Did you choose appropriate mouthwash for managing chemoradiotherapy-induced oral mucositis? The therapeutic effect compared by a Bayesian network meta-analysis.

Abstract

BackgroundOral mucositis (OM) is one of the most common adverse effects of radiotherapy and chemotherapy. It greatly affects the patients' quality of life and hinders cancer treatment implementation. Treating OM with mouthwash is a widely used strategy that can effectively relieve symptoms and promote healing. However, the wide mouthwash selection confuses clinicians. This Bayesian network meta-analysis aimed to compare the effects of various mouthwash types used to treat OM and provide high-level evidence-based recommendations for OM treatment.MethodsDatabase search included PubMed, Embase, Cochrane Library, and Web of Science from inception to April 21, 2022. The primary outcome was OM score improvement following the World Health Organization grades. The randomized controlled trial (RCT) bias risk assessment tool provided in the Cochrane Handbook assessed the studies' risk of bias. We performed pairwise and Bayesian network meta-analysis with random effects following the PRISMA guideline.ResultsThe study included 13 RCTs with 570 patients. Pairwise comparisons showed that povidone-iodine was more effective than chlorhexidine (weighted mean difference [WMD], −2.64; 95% confidence interval [CI], −2.72 to −2.56) but inferior to granulocyte-macrophage colony-stimulating factor (GM-CSF; WMD, 0.20; 95% CI, 0.06–0.34) after one week of mouthwash treatment. Vitamin E (WMD, −0.94; 95% CI, −1.03 to −0.85), natural drugs (WMD, −0.93; 95% CI, −1.46 to −0.40), and phenytoin (WMD, −0.38; 95% CI, −0.59 to −0.17) exhibited better therapeutic effects than a placebo after three weeks of treatment. Bayesian network meta-analysis showed that povidone-iodine was superior to chlorhexidine in treating OM (WMD, 2.63; 95% CI, 0.20–5.01). Other mouthwashes showed no significant differences. Rank probability indicated that the best OM therapeutic mouthwashes were GM-CSF (54%), vitamin E (24%), and natural drugs (43%) after one, two, and three weeks of treatment, respectively.ConclusionGM-CSF was the most effective mouthwash type for OM treatment. When considering the cost and effectiveness, povidone-iodine and sodium bicarbonate might be the most advantageous. Furthermore, natural drugs have the same potential in treating OM. Safety and acceptability are their most outstanding characteristic.

Royal Jelly: Biological Action and Health Benefits

“…The level of normal tissue damage following chemoradiotherapy depends on the dose, fractionation schedule, and volume of the treated tissue. A beneficial effect of RJ in reducing chemoradiotherapy-induced oral mucositis in head and neck cancer patients and animal models was also observed [ 326 , 327 , 328 , 329 , 330 , 331 ]. For example, the application of RJ films (10% and 30%) accelerated recovery from a 5-FU-induced injury by showing the free radical-scavenging activity and by reducing the myeloperoxidase activity and production of pro-inflammatory cytokines in hamsters [ 327 , 329 , 330 ].…”

“…An overview of the molecular and cellular mechanisms of RJ is shown in Table 5, while the doses of RJ used in some clinical trials are shown in Table 6. [307] RJ − reduces oxidative stress and levels of IL-6, IL-8, and TNF-α [292,298,299,[327][328][329][330][331] Note: Aβ, amyloid beta; ACE, angiotensin-converting enzyme; Ach, acetylcholine; Akt, protein kinase B; ALP, alkaline phosphatase; ALT, alanin-aminotransferase; AMPK, AMP-activated protein kinase; anti-OVA, antibodies that detect ovalbumin; AP-1, Activator protein 1; ApoA-I, apolipoprotein A-I; Apo-B, apolipoprotein B; APP, amyloid precursor protein; ARE, antioxidant response element; AST, aspartate aminotransferase; ATF4, activating transcription factor-4; ATM, ataxia telangiectasia-mutated; ATR, ataxia telangiectasia-mutated and Rad3-related; BACE1, beta-site APP cleaving enzyme 1; BAT, brown adipose tissue; Bax, Bcl-2associated X protein; BBB, blood-brain barrier; Bcl-2, B-cell lymphoma- mTOR, mammalian target of rapamycin; MUC2, mucin; NaMN, nicotinic acid mononucleotide; NEP, neprilysin; NFAT c1, nuclear factor of activated T cell; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NGF, nerve growth factor; NLRP1, NOD-like receptor (NLR) family pyrin domain-containing 1; NO, nitric oxide; Nrf2, nuclear factor E2-related factor 2; OPG, osteoprotegerin; Osx, Osterix; OVX, ovariectomy; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1 alpha; PI3K, phosphatidylinositol 3-kinase; PPAR-γ, peroxisome proliferator-activated receptor gamma; PTEN, phosphatase and tensin homolog; RAGE, receptor for advanced glycation end products; RANK, receptor activator of nuclear factor-κB; RANKL, receptor activator of NF-κB ligand; RB, retinoblastoma gene; RCC, renal cell carcinoma; ROS, reactive oxygen species; RUNX2, runt-related transcription factor 2; S6K1, S6 kinase 1; SASP, senescenceassociated secretory phenotype; SCFAs, short-chain fatty acids; SOD, superoxide dismutase; T, Testosterone; T3, triiodothyronine; T4, thyroxine; TC, total cholesterol; TGF-β, transforming growth factor-beta; TNF-α, Tumor Necrosis Factor alpha; TNBS, 2, 4,6-trinitrobenzene sulfonic acid; TRP-1, tyrosinase-related protein 1; TRP-2, tyrosinase-related protein 2; TSH, thyroid stimulating hormone; UCP1, uncoupling protein 1; VLDL-C, very-low-density lipoprotein cholesterol; VSMCs, vascular smooth muscle cells. For premature babies 50 mg to 1 g per day − growth and development − strengthen immunity and nervous system [6] Children:…”

“…They reported a significantly shorter mean time for the resolution of oral mucositis in the RJ group. These data suggest that RJ possesses a healing effect against the chemotherapy- and radiotherapy-induced oral mucositis that is largely mediated by the anti-inflammatory and anti-oxidative activities of RJ [ 328 , 331 ].…”