High-level Evidence Exists for Low-level Laser Therapy on Chemoradiotherapy-induced Oral Mucositis in Cancer Survivors.

Sir,

I would like to bring to attention, the role of low-level or low-powered laser therapy (LLLT) in palliative care settings for prevention and treatment of radiation/chemotherapy-induced or chemoradiotherapy (CRT)-induced oral mucositis (OM) in cancer survivors.

OM is a common dose-limiting debilitating treatment-related complication in cancer survivors characterized by erythematous, atrophic, erosive, or ulcerative lesions.[1] OM results from two major mechanisms: Direct toxicity on the mucosa and myelosuppression due to the treatment; and its pathophysiology includes four interdependent phases: An initial inflammatory/vascular phase, an epithelial phase, an ulcerative/bacteriological phase, and a healing phase.[2]

Conservative treatment methods include topical anesthetics, cocktail mixtures, and mucosal coating agents, and physical agents like cryotherapy and laser therapy.[3] Cancer survivors who had CRT-induced OM had altered affective state with greater impairment in quality of life compared to those who did not.[4] Two systematic reviews[5],[6] and six randomized controlled trials[7],[8],[9],[10],[11],[12] were found in our preliminary search of PubMed database. Both systematic reviews confirmed moderate to strong evidence of efficacy for LLLT in OM.

SYSTEMATIC REVIEWS

Bjordal et al.[6] in their systematic review found 11 randomized placebo-controlled trials with a total of 415 patients; and found that the relative risk (RR) for developing OM was significantly reduced after LLLT compared with placebo LLLT, with greater effect for doses above 1 J. LLLT also reduced the duration, oral mucositis severity, and had similar side effects versus placebo LLLT.

Bensadoun and Nair[5] in their ‘state-of-the-art’ review identified 33 relevant articles and a pooled meta-analysis showed that LLLT reduced risk of oral mucositis, reduced duration, severity of oral mucositis and reduced number of days with oral mucositis. The authors recommended red or infrared LLLT for prophylaxis (output between 10-100 mW, dose of 2-3 J/cm2/cm2) and for therapeutic effect-max 4 J/cm2, application on single spot rather than scanning motion.

RANDOMIZED CONTROLLED TRIALS

Prevention and treatment

Two randomized trials studied preventive and therapeutic role of LLLT in OM, both of them found significant positive benefits without any adverse effects.

Maiya et al.[7] studied the effect of low-level helium-neon (He-Ne) laser in the prevention and treatment of radiation induced mucositis in 50 patients with stages II-IV head and neck cancer who were randomly assigned to He-Ne laser (wavelength 632.8 nm and output of 10 mW) or oral analgesics, local application of anesthetics, 0.9 per cent saline and povidine wash. The study group had lower pain scores and grade of mucositis compared to control group post-treatment, and without any adverse effect or reactions. Carvalho et al.[8] studied dose-specific effects of LLLT in 70 patients with malignant neoplasms in the oral cavity or oropharynx who were randomized into two low-level laser therapy groups: Group 1 (660 nm/15 mW/3.8 J/cm2/spot size 4 mm2) or Group 2 (660 nm/5 mW/1.3J/cm2/spot size 4 mm2). The patients in Group 1 had longer duration to present mucositis grade II, lesser mucositis grade in 2 weeks, and lower pain levels than Group 2.

Prevention

There were three randomized trials on prevention of OM using LLLT and although reductions in CRT interruptions were observed, progression of OM was not reduced by LLLT which questions its preventive use. Bensadoun et al.[9] conducted a randomized multicenter double-blind trial for the prevention of acute radiation-induced stomatitis in 30 patients who were randomized to receive He-Ne LLLT (60 mW, 6328 nm) or placebo light treatment. LLLT group had lesser frequency of Grade 3 mucositis and “severe pain”. Cruz et al.[10] in their randomized clinical trial randomly assigned 29 patients to the laser group and 31 in the control group. Their study showed no evidence of benefit for the use of low-energy laser in children. Gouvκa de Lima et al.[11] in their randomized, double-blind, Phase III study of 75 patients administered either gallium-aluminum-arsenide LLL therapy 2.5 J/cm2 to 37 patients or placebo laser to 38 patients. Although LLLT was not effective in reducing severe oral mucositis, it reduced RT interruptions in these head-and-neck cancer patients.

Treatment

There was one randomized trial exclusively on treatment of OM using LLLT by Gautam et al.[12] who used prophylactic Helium Neon (He-Ne) Laser for the prevention and treatment of CRT-induced OM in 121 primary oral cancer patients given laser (n = 60) and placebo (n = 61). The laser group had lesser incidence of severe OM, pain, opioid analgesic use, duration of severe OM, without requiring CRT interruptions.

It is imperative that moderate to strong level evidence be translated into palliative care by using LLLT for patients with CRT-induced OM in order to provide effective symptom control and enhance quality of life in cancer survivors. Can palliative care physicians consider LLLT a viable and feasible therapeutic option during evidence-informed clinical decision making for treatment selection in cancer survivors with CRT-induced OM?