German physicians' perceptions and views on complementary medicine in pediatric oncology: a qualitative study.

Complementary and alternative medicine (CAM) use in children with cancer has a high prevalence. If (parents of) patients bring up the topic of CAM, pediatric oncologists (POs) face considerable challenges regarding knowledge and professional behavior. In this study, we explore German POs' understanding of CAM and related attitudes as well as challenges and strategies related to CAM discussions by means of semi-structured interviews analyzed according to principles of qualitative thematic analysis with parents of children with cancer. We could conduct 14 interviews prior to theoretical saturation. The interviews had a duration of 15-82 min (M = 30.8, SD = 18.2). Professional experience in pediatric oncology was between 0.5 and 26 years (M = 13.8, SD = 7.6). Main themes identified were a heterogeneous understanding and evaluation of CAM, partly influenced by personal experiences and individual views on plausibility; the perception that CAM discussions are a possible tool for supporting parents and their children and acknowledgement of limitations regarding implementation of CAM discussions; and uncertainty and different views regarding professional duties and tasks when being confronted with CAM as a PO. Our interdisciplinary interpretation of findings with experts from (pediatric) oncology, psychology, and ethics suggests that there is need for development of a consensus on the minimal professional standards regarding addressing CAM in pediatric oncology.

Utilisation of complementary medicine in cancer patients and survivors: Expected benefits and its association to psychosocial factors.

INTRODUCTION: Previous research showed that various factors are associated with the use of complementary medicine (CM) in cancer patients. This study aimed to analyse the expected benefits of CM use in its association with medical, sociodemographic and psychosocial variables. METHODS: In a cross-sectional survey, we assessed the use of CM, expected benefits of CM, depression and quality of life. An exploratory factor analysis (EFA) was performed. Multiple regression analysis was carried out with the factors derived from the EFA as dependent variables. RESULTS: Based on 292 cancer CM user, EFA revealed two factors: a supportive effect (SPE) and an antitumoral effect (ATE). In the multiple regression analysis, reduced emotional functioning and the diagnosis of breast cancer are associated with the higher expectation of a supportive effect of CM (p < 0.001), explaining 7.1% of the variance. Emotional functioning, educational level and metastases are associated with higher expectation of an antitumoral effect of CM (p < 0.001) and explained 14.8% of the variance. DISCUSSION: This study provides evidence that two overall domains (supportive effect and anti-tumoural effect) characterise the benefits of CM expected by cancer patients. Psychosocial and medical variables are associated with both domains, but explain only small proportion of the variance.

Green tea (Camellia sinensis) for the prevention of cancer.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. OBJECTIVES: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. SEARCH METHODS: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. SELECTION CRITERIA: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. DATA COLLECTION AND ANALYSIS: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. MAIN RESULTS: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. AUTHORS' CONCLUSIONS: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.

Herb-drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment.

PURPOSE: To develop a system to estimate the risk of herb-drug interactions that includes the available evidence from clinical and laboratory studies, transparently delineates the algorithm for the risk estimation, could be used in practice settings and allows for adaptation and update. METHODS: We systematically searched Drugbank, Transformer, Drug Information Handbook, European and German Pharmacopoeia and MEDLINE for studies on herb-drug interactions of five common medicinal plants (coneflower, ginseng, milk thistle, mistletoe and St. John's wort). A diverse set of data were independently extracted by two researchers and subsequently analysed by a newly developed algorithm. Results are displayed in the form of interaction risk categories. The development of the algorithm was guided by an expert panel consensus process. RESULTS: From 882 publications retrieved by the search, 154 studies were eligible and provided 529 data sets on herbal interactions. The developed algorithm prioritises results from clinical trials over case reports over in vitro investigations and considers type of study, consistency of study results and study outcome for clinical trials as well as identification, permeability, bioavailability, and interaction potency of an identified herbal perpetrator for in vitro investigations. Risk categories were assigned to and dynamically visualised in a colour-coded matrix format. CONCLUSIONS: The novel algorithm allows to transparently generate and dynamically display herb-drug interaction risks based on the available evidence from clinical and laboratory pharmacologic studies. It provides health professionals with readily available and easy updatable information about the risk of pharmacokinetic interactions between herbs and oncologic drugs.

Selenium for preventing cancer.

BACKGROUND: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation. AUTHORS' CONCLUSIONS: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

A consultation training program for physicians for communication about complementary medicine with breast cancer patients: a prospective, multi-center, cluster-randomized, mixed-method pilot study.

BACKGROUND: The aim was to develop and evaluate a training program for physicians for communicating with breast cancer patients about complementary medicine (CM). METHODS: In a cluster-randomized pilot trial eight breast cancer centers (two physicians per center) were randomized to either a complementary communication training program (9 h e-learning + 20 h on-site skills training) or to a control group without training. Each physician was asked to consult ten patients for whom he or she is not the physician in charge. We used mixed methods: Quantitative outcomes included physicians' assessments (empathy, complexity of consultation, knowledge transfer) and patients' assessments (satisfaction, empathy, knowledge transfer). For qualitative analyses, 15 (eight in the training and seven in the control group) videotaped consultations were analyzed based on grounded theory, and separate focus groups with the physicians of both groups were conducted. RESULTS: A total of 137 patients were included. Although cluster-randomized, physicians in the two groups differed. Those in the training group were younger (33.4 ± 8.9 vs. 40.0 ± 8.5 years) and had less work experience (5.4 ± 8.9 vs. 11.1 ± 7.4 years). Patient satisfaction with the CM consultation was relatively high on a scale from 0 to 24 and was comparable in the two groups (training group: 19.4 ± 4.6; control group 20.5 ± 4.1). The qualitative findings showed that physicians structured majority of consultations as taught during the training. Comparing only the younger and less CM experienced physicians, those trained in CM communication felt more confident discussing CM-related topics than those without training. CONCLUSION: A CM communication-training program might be especially beneficial for physicians with less consulting experience when communicating about CM-related issues. A larger trial using more suitable quantitative outcomes needs to confirm this. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02223091 , date of registration: 7 February 2014.

Laetrile treatment for cancer.

BACKGROUND: Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous. OBJECTIVES: To assess the alleged anti-cancer effect and possible adverse effects of laetrile and amygdalin. SEARCH METHODS: We searched the following databases: CENTRAL (2014, Issue 9); MEDLINE (1951-2014); EMBASE (1980-2014); AMED; Scirus; CINAHL (all from 1982-2015); CAMbase (from 1998-2015); the MetaRegister; the National Research Register; and our own files. We examined reference lists of included studies and review articles and we contacted experts in the field for knowledge of additional studies. We did not impose any restrictions of timer or language. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We searched eight databases and two registers for studies testing laetrile or amygdalin for the treatment of cancer. Two review authors screened and assessed articles for inclusion criteria. MAIN RESULTS: We located over 200 references, 63 were evaluated in the original review, 6 in the 2011 and none in this update. However, we did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk-benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative.

Selenium for preventing cancer.

BACKGROUND: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS: Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Education about complementary and alternative medicine in cancer self-help groups by trained peers.

PURPOSE: On average, about 50% of cancer patients use complementary and alternative medicine (CAM) in addition to conventional cancer treatment. Since there is a high need for information, patients often search for information about CAM and share experiences with peers, especially in self-help groups. In this study, we tested and evaluated an educational concept developed for group leaders of cancer self-help groups on how to approach the topic of CAM in their peer groups. METHODS: The educational concept has been developed and piloted with health care professionals and representatives from different self-help organizations in Germany. It aims to inform and discuss the possibilities and limitations of CAM in terms of scientific evidence, to reflect user behavior, and to provide a guide on how to find and evaluate reliable and evidence-based information sources. First, self-help group leaders took part in an on-site training where they were educated on various CAM topics with the goal of being able to conduct the educational concept in their respective self-help groups. Then, the educated group leaders performed this concept in their groups. The educational concept was evaluated by both the group leaders and participants with respect to acceptance, usefulness, and satisfaction using paper-pencil questionnaires. The study was conducted in Germany based on an observational study design with a six-month follow-up. For the analyses, descriptive and univariate statistics for dependent samples were used. RESULTS: A total of n = 50 interested group leaders conducted the educational program in their groups. The most common implementation barriers were organizational or structural problems, as well as the feeling of being overwhelmed with managing the program in their groups. A total of n = 423 participants were educated with this program by their respective group leaders. The majority felt satisfied with the educational program and improved their knowledge about CAM. At the six months follow-up (T2), significantly more participants had consulted their physicians to inform themselves about CAM and felt more confident in finding reliable information about CAM. CONCLUSIONS: In this observational study, we have managed to successfully implement an educational concept with respect to the topic of CAM in cancer self-help groups. Based on the results, the concept approach will be modified to include both a CAM- professional and group leader to train the self-help groups. In the future, the effects of the program should be tested by a randomized trial.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients.

BACKGROUND: High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia. OBJECTIVES: To assess the effect of prophylactic colony-stimulating factors (CSFs) in reducing the incidence and duration of FN, and all-cause and infection-related mortality during chemotherapy in patients with breast cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing CSFs (any dose) with placebo or no treatment in patients with breast cancer at any stage, at risk of developing FN while undergoing any type of chemotherapy. DATA COLLECTION AND ANALYSIS: We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for binary outcomes. At least two review authors independently extracted data and assessed the risk of bias of the included studies. Trial authors were contacted for further details when information was unclear. MAIN RESULTS: We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged as being at least at moderate risk of bias. The strength of the evidence was weak for the majority of outcomes, which was mostly because of the small numbers of evaluable patients, varying definitions, as well as unclear measurements of the trials' outcomes and uncertain influences of supportive treatments on them. In most trials, the chemotherapy regimens had a risk of FN that was below the threshold at which current guidelines recommend routine primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity which can be explained by possible differential effects of G-CSFs and GM-CSFs and different definitions of FN. A significant reduction in early mortality was observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 patients; wherein 19 of these 23 events occurred in one study and 17 events were attributed to progression of the disease by the study authors. For infection-related mortality, there were no significant differences between CSF and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the scheduled dose of chemotherapy did not differ between CSF-treated and control groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number needed to treat for an additional harmful outcome (NNTH) 3) and injection-site reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). AUTHORS' CONCLUSIONS: In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of benefit in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.

A Randomized, Controlled Pilot Study to Evaluate the Immediate Effect of Targeted Exercise Therapy on Cancer-Related Fatigue in Cancer Survivors: The FatiGO Study.

OBJECTIVES: Cancer-related fatigue (CRF) is a clinically relevant side effect that impairs cancer survivors after treatment cessation. Exercise interventions have proven effective; however, specific exercise modalities remain untested. The purpose of this study was to evaluate the feasibility of daily fatigue screenings and to show the impact of various exercise interventions on CRF. METHODS: The randomized controlled pilot study ran for 4 weeks with 3 training sessions per week, in 5 groups: endurance versus strength (moderate- and vigorous-intensity levels for each) compared to a non-active control group. The primary outcome was feasibility; more specifically, it was evaluated whether the documentation with the Numerical Rating Scale (NRS) on a daily basis and the Multidimensional Fatigue Inventory (MFI) on a weekly basis are usable assessments to generate information about CRF. RESULTS: Over the course of the 4-week intervention, 8.3% of the participants (n = 3) dropped out. Thirty-three of the initial 36 participants completed the exercise sessions with an adherence of 95%. Measurements of daily fatigue were collected three times per day, 85% of which were completely filled out. In regard to weekly fatigue, all but one of the questionnaires were submitted (99.5%). Neither during the intervention nor during the tests did any serious adverse events occur within the FatiGO study; hence, the exercise intervention is considered to be feasible for participants. CONCLUSIONS: This pilot study showed the feasibility of close-meshed daily fatigue screening. Preliminary data indicate that cancer survivors are able to train in high-intensity ranges with tendencies toward decreased fatigue. Therefore, practicability of the study design is shown. Further results are expected within the prospective multicenter trial.

Meta-Analysis of Randomized Controlled Trials on Yoga, Psychosocial, and Mindfulness-Based Interventions for Cancer-Related Fatigue: What Intervention Characteristics Are Related to Higher Efficacy?

Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research.

Interprofessional evidence-based counselling programme for complementary and integrative healthcare in patients with cancer: study protocol for the controlled implementation study CCC-Integrativ.

INTRODUCTION: According to international literature, patients with cancer wish to have information on complementary and integrative healthcare (CIH). Medical guidelines recommend actively approaching patients with cancer discussing potential benefits and risks of individual CIH methods. While some CIH methods, for example, acupuncture and yoga, have been proven effective in high-quality studies, other CIH methods lack studies or bear the risk of interactions with chemotherapeutics, for example, herbal drugs. Therefore, an evidence-based interprofessional counselling programme on CIH will be implemented at four Comprehensive Cancer Centres in the federal state of Baden-Wuerttemberg, Germany. METHODS AND ANALYSIS: A complex intervention consisting of elements on patient, provider and system levels will be developed and evaluated within a multilayer evaluation design with confirmatory evaluation on patient level. Patients with a cancer diagnosis within the last 6 months will receive three individual counselling sessions on CIH within 3 months (=intervention on patient level). The counselling will be provided by an interprofessional team of medical and nursing staff. For this purpose, an intensive online training programme, a CIH knowledge database and an interprofessional team-building process were developed and implemented (=intervention on provider level). Moreover, training events on the basics of CIH are offered in the outpatient setting (=intervention on system level). Primary outcome of the evaluation at the patient level is patient activation measured (PAM) with the PAM-13 after 3 months. Secondary outcomes, for example, quality of life, self-efficacy and clinical parameters, will be assessed at baseline, after 3 months and at 6 months follow-up. The intervention group (n=1000) will be compared with a control group (n=500, treatment as usual, no CIH counselling. The outcomes and follow-up times in the control group are the same as in the intervention group. Moreover, the use of health services will be analysed in both groups using routine data. A qualitative-quantitative process evaluation as well as a health economic evaluation will identify relevant barriers and enabling factors for later roll-out. ETHICS AND DISSEMINATION: The study has been approved by the appropriate Institutional Ethical Committee of the University of Tuebingen, No. 658/2019BO1. The results of these studies will be disseminated to academic audiences and in the community. TRIAL REGISTRATION NUMBER: DRKS00021779; Pre-results.

Laetrile treatment for cancer.

BACKGROUND: Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous. OBJECTIVES: To assess the alleged anti-cancer effect and possible adverse effects of laetrile and amygdalin. SEARCH METHODS: We searched the following databases: CENTRAL (2011, Issue 1); MEDLINE (1951-2011); EMBASE (1980-2011); AMED; Scirus; CancerLit; CINAHL (all from 1982-2011); CAMbase (from 1998-2011); the MetaRegister; the National Research Register; and our own files. We examined reference lists of included studies and review articles and we contacted experts in the field for knowledge of additional studies. We did not impose any restrictions of timer or language. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We searched eight databases and two registers for studies testing laetrile or amygdalin for the treatment of cancer. Two review authors screened and assessed articles for inclusion criteria. MAIN RESULTS: We located over 200 references, 63 were evaluated in the original review and an additional 6 in this update. However, we did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk-benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative.

Thymic peptides for treatment of cancer patients.

BACKGROUND: Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy. OBJECTIVES: To evaluate the effectiveness of pTE and sTP for the management of cancer. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010). SELECTION CRITERIA: Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis. MAIN RESULTS: We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10  for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23,  P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias. AUTHORS' CONCLUSIONS: Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

Selenium for preventing cancer.

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for1. an aetiological relationship between selenium exposure and cancer risk in women and men?2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio (OR) 0.69 (95% confidence interval (CI) 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics.The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

Nursing Procedures for the Prevention and Treatment of Mucositis Induced by Cancer Therapies: Clinical Practice Guideline Based on an Interdisciplinary Consensus Process and a Systematic Literature Search.

BACKGROUND: Patients with cancer receiving tumor therapy often suffer from oral mucositis. OBJECTIVES: The aim of this project was to summarize experiences with nursing procedures by experts in integrative oncology and to establish recommendations for nursing interventions that can prevent or cure mucositis. METHODS: The study design was an interdisciplinary consensus process based on a systematic literature search. RESULTS: The panel discussed and agreed on 19 nursing procedures, which included mouthwashes, such as teas, supplements, oil applications, and different kinds of ice cubes to suck, as well as flaxseed solution, propolis, and mare milk. Twelve interventions were classified as effective, with effectiveness for OraLife, propolis, sea buckthorn pulp oil, marshmallow root tea also for xerostomia, Helago chamomile oil, mare milk, and Saliva Natura rated as highly effective in clinical experience. In the systematic literature search, a total of 12 out of 329 randomized controlled trials and meta-analyses on chamomile (n = 3), Calendula (n = 1) and sage (n = 1), propolis (n = 2), and sucking ice cubes (cryotherapy; n = 5) met all inclusion criteria. Trial evidence for effectiveness in oral mucositis was revealed for propolis and cryotherapy. CONCLUSIONS: The current evidence supports the use of some nursing procedures (f.e. propolis for 2 and 3 grade mucositis) for improving oral mucositis during cancer therapies. There is still a need to define general clinical practice guidelines for the supportive treatment of mucositis, as well as for more interdisciplinary research in this area.

Educational Program in Complementary and Alternative Medicine for Cancer Self-Help Groups.

BACKGROUND: The use of complementary and alternative medicine (CAM) among cancer patients is estimated to be approximately 40%. In self-help groups there is a need for information about CAM. This pilot study aimed to develop and evaluate a CAM educational program for cancer self-help groups. METHODS: The educational program was developed in cooperation with health professionals and representatives of cancer self-help organizations. Participants were trained to increase their knowledge about CAM, to reflect their user behavior, and to use evidence-based information. Self-help group leaders were educated along the curriculum and motivated to carry out the course in their groups. Using questionnaires it was evaluated in terms of acceptance, feasibility, and satisfaction by participants. RESULTS: A total of 171 self-help group leaders were educated. In a pilot run 7 implemented the course in their groups, with a total of 70 participants. Most of them (n = 60, 85.7%) appreciated its contents and material and would recommend it. Overall acceptance and satisfaction were high. CONCLUSIONS: The educational program was implemented successfully in a small sample and showed positive results for acceptance and feasibility. In addition to consultation by experts, it can be a good option to inform cancer survivors about CAM.

KOKON: A Germany-Wide Collaborative Research Project to Identify Needs, Provide Information, Foster Communication and Support Decision-Making about Complementary and Alternative Medicine in Oncology.

BACKGROUND: The German Cancer Aid set up a priority research programme with the intention to generate high-quality information based on evidence and to make this information easily accessible for health-care professionals and advisors, researchers, patients, and the general public. SUMMARY: The Kompetenznetz Komplementärmedizin in der Onkologie (KOKON) received 2 funding periods within this programme. During the first funding period, KOKON assessed patients' and health-care professionals' informational needs, developed a consulting manual for physicians, developed an education programme for self-help groups, set up a knowledge database, and developed a pilot information website for patients. Funding period 2 continues with work that allows cancer patients and health-care professionals to make informed decisions about complementary and alternative medicine (CAM). For this aim, KOKON evaluates training programmes for physicians (oncology physicians, paediatric oncologists, and general practitioners) and for self-help groups. All training programmes integrate results from an analysis of the ethical, psychological, and medical challenges of CAM in the medical encounter, and the knowledge database is being extended with issues related to CAM for supportive and palliative care. Key Message: A Germany-wide collaborative research project to identify needs, provide information, foster communication, and support decision-making about CAM in oncology is being set up.

Defining Criteria for Guiding Cancer Patients to Find a Reputable Complementary Medicine Provider: Results of a Literature Review and a Consensus Procedure.

PURPOSE: Even in cases of positive evidence for complementary medicine (CM) therapies, it is still difficult for cancer patients to identify reputable providers. The aim of this study was to develop and evaluate a criteria list to provide guidance to cancer patients seeking a reputable CM provider. METHODS: The design combined a literature review, an expert consensus procedure (n=15) and an assessment from three stakeholder perspectives (patients (n=18), CM providers (n=26) and oncology physicians (n=20)). RESULTS: A total of 30 existing CM criteria were extracted from the literature, and 12 more were added by the experts. The main challenge was to define criteria that could easily be applied by the patients. A final comprehensive list of 8 criteria guiding cancer patients to find a reputable CM provider was developed. CONCLUSION: Health professionals and cancer information services might find the criteria list helpful when aiming to strengthen patients' awareness of quality-related factors associated with CM providers. The criteria developed might be helpful when standards are established for quality assurance in CM in oncology.