The Research Bites series focuses on scientific summaries, analyses and reviews of the latest research in the areas of clinical, paediatric and oncology nutrition.

Potential for honey and photobiomodulation therapy for the management of oral mucositis in paediatric cancer patients

A new sub-analysis of data from studies involving paediatric patients shows that the use of honey and photobiomodulation therapy in the management of oral mucositis has encouraging potential. 

Oral Mucositis (OM) that occurs as a result of cancer therapy, such as chemotherapy (CT), radiotherapy (RT), radio-chemotherapy (RT-CT) and hematopoietic stem cell transplantation (HSCT), can cause significant pain, discomfort and hinder eating. In a healthy oral mucosa, complete replacement of the epithelial cell layer takes about 4 to 8 days however, in patients with OM, it takes about 20 days to initialise and heal. Such a complication has a significant disruptive impact on a patient’s quality of life, treatment outcomes as well as health care cost (Courtois). In children, OM can hamper oral intake and nutritional status, and as a result, in severe cases, parenteral nutrition may be indicated1.

Clinical practice guidelines for the management of OM in adult patients have been published by The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) since 2003 and the most recent one was published in 2019-2020. A sub-analysis study based on this systematic review was carried out by Silva-Gomes et al on behalf of the Mucositis Study Group. It aimed to highlight clinical practice guidelines and presently available evidence regarding interventions for the management of cancer therapy-induced OM in paediatric patients. The results of the sub-analysis study were published in November 2020 and is the source paper for this synopsis.2

The authors of the sub-analysis study analysed a total of 45 published papers that pertained to the paediatric population. They included 20 randomised control trials (RCT), six comparator RCTs, four non-randomized comparative (comparing intervention to a placebo-control or no treatment), one cross-over, five before-and-after, four case-control, and five cohort studies in the sub-analysis. Studies were scored for their level of evidence (LoE) based on previously published and accepted criteria (Somerfield criteria and Hadom criteria). The authors collected data regarding adverse effects and compliance from the original publications. 

The results from this sub-analysis were presented as guidelines based on the category of intervention. These categories were as follows: (1) Efficacy studies on basic oral care (2) Efficacy studies about anti-inflammatory agents (3) Efficacy studies about antimicrobials, mucosal coating agents, anaesthetics, and analgesics (4) Efficacy studies about growth factors and cytokines (5) Efficacy studies about natural and miscellaneous agents (6) Efficacy studies on cryotherapy, and (7) Efficacy studies on photobiomodulation (PBM). 

Of all the different interventions that were analysed as categorised above, the authors found higher LoE in the studies, that involved basic oral care, application of honey to the affected area, and use of PBM for the management of OM. 

The authors found that the degree of OM and OM-related pain decreased when patients were educated about basic oral care before CT and when they complied with multi-agent combination oral care protocols. 

The  guideline for the potential use of honey in the management of OM was derived from a study that conducted an RCT on 90 children (average age of 6.9 years) with acute lymphoblastic leukaemia and in the consolidation phase of treatment with OM grades 2 and 3. It involved the application of 15 gms of honey topically to the affected area three times a day for 10 days or till the ulcer healed. One of the exclusion criteria for this study was the presence of neutropenia (absolute neutrophilic count [ANC] ≤ 1500/mm3)3,4.  It was observed that in the children with grade 2 mucositis, recovery time was 3.6 ± 0.8 days and in children with grade 3 mucositis, recovery time was 5.4 ± 1.1 days. No adverse events were reported in the original study when honey was the intervention.4 Therefore, the authors proposed the potential use of honey to help reduce the healing time of ulcerative OM.

Photobiomodulation (PBM) also known as Low-Level Laser Light Therapy (LLLT) is a non-thermal and non-invasive procedure that employs low-level power light to relieve pain, reduce inflammation and heal wounds. It involves the application of low-powered light sources at a given wavelength for some time on sites of injury to speed up the cellular regeneration processes.5  This sub-analysis paper reported the results of one RCT and two cohort studies in which PBM was the intervention. These studies showed that use of both intra-oral and extra-oral PBM significantly decrease the severity of OM and OM associated pain reduction in paediatric patients.2

The authors mention that due to lack of robustness and poor quality study designs, protocols for paediatric cancer population may need to be extrapolated from studies done in adult patients. They also mention that deficiencies in the study design and the combinations of interventional agents in single study protocols compromise a definitive conclusion about effective intervention for OM. 

However, the main important summary points made in the sub-analysis paper for pediatric patients were as follows: (1)  that chewing gum does not prevent OM (2) implementation of basic oral care protocol is very suitable and (3) the “intriguing evidence” of efficacy of honey and PBM for management of OM. 

Source: Miranda-Silva W, Gomes-Silva W et al. MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients. Support Care Cancer, Nov 6 2020. PMID: 33156403

References:

  1. Gandhi K et al. Prevalence of Oral Complications occurring in a Population of Pediatric Cancer Patients receiving Chemotherapy. Int.J.Clin.Pediatr.Dent. 2017; 10(2): 166–171
  2. Miranda-Silva W et al. MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients. Support Care Cancer, 2020. doi: 10.1007/s00520-020-05803-4 PMID: 33156403
  3. Honey and a Mixture of Honey, Beeswax and Olive oil propolis extract in treatment of chemotherapy-induced oral mucositis. https://clinicaltrials.gov/ct2/show/NCT01431729 Last accessed on 28th May 2021
  4. Abdulrhman M et al Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: a randomized controlled pilot study Pediatr Hematol Oncol  2012;29(3):285-92.
  5. Courtois, E., Bouleftour, W., Guy, JB. et al. Mechanisms of PhotoBioModulation (PBM) focused on oral mucositis prevention and treatment: a scoping review. BMC Oral Health 21, 220 (2021)

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