Antimicrobial photodynamic therapy for the treatment of oral mucositis-A comparative study.

OBJECTIVES: The aim was to evaluate the effectiveness of photobiomodulation and antimicrobial photodynamic therapy in the treatment of oral mucositis. BACKGROUND: Oral Mucositis is a frequent complication of oral cavity and oropharynx cancer. Considering the OM aggravation by microorganisms contamination, disinfection provide by antimicrobial photodynamic therapy could be an effective approach. MATERIAL AND METHODS: This comparative study included fourteen patients undergoing radiochemotherapy for oral cavity and oropharynx cancer treatment, who developed oral mucositis. CONTROL GROUP: photobiomodulation. Intervention group: photobiomodulation and antimicrobial photodynamic therapy. The lesion size, duration, pain, and identification of microorganisms were evaluated. RESULTS: The mean reduction in oral mucositis size in the intervention group was 0.70 cm² (±0.35) and 0.30 cm² (±1.10) for the control group. The mean duration of oral mucositis was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had a mean reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). In the intervention group, the predominant isolated microbiota was featured as mixed culture (n = 4/ 50%), followed of Gram Positive (n = 3/ 37.50%), and Gram Negative (n = 1/ 12.55%). In the control group, mixed culture was also more frequent (n = 4 / 66%), followed by Gram Positive (n = 2 /34%). Gram Negative was not predominantly isolated in the control group. CONCLUSION: No statistical significance was found between PBM-T alone and PBM-T + PDT. However, the better outcomes reached by PBM-T + PDT group would suggest there could be a role for combined treatment in the management of OM lesions.

Mucosite oral em pacientes com câncer de cabeça e pescoço: limitações das escalas de graduação, avaliação da terapia fotodinâmica antimicrobiana no tratamento e associação com microbioma oral / Oral mucositis in patients with head and neck cancer: limitations of grading scales, evaluation of antimicrobial photodynamic therapy in treatment and association with oral microbiome

O câncer de cabeça e pescoço (CCP) é uma das principais causas de morbidade e mortalidade em todo mundo. Cirurgia, radioterapia (RT) e quimioterapia (QT) são os principais tratamentos empregados. Contudo, pacientes submetidos a RT e QT podem apresentar complicações como mucosite oral (MO). A terapêutica mais recomendada para MO é a fotobiomodulação (FTBM). Há diversas escalas para graduação da MO, entretanto elas apresentam limitações quando aplicadas em pacientes com CCP. Por esse motivo, foi desenvolvido uma revisão da literatura para descrever as escalas mais utilizadas e apontar as limitações. Microrganismos podem agravar a cicatrização da MO. Diante disso, a terapia fotodinâmica antimicrobiana (aPDT), poderia complementar a ação da FTBM. Assim, foi realizado estudo comparativo entre o uso da FTBM isolada e FTBM + aPDT no tratamento da MO. Mudanças no microbioma oral induzidas pela RT e seu papel no agravamento das complicações, como MO, vem sendo descrito. Em razão disso, amostras da cavidade oral dos pacientes com CCP foram coletadas com swab antes da RT (T0), entre 12 e 16 Grays (Gy) (T1), entre 30 e 36 Gy (T2) e acima de 60 Gy (T3) para caracterização molecular por meio da amplificação e sequenciamento das regiões v1-v2 do gene 16S rRNA. As escalas da World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG e National Cancer Institute ­ NCI foram as mais utilizadas e todas apresentaram limitações associadas principalmente com a dificuldade de diferenciar entre os sinais e sintomas da MO e os do tumor, como por exemplo a disfagia. O estudo comparativo (FTBM isolada X FTBM + aPDT) foi composto por 14 pacientes, com câncer de boca e orofaringe submetidos a RT e QT concomitantes, com 6 pacientes no grupo FTBM isolada e 8 no grupo FTBM + aPDT. A média de redução no tamanho da MO no grupo intervenção foi de 0,70 cm2 (±0,35) e 0,30 cm2 (±1,10) no grupo controle. A média de duração foi de 18,37 dias (±12,12) para o grupo intervenção e 23 dias (±14,78) para o grupo controle. O grupo intervenção teve redução média de 3,40 pontos na escala de dor (±2,44), enquanto o grupo controle teve 0,17 (±2,28). O estudo prospectivo que avaliou o microbioma oral (filo e gênero) ao longo da RT foi composto por 49 pacientes com CCP. Intrigantemente não foi observado diferença no microbioma oral dos pacientes que apresentaram MO (n=31) daqueles que não apresentaram (n=18). Interessantemente foi observado ao final da RT (T3) diminuição de Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001), gêneros associados ao câncer. Não há uma escala ideal para a avaliação da mucosite oral em pacientes com CCP. A mensuração das lesões de MO associada aos dados de dor e duração da MO pode ser uma forma mais eficaz de avaliação. A combinação de FTBM + aPDT parece ser uma abordagem promissora para descontaminar lesões de MO. Não foi observado diferença no microbioma oral de pacientes com e sem MO. Mudanças na composição do microbioma oral foram observadas durante a RT.

Head and neck cancer (HNC) is one of the main causes of morbidity and mortality worldwide. Surgery, radiotherapy (RT) and chemotherapy (CT) are the main treatments used. However, patients undergoing RT and CT may present complications such as oral mucositis (OM). The most recommended therapy for OM is photobiomodulation (PBM-T). There are several scales for grading OM, however they have limitations when applied to patients with HNC. For this reason, a literature review was developed to describe the most used scales and point out the limitations. Microorganisms can aggravate OM healing. Therefore, antimicrobial photodynamic therapy (aPDT) could complement the action of PBM-T. Thus, a comparative study was carried out between the use of PBM-T alone and PBM-T + aPDT in the treatment of OM. RT-induced changes in the oral microbiome and its role in worsening complications such as OM have been described. For this reason, samples from the oral cavity of patients with HNC were collected with a swab before RT (T0), between 12 and 16 Grays (Gy) (T1), between 30 and 36 Gy (T2) and above 60 Gy (T3) for molecular characterization through amplification and sequencing of regions v1-v2 of the 16S rRNA gene. The World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG and National Cancer Institute - NCI scales were the most used and all had limitations mainly associated with the difficulty of differentiating between the signs and symptoms of OM and those of the tumor, such as example dysphagia. The comparative study (isolated PBM-T X PBM-T + aPDT) consisted of 14 patients with oral and oropharyngeal cancer who underwent concomitant RT and CT, with 6 patients in the isolated PBM-T group and 8 in the PBM-T + aPDT group. The mean reduction in OM size in the intervention group was 0.70 cm2 (±0.35) and 0.30 cm2 (±1.10) in the control group. The mean duration was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had an average reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). The prospective study that evaluated the oral microbiome (phylum and genus) during RT consisted of 49 patients with HNC. Intriguingly, no difference was observed in the oral microbiome of patients who had OM (n=31) and those who did not (n=18). Interestingly, a decrease in Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001) was observed at the end of RT (T3), genera associated with cancer. There is no ideal scale for assessing oral mucositis in patients with HNC. Measurement of OM lesions associated with data on pain and duration of OM may be a more effective form of evaluation. The combination of PBM- T + aPDT appears to be a promising approach to decontaminate OM lesions. No difference was observed in the oral microbiome of patients with and without OM. Changes in oral microbiome composition were observed during RT.