Trismo e radioterapia de cabeça e pescoço: revisão sistemática com meta-análise de fatores de risco e ensaio clínico triplo-cego com fotobiomodulação preventiva

Abstract

Patients undergoing radiotherapy (RT) with or without associated chemotherapy (CT) in the head and neck region commonly develop trismus during and after treatment, leading to a significant decrease in masticatory efficacy and quality of life. Evidence has suggested that Photobiomodulation (PBMT) with low-level laser (LLLT) may act in the prevention of RT-induced trismus. The aim of the study is to evaluate the role of RT associated or not with CT in the prevalence of trismus in patients with head and neck cancer (HNC), through a systematic review, and to conduct a clinical trial to verify the efficacy of PBMT in the prevention of trismus in these patients. First, a systematic review of the literature guided by PRISMA and registered in PROSPERO (CRD42021255377) was carried out with the following starting question: (P) in patients with head and neck cancer (E) treated with chemoradiotherapy (C) compared to patients treated only with radiotherapy (O) is there a higher prevalence of trismus or chewing difficulty? For this, 963 articles were screened in the PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO and gray literature databases (Open Grey, Google Scholar and ProQuest). Eight articles were included for qualitative and quantitative synthesis of prevalence by inverse variance method and random effects, heterogeneity analysis [I2 and Tau2], one-of-out analysis and Eggs and Begg tests, risk of bias analysis (Newcastle Ottawa Scale) and quality of evidence (GRADE). The eight selected articles included 2332 patients and presented low risk of bias. Radiochemotherapy significantly increased (p=0.0003) the prevalence of trismus by 2.55 (95% CI = 1.53-4.23) times compared to RT, with significant heterogeneity (I2 = 59%, p=0.010), but low (Tau2=0.29). Trismus was directly related to worse quality of life, the one-of-out analysis showed no significant difference between the studies and GRADE demonstrated an important level of evidence. The second phase of the study: a phase II clinical trial, randomized, triple-blind, placebo-controlled, guided by the CONSORT (Consolidated Standards of Reporting Trials) guidelines and registered in REBEC (Brazilian Registry of Clinical Trials). Forty-six patients undergoing RT for HNC were included. Patients were equally and randomly allocated into PBMT and PBMT placebo groups and evaluated daily by measuring mouth opening, pain on mouth opening and pain on palpation of the masticatory muscles using the Visual Analogue Scale (VAS). An extraoral infrared laser (~808nm) with a power of 0.1W, energy of 3J, 30s (107J/cm2) per point was used, applied extraorally to the anterior temporal (MT), masseter (MM) and temporomandibular joints (TMJ) muscles and intraorally to the medial pterygoid (MP) muscle. The food quality inventory (ASGP) and quality of life (QoL) analysis (OHIP-14) were applied. Student's t-test, Mann-Whitney test and linear regression models were used (p<0.05). Patients in the PBMT group presented a smaller reduction in mouth opening (-0.15±4.51 mm vs -3.75±3.69 mm, p=0.005), as well as less pain on palpation of the masticatory muscles throughout radiotherapy (right MM: 9.5% (p=0.584) vs 46.2% (p=0.005); left MM: -13.5% (p=0.439) vs 49.3% (p=0.003); right T: -48.1% (p=0.003) vs 18.9% (p=0.274); left T: -15.7% (p=0.365) vs 52.1% (p=0.001); right MP: -62.5% (p<0.001) vs -14.6% (p=0.402); left MP: 18.6% (p=0.282) vs 51.3% (p=0.002); right TMJ: - 9.4% (p=0.589) vs 76.6% (p<0.001); left TMJ: 9.8% (p=0.574) vs 19.2% (p=0.267)), in addition to a lower prevalence of trismus (grade 1, p=0.002) compared to the placebo group. The DMFT, OHIP-14 and ASGP scores did not differ between groups (p>0.05). No difference was observed in mouth opening (M1-M6) after treatment. PBMT was effective in preventing trismus and pain in the masticatory muscles during radiotherapy treatment.