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1.
Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.
Kahale, LA, Hakoum, MB, Tsolakian, IG, Matar, CF, Terrenato, I, Sperati, F, Barba, M, Yosuico, VE, Schünemann, H, Akl, EA
The Cochrane database of systematic reviews. 2018;(6):CD006650
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Abstract
BACKGROUND Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments. OBJECTIVES To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer. SEARCH METHODS We conducted a literature search including a major electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE (Ovid), and Embase (Ovid); handsearching conference proceedings; checking references of included studies; use of the 'related citation' feature in PubMed and a search for ongoing studies in trial registries. As part of the living systematic review approach, we run searches continually, incorporating new evidence after it is identified. Last search date 14 May 2018. SELECTION CRITERIA Randomized controlled trials (RCTs) assessing the benefits and harms of long-term treatment with LMWHs, DOACs or VKAs in people with cancer and symptomatic VTE. DATA COLLECTION AND ANALYSIS We extracted data in duplicate on study characteristics and risk of bias. Outcomes included: all-cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and health-related quality of life (QoL). We assessed the certainty of the evidence at the outcome level following the GRADE approach (GRADE handbook). MAIN RESULTS Of 15,785 citations, including 7602 unique citations, 16 RCTs fulfilled the eligibility criteria. These trials enrolled 5167 people with cancer and VTE.Low molecular weight heparins versus vitamin K antagonistsEight studies enrolling 2327 participants compared LMWHs with VKAs. Meta-analysis of five studies probably did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on mortality up to 12 months of follow-up (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.13; risk difference (RD) 0 fewer per 1000, 95% CI 45 fewer to 48 more; moderate-certainty evidence). Meta-analysis of four studies did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on major bleeding (RR 1.09, 95% CI 0.55 to 2.12; RD 4 more per 1000, 95% CI 19 fewer to 48 more, moderate-certainty evidence) or minor bleeding (RR 0.78, 95% CI 0.47 to 1.27; RD 38 fewer per 1000, 95% CI 92 fewer to 47 more; low-certainty evidence), or thrombocytopenia (RR 0.94, 95% CI 0.52 to 1.69). Meta-analysis of five studies showed that LMWHs probably reduced the recurrence of VTE compared to VKAs (RR 0.58, 95% CI 0.43 to 0.77; RD 53 fewer per 1000, 95% CI 29 fewer to 72 fewer, moderate-certainty evidence).Direct oral anticoagulants versus vitamin K antagonistsFive studies enrolling 982 participants compared DOACs with VKAs. Meta-analysis of four studies may not rule out a beneficial or harmful effect of DOACs compared to VKAs on mortality (RR 0.93, 95% CI 0.71 to 1.21; RD 12 fewer per 1000, 95% CI 51 fewer to 37 more; low-certainty evidence), recurrent VTE (RR 0.66, 95% CI 0.33 to 1.31; RD 14 fewer per 1000, 95% CI 27 fewer to 12 more; low-certainty evidence), major bleeding (RR 0.77, 95% CI 0.38 to 1.57, RD 8 fewer per 1000, 95% CI 22 fewer to 20 more; low-certainty evidence), or minor bleeding (RR 0.84, 95% CI 0.58 to 1.22; RD 21 fewer per 1000, 95% CI 54 fewer to 28 more; low-certainty evidence). One study reporting on DOAC versus VKA was published as abstract so is not included in the main analysis.Direct oral anticoagulants versus low molecular weight heparinsTwo studies enrolling 1455 participants compared DOAC with LMWH. The study by Raskob did not rule out a beneficial or harmful effect of DOACs compared to LMWH on mortality up to 12 months of follow-up (RR 1.07, 95% CI 0.92 to 1.25; RD 27 more per 1000, 95% CI 30 fewer to 95 more; low-certainty evidence). The data also showed that DOACs may have shown a likely reduction in VTE recurrence up to 12 months of follow-up compared to LMWH (RR 0.69, 95% CI 0.47 to 1.01; RD 36 fewer per 1000, 95% CI 62 fewer to 1 more; low-certainty evidence). DOAC may have increased major bleeding at 12 months of follow-up compared to LMWH (RR 1.71, 95% CI 1.01 to 2.88; RD 29 more per 1000, 95% CI 0 fewer to 78 more; low-certainty evidence) and likely increased minor bleeding up to 12 months of follow-up compared to LMWH (RR 1.31, 95% CI 0.95 to 1.80; RD 35 more per 1000, 95% CI 6 fewer to 92 more; low-certainty evidence). The second study on DOAC versus LMWH was published as an abstract and is not included in the main analysis.Idraparinux versus vitamin K antagonistsOne RCT with 284 participants compared once-weekly subcutaneous injection of idraparinux versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) for three or six months. The data probably did not rule out a beneficial or harmful effect of idraparinux compared to VKAs on mortality at six months (RR 1.11, 95% CI 0.78 to 1.59; RD 31 more per 1000, 95% CI 62 fewer to 167 more; moderate-certainty evidence), VTE recurrence at six months (RR 0.46, 95% CI 0.16 to 1.32; RD 42 fewer per 1000, 95% CI 65 fewer to 25 more; low-certainty evidence) or major bleeding (RR 1.11, 95% CI 0.35 to 3.56; RD 4 more per 1000, 95% CI 25 fewer to 98 more; low-certainty evidence). AUTHORS' CONCLUSIONS For the long-term treatment of VTE in people with cancer, evidence shows that LMWHs compared to VKAs probably produces an important reduction in VTE and DOACs compared to LMWH, may likely reduce VTE but may increase risk of major bleeding. Decisions for a person with cancer and VTE to start long-term LMWHs versus oral anticoagulation should balance benefits and harms and integrate the person's values and preferences for the important outcomes and alternative management strategies.Editorial note: this is a living systematic review (LSR). LSRs offer new approaches to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
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How much does reduced food intake contribute to cancer-associated weight loss?
Martin, L, Kubrak, C
Current opinion in supportive and palliative care. 2018;(4):410-419
Abstract
PURPOSE OF REVIEW An international consensus group defined cancer cachexia as a syndrome of involuntary weight loss, characterized by loss of skeletal muscle (with or without fat loss), which is driven by a variable combination of reduced food intake and altered metabolism.This review presents recent studies that evaluated the contribution of reduced food intake to cancer-associated weight loss. RECENT FINDINGS Four studies examined food intake in relation to weight loss. Heterogeneity among studies rendered aggregation and interpretation of results challenging. Despite these limitations, reduced food intake had consistent significant, independent associations with weight loss. However, reduced food intake did not explain all the variation in weight loss; and limited data suggests factors related to alterations in metabolism (e.g. increased resting energy expenditure, systemic inflammation) are also contributing to weight loss. SUMMARY Reduced food intake is a significant contributor to cancer-associated weight loss. Understanding the magnitude of the association between food intake and weight loss may improve when it is possible to account for alterations in metabolism. Efforts to align clinical assessments of food intake to reduce heterogeneity are needed.
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3.
The management strategies of cancer-associated anorexia: a critical appraisal of systematic reviews.
Zhang, F, Shen, A, Jin, Y, Qiang, W
BMC complementary and alternative medicine. 2018;(1):236
Abstract
BACKGROUND Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as the best guide. Considering the methodology quality of SRs varies, we undertook a comprehensive overview, and critical appraisal of pertinent SRs. METHODS Eight databases (between the inception of each database and September 1, 2017) were searched for SRs on the management of cancer-related anorexia. Two researchers evaluated the methodological quality of each SR by using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Characteristics of the "high quality" SRs were abstracted, included information on relevant studies numbers, study design, population, intervention, control, outcome and result. RESULTS Eighteen SRs met the inclusion criteria. The R-AMSTAR scores of methodological quality ranged from 18 to 41 out of 44, with an average score of 30. Totally eight SRs scored ≥31 points, which showed high methodological quality, and would be used for data extraction to make summaries. Anamorelin had some positive effects to relieve cancer anorexia-cachexia syndrome (CACS) and improve the quality of life (QoL). Megestrol Acetate (MA) could improve appetite, and was associated with slight weight gain for CACS. Oral nutritional interventions were effective in increasing nutritional intake and improving some aspects of QoL in patients with cancer who were malnourished or at nutritional risk. The use of thalidomide, Eicosapentaenoic Acid, and minerals, vitamins, proteins, or other supplements for the treatment of cachexia in cancer were uncertain, and there was inadequate evidence to recommend it to clinical practices, the same situation in Chinese Herb Medicine and acupuncture (acupuncture and related therapies were effective in improving QoL) for treating anorexia in cancer patients, warranting further RCTs in these areas. CONCLUSIONS Anamorelin, MA, oral nutrition interventions, and acupuncture could be considered to be applied in patients with cancer-related anorexia. Future RCTs and SRs with high quality on the pharmaceutical or non-pharmaceutical interventions of anorexia in cancer patients are warranted.
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4.
Role of iodide metabolism in physiology and cancer.
De la Vieja, A, Santisteban, P
Endocrine-related cancer. 2018;(4):R225-R245
Abstract
Iodide (I-) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I- is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I- recycling. New research supports the exciting idea that I- participates as a protective antioxidant and can be oxidized to hypoiodite, a potent oxidant involved in the host defense against microorganisms. This was possibly the original role of I- in biological systems, before the appearance of TH in evolution. I- per se participates in its own regulation, and new evidence indicates that it may be antineoplastic, anti-proliferative and cytotoxic in human cancer. Alterations in the expression of I- transporters are associated with tumor development in a cancer-type-dependent manner and, accordingly, NIS, CFTR and ANO1 have been proposed as tumor markers. Radioactive iodide has been the mainstay adjuvant treatment for thyroid cancer for the last seven decades by virtue of its active transport by NIS. The rapid advancement of techniques that detect radioisotopes, in particular I-, has made NIS a preferred target-specific theranostic agent.
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Emerging roles of long non-coding RNAs in tumor metabolism.
Sun, H, Huang, Z, Sheng, W, Xu, MD
Journal of hematology & oncology. 2018;(1):106
Abstract
Compared with normal cells, tumor cells display distinct metabolic characteristics. Long non-coding RNAs (lncRNAs), a large class of regulatory RNA molecules with limited or no protein-coding capacity, play key roles in tumorigenesis and progression. Recent advances have revealed that lncRNAs play a vital role in cell metabolism by regulating the reprogramming of the metabolic pathways in cancer cells. LncRNAs could regulate various metabolic enzymes that integrate cell malignant transformation and metabolic reprogramming. In addition to the known functions of lncRNAs in regulating glycolysis and glucose homeostasis, recent studies also implicate lncRNAs in amino acid and lipid metabolism. These observations reveal the high complexity of the malignant metabolism. Elucidating the metabolic-related functions of lncRNAs will provide a better understanding of the regulatory mechanisms of metabolism and thus may provide insights for the clinical development of cancer diagnostics, prognostics and therapeutics.
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The Effect of Evidence-Based Nutrition Clinical Care Pathways on Nutrition Outcomes in Adult Patients Receiving Non-Surgical Cancer Treatment: A Systematic Review.
Dewar, SL, Porter, J
Nutrition and cancer. 2018;(3):404-412
Abstract
Nutritional decline associated with non-surgical cancer treatment has been well documented. The implementation of an evidence-based nutrition care pathway is one approach suggested to improve the nutrition outcomes of this group of patients. We aimed to systematically review published original research to determine whether evidence-based nutrition clinical care pathways, as compared with usual care, improve outcomes for patients receiving non-surgical cancer treatment. The review was registered with PROSPERO (CRD42017048816) and followed PRISMA guidelines. The search strategy was conducted in four databases, and supplemented by an internet search, from inception to October 2016. Study quality was assessed using the Quality Criteria Checklist for Primary Research. Results were synthesized descriptively. Six reports of five studies formed the final library with a range of interventions and control practices investigated across several diagnostic groups. Nutrition outcomes were reported using multiple approaches with either no effect, or in favor of the clinical pathway intervention. Risk of bias was low in two studies with some risk in the remaining three studies. It was not possible to determine whether the effect on nutritional outcomes was attributable to care pathway implementation. The need to extend the evidence base through high-quality clinical trials was evident.
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Lifestyle changes in cancer patients undergoing curative or palliative chemotherapy: is it feasible?
Vassbakk-Brovold, K, Berntsen, S, Fegran, L, Lian, H, Mjåland, O, Mjåland, S, Nordin, K, Seiler, S, Kersten, C
Acta oncologica (Stockholm, Sweden). 2018;(6):831-838
Abstract
INTRODUCTION This study aimed to explore the feasibility of an individualized comprehensive lifestyle intervention in cancer patients undergoing curative or palliative chemotherapy. MATERIAL AND METHODS At one cancer center, serving a population of 180,000, 100 consecutive of 161 eligible newly diagnosed cancer patients starting curative or palliative chemotherapy entered a 12-month comprehensive, individualized lifestyle intervention. Participants received a grouped startup course and monthly counseling, based on self-reported and electronically evaluated lifestyle behaviors. Patients with completed baseline and end of study measurements are included in the final analyses. Patients who did not complete end of study measurements are defined as dropouts. RESULTS More completers (n = 61) vs. dropouts (n = 39) were married or living together (87 vs. 69%, p = .031), and significantly higher baseline physical activity levels (960 vs. 489 min.wk-1, p = .010), more healthy dietary choices (14 vs 11 points, p = .038) and fewer smokers (8 vs. 23%, p = .036) were observed among completers vs. dropouts. Logistic regression revealed younger (odds ratios (OR): 0.95, 95% confidence interval (CI): 0.91, 0.99) and more patients diagnosed with breast cancer vs. more severe cancer types (OR: 0.16, 95% CI: 0.04, 0.56) among completers vs. dropouts. Improvements were observed in completers healthy (37%, p < 0.001) and unhealthy dietary habits (23%, p = .002), and distress (94%, p < .001). No significant reductions were observed in physical activity levels. Patients treated with palliative intent did not reduce their physical activity levels while healthy dietary habits (38%, p = 0.021) and distress (104%, p = 0.012) was improved. DISCUSSION Favorable and possibly clinical relevant lifestyle changes were observed in cancer patients undergoing curative or palliative chemotherapy after a 12-month comprehensive and individualized lifestyle intervention. Palliative patients were able to participate and to improve their lifestyle behaviors.
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ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer.
Krupenko, SA, Krupenko, NI
Advances in experimental medicine and biology. 2018;:127-143
Abstract
Epidemiological studies implicate excess ethanol ingestion as a risk factor for several cancers and support the concept of a synergistic effect of chronic alcohol consumption and folate deficiency on carcinogenesis. Alcohol consumption affects folate-related genes and enzymes including two major folate-metabolizing enzymes, ALDH1L1 and ALDH1L2. ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase) is a regulatory enzyme in folate metabolism that controls the overall flux of one-carbon groups in folate-dependent biosynthetic pathways. It is strongly and ubiquitously down-regulated in malignant tumors via promoter methylation, and recent studies underscored this enzyme as a candidate tumor suppressor and potential marker of aggressive cancers. A related enzyme, ALDH1L2, is the mitochondrial homolog of ALDH1L1 encoded by a separate gene. In contrast to its cytosolic counterpart, ALDH1L2 is expressed in malignant tumors and cancer cell lines and was implicated in metastasis regulation. This review discusses the link between folate and cancer, modifying effects of alcohol consumption on folate-associated carcinogenesis, and putative roles of ALDH1L1 and ALDH1L2 in this process.
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Cannabinoids for nausea and vomiting related to chemotherapy: Overview of systematic reviews.
Schussel, V, Kenzo, L, Santos, A, Bueno, J, Yoshimura, E, de Oliveira Cruz Latorraca, C, Pachito, DV, Riera, R
Phytotherapy research : PTR. 2018;(4):567-576
Abstract
Nausea and vomiting are common and distressing adverse events of chemotherapy. This review focuses on the findings and quality of systematic reviews (SRs) of cannabinoids for chemotherapy-induced nausea and vomiting (CINV). Review of SRs, a systematic literature search, was conducted in several electronic databases and included SRs evaluating cannabinoids for CINV in cancer patients. Methodological quality and quality of reporting were evaluated by AMSTAR and PRISMA, respectively. Initial search retrieved 2,206 records, and 5 SRs were included. On the basis of findings of the sole SR judged as high methodological quality, cannabinoids seem to be more effective than placebo, equal to prochlorperazine for reducing CINV, and to be preferred by patients. The response to different combinations of antiemetic agents seems to be equal to 1 antiemetic alone. The average of AMSTAR score was 5, and the average of PRISMA score was 13.2. Cannabinoids represent a valuable option for treating CINV, despite the adverse events related to treatment, such as drowsiness and cognitive impairment. There is no good quality evidence to recommend or not the use of cannabinoids for CINV. More studies are still needed to evaluate the effectiveness of cannabinoids when compared with modern antiemetics.
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Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics.
Cheng, YY, Hsieh, CH, Tsai, TH
Journal of food and drug analysis. 2018;(2S):S88-S95
Abstract
With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. Therefore, this study aimed to collect the results of pharmacokinetic studies relating to the concurrent use of cancer chemotherapy and complementary and alternative therapies. According to the National Health Insurance (NHI) database in Taiwan and several publications, the three most commonly prescribed formulations for cancer patients are Xiang-Sha-Liu-Jun-Zi-Tang, Jia-Wei-Xiao-Yao-San and Bu-Zhong-Yi-Qi-Tang. The three most commonly prescribed single herbs for cancer patients are Hedyotis diffusa, Scutellaria barbata, and Astragalus membranaceus. Few studies have discussed herb-drug interactions involving these herbs from a pharmacokinetics perspective. Here, we reviewed Jia-Wei-Xiao-Yao-San, Long-Dan-Xie-Gan-Tang, Curcuma longa and milk thistle to provide information based on pharmacokinetic evidence for healthcare professionals to use in educating patients about the risks of the concomitant use of various remedies.