, failure to achieve lengthening goal, introduction of a new pathology, or permanent sequelae. However, as no standardized reporting method for complications exists, the true complication rates might be different. [ABSTRACT FROM AUTHOR]

Rehabilitation and palliative care may play an important role in addressing the problems and needs perceived by socioeconomically disadvantaged patients with advanced cancer. However, no study has synthesized existing research on rehabilitation and palliative care for socioeconomically disadvantaged patients with advanced cancer. The study aimed to map existing research of rehabilitation and palliative care for patients with advanced cancer who are socioeconomically disadvantaged. A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A systematic literature search was performed in CINAHL, PubMed and EMBASE. Two reviewers independently assessed abstracts and full-text articles for eligibility and performed data extraction. Both qualitative and quantitative studies published between 2010 and 2019 were included if they addressed rehabilitation or palliative care for socioeconomically disadvantaged (adults ≥18 years) patients with advanced cancer. Socioeconomic disadvantage is defined by socioeconomic position (income, educational level and occupational status). In total, 11 studies were included in this scoping review (138,152 patients and 45 healthcare providers) of which 10 were quantitative studies and 1 was a qualitative study. All included studies investigated the use of and preferences for palliative care, and none focused on rehabilitation. Two studies explored health professionals' perspectives on the delivery of palliative care. Existing research within this research field is sparse. Future research should focus more on how best to reach and support socioeconomically disadvantaged people with advanced cancer in community-based rehabilitation and palliative care. [ABSTRACT FROM AUTHOR]

To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs). We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach. We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59–3.66, p <.001; WMD in RMPFST6: −1.01, 95% CI: −1.65 to −0.37, p =.002; WMD in RMPFST12: −2.64, 95% CI: −4.40 to −0.88, p =.003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, p =.069; WMD in RMPFST6: −1.23 vs −0.07, p =.005; WMD in RMPFST12: −3.29 vs −0.12, p =.003). The quality of summarized evidence was judged to be low. There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs. [ABSTRACT FROM AUTHOR]

Radiotherapy is an emerging treatment strategy for nodal oligorecurrent prostate cancer (PCa) patients. However, large heterogeneities exist in the RT regimens used, with series reporting the use of elective nodal radiotherapy (ENRT) strategies and others the delivery of focal treatments to the relapsing nodes with Stereotactic Body Radiotherapy (SBRT). In this systematic review of the literature we compared the oncological outcomes and toxicity of the different RT regimens for nodal oligorecurrent PCa patients, with the aim of defining the optimal RT target volume in this setting. We performed a systemic search on the Pubmed database to identify articles reporting on the use of ENRT or SBRT for oligometastatic PCa with nodal recurrence. Twenty-two articles were analyzed, including four prospective phase II trials (3 with SBRT and 1 with ENRT). Focal SBRT, delivered with an involved node, involved site, and involved field modality, was the most commonly used strategy with 2-year progression-free survival (PFS) rates ranging from 16 to 58% and a very low toxicity profile. Improved PFS rates were observed with ENRT strategies (52–80% at 3 years) compared to focal SBRT, despite a slightly higher toxicity rate. One ongoing randomized phase II trial is comparing both modalities in patients with nodal oligorecurrent PCa. With a large variability in patterns of practice, the optimal RT strategy remains to be determined in the setting of nodal oligorecurrent PCa. Ongoing randomized trials and advances in translational research will help to shed light on the best management for these patients.. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the fourth leading cause of cancer-associated death in the world. The 5-year local recurrence rates in patients undergoing multimodality therapy are approximately 5–10%. The standard approach to treat locally recurrent rectal is re-irradiation followed by surgical resection. Recent reports have suggested that the treatment outcomes with carbon ion radiation therapy (CIRT) in recurrent rectal cancer are promising and have superior results compared to photon therapy. Hence, we performed a systematic review to evaluate the patterns of care and treatment outcomes of recurrent rectal cancer patients treated with CIRT. We performed a systematic search to identify the articles that reported on CIRT use in recurrent rectal cancer. Systematic search of PubMed and Cochrane Central resulted in 98 abstracts. Eight studies fulfilled the predefined inclusion criteria. Among eight studies, one study is a prospective phase I/II study done in Japan; three prospective studies are ongoing (PANDORA-01 trial, HIMAT1351trial, and a phase II study of reirradiation for prior CIRT), and five studies are institutional reports on role of CIRT. These studies were predominantly reported from Japan and Germany. All reports except one were performed in patients who have not received prior radiation. The most commonly utilized treatment prescription was 73.4 Gy (RBE) in 16 fractions over 4 weeks in patients without any prior history of radiation and 36 Gy in 12 fractions over 3 weeks at 3 Gy per fraction in patients with prior photon radiation to the pelvis. There is one ongoing trial assessing the role of carbon ion re-irradiation in patients who had prior CIRT for rectal cancer. CIRT holds immense promise in improving outcomes in locally recurrent rectal cancer. There is a need for more multi-institutional prospective clinical trials to assess the role of CIRT. [ABSTRACT FROM AUTHOR]

Background: The objective of the study was to assess the effect of prophylactic antibiotics on the outcome of bone augmentation and subsequent dental implant placement by combining the recommended quality assessment methods for systematic reviews and primary studies.Materials and methods: This is a complex systematic review in which systematic reviews as well as primary studies are scrutinised. A search of Medline (OVID), The Cochrane Library (Wiley) and EMBASE, PubMed and Health technology assessment (HTA) organisations as-well as a complementary hand-search was carried out. Selected primary studies were assessed using GRADE. Each study was reviewed by three authors independently.Results: Abstract screening yielded six potential systematic reviews allocated for full-text inspection. A total of ten primary studies were read in full-text. No relevant systematic reviews regarding the topic of this article were found. The quality assessment resulted in two primary studies with a moderate risk of bias. Of the two studies with a moderate risk of bias, one compared a single dose of clindamycin 600 mg preoperatively with the same preoperative dose followed by four doses of 300 mg every 6 h. The second study compared a single dose prophylaxis of two different types of antibiotic compounds.Conclusion: In conclusion, the scientific evidence regarding the use of antibiotic prophylaxis for reducing the risk of infection in conjunction with bone augmentation procedures during dental implant placement is very limited. The infection rate as compared to nonusage of prophylactic antibiotics, selection of the most suitable compound, and the optimal duration of prophylactic treatment is still unknown. [ABSTRACT FROM AUTHOR]

Introduction: Considering the importance of empowering patients and their families by providing appropriate information and education, it seems smartphone apps provide a good opportunity for this group. The purpose of this review was to identify studies which used smartphone apps to help children and adolescents with cancer and their families. Method: Arksey and O'Malley's framework was employed in this review. To examine the evidence on the design and use of smartphone apps for the target group, PubMed, Embase, Scopus and Web of Science databases were searched from 2007 to November 2018. Results: Twenty-four articles met the inclusion criteria, with 33% being conducted in the USA and 21% in Canada. Moreover, in 20 studies (83%), app was specifically designed for children and adolescents, with only three studies (13%) for parents and one study (4%) for both. The main modules of smartphone apps in these studies included symptom assessment (90%), provision of information and education (74%), communication with caregivers (57%), social support (30%) and calendar and reminder (21%). Conclusions: Due to the easy access to smartphones without a costly infrastructure compared to landline phones, the use of mobile health (m-Health) has become a suitable method of providing healthcare services, especially for cancer. Use of smartphone apps, increases patient and families' access to reliable and suitable education and information regarding the disease. Thus, healthcare policy-makers in developing or underdeveloped countries can exploit the health-related potentials of m-Health following the experience of developed countries. [ABSTRACT FROM AUTHOR]

Background and purpose — Instability following primary total knee arthroplasty (TKA) is, according to all national registries, one of the major failure mechanisms leading to revision surgery. However, the range of soft-tissue laxity that favors both pain relief and optimal knee function following TKA remains unclear. We reviewed current evidence on the relationship between instrumented knee laxity measured postoperatively and outcome scores following primary TKA. Patients and methods — We conducted a systematic search of PubMed, Embase, and Cochrane databases to identify relevant studies, which were cross-referenced using Web of Science. Results — 14 eligible studies were identified; all were methodologically similar. Both sagittal and coronal laxity measurement were reported; 6 studies reported on measurement in both extension and flexion. In knee extension from 0° to 30° none of 11 studies could establish statistically significant association between laxity and outcome scores. In flexion from 60° to 90° 6 of 9 studies found statistically significant association. Favorable results were reported for posterior cruciate retaining (CR) knees with sagittal laxity between 5 and 10 mm at 75-80° and for knees with medial coronal laxity below 4° in 80-90° of flexion. Interpretation — In order to improve outcome following TKA careful measuring and adjusting of ligament laxity intraoperatively seems important. Future studies using newer outcome scores supplemented by performance-based scores may complement current evidence. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is an advanced method allowing en bloc resection of large and complex lesions in colon and rectum. Herein, the European experience of colorectal ESD was systematically reviewed in the medical literature to determine the clinical efficacy and safety of colorectal ESD in Europe. Material and methods: A systematic search of PubMed for full-text studies including more than 20 cases of colorectal ESD emanating from European centres was performed. Data were independently extracted by two authors using predefined data fields, including efficacy and safety. Results: We included 15 studies containing a total of 1404 colorectal ESD cases (41% in the colon) performed between 2007 and 2018. Lesion size was 40 mm (range 24–59 mm) and procedure time was 102 min (range 48–176 min). En bloc resection rate was 83% (range 67–93%) and R0 resection rate was 70% (range 35–91%). Perforation rate was 7% (range 0–19%) and bleeding rate was 5% (range 0–12%). The percentage of ESD cases undergoing emergency surgery was 2% (range 0–6%). Additional elective surgery was performed in 3% of all cases due to histopathological findings showing deep submucosal invasion or more advanced cancer. The recurrence rate was 4% (range 0–12%) after a median follow-up time of 12 months (range 3–24 months). Conclusions: This review shows that ESD is effective and safe for treating large and complex colorectal lesions in Europe although there is room for improvement. Thus, it is important to develop standardized and high-quality educational programs in colorectal ESD in Europe. [ABSTRACT FROM AUTHOR]

Introduction: Large anatomical variations can be observed during the treatment course intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), leading to potential dose variations. Adaptive radiotherapy (ART) uses one or several replanning sessions to correct these variations and thus optimize the delivered dose distribution to the daily anatomy of the patient. This review, which is focused on ART in the HNC, aims to identify the various strategies of ART and to estimate the dosimetric and clinical benefits of these strategies. Material and methods: We performed an electronic search of articles published in PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a total of 134 articles assessed for eligibility, 29 articles were ultimately retained for the review. Eighteen studies evaluated dosimetric variations without ART, and 11 studies reported the benefits of ART. Results: Eight in silico studies tested a number of replanning sessions, ranging from 1 to 6, aiming primarily to reduce the dose to the parotid glands. The optimal timing for replanning appears to be early during the first two weeks of treatment. Compared to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6 Gy and the maximum dose to the spinal cord from 0.1 to 4Gy while improving target coverage and homogeneity in most studies. Only five studies reported the clinical results of ART, and three of those studies included a non-randomized comparison with standard IMRT. These studies suggest a benefit of ART in regard to decreasing xerostomia, increasing quality of life, and increasing local control. Patients with the largest early anatomical and dose variations are the best candidates for ART. Conclusion: ART may decrease toxicity and improve local control for locally advanced HNC. However, randomized trials are necessary to demonstrate the benefit of ART before using the technique in routine practice. [ABSTRACT FROM AUTHOR]

Background: Otitis media (OM) and associated hearing problems may be side effects to radiotherapy of the head and neck region and affect patient quality of life. The condition is associated with the tumor location. Objective: To perform a systematic review concerning the present knowledge of the risk of OM after radiotherapy of the head and neck. Methods: A comprehensive search of PubMed and Embase was carried out between 1 October 2015 and 6 February 2017. The search strategy followed the PRISMA guideline for systematic reviews. Results: Of 597 articles 11 fulfilled the inclusion criteria. Seven were retrospective and four prospective. There were no randomized controlled trials. Eight studies concerned nasopharyngeal cancer. One study concerned cancer of the parotid gland and two studies concerned other locations of head and neck cancer. Meta-analysis could not be done due to heterogeneity between the studies. The incidence of OM varied considerably (range 8-29%). Conclusions: The incidence of OM is high after radiotherapy of cancer of the upper head and neck area and the Eustachian tube (ET) irradiation dosage seems associated with development of OM, but the literature is poor. Research is needed to designate patients at risk of developing OM after radiotherapy. Preferably through analysis of dosage relationships between the ET and middle ear, and development of OM. Reporting of OM should be per ear and follow standardized protocols of middle ear assessment before and after radiotherapy. Furthermore, there is a need to find new ways to prevent and treat radiation-induced OME, preferably through randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated (HRT) prostate radiation therapy has the potential to deliver a higher biologically effective dose over a shorter time compared with conventional fractionation (CRT). HRT, giving fewer fractions each with higher dose, might improve the therapeutic ratio, resource use and patient convenience but the toxicity is still controversial. Our objective was to compare the gastroinstestinal (GI) and genitourinary (GU) toxicity of HRT versus CRT. Methods: Systematic review and meta-analysis of randomized clinical trials studies in PubMed, Cochrane and EMBASE databases published through December 2016 was done. Only randomized trials that evaluated patients with localized prostate cancer (PCa) undergoing CRT or HRT were included. In these studies, the daily dose was 1.8 Gy or 2Gy per day for CRT and 2.4 to 3.4 Gy for HRT. Results: 7317 patients in nine studies were analyzed. Six studies included acute GU toxicity data which showed similar rates for both HRT and CRT (32.6vs. 31.9%; RD 0.00; 95% CI; -0.03,0.03; p = .81; I2 = 0%). Similarly, seven studies showed no difference in late GU toxicity based on treatment schedule (28.7 vs. 28.0%; RD -0.01; 95% CI; -0.04,0.03; p = .67; I2 = 52%). GI toxicity at three months after radiotherapy was higher in patients treated with HRT in six studies (27.5 vs. 21.9%; RD 0.06; 95% CI; 0.02,0.10; p = .004; I2 = 39%); however, eight studies showed GI toxicity 12 months or more after radiotherapy that was statistically the same (12.9 HRT vs. 16.2% CRT; RD -0.01; 95% CI; -0.04,0.02; p = .41; I2 = 58%). Conclusion: In meta-analysis of the available randomized trials on moderate HRT versus CRT for prostate cancer, acute and late GU toxicity were similar for both treatment schemes. While HRT was associated with higher acute GI toxicity, late toxicity was [ABSTRACT FROM AUTHOR]

Background: Large variations in the shape and size of the bladder volume are commonly observed in bladder cancer radiotherapy (RT). The clinical target volume (CTV) is therefore frequently inadequately treated and large isotropic margins are inappropriate in terms of dose to organs at risk (OAR); thereby making adaptive radiotherapy (ART) attractive for this tumour site. There are various methods of ART delivery, however, for bladder cancer, plan libraries are frequently used. Material and methods: A review of published studies on plan libraries for bladder cancer using four databases (Pubmed, Science Direct, Embase and Cochrane Library) was conducted. The endpoints selected were accuracy and feasibility of initiation of a plan library strategy into a RT department. Results: Twenty-four articles were included in this review. The majority of studies reported improvement in accuracy with 10 studies showing an improvement in planning target volume (PTV) and CTV coverage with plan libraries, some by up to 24%. Seventeen studies showed a dose reduction to OARs, particularly the small bowel V45Gy, V40Gy, V30Gy and V10Gy, and the rectal V30Gy. However, the occurrence of no suitable plan was reported in six studies, with three studies showing no significant difference between adaptive and non-adaptive strategies in terms of target coverage. In addition, inter-observer variability in plan selection appears to remain problematic. The additional resources, education and technology required for the initiation of plan library selection for bladder cancer may hinder its routine clinical implementation, with eight studies illustrating increased treatment time required. Conclusions: While there is a growing body of evidence in support of plan libraries for bladder RT, many studies differed in their delivery approach. The advent of the clinical use of the MRI-linear accelerator will provide RT departments with the opportunity to consider daily online adaption for bladder cancer as an alternate to plan library approaches. [ABSTRACT FROM AUTHOR]

Background:There is an increased attention to and demand for patient empowerment in cancer treatment and follow-up programs. Patient empowerment has been defined as feeling in control of or having mastery in relation to cancer and cancer care. This calls for properly developed questionnaires assessing empowerment from the user perspective. The aim of this review was to identify questionnaires and subscales measuring empowerment and manifestations of empowerment among cancer patients. Materials and methods:We conducted a systematic search of the PubMed, PsycINFO and CINAHL databases. Empowerment and multiple search terms associated with empowerment were included. We included peer-reviewed articles published in English, which described questionnaires measuring empowerment or manifestations of empowerment in a cancer setting. In addition, the questionnaire had to be a patient-reported outcome measure for adult cancer patients. Results:Database searches identified 831 records. Title and abstract screening resulted in 482 records being excluded. The remaining 349 full text articles were retrieved and assessed for eligibility. This led to the inclusion of 33 individual instruments measuring empowerment and manifestations of empowerment. Of these, only four were specifically developed to measure empowerment, and two were originally developed for the cancer setting, whereas the remaining two were developed elsewhere, but adapted to the cancer setting. The other 29 questionnaires were not intended to measure the concept of empowerment, but focused on patient-centered care, patient competence, self-efficacy, etc. However, they were included because part of the instrument (at least five items) was considered to measure empowerment or manifestations of empowerment. Conclusion:Our study provides an overview of the available questionnaires, which can be used by researchers and practitioners who wish to measure the concept of empowerment among cancer patients. Very few questionnaires were explicitly developed to explore empowerment, and the review brings to light a significant lack of questionnaires that measure patient empowerment comprehensively. [ABSTRACT FROM AUTHOR]

Background and purpose -- Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation -- Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are confl icting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. [ABSTRACT FROM AUTHOR]

Background:Proton beam therapy (PBT) is increasingly being used globally to treat a variety of malignancies. This is the first review assessing PBT for gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed. Material and methods:Systematic searches of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology were conducted for publications. There were no restrictions on publication dates. Sixteen original investigations were identified and analyzed for this review. Results:The available evidence for PBT in treating gynecologic cancers is of both low quantity and quality. The most studied scenarios for PBT include treatment of para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy, and these also represent indications with the greatest opportunity for demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown significantly decreased dose to OARs, such as the rectum, bladder, bowel, kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more pronounced within the low-dose volumes than the higher dose volumes, which radiobiologically could be expected to lower second malignancy rates. Clinical data, though no level 1 evidence, show appropriate stage-specific tumor control and outcomes with PBT treatment, along with low toxicity rates. Conclusion:The existing data, albeit limited, warrant and can help guide larger scale and higher quality studies addressing whether PBT could provide clinically meaningful differences in toxicities and outcomes in women with gynecologic neoplasms. [ABSTRACT FROM PUBLISHER]

Background and purpose — Studies of fracture healing have mainly dealt with shaft fractures, both experimentally and clinically. In contrast, most patients have metaphyseal fractures. There is an increasing awareness that metaphyseal fractures heal partly through mechanisms specific to cancellous bone. Several new models for the study of cancellous bone healing have recently been presented. This review summarizes our current knowledge of cancellous fracture healing. Methods — We performed a review of the literature after doing a systematic literature search. Results — Cancellous bone appears to heal mainly via direct, membranous bone formation that occurs freely in the marrow, probably mostly arising from local stem cells. This mechanism appears to be specific for cancellous bone, and could be named inter-trabecular bone formation. This kind of bone formation is spatially restricted and does not extend more than a few mm outside the injured region. Usually no cartilage is seen, although external callus and cartilage formation can be induced in meta­physeal fractures by mechanical instability. Inter-trabecular bone formation seems to be less sensitive to anti-inflammatory treatment than shaft fractures. Interpretation — The unique characteristics of inter-trabecular bone formation in metaphyseal fractures can lead to differences from shaft healing regarding the effects of age, loading, or drug treatment. This casts doubt on generalizations about fracture healing based solely on shaft fracture models. [ABSTRACT FROM PUBLISHER]

Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, its specific impact on hyperglycemia has not been well understood. We performed a meta-analysis of randomized controlled trials to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Material and methods: PubMed and American Society of Clinical Oncology conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without other agents. Heterogeneity tests were performed to examine between-study differences in hyperglycemia, and the incidence and relative risk of all- and high-grade hyperglycemia attributable to everolimus were determined using both random- or fixed-effects models. Results: A total of seven phase III and two phase II RCTs with various tumors, encompassing a total of 3879 cancer patients, were included in our analysis. Everolimus significantly increased the risk of all-grade (RR =2.60, 95% CI 2.03–3.31, p < 0.001) and high-grade (RR =3.0, 95% CI 1.72–5.23; p < 0.001) hyperglycemia. The incidences of all- and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI 3.4–13.2%) and 2.5% (95% CI 1.2–4.9%), respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (p < 0.001), with the highest incidence seen in renal cell carcinoma (RCC) (27.2%, 95% CI 22.2–32.8%) and the lowest in breast cancer (3.3%, 95% CI 1.3–8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusion: The specific risk of hyperglycemia attributable to everolimus may vary significantly with tumor types. Close monitoring should be given to patients at high risk, such as RCC. [ABSTRACT FROM AUTHOR]

Background.Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and -PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy. Material and methods.Literatures were searched and collected in Medline/PubMed. Results.LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules. LAG-3 negatively regulates T cell proliferation, homeostasis and function. IMP321 is formed of an extracellular portion of human LAG-3 fused to the Fc fraction of human IgG1 and has shown increased T cell responses and tolerability in phase I studies on advanced renal cell cancer. When combined with paclitaxel, IMP321 has exerted immune enhancement and tumor inhibition with no significant IMP321-related adverse events. TIM-3 belongs to the TIM family and mainly negatively regulates Th1 immunity. The TIM-3/galectin-9 pathway contributes to the suppressive tumor microenvironment. TIM-3 overexpression is associated with poor prognosis in a variety of cancers. Both LAG-3 and TIM-3 are coexpressed with other immune checkpoints. The application of LAG-3 or TIM-3 does play an important role in anti-tumor responses, and maybe better when combing with anti-CTLA-4 and anti-PD-1/L1 antibodies. Conclusions.These two immune checkpoints play crucial roles in cancer development and may be used in future clinical practice of cancer therapy. [ABSTRACT FROM PUBLISHER]

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. In parallel with the rising incidence of cancer and improved treatment, there is a continuous increase in the number of patients living with cancer as a chronic condition. Many cancer patients experience long-term disability and require continuous oncological treatment, care and support. The aim of this review is to evaluate the most recent data on the effects of rehabilitation among patients with advanced cancer. Material and methods. A systematic review was conducted according to Fink's model. Only randomized controlled trials (RCTs) published in 2009-2014 were included. Medline/PubMed and Cochrane databases were searched; five groups of keywords were used. The articles were evaluated for outcome and methodological quality. Results. Thirteen RCTs (1169 participants) were evaluated. Most studies were on the effects of physical exercise in patients with advanced cancer (N = 7). Physical exercise was associated with a significant improvement in general wellbeing and quality of life. Rehabilitation had positive effects on fatigue, general condition, mood, and coping with cancer. Conclusions. Rehabilitation is needed also among patients with advanced disease and in palliative care. Exercise improves physical performance and has positive effects on several other quality of life domains. More data and RCTs are needed, but current evidence gives an indication that rehabilitation is suitable and can be recommended for patients living with advanced cancer. [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]

Background and purpose - We reviewed the current state of research on microRNAs in age-related diseases in cartilage and bone. Methods - PubMed searches were conducted using separate terms to retrieve articles on (1) the role of microRNAs on aging and tissue degeneration, (2) specific microRNAs that influence cellular and organism senescence, (3) microRNAs in age-related musculoskeletal conditions, and (4) the diagnostic and therapeutic potential of microRNAs in age-related musculoskeletal conditions. Results - An increasing number of studies have identified microRNAs associated with cellular aging and tissue degeneration. Specifically in regard to frailty, microRNAs have been found to influence the onset and course of age-related musculoskeletal conditions such as osteoporosis, osteoarthritis, and posttraumatic arthritis. Both intracellular and extracellular microRNAs may be suitable to function as diagnostic biomarkers. In particular Interpretation - The research data currently available suggest that microRNAs play an important role in orchestrating age-related processes and conditions of the musculoskeletal system. Further research may help to improve our understanding of the complexity of these processes at the cellular and extracellular level. The option to develop microRNA biomarkers and novel therapeutic agents for the degenerating diseases of bone and cartilage appears to be promising. [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]