Fotobiomodulação com led versus laser no manejo da mucosite oral em pacientes com câncer de cabeça e pescoço e os fatores limitantes da terapia fotodinâmica contra Candida albicans

Abstract

Oral mucositis (OM) is a debilitating complication of chemoradiotherapy (CRT) in head and neck cancer (HNC) patients, severely impacting quality of life. Intraoral photobiomodulation (PBM) is an effective therapy in this context, primarily utilizing low-level laser. However, the literature still lacks studies using light-emitting diodes (LED) for this purpose, which may be a more accessible and adaptable tool. Furthermore, patients with HNC and OM are more susceptible to oral infections by opportunistic microorganisms, such as Candida albicans (C. albicans), requiring a different therapeutic approach. Antimicrobial photodynamic therapy (aPDT) is effective against a broad spectrum of microorganisms but faces challenges in eradicating infections caused by C. albicans. This thesis contains four chapters aimed at summarizing the literature on the efficacy of PBM in OM management, as well as comparing OM management with LED versus laser in patients undergoing CRT. The susceptibility of a C. albicans strain devoid of superoxide dismutases (SODs 4, 5, and 6) to methylene blue (MB)-mediated aPDT was also investigated, measuring the generation of reactive oxygen species (ROS). Methodologically, an overview of systematic reviews on the use of PBM in OM management in patients undergoing CRT for HNC treatment was conducted. Additionally, a triple-blind randomized clinical trial was performed with 37 patients who received PBM with laser (660 nm) or LED (635 nm), both with a fluence of 6.2 J/cm², three times a week. Primary outcomes were OM incidence, severity, duration, and pain. C. albicans biofilms with and without SODs were cultured for 24 h and subjected to aPDT (50 μM methylene blue and 73 J/cm² at 660 nm), quantified by colony-forming unit counts. ROS generation was measured by the degradation of anthracene exposed to toluidine blue (TBO) and MB under red light (193 J/cm² at 636 nm and 125 J/cm² at 660 nm, respectively). Results indicated 16 systematic reviews favorable to PBM. In the clinical trial, there was no statistically significant difference in OM incidence (31.6% Laser vs. 44.4% LED; p=0.50), severity, and duration (p>0.05). The LED group showed a statistical difference regarding pain (p=0.006), although the mean VAS value (4.4 ± 2.5) remained within that observed in similar studies. There was no difference between C. albicans strains with and without SODs (p>0.99) in susceptibility to aPDT. Higher ROS generation was observed at moderate photosensitizer concentrations (40 μM for TBO and 10 μM for MB). It is concluded that PBM is an effective strategy in OM management, and intraoral PBM with LED is clinically comparable to laser, representing a viable alternative. The absence of SODs in C. albicans did not make it more susceptible to aPDT, suggesting other evasion mechanisms. Increasing dye concentration for greater aPDT effectiveness should be viewed with caution, as ROS production may decrease.