These 2 systematic reviews generally support efficacy of topical oral agents in reducing the symptoms of OM in patients with head and/or neck cancer. The first review evaluated effects of all topical agents on patients with OM following head and neck cancer treatment with CT, RT, or combined CT and RT.4 Patients undergoing RT were more likely to endure OM. Wide outcome variability resulting from use of different outcome measures and a variety of topical treatments in patients receiving CT, RT, or both, contributed to data heterogeneity, thus obscuring the results described. The second review5 had more homogeneous data as it focused more narrowly on the effects of 1 topical agent compared with control treatment of RT-induced OM, which occurred to some degree in all patients. The review by Tian et al5 consistently analyzed severe validated OM outcomes. These studies teach the value of measuring and analyzing the severity of patient-centered outcomes. Focusing on severe or intolerable OM events not only addressed outcomes most important to patients, but it also disclosed important effects of honey improving clinically important outcomes relating to maintaining overall health and continuing RT treatment to eradicate the head and/or neck cancer.4,5 Whatever type of wound a clinician is planning to study, they can learn from comparing these 2 meta-analyses. How a provider measures outcomes is vital to the success of any wound care study. It is necessary to include and plan to analyze recognized ordinal or ratio data validly reflecting patient-centered outcome measures6 in ways that reflect outcome severity important to both the clinician and patient. For example, if measuring effects of an intervention on surgical site infections (SSI), document a reliable,7 valid8 severity measure, not merely SSI incidence. This will increase the impact of one’s research and help improve outcomes for the patients everyone may become.
Managing Oral Mucositis in Patients With Cancer
Dear Readers
Patients with oral mucositis (OM) have inflamed epithelial lesions of the mouth that progress to form painful ulcerations with submucosal hemorrhaging and infection. Oral mucositis makes it painful to eat, drink, and speak, resulting in distress, weight loss, and declining health.1 These symptoms occur in up to 40% of patients within 5 to 10 days after beginning chemotherapy (CT), and in nearly all patients within 1 to 2 weeks of starting radiotherapy (RT) for head and neck cancer.1 Oral mucositis can be severe enough to interrupt treatment and reduce survival rates.2 In 2014, the Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology released OM treatment guidelines aiming to provide nutritional support, while reducing pain, inflammation, hemorrhaging, and oral microbial contamination.3 This installment of Evidence Corner explores 2 recent systematic reviews of randomized controlled trial (RCT) evidence informing clinical decisions in ways that may change thoughts about effective topical OM treatment.4,5
Systematic Review of all topical OM treatments
Reference: Sant Ana G, Normando AGC, De Toledo I, Dos Reis PED, Guerra ENS. Topical treatment of oral mucositis in cancer patients: a systematic review of randomized clinical trials. Asian Pac J Cancer Prev. 2020;21(7):1851–1866. doi:10.31557/APJCP.2020.21.7.1851
Rationale: There is no standardized evidence-based topical oral home care therapy to prevent or treat the pain and adverse effects of OM for patients undergoing CT or RT for head and neck cancer.
Objective: Conduct a systematic review of published RCT evidence supporting safety and efficacy of topical therapies used to treat OM in those undergoing CT or RT for cancer treatment.
Methods: Cochrane Library, CINAHL, EBSCO, LILACS, Livivo, PubMed, SCOPUS, and Web of Science reference databases and gray literature were searched for RCTs published between 1990 and 2018 reporting the effects of topical creams, ointments, jellies, and mouthwashes on OM in patients 18 years of age or older undergoing CT or RT. Studies on preventive measures, use of hematopoietic stem cell transplantation, and redundant samples were excluded from the analysis. All searches met Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two authors reviewed full-text publications in the English language of qualifying studies and assessed study heterogeneity and Cochrane risk of bias. The 2 authors tabulated publication author, year, and country; patients’ ages in years and cancer type; treatment interventions, control interventions, and sample sizes; follow-up periods; and main conclusions. A reduction in the severity grade of OM documented per the World Health Organization (WHO) assessment scale was the primary outcome. Secondary outcomes were erythema scores, wound healing, pain intensity, and ability to eat and drink.
Results: Among the initial 994 citations identified in the databases, 23 RCTs in 1169 patients with OM qualified for descriptive analysis. Most patients (n = 552) had head and neck cancer and received CT alone. Five RCTs had low risk of bias, with the remainder being of unclear risk (12 RCTs) or high risk (6 RCTs). Twenty-one of the 23 RCTs showed that mouthwashes generally improved oral hygiene, moistened the oral cavity, and reduced pain and infection symptoms, but no single therapy emerged as a standard intervention for preventing or treating OM. Topical honey and related interventions (propolis and royal jelly) reduced early OM inflammation and promoted epithelial healing, but these benefits did not persist. Anti-inflammatory agents had mixed effects on OM. A sodium bicarbonate mouthwash containing Plantago major reduced healing time from 7 days to 5 days and an aloe vera mouth wash reduced pain from day 3 through day 14. A mouthwash containing the analgesic phenytoin improved pain and quality of life. Nine studies reported improved oral hygiene and reduced sepsis using various mouthwashes.
Authors’ Conclusions: Mouthwashes containing topical natural agents improved pain and quality of life for patients with OM. Heterogeneity of RCT results revealed the need to standardize OM assessment measures and intervention parameters to permit cross-RCT comparisons.
Topical oral honey reduced radiation-induced OM symptoms
Reference: Tian X, Xu L, Liu X, Wang CC, Xie W, Jiménez-Herrera MF, Chen W. Impact of honey on radiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis. Ann Palliat Med. 2020 Jul;9(4):1431–1441. doi:10.21037/apm-20-44
Rationale: Oral mucositis is a frequent and distressing complication for patients undergoing RT for head and neck cancer, often interrupting treatment. Effects of topical honey on preventing and treating OM in these patients remain unclear.
Objective: Perform an updated systematic review of evidence exploring effects of topical honey on RT-induced OM in patients with head and/or neck cancer.
Methods: Using Cochrane systematic review and PRISMA methods and tools, the authors searched the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, EMBASE, and PubMed for RCT and non-randomized clinical controlled trials (CCTs) published in Chinese or English from inception through October 2019. The trials studied adults receiving RT to treat head and/or neck cancer and compared effects on OM of topical oral honey with either a control or no treatment. The primary outcome reviewed was incidence of intolerable or severe OM (WHO assessment scale or Oral Mucositis Assessment Scale grade 3 or grade 4). Secondary outcomes were incidence of any documented OM, incidence of weight gain or maintenance, percentage of patients interrupting RT due to OM (as indicated by study withdrawal), and safety evaluated as adverse events related to honey. Two authors searched the 4 databases for qualifying studies, assessed risk of study bias, and tabulated study information including the following: lead author last name and country, publication year, honey and control sample sizes, sex ratio, patient age range, intervention and radiation parameters, and outcomes of interest. Meta-analyses of primary and secondary outcomes were conducted using a pre-set value of P less than or equal to 0.05 to establish statistical significance of results.
Results: Among 144 studies retrieved by the search, 7 studies published from 2003 to 2017 qualified for meta-analysis. The 5 RCTs (2 double-blind) and 2 CCTs all had low to moderate bias and verified comparability of honey and control groups at baseline. Meta-analysis of 6 studies (330 patients) reported reduced incidence of severe OM in honey-treated patients compared with standard protocols, saline or water mouthwashes, and lignocaine gel (P < .0001). Separate analysis of the seventh study, which reported severe OM differently from the other 6 studies, also found reduced incidence of severe OM (P < .03). Meta-analysis of the 2 studies each documenting OM-induced RT interruption and static or positive weight gain found each of these outcomes improved in patients treated with honey, with P equaling 0.05 for honey effect on reducing treatment interruptions and P less than 0.001 for honey stabilizing or increasing patient body weight. No honey-related complications or adverse events were observed.
Authors' Conclusions: Oral honey may reduce the incidence of severe RT-induced OM while stabilizing patient body weight and permitting uninterrupted RT in patients with head and/or neck cancer.
References
1. Miranzadeh S, Adib-Hajbaghery M, Soleymanpoor L, Ehsani M. Effect of adding the herb Achillea millefolium on mouthwash on chemotherapy induced oral mucositis in cancer patients: a double-blind randomized controlled trial. Eur J Oncol Nurs. 2015;19(3):207–213. doi:10.1016/j.ejon.2014.10.019
2. Ferreira EB, Vasques CI, Gadia R, et al. Topical interventions to prevent acute radiation dermatitis in head and neck cancer patients: a systematic review. Support Care Cancer. 2017;25(3):1001–1011. doi:10.1007/s00520-016-3521-7
3. Lalla RV, Bowen J, Barasch A, et al; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453–1461. doi:10.1002/cncr.28592
4. Sant Ana G, Normando AGC, De Toledo I, Dos Reis PED, Guerra ENS. Topical treatment of oral mucositis in cancer patients: a systematic review of randomized clinical trials. Asian Pac J Cancer Prev. 2020;21(7):1851–1866. doi:10.31557/APJCP.2020.21.7.1851.
5. Tian X, Xu L, Liu X, et al. Impact of honey on radiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis. Ann Palliat Med. 2020;9(4):1431-1441. doi:10.21037/apm-20-44.
6. Driver VR, Gould LJ, Dotson P, Allen LL, Carter MJ, Bolton LL. Evidence supporting wound care end points relevant to clinical practice and patients’ lives. Part 2. Literature survey. Wound Repair Regen. 2019;27(1):80-89.
7. McIsaac C, Bolton LL. Reliability and feasibility of registered nurses conducting web-based surgical site infection surveillance in the community: a prospective cohort study. Int Wound J. 2020;17:1750–1763.
8. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309–332.
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