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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: 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]

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]

Objective. Screening for distress is controversial with many advocates and detractors. Previously it was reasonable to assert that there was a lack of evidence but this position is no longer tenable. The question is now: what does the evidence show and, in particular, when is screening successful and when is screening unsuccessful? The aim of this paper is to review the most up-to-date recent findings from randomized and non-randomized trials regarding the merits of screening for distress in cancer settings. Methods. A search was made of the Embase/Medline and Web of knowledge abstract databases from inception to December 2012. Online theses and experts were contacted. Inclusion criteria were interventional (randomized and non-randomized) trials concerning screening for psychological distress and related disorders. Studies screening for quality of life were included. Results. Twenty-four valid interventional studies of distress/QoL screening were identified, 14 being randomized controlled trials (RCTs). Six of 14 screening RCTs reported benefits on patient well-being and an additional three showed benefits on secondary outcomes such as communication between clinicians and patients. Five randomized screening trials failed to show any benefits. Only two of 10 non-randomized sequential cohort screening studies reported benefits on patient well-being but an additional six showed secondary benefits on quality of care (such as receipt of psychosocial referral). Two non-randomized screening trials failed to show benefits. Of 24 studies, there were 17 that reported some significant benefits of screening on primary or secondary outcomes, six that reported no effect and one that reported a non-significantly deleterious effect upon communication. Across all studies, barriers to screening success were significant. The most significant barrier was receipt of appropriate aftercare. The proportion of cancer patients who received psychosocial care after a positive distress screen was only one in three. Screening was more effective when it was linked with mandatory intervention or referral. Conclusions. Screening for distress/QoL is likely to benefit communication and referral for psychosocial help. Screening for distress has the potential to influence patient well-being but only if barriers are addressed. Quality of care barriers often act as a rate limiting step. Key barriers are lack of training and support, low acceptability and failure to link treatment to the screening results. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of data on incidence and mechanisms of long-term gastrointestinal consequences after chemoradiotherapy for anal cancer. Most of the adverse effects reported were based on traditional external beam radiotherapy whilst only short-term follow-ups have been available for intensity-modulated radiotherapy, and there is lack of knowledge about consequences of doseescalation radiotherapy. Method: A systematic literature review. Results: Two thousand nine hundred and eighty-five titles (excluding duplicates) were identified through the search; 130 articles were included in this review. The overall incidence of late gastrointestinal toxicity was reported to be 7-64.5%, with Grade 3 and above (classified as severe) up to 33.3%. The most commonly reported late toxicities were fecal incontinence (up to 44%), diarrhea (up to 26.7%), and ulceration (up to 22.6%). Diarrhea, fecal incontinence and buttock pain were associated with lower scores in radiotherapy specific quality of life scales (QLQ-CR29, QLQ-C30, and QLQ-CR38) compared to healthy controls. Intensity-modulated radiation therapy appears to reduce late toxicity. Conclusion: Late gastrointestinal toxicities are common with severe toxicity seen in one-third of the patients. These symptoms significantly impact on patients' quality of life. Prospective studies with control groups are needed to elucidate long-term toxicity. [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: Supporting unemployed or work-disabled cancer survivors in their work participation can have extensive individual and societal benefits. We aimed to identify and summarise interventions for work participation of unemployed or work-disabled cancer survivors. Methods: Five databases (Medline, Embase, PsycINFO, CINAHL and Cochrane Library) were systematically searched for quantitative studies on interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors. Work participation refers to participation in the workforce, fulfilling one's work role. Manual and automatic screening (with ASReview software) were performed on titles and abstracts, followed by manual full-text screening. Data were extracted regarding study, patient and intervention characteristics, and work participation outcomes. Risk of bias (RoB) was assessed using the Cochrane RoB2 and QUIPS tools. Results: We identified 10,771 articles, of which we included two randomised controlled trials (RCTs), of which one feasibility RCT, and three cohort studies. In total, 1862 cancer survivors were included, with predominantly breast cancer. Work participation was mainly measured as time to return to work (RTW) and RTW rate. Interventions included components of coaching (e.g., psychological or rehabilitation), training (e.g., building confidence and managing fatigue) and self-management. Two RCTs with unclear RoB did not show an effect of multicomponent interventions compared to care as usual. One cohort study found a significant effect of a psycho-educational intervention on RTW rates, with moderate RoB. The other two cohort studies, with moderate RoB, reported significant associations between components including job search and placement assistance, and work participation. Discussion: Only few interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors, have been evaluated. In two cohort studies, promising components for future multicomponent interventions were identified. However, findings suggest that more evidence is necessary on such multicomponent interventions, in which elements explicitly directed at work and including the workplace should be included. [ABSTRACT FROM AUTHOR]

Background:Decision making regarding cancer treatment is challenging and there is a need for clinical parameters that can guide these decisions. As physical performance appears to be a reflection of health status, the aim of this systematic review is to assess whether physical performance tests (PPTs) are predictive of the clinical outcome and treatment tolerance in cancer patients. Methods:A literature search was conducted on 2 April 2015 in the electronic databases Medline and Embase to identify studies focusing on the association between objectively measured PPTs and outcome. No limitations in language or publication dates were applied. Results:The search retrieved 9680 articles, 16 publications were included involving 4187 patients with various cancer types and different treatments. Reported median or mean age varied from 58 to 78 years. Nine studies used the Timed Up & Go (TUG) test, five the Short Physical Performance Battery (SPPB) and five studies focused on gait speed. Poorer TUG, SPPB and gait speed outcome were associated with decreased survival. TUG, SPPB and gait speed were also associated with treatment-related complications. Furthermore, two studies reported an association between poorer TUG and SPPB outcome with higher rates of functional decline. Conclusion:PPTs appear to show a significant correlation with survival and these tests could be used as a prognostic tool, particular for older adult patients. A less explicit correlation for treatment-related complications and functional decline was also found. To optimize decision making, future research should focus on developing and validating individualized treatment algorithms that incorporate PPTs in addition to cancer- and treatment-related variables. [ABSTRACT FROM PUBLISHER]

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

To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks. [ABSTRACT FROM AUTHOR]

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

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]

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]

Short-course radiotherapy with consolidation chemotherapy (SCRT-CCT) has emerged as a promising alternative to the long course chemoradiotherapy (LCRT) regimen in locally advanced rectal cancer management. The systematic review and meta-analysis is aimed at summarizing current evidence on SCRT-CCT and comparing it to LCRT. Electronic databases of MEDLINE, Web of Science, and Cochrane library were searched using a predefined search strategy returning 3314 articles. This review included 11 studies (6 randomized trials and 5 non-randomized studies) on SCRT-CCT regimen based on seven different cohorts. Weighted arithmetic means and forest plots were generated to determine summary estimates. The probability of achieving pathological complete response (pCR) was higher with SCRT-CCT compared to LCRT (risk ratio [RR] = 1.75, 95% confidence interval [CI]: 1.41–2.19). No statistically significant difference in 3-year overall survival (OS) was observed between the two groups (RR= 1.06, 95% CI: 0.98–1.14). The weighted arithmetic mean of 3-year OS and pCR was 83.6% versus 80.9%, and 24.5% versus 13.6% for SCRT-CCT and LCRT, respectively. R0 resection and T-downstaging rates ranged from 69.2–100% to 47–75% for SCRT-CCT, and 71–92.3% and 41–75% for LCRT, respectively. The regimens had similar compliance, postoperative, and late toxicity, however, acute toxicity rates varied primarily due to differences in treatment protocols. This review highlights the ability of SCRT-CCT to produce improved tumor response with comparable OS, R0 resection, and T-downstaging at the cost of increased acute toxicity. However, heterogeneity in treatment protocols across studies makes it difficult to provide definitive conclusions regarding the regimen. Several ongoing trials are expected to provide further evidence confirming the findings of RAPIDO trial and detail appropriate SCRT-CCT protocols to improve oncological outcomes, minimize toxicity, and determine its effectiveness as the standard-of-care for locally advanced rectal cancer patients. [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]

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]

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

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: To determine the frequency of discordance in programmed death-ligand 1(PD-L1) expression between primary tumors and paired distant metastases in advanced cancers. Methods: We searched MEDLINE and EMBASE for eligible studies and assessed their methodologic quality using QUADAS-2 tool. We estimated the discordant rates (positive to negative or vice versa) of PD-L1 expression in primary tumors and paired distant metastases using logistic-normal random effects model. We performed subgroup analyses based on the PD-L1 status of primary tumors (positive or negative), location of primary tumors (lung or others) and distant metastases (central nervous system or others), timing of distant metastases (synchronous or metachronous), positivity thresholds of PD-L1 expression (1% or 5%) and types of antibody clones used (E1L3N or SP142). Results: Thirteen eligible studies including 451 cases were identified. The included studies were judged to have low to unclear risk of bias. The pooled estimate of discordant rates in PD-L1 expression was 31% (95% CI= 19–47%), with high heterogeneity across the studies (I2 = 75%). There was no significant effect modification in the discordant rates according to the predefined subgroups. Conclusion: Approximately one-third of advanced cancer cases have discordance in PD-L1 expression between primary tumors and paired distant metastases. A more liberal testing of PD-L1 expression in both primary and metastatic tumors is recommended in order to identify patients who may benefit from immune checkpoint blockade treatment. Further research exploring the mechanisms and its impact are warranted. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated bortezomib-induced neurotoxicity in patients with multiple myeloma. Topics discussed include the development of demyelinating polyradiculoneuritis following treatment with bortezomib, the neurological presentation of bortezomib-induced toxicity including numbness, pain paraesthesia and bilateral motor deficits, and possible pathogenic mechanisms for bortezomib-induced peripheral neuropathy.

Background: Hepatocellular carcinoma (HCC) incidence is rising worldwide, especially due to increased detection of early-stage or small-sized tumors. Nevertheless, most of the patients are still not qualified for surgical resection at diagnosis due to the localization of the tumor, underlying liver disease or comorbidities. Stereotactic body radiation therapy (SBRT) is a radiotherapy modality which can deliver a high dose of radiation to the target tissue with a high degree of precision. It shows promise in terms of efficacy and morbidity. Material and methods: The aim of this systematic review is to summarize current knowledge on patient-specific outcomes of SBRT for small HCC including overall survival, local control, the effect of dose escalation and the toxicity of the treatment. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After a comprehensive database search, 16 studies (973 patients with 1034 lesions) were included in qualitative and quantitative analyses; 14 of them were retrospective. Results: Average tumor diameter was 23 mm and 95% of patients were in good general condition. Median BED10 (biologically equivalent dose calculated for α/β ratio of 10 Gy) was 100 Gy (range 59.5–180 Gy). Mean weighted local control across studies was 94%, 92% and 93% at 1, 2, and 3 years, respectively. Mean weighted overall survival across studies was 90.9%, 67.5% and 73.4% at 1, 2, and 3 years, respectively. There were 171 grade 1–2 toxicities (17.5%) and 53 ≥ grade 3 toxicities (5.3%). There was no treatment-associated mortality. Conclusion: SBRT offers high local control with overall survival that is comparable with radiofrequency ablation and surgery. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of published studies. Therefore, there is a need for better reporting and prospective studies to univocally recommend SBRT as a definitive treatment option in the guidelines for small HCCs. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common and distressing cancer symptom that negatively affects the quality of life. Many scales have been developed to assess cancer-related fatigue. The properties of the scales vary in terms of dimensionality, reliability, validity, length and method of administration. Insufficient of psychometric properties may affect the accuracy of scales findings, that may lead result obtained questionable. The main objective of this review was to conduct a quality assessment of the psychometric properties of cancer-related fatigue scales to identify appropriate scales that could be used in research and clinical practice. Method: A systematic search was carried out to identify validated scales that measure cancer-related fatigue. Five databases were searched: CINAHL, MEDLINE, EMBASE, PsycINFO, Cochrane Library. This review was conducted following the PRISMA and Terwee et al.'s quality assessment guidelines to evaluate the psychometric properties of the studies. Result: Seventy-one different studies published between 1970 and 2018 met the inclusion criteria. Twenty-five scales were identified. Of these, eighteen were multidimensional and seven were uni-dimensional, containing between 4 and 72 items. Reliability and/or validity information was missing for many scales. Four scales met the quality assessment criteria and were reported as the most appropriate for measuring fatigue in cancer patients. Conclusion: Further psychometric testing is required for other scales. Developing a universally-defined tool kit for the assessment of cancer-related fatigue may help clarify the concept of fatigue and promote a systematic approach to fatigue measurement. [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: 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: The α/β values for prostate cancer (PCa) are usually assumed to be low (1.0-1.8 Gy). This study estimated the α/β values of PCa from phase III randomized trials of conventional (CRT) versus hypofractionated (HRT) external beam radiotherapy (RT), reported as isoeffective in terms of their 5-year biochemical (BF) or biochemical and/or clinical failure (BCF) rates. Material and methods: The α/β for each trial was estimated from the equivalent biological effective doses using the linear-quadratic model for each of their HRT and CRT schedules. The cumulative outcomes of these trials were evaluated by meta-analysis for odds ratio (OR), risk ratio (RR) and risk difference (RD). Results: Eight trials from seven studies, randomized 6993 patients between CRT (n¼2941) and HRT (n¼4052). RT treatment varied between the two treatment groups in terms of dose/fraction, total dose, overall treatment time and %patients on androgen deprivation therapy (ADT). Differences in OR, RR, and RD for both BF and BCF were nonsignificant. The computed α/β ranged from 1.3 to 11.1 Gy (4.9± 3.9 Gy; 95% CI: 1.6-8.2). On multivariate regression, %ADT was the sole determinant of computed α/β (model R2: 0.98, p<.001). Conclusions: Clinically estimated α/β for PCa from isoeffective randomized trials using known variables in the linear-quadratic expression ranged between 1.3 and 11.1 Gy. The estimated α/β values were inversely related to %ADT usage, which should be considered when planning future RT dose-fractionation schedules. [ABSTRACT FROM AUTHOR]

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

Background: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:Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management. Methods:A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease. Results:The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal. Conclusions:Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care. [ABSTRACT FROM AUTHOR]

Background:Electrochemotherapy, the combination of electroporation and chemotherapy, is mainly used in the palliative setting for treatment of cutaneous and subcutaneous metastases; however, new applications are continuously being explored. Patients with head and neck cancer are primarily treated with surgery and/or radio-chemotherapy. In the setting of local recurrence with no further curative treatment options available, electrochemotherapy could be of value. We therefore performed a systematic search of the present literature. Materials and methods:Eligible studies presented data from patients with head and neck cancer treated across the mucosal surface with electrochemotherapy. The search resulted in 11 studies with a total of 72 patients. Results:Overall complete response was reported as good, especially in primary small tumors. Side effects were minor in primary tumors whereas large, recurrent tumors displayed more frequent side effects and some serious adverse events. Design and structure of the studies differed considerably, making general comparisons difficult. Conclusion:Few studies concerning electrochemotherapy on mucosal head and neck tumors are available and they are not easily comparable. Overall response to treatment is good; nonetheless, further systematic studies are warranted. [ABSTRACT FROM PUBLISHER]

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]

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.R-CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma. It was suggested that decreasing the treatment interval from three weeks (CHOP-21) to two weeks (CHOP-14) may improve survival and disease control of patients with aggressive lymphoma. Purpose.To evaluate the effect of CHOP-like-14 (with or without rituximab) compared to standard CHOP-like -21 on overall survival (OS), disease control and toxicity of patients with aggressive non-Hodgkin lymphoma. Methods.Systematic review and meta-analysis of RCTs. In October 2014 we searched The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Authors were contacted for complementary data. The primary outcome was OS. Results.We identified seven trials (4073 patients), conducted between the years 1999 and 2008. Trials were at low or unclear risk for selection bias, and at low or unclear risk of attrition bias. CHOP-like-14 improved OS of patients with aggressive lymphoma compared to the same regimen given every 21 days (all trials): HR of death 0.86, 95% confidence interval (CI) 0.77–0.97. There was no OS difference between rituximab-CHOP-like 14 to rituximab-CHOP-like-21 (3 trials): HR 0.93 95% CI 0.78–1.10. The rates of progression or death, complete response, treatment-related mortality, grade 3–4 infection, and discontinuation were similar between groups. Conclusion.R-CHOP-21 remains the standard of care for patient with aggressive B-cell lymphoma. CHOP-14 can be considered as in case rituximab is omitted. [ABSTRACT FROM PUBLISHER]

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]