PURPOSE: To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients.
METHODS: We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis.
RESULTS: We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects.
CONCLUSIONS: Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.
AIMS: To review scientific evidence related to oral cryotherapy to prevent oral mucositis after cancer therapy.
BACKGROUND: Oral mucositis is a common complication of cancer therapy. In the most severe form of oral mucositis, patients cannot eat or drink at all and must receive nutrition and fluid replacement through parenteral support. Topical cooling of the oral mucosa may be an option for the prevention of oral mucositis.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: The literature search was performed using the Ovid MEDLINE, Embase, Cochrane Library, and CINAHL Complete electronic databases for articles published up to 2017. The reference lists of all retrieved articles were manually reviewed to identify additional relevant studies.
RESULTS: Of 353 publications, 15 randomized controlled trials, involving 919 cancer patients, conducted between 1994 and 2017 were included in the present meta-analysis. Oral cryotherapy, applied during treatment of solid cancers, led to a statistically lower level (P < .05) of oral mucositis overall, and of the more severe grades (3-4 and 2-4).
CONCLUSIONS: Results of this study provide a scientific basis for oral cryotherapy as a viable nursing intervention that can significantly reduce the occurrence of severe oral mucositis.
Background and objectives: Oral mucositis is one of the main adverse events of cancer treatment with chemotherapy or radiation therapy. It presents as erythema, atrophy or/and ulceration of oral mucosa. It occurs in almost all patients, who receive radiation therapy of the head and neck area and from 20% to 80% of patients who receive chemotherapy. There are few clinical trials in the literature proving any kind of treatment or prevention methods to be effective. Therefore, the aim of this study is to perform systematic review of literature and examine the most effective treatment and prevention methods for chemotherapy or/and radiotherapy induced oral mucositis. Materials and methods: Clinical human trials, published from 1 January 2007 to 31 December 2017 in English, were included in this systematic review of literature. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocol was followed while planning, providing objectives, selecting studies and analyzing data for this systematic review. "MEDLINE" and "PubMed Central" databases were used to search eligible clinical trials. Clinical trials researching medication, oral hygiene, cryotherapy or laser therapy efficiency in treatment or/and prevention of oral mucositis were included in this systematic review. Results: Results of the studies used in this systematic review of literature showed that laser therapy, cryotherapy, professional oral hygiene, antimicrobial agents, Royal jelly, L. brevis lozenges, Zync supplementation and Benzydamine are the best treatment or/and prevention methods for oral mucositis. Conclusions: Palifermin, Chlorhexidine, Smecta, Actovegin, Kangfuxin, L. brevis lozenges, Royal jelly, Zync supplement, Benzydamine, cryotherapy, laser therapy and professional oral hygiene may be used in oral mucositis treatment and prevention.
PURPOSE: Traditional and complementary medicine (T&CM) use in children with cancer is well established among high-income, upper middle-income, low-middle-income, and low-income countries (HIC, UMIC, LMIC, LIC, respectively). In HIC, a developing body of evidence exists for several T&CM therapies; however, evidence in other income settings is less well described despite a significantly higher use when compared to reports from HIC. The aim of this systematic review was to evaluate the evidence for T&CM for a variety of supportive care indications among children with cancer.
METHODS: We performed a systematic review following the PRISMA guidelines of randomized, controlled clinical trials from inception through September 2016. Our eligibility criteria were limited to T&CM studies performed in children and adolescents undergoing treatment for a pediatric malignancy.
RESULTS: Of 6342 studies identified, 44 met inclusion criteria. Two clinical trials reported on acupuncture, 1 reported on aromatherapy, 9 evaluated massage therapy, and 32 reported on dietary supplements. Twenty-two studies were performed in HIC, 15 in UMIC, and 7 in LMIC. T&CM therapies were most commonly investigated for the prevention or management of mucositis, weight loss, and febrile neutropenia. Encouraging results were reported for select interventions; however, the majority of studies were classified as poor to fair quality.
CONCLUSION: Our search revealed numerous clinical studies investigating the use of T&CM for supportive care purposes in pediatric oncology in HIC, UMIC, and LMIC. Although limited, these results could inform supportive care resource allocation and indicate where T&CM may serve to fill gaps where access to care may be limited.
PURPOSE: To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT).
METHODS: The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations.
RESULTS: We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children.
CONCLUSIONS: All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted.
BACKGROUND: Dental plaque associated gingivitis is a reversible inflammatory condition caused by accumulation and persistence of microbial biofilms (dental plaque) on the teeth. It is characterised by redness and swelling of the gingivae (gums) and a tendency for the gingivae to bleed easily. In susceptible individuals, gingivitis may lead to periodontitis and loss of the soft tissue and bony support for the tooth. It is thought that chlorhexidine mouthrinse may reduce the build-up of plaque thereby reducing gingivitis.
OBJECTIVES: To assess the effectiveness of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for the control of gingivitis and plaque compared to mechanical oral hygiene procedures alone or mechanical oral hygiene procedures plus placebo/control mouthrinse. Mechanical oral hygiene procedures were toothbrushing with/without the use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment.To determine whether the effect of chlorhexidine mouthrinse is influenced by chlorhexidine concentration, or frequency of rinsing (once/day versus twice/day).To report and describe any adverse effects associated with chlorhexidine mouthrinse use from included trials.
SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 28 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 28 September 2016); MEDLINE Ovid (1946 to 28 September 2016); Embase Ovid (1980 to 28 September 2016); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 28 September 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA: We included randomised controlled trials assessing the effects of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for at least 4 weeks on gingivitis in children and adults. Mechanical oral hygiene procedures were toothbrushing with/without use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment. We included trials where participants had gingivitis or periodontitis, where participants were healthy and where some or all participants had medical conditions or special care needs.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where feasible. For continuous outcomes, we used means and standard deviations to obtain the mean difference (MD) and 95% confidence interval (CI). We combined MDs where studies used the same scale and standardised mean differences (SMDs) where studies used different scales. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. Due to anticipated heterogeneity we used random-effects models for all meta-analyses.
MAIN RESULTS: We included 51 studies that analysed a total of 5345 participants. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however, this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect. Gingivitis After 4 to 6 weeks of use, chlorhexidine mouthrinse reduced gingivitis (Gingival Index (GI) 0 to 3 scale) by 0.21 (95% CI 0.11 to 0.31) compared to placebo, control or no mouthrinse (10 trials, 805 participants with mild gingival inflammation (mean score 1 on the GI scale) analysed, high-quality evidence). A similar effect size was found for reducing gingivitis at 6 months. There were insufficient data to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 (moderate or severe levels of gingival inflammation). Plaque Plaque was measured by different indices and the SMD at 4 to 6 weeks was 1.45 (95% CI 1.00 to 1.90) standard deviations lower in the chlorhexidine group (12 trials, 950 participants analysed, high-quality evidence), indicating a large reduction in plaque. A similar large reduction was found for chlorhexidine mouthrinse use at 6 months. Extrinsic tooth staining There was a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 4 to 6 weeks. The SMD was 1.07 (95% CI 0.80 to 1.34) standard deviations higher (eight trials, 415 participants analysed, moderate-quality evidence) in the chlorhexidine mouthrinse group. There was also a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 7 to 12 weeks and 6 months. Calculus Results for the effect of chlorhexidine mouthrinse on calculus formation were inconclusive. Effect of concentration and frequency of rinsing There were insufficient data to determine whether there was a difference in effect for either chlorhexidine concentration or frequency of rinsing. Other adverse effects The adverse effects most commonly reported in the included studies were taste disturbance/alteration (reported in 11 studies), effects on the oral mucosa including soreness, irritation, mild desquamation and mucosal ulceration/erosions (reported in 13 studies) and a general burning sensation or a burning tongue or both (reported in nine studies).
AUTHORS' CONCLUSIONS: There is high-quality evidence from studies that reported the Löe and Silness Gingival Index of a reduction in gingivitis in individuals with mild gingival inflammation on average (mean score of 1 on the 0 to 3 GI scale) that was not considered to be clinically relevant. There is high-quality evidence of a large reduction in dental plaque with chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for 4 to 6 weeks and 6 months. There is no evidence that one concentration of chlorhexidine rinse is more effective than another. There is insufficient evidence to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 indicating moderate or severe levels of gingival inflammation. Rinsing with chlorhexidine mouthrinse for 4 weeks or longer causes extrinsic tooth staining. In addition, other adverse effects such as calculus build up, transient taste disturbance and effects on the oral mucosa were reported in the included studies.
AIM: The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy.
BACKGROUND: Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence.
DESIGN: Quantitative systematic review.
DATA SOURCES: Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy.
REVIEW METHODS: Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose.
RESULTS: Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each.
CONCLUSION: There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions.
INTRODUCTION: The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients.
MATERIAL AND METHODS: An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words "oral mucositis", "prevention" and "treatment" with the terms "chemotherapy" and "radiotherapy" by means of the boolean operators "AND" and "NOT". A total of 268 articles were obtained, of which 96 met the inclusion criteria.
RESULTS: Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation.
CONCLUSIONS: Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis - though further studies are needed to confirm the results obtained.
KEY WORDS: Chemotherapy-Induced Oral Mucositis Treatment.
OBJECTIVES: Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.
METHODS: PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay.
RESULTS: Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively).
CONCLUSIONS: Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.
BACKGROUND: It is well documented that malnutrition is a common complication of paediatric malignancy and its treatment. Malnutrition can often be a consequence of cancer itself or a result of chemotherapy. Nutritional support aims to reverse malnutrition seen at diagnosis, prevent malnutrition associated with treatment and promote weight gain and growth. The most effective and safe forms of nutritional support in children and young people with cancer are not known.
OBJECTIVES: To determine the effects of any form of parenteral (PN) or enteral (EN) nutritional support, excluding vitamin supplementation and micronutrient supplementation, in children and young people with cancer undergoing chemotherapy and to determine the effect of the nutritional content of PN and EN. This is an update of a previous Cochrane review.
SEARCH METHODS: We searched the following databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the National Research Register (2007) and Dissertations & Theses (2007). Experts in the field were also contacted for information on relevant trials. For this update, we searched the same electronic databases from 2006 to September 2013. We also scrutinised the reference lists of included articles to identify additional trials.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any form of nutritional support with another, or control, in children or young people with cancer undergoing chemotherapy.
DATA COLLECTION AND ANALYSIS: Two authors independently selected trials. At least two authors independently assessed quality and extracted data. We contacted trialists for missing information.
MAIN RESULTS: The current review included the eight trials from the initial review and six new trials which randomised 595 participants (< 21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The trials were all of low quality with the exception of two of the trials looking at glutamine supplementation. One small trial found that compared to EN, PN significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33), serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00, 95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One trial comparing peripheral PN and EN with central PN found that mean daily weight gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI -26.81 to -3.19) were significantly less for the peripheral PN and EN group, whereas mean change in serum albumin was significantly greater for that group (MD 0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found an increase in mean energy intake (% recommended daily amount) in children fed an energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to 39%). Three studies looked at glutamine supplementation. The evidence suggesting that glutamine reduces severity of mucositis was not statistically significant in two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and differences in reduction of infection rates were also not significant in two studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one study compared olive oil based PN to standard lipid containing PN. Despite similar calorie contents in both feeds, the standard lipid formula lead to greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study compared standard EN with fructooligosaccharide containing EN. There was no difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to 0.33), with adverse effects (nausea) occurring equally between the groups (RR 0.92, 95% CI 0.48 to 1.74).
AUTHORS' CONCLUSIONS: There is limited evidence from individual trials to suggest that PN is more effective than EN in well-nourished children and young people with cancer undergoing chemotherapy. The evidence for other methods of nutritional support remains unclear. Limited evidence suggests an energy dense feed increases mean daily energy intake and has a positive effect on weight gain. Evidence suggesting glutamine supplementation reduces incidence and severity of mucositis, infection rates and length of hospital stay is not statistically significant. Further research, incorporating larger sample sizes and rigorous methodology utilising valid and reliable outcome measures, is essential.
To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients.
METHODS:
We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis.
RESULTS:
We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects.
CONCLUSIONS:
Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.
