Cancer Therapy-induced Mucositis Research Articles

An Innovative Approach to Clinical Practice Guideline Adaptation in the Nursing Profession in a Developing Country.

IntroductionHealthcare professionals should seek the necessary resources to improve the quality of care. Given the cultural, social, and economic differences, in every health care system, there are increasing needs for the adapted versions of clinical practice guidelines (CPGs). This study aimed to introduce an innovative CPG adaptation approach for nurses working in a developing country.MethodsThis study is comprised of three sections: a. An extensive systematic search of the literature, b. The adaptation process, c. Interviews, which were held with stakeholders, users and/or the target population. We applied all of the stages of guideline adaptation process according to Adaptation Resource Toolkit, with the integration of the findings of a systematic literature search and a qualitative content analysis in an “adolopted” new CPG.ResultsIn this study, we applied a mix of three methods namely adoption, adaptation and development (adolopment) of recommendations to save time, cost, and manpower efficiently. Moreover, we integrated the utilized qualitative research method and literature review with the adolopment approach to develop the recommendations.ConclusionGiven there is a paucity of nursing clinical practice guidelines (NCPGs) in the nursing management of cancer therapy-induced mucositis and to save time and costs, the findings emerging from the adoption, adaptation, and de novo guideline development by a panel of experts and qualitative content analysis (QCA) method were integrated to achieve a more comprehensive nursing practice guideline.

Photobiomodulation effects on head and neck squamous cell carcinoma (HNSCC) in an orthotopic animal model.

Photobiomodulation (PBM) has shown efficacy in preventing and treating cancer therapy-induced mucositis and dermatitis. However, there is contradictory information regarding the effect of PBM on (pre)malignant cells, which has led to questions regarding the safety of this technique. We address this issue using an orthotopic mouse model (Cal-33) with human squamous cell carcinoma of the oral cavity. Mice with actively growing orthotopic Cal-33 head and neck carcinoma tumors were divided into 4 groups: control, PBM only, radiation therapy (RT) only, and PBM + RT. We performed three experiments: (1) PBM at 660nm, 18.4J/cm2, and 5 RT × 4Gy doses delivered daily; (2) PBM at 660nm, 18.4J/cm2, and 1 × 15Gy RT; and (3) PBM at 660nm + 850nm, 45mW/cm2, 3.4J/cm2, and 1 × 15Gy RT. Mice were weighed daily and tumor volumes were evaluated by IVIS. Survival time was also evaluated. Animals treated with RT survived significantly longer and had significantly smaller tumor volume when compared with the control and PBM-only treatment groups. No significant differences were noted between the RT alone and PBM + RT groups in any of the experiments. Our results suggest that PBM at the utilized parameters does not provide protection to the tumor from the killing effects of RT.

Photobiomodulation or low-level laser therapy in the management of cancer therapy-induced mucositis, dermatitis and lymphedema.

There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT) also known as PhotoBioModulation (PBM) when used for the prevention and/or treatment of oral mucositis in patients undergoing radiotherapy for head and neck cancer, or high-dose chemotherapy regimens. This review aims at giving the state of the art of this technique in this indication. Recent advances in LLLT/PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with cancer treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The article discusses LLLT/PBM mechanisms of action, dosimetry, and safety, and aims to identify some cancer treatment side-effects for which LLLT/PBM may prove to be effective (oral mucositis, radiation dermatitis, lymphedema). In addition, LLLT/PBM parameters for each of these complications are suggested and future research directions are discussed.

A Review of the Quality of Extant Clinical Practice Guidelines in Cancer Therapy-Induced Mucositis

Context: Oral mucositis is a common complication in patients with cancer therapy. Oral and dental care should be considered as a vital component of caring before, during and after chemotherapy. This study aimed to assess the methodological quality of existing CPGs about cancer therapy-induced mucositis. Evidence Acquisition: We conducted a review of extant CPGs for the management of mucositis. After screening the guidelines based on inclusion and exclusion criteria, three CPGs were selected and assessed by 5 appraisers by using AGREE II instrument. Results: Assessed CPGs gained the highest scores in the clarity of the presentation domain. Scope, purpose (median score, 63.3%), and stakeholder involvement (median score, 54.4%) were found respectively and the lowest scores were in editorial independence domain. The scores in applicability (median score, 30%), rigor of development (median score, 28.8%), and editorial independence (median score, 26.7%) domains were unfavorable. Also, every appraiser scored the overall quality of CPGs. Conclusions: Quality of mucositis CPGs needs to be improved. In other words, designing high-quality CPGs in this area is necessary.

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06−08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer.

Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis - current evidence and potential clinical applications.

Gastrointestinal mucositis is defined as inflammation and/or ulcers of the gastrointestinal tract occurring as a complication of chemotherapy and radiation therapy, and affects about 50% of all cancer patients. To assess the role of gut microbiota in the pathogenesis of gastrointestinal mucositis and the potential for manipulations of the microbiota to prevent and to treat mucositis. Search of the literature published in English using Medline, Scopus and the Cochrane Library, with main search terms 'intestinal microbiota', 'bacteremia', 'mucositis', 'chemotherapy-induced diarrhoea', 'chemotherapy-induced mucositis', 'radiotherapy-induced mucositis'. The gut microbiota plays a major role in the maintenance of intestinal homoeostasis and integrity. Patients receiving cytotoxic and radiation therapy exhibit marked changes in intestinal microbiota, with most frequently, decrease in Bifidobacterium, Clostridium cluster XIVa, Faecalibacterium prausnitzii, and increase in Enterobacteriaceae and Bacteroides. These modifications may contribute to the development of mucositis, particularly diarrhoea and bacteraemia. The prevention of cancer therapy-induced mucositis by probiotics has been investigated in randomised clinical trials with some promising results. Three of six trials reported a significantly decreased incidence of diarrhoea. One trial reported a decrease in infectious complications. The gut microbiota may play a major role in the pathogenesis of mucositis through the modification of intestinal barrier function, innate immunity and intestinal repair mechanisms. Better knowledge of these effects may lead to new therapeutic approaches and to the identification of predictive markers of mucositis.

The multifunctional alarmin HMGB1 with roles in the pathophysiology of sepsis and cancer

Although originally described as a highly conserved nuclear protein involved in DNA replication, transcription and repair, high-mobility group box-1 protein (HMGB1) has emerged as a key mediator in the regulation of immune responses to infection and sterile injury by exhibiting all the properties of a prototypic 'alarmin'. These include rapid passive release in response to pathogenic infection and/or traumatic injury, active secretion providing for chemotactic and cytokine-like function and an ability to resolve inflammation, including tissue repair and remodelling. In this review, we will give an overview of the post-translational modifications necessary for such diversity in biological activity, concentrating particularly on how differences in oxidation of highly conserved redox-sensitive cysteine residues can potentiate inflammatory responses and dictate cellular fate. We will also review the most recent literature on HMGB1 and its involvement in the pathophysiology of sepsis and cancer, as well as cancer therapy-induced mucositis.

Antibacterial and Antiinflammatory Kinetics of Curcumin as a Potential Antimucositis Agent in Cancer Patients

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50–200 μM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 μM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 μM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis

To discuss the promising state of the art low-level laser therapy (LLLT) for preventive and therapeutic usage in oral mucositis due to cancer therapy. Photomedicine using LLLT is very effective with intraoral and extraoral devices in the management of oral mucositis, based on several studies including randomized control studies. A systematic review identified 33 relevant articles that were subjected to meta-analysis based on which laser parameters in routine practice are being defined. Meta-analysis showed that LLLT reduced risk of oral mucositis with relative risk (RR) 2.45 [confidence interval (CI) 1.85-3.18], reduced duration, severity of oral mucositis and reduced number of days with oral mucositis (4.38 days, P = 0.0009). RR was similar between the red (630-670 nm) and infrared (780-830 nm) LLLT. Pain-relieving effect based on the Cohen scale was at 1.22 (CI 0.19-2.25). No adverse side effects of LLLT were reported; hence, we recommend red or infrared LLLT with diode output between 10-100 mW, dose of 2-3 J/cm2/cm2 for prophylaxis and 4 J/cm2 (maximum limit) for therapeutic effect, application on single spot rather than scanning motion. Lesions must be evaluated by a trained clinician and therapy should be repeated daily or every other day or a minimum of three times per week until resolution. There is moderate-to-strong evidence in favor of LLLT at optimal doses as a well tolerated, relatively inexpensive intervention for cancer therapy-induced oral mucositis. It is envisaged that LLLT will soon become part of routine oral supportive care in cancer.

Teduglutide ([Gly2]GLP‐2) protects small intestinal stem cells from radiation damage

Glucagon-like peptide-2 and its dipeptidyl peptidase (DP-IV) resistant analogue teduglutide are trophic for the gastrointestinal epithelium. Exposure increases villus height and crypt size and results in increased overall intestinal weight. As these effects may be mediated through stimulation of the stem cell compartment, they may promote intestinal healing and act as potential anti-mucositis agents in patients undergoing cancer chemotherapy. A study was initiated to investigate the protective effects of teduglutide on the murine small intestinal epithelium following gamma-irradiation using the crypt microcolony assay as a measure of stem cell survival and functional competence. Teduglutide demonstrated intestinotrophic effects in both CD1 and BDF1 mouse strains. In BDF1 mice, subcutaneous injection of GLP-2 or teduglutide (0.2 mg/kg/day, b.i.d.) for 14 days increased intestinal weight by 28% and resulted in comparable increases in crypt size, villus height and area. Teduglutide given daily for 6 or 14 days prior to whole body, gamma-irradiation significantly increased crypt stem cell survival when compared with vehicle-treated controls. The mean levels of protection over a range of doses provided protection factors from 1.3 to 1.5. A protective effect was only observed when teduglutide was given before irradiation. These results suggest that teduglutide has the ability to modulate clonogenic stem cell survival in the small intestine and this may have a useful clinical application in the prevention of cancer therapy-induced mucositis.

Scope and epidemiology of cancer therapy-induced oral and gastrointestinal mucositis

OBJECTIVE: To discuss the scope and epidemiology of cancer therapy-induced mucositis. DATA SOURCE: Peer-reviewed articles and book chapters. CONCLUSION: Mucositis is a frequent and costly complication of cancer treatment. The risk of cancer therapy-induced mucositis varies depending on a number of patient- and treatment-related factors. IMPLICATIONS FOR NURSING PRACTICE: An awareness of the risk factors associated with mucositis will allow nurses to identify cancer patients at greatest risk and incorporate supportive care measures into their management plans.