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Role of honey in preventing radiation-induced oral mucositis: a meta-analysis of randomized controlled trials.
An, W, Li, S, Qin, L
Food & function. 2021;(8):3352-3365
Abstract
BACKGROUND Radiotherapy-induced mucositis easily arouses oral ulceration, pain and xerostomia. Intense pain, difficulty swallowing and speaking greatly affect the quality of life and the treatment process. OBJECTIVE This study aimed to examine the effects of honey in preventing and treating radiotherapy-induced mucositis in patients with head and neck cancer using a different analytical strategy. METHODS Articles published until July 2020 were searched across PubMed, Embase, and Cochrane Library databases. Randomized controlled trials that evaluated honey were assessed by two reviewers. The number of mucositis incidences was the primary outcome. Weight loss, pain scale and incidence of severe pain were pooled to be calculated as secondary outcomes. Statistical analyses were conducted using RevMan5.3 software. The funnel plot was used to detect publication bias. RESULTS Overall, 11/179 records with 715 patients who received radiotherapy were included. Honey significantly reduced the incidence of grade 2 (OR: 0.43, 95%CI: 0.54-0.98, P = 0.03), grade 3 (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.16-0.35, P < 0.001) and grade 4 mucositis (OR: 0.17, 95%CI: 0.08-0.36, P < 0.001). In grade 1 (OR: 1.54, 95%CI: 1.15-2.06, P = 0.003), and honey was not significant in preventing radiation-induced mucositis. The incidence of unbearable pain was lower in the honey group at all grades (OR: -0.20, 95%CI: -0.33 to -0.07). The effect of honey on weight loss and pain score was not statistically significant. CONCLUSION Honey can prevent and alleviate grade 2-4 mucositis, especially in high grade mucositis. Honey also provides some relief from severe pain. But, more evidence is required to prove that honey is an effective substance for relieving pain or minimizing weight loss.
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Diagnostic Accuracy of Amino Acid and FDG-PET in Differentiating Brain Metastasis Recurrence from Radionecrosis after Radiotherapy: A Systematic Review and Meta-Analysis.
Li, H, Deng, L, Bai, HX, Sun, J, Cao, Y, Tao, Y, States, LJ, Farwell, MD, Zhang, P, Xiao, B, et al
AJNR. American journal of neuroradiology. 2018;(2):280-288
Abstract
BACKGROUND Current studies that analyze the usefulness of amino acid and FDG-PET in distinguishing brain metastasis recurrence and radionecrosis after radiation therapy are limited by small cohort size. PURPOSE Our aim was to assess the diagnostic accuracy of amino acid and FDG-PET in differentiating brain metastasis recurrence from radionecrosis after radiation therapy. DATA SOURCES Studies were retrieved from PubMed, Embase, and the Cochrane Library. STUDY SELECTION Fifteen studies were included from the literature. Each study used PET to differentiate radiation necrosis from tumor recurrence in contrast-enhancing lesions on follow-up brain MR imaging after treating brain metastasis with radiation therapy. DATA ANALYSIS Data were analyzed with a bivariate random-effects model. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were pooled, and a summary receiver operating characteristic curve was fit to the data. DATA SYNTHESIS The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of PET were 0.85, 0.88, 7.0, 0.17, and 40, respectively. The area under the receiver operating characteristic curve was 0.93. On subgroup analysis of different tracers, amino acid and FDG-PET had similar diagnostic accuracy. Meta-regression analysis demonstrated that the method of quantification based on patient, lesion, or PET scan (based on lesion versus not, P = .07) contributed to the heterogeneity. LIMITATIONS Our study was limited by small sample size, and 60% of the included studies were of retrospective design. CONCLUSIONS Amino acid and FDG-PET had good diagnostic accuracy in differentiating brain metastasis recurrence from radionecrosis after radiation therapy.
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Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers.
Lawrie, TA, Green, JT, Beresford, M, Wedlake, L, Burden, S, Davidson, SE, Lal, S, Henson, CC, Andreyev, HJN
The Cochrane database of systematic reviews. 2018;(1):CD012529
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Abstract
BACKGROUND An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). OBJECTIVES To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. SEARCH METHODS We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017. We also searched clinical trial registries. SELECTION CRITERIA We included randomised controlled trials (RCTs) of interventions to prevent adverse gastrointestinal effects of pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic cancers, including radiotherapy techniques, other aspects of radiotherapy delivery, pharmacological interventions and non-pharmacological interventions. Studies needed a sample size of 20 or more participants and needed to evaluate gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric parameters only. We also excluded trials of interventions to treat acute gastrointestinal symptoms, trials of altered fractionation and dose escalation schedules, and trials of pre- versus postoperative radiotherapy regimens, to restrict the vast scope of the review. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology. We used the random-effects statistical model for all meta-analyses, and the GRADE system to rate the certainty of the evidence. MAIN RESULTS We included 92 RCTs involving more than 10,000 men and women undergoing pelvic radiotherapy. Trials involved 44 different interventions, including radiotherapy techniques (11 trials, 4 interventions/comparisons), other aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological interventions (38 trials, 16 interventions), and non-pharmacological interventions (29 trials, 13 interventions). Most studies (79/92) had design limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear risk of bias and 29 studies had a high risk of bias. Main findings include the following:Radiotherapy techniques: Intensity-modulated radiotherapy (IMRT) versus 3D conformal RT (3DCRT) may reduce acute (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.26 to 0.88; participants = 444; studies = 4; I2 = 77%; low-certainty evidence) and late gastrointestinal (GI) toxicity grade 2+ (RR 0.37, 95% CI 0.21 to 0.65; participants = 332; studies = 2; I2 = 0%; low-certainty evidence). Conformal RT (3DCRT or IMRT) versus conventional RT reduces acute GI toxicity grade 2+ (RR 0.57, 95% CI 0.40 to 0.82; participants = 307; studies = 2; I2 = 0%; high-certainty evidence) and probably leads to less late GI toxicity grade 2+ (RR 0.49, 95% CI 0.22 to 1.09; participants = 517; studies = 3; I2 = 44%; moderate-certainty evidence). When brachytherapy (BT) is used instead of external beam radiotherapy (EBRT) in early endometrial cancer, evidence indicates that it reduces acute GI toxicity (grade 2+) (RR 0.02, 95% CI 0.00 to 0.18; participants = 423; studies = 1; high-certainty evidence).Other aspects of radiotherapy delivery: There is probably little or no difference in acute GI toxicity grade 2+ with reduced radiation dose volume (RR 1.21, 95% CI 0.81 to 1.81; participants = 211; studies = 1; moderate-certainty evidence) and maybe no difference in late GI toxicity grade 2+ (RR 1.02, 95% CI 0.15 to 6.97; participants = 107; studies = 1; low-certainty evidence). Evening delivery of RT may reduce acute GI toxicity (diarrhoea) grade 2+ during RT compared with morning delivery of RT (RR 0.51, 95% CI 0.34 to 0.76; participants = 294; studies = 2; I2 = 0%; low-certainty evidence). There may be no difference in acute (RR 2.22, 95% CI 0.62 to 7.93, participants = 110; studies = 1) and late GI toxicity grade 2+ (RR 0.44, 95% CI 0.12 to 1.65; participants = 81; studies = 1) between a bladder volume preparation of 1080 mls and that of 540 mls (low-certainty evidence). Low-certainty evidence on balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes.Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking.Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. AUTHORS' CONCLUSIONS Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However, evidence on some potential interventions shows that they probably have no role to play in reducing RT-related GI toxicity. More RCTs are needed for interventions with limited evidence suggesting potential benefits.
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Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non-small cell lung cancer-A meta-analysis.
Zhang, W, Li, J, Li, R, Zhang, Y, Han, M, Ma, W
Brachytherapy. 2018;(2):439-448
Abstract
PURPOSE This meta-analysis was conducted to investigate the efficacy and safety of 125I brachytherapy for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS Trials comparing 125I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS). RESULTS Fifteen studies including 1188 cases were included. The pooled result indicated that there were significant differences in ORR, DCR, and OS between 125I brachytherapy combined with chemotherapy and chemotherapy alone, but no statistic differences in gastrointestinal symptoms, leukopenia, myelosuppression, and hemoglobin reduction. Patients treated with 125I brachytherapy combined with chemotherapy have a higher relative risk of pneumothorax, bloody sputum, and pneumorrhagia compared with chemotherapy alone. Seeds migration only occurred in the group treated with 125I brachytherapy. There were significant differences in ORR, DCR, and myelosuppression between 125I brachytherapy alone and chemotherapy. CONCLUSIONS 125I brachytherapy combined with chemotherapy can significantly enhance the clinical efficacy and improve the OS of patients with advanced NSCLC without increasing the incidence of complications of chemotherapy. 125I brachytherapy alone can significantly enhance the clinical efficacy and reduce the incidence of myelosuppression compared with chemotherapy. However, 125I brachytherapy may cause lung injury. Large sample and higher-quality randomized controlled trials are needed to confirm the pooled results of complications.
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The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: a systematic review and meta-analysis.
Wang, YH, Yao, N, Wei, KK, Jiang, L, Hanif, S, Wang, ZX, Pei, CX
European journal of clinical nutrition. 2016;(11):1246-1253
Abstract
A systematic review and meta-analysis were designed to evaluate the efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer. We searched the Cochrane Library, PubMed, EMBASE and Web of Science up to November 2015. We also hand searched the citation lists of included studies and previously identified systematic reviews to identify further relevant trials. Odds ratio (OR) was used to compare efficacy, and the pooled OR was estimated using a random effects model; heterogeneity was assessed with Cochran's Q and the Higgins' I2-test. Two reviewers assessed trial quality and extracted data independently. Analysis and bias for each included study were performed using Review Manager 5.2. Nine randomized and placebo-controlled studies (N=1265 participants) were included for assessing efficacy, of which seven were about radiotherapy and two about chemotherapy. Probiotic groups were compared with control groups with respect to the the incidence of diarrhea, OR=0.47 (95% confidence interval 0.28-0.76; P=0.002). Eleven studies, including 1612 people (873 consuming probiotics and 739 not consuming probiotics), were used for the analysis of safety of probiotics. Of the 11 studies, seven studies had no adverse events (AEs) caused by probiotics, whereas four studies reported varying degrees of AEs in their treatment. Probiotics may have a beneficial effect in prevention of chemoradiotherapy-induced diarrhea generally, especially for Grade⩾2 diarrhea. Probiotics may rarely cause AEs.
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A systematic review and meta-analysis of probiotics for the management of radiation induced bowel disease.
Hamad, A, Fragkos, KC, Forbes, A
Clinical nutrition (Edinburgh, Scotland). 2013;(3):353-60
Abstract
BACKGROUND & AIMS A meta-analysis to estimate the efficacy of probiotics in prevention of radiation-induced bowel disease after pelvic radiotherapy has been performed. Previous attempts have arguably failed to provide a comprehensive analysis of clinical trials and their outcomes. METHODS We searched for studies indexed in Medline, EMBASE, Cochrane Library, and on-line clinical trials registers. There was no language or time limit. Each study was evaluated for methodological quality and outcomes. We identified four outcomes on which to perform meta-analysis: incidence of diarrhoea, loperamide use, watery, and soft stools (Bristol Stool Chart). Odds ratio (OR) was used to compare efficacy, and the pooled OR was estimated using a random effects model; heterogeneity was assessed with Cochran's Q and Higgins I(2) test. Analyses were performed using Review Manager 5.2. RESULTS Ten studies were included in our systematic review, of which six were subjected to meta-analysis to compare probiotics against placebo. Quality assessment showed an unclear risk due to incomplete outcome data and lack of performance of intention-to-treat analysis, while blinding and randomization issues were present in certain studies. Pooled results showed heterogeneity (Cochran's Q: p < 0.05; I(2): high). However the pooled OR for the incidence of diarrhoea, synthesized from 6 studies, significantly favoured the use of probiotics over control (OR = 0.44, 95% CI 0.21-0.92). Numerically, but not statistically, probiotics seem to decrease loperamide use (OR = 0.29, 95% CI 0.01-6.80) and the incidence of watery stools (OR = 0.36, 95% CI 0.05-2.81). CONCLUSIONS In conclusion, probiotic supplementation shows a probable beneficial effect in the prevention, and possible benefit in the treatment, of radiation-induced diarrhoea.
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Nutritional interventions for reducing gastrointestinal toxicity in adults undergoing radical pelvic radiotherapy.
Henson, CC, Burden, S, Davidson, SE, Lal, S
The Cochrane database of systematic reviews. 2013;(11):CD009896
Abstract
BACKGROUND Across the developed world, an estimated 150,000 to 300,000 people are treated annually with pelvic radiotherapy and 80% will develop gastrointestinal (GI) symptoms during treatment. Acute GI symptoms are associated with a greater risk of chronic, often debilitating, GI symptoms. Up to one-third of patients are malnourished before pelvic radiotherapy and up to four-fifths of patients lose weight during treatment. Malnutrition is linked to a higher risk of GI toxicity, which can lead to breaks in radiotherapy and early cessation of chemotherapy, thus compromising the efficacy of the primary cancer treatment. OBJECTIVES To assess the effects of nutritional interventions for reducing GI toxicity in adults undergoing radical pelvic radiotherapy. SEARCH METHODS We searched the Cochrane Gynaecological Cancer Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2012, MEDLINE and EMBASE to May 2012. We handsearched the citation lists of included studies and previous systematic reviews identified to identify further relevant trials. SELECTION CRITERIA We included studies if they were randomised controlled trials (RCTs) or non-randomised studies with concurrent comparison groups including quasi-randomised trials, cluster RCTs, non-randomised trials, prospective and retrospective cohort studies, and case series of 30 or more patients. We only included studies if they assessed the effect of a nutritional intervention in adults aged 18 years or over undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded patients with stomas and a previous history of inflammatory bowel disease. Nutritional support interventions could be provided at any stage before or during pelvic radiotherapy and included dietary counselling; dietary modification of fibre, lactose or fat; supplementary foods or drinks or fortified foods; standard oral nutrition supplements including polymeric-, peptide- or amino acid-based supplements and those where novel substrates have been added; enteral tube feeds; or parenteral nutrition (partial or total). We excluded probiotics, prebiotics and synbiotics. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. We assessed bias for each of the included studies using the bias assessment tables in the Cochrane software Review Manager5. We performed meta-analysis, when indicated, using the Mantel-Haenszel fixed-effect method or inverse variance fixed-effect method displayed with heterogeneity. We undertook meta-analyses on trials evaluating dietary modification against standard treatment for diarrhoea at the end of radiotherapy and for change in weight from baseline to end of radiotherapy. MAIN RESULTS The searches identified 7558 titles, and we excluded 7513 during title and abstract searches. We reviewed 45 papers in full, and excluded 39. We identified four studies on handsearching of the references, which, along with the six eligible papers from the database search, led to 10 studies being included. Four studies, three of which were RCTs and one prospective study, investigated the effect of elemental diet on GI symptoms; one RCT investigated the effect of dietary modification and elemental diet; and five RCTs investigated dietary modification. Studies were varied in terms of risk of bias. Data were dichotomised for presence and absence of diarrhoea at the end of radiotherapy for four trials evaluating dietary modification comprising modified fat, lactose, fibre or combinations of these dietary changes. A reduction in diarrhoea was demonstrated with nutritional intervention (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.51 to 0.87, four studies, 413 participants, moderate quality of evidence) with low heterogeneity (Chi(2) = 3.50, I(2) = 14%). Two trials evaluating dietary modification on weight change (comparing baseline and end of radiotherapy) showed no difference between intervention or control (mean difference (MD) -0.57 kg; 95% CI -1.22 to 0.09) with low heterogeneity (Chi(2) = 1.41, I(2) = 29%). Generally adverse effects were poorly reported in included studies. Elemental diet in particular was poorly tolerated. GI symptoms or toxicity > 6 months after radiotherapy was not reported in included studies AUTHORS' CONCLUSIONS There have been benefits demonstrated with dietary modification during pelvic radiotherapy to reduce diarrhoea. Those diets included single interventions or combinations of modified fat, lactose-restriction, fat-restriction and fibre supplementation. We were unable to meta-analyse elemental diet, as data were not available. We considered some of the studies to be at high risk of bias. There have been recent advances in novel, more targeted radiotherapy techniques, such that the findings of older studies need to be interpreted with caution. In addition, there were problems with compliance and palatability with some of the interventions, particularly elemental diet, which limits its usefulness in clinical practice.
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Radiation associated brainstem injury.
Mayo, C, Yorke, E, Merchant, TE
International journal of radiation oncology, biology, physics. 2010;(3 Suppl):S36-41
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Abstract
Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumes of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions 64 Gy.