Low-level laser therapy in treatment of chemoradiotherapy-induced mucositis in head and neck cancer: results of a randomised, triple blind, multicentre phase III trial

Abstract

Background Low-level laser therapy (LLLT) also called Photobiomodulation therapy (PBMT) could reduce oral mucositis (OM) incidence and severity in head and neck cancer patients treated by chemoradiotherapy, however randomised data about efficacy and safety are missing with curative dose 4 J/cm 2 . Methods This phase III trial was conducted in patients with oral cavity, or oro/hypopharyngeal cancers (stage III or IV). Patients were treated by lasertherapy on OM lesions grade ≥ 2 (4 J/cm 2 or placebo), during chemoradiotherapy and until recovery. Severity of OM (incidence and duration of grades ≥3) was used as primary endpoint and blindly assessed. Results Among 97 randomised patients, 83 patients (85.6%) could be assessed finally (erroneous inclusions, chemoradiotherapy interruptions) and 32 patients had no lasertherapy because of unreachable OM lesions. Randomisation and population characteristics (sex ratio, age, chemoradiotherapy procedures, toxicities incidence) were still comparable between the two LLLT/PBMT groups. An acute OM (grade ≥ 3) was observed in 41 patients (49.4%): 23 patients (54.8%) of the active laser group versus 18 (43.9%) in the control group (modified intend to treat, p = 0.32). Median time before occurrence of OM ≥ grade 3 in half of the patients was 8 weeks in active laser group (vs. 9 weeks in control group). However, 95% of patients exhibited a very good tolerance of LLLT/PBMT. Conclusions This study assessed LLLT/PBMT according to the Multinational Association of Supportive care in Cancer recommendations but lacked power. LLLT/PBMT was well tolerated with a good safety profile, which promotes its use in clinical routine for severe OM treatment. Trial registration ClinicalTrials.gov Identifier: NCT01772706 . Title: Laser Mucite ORL: Effectiveness of Laser Therapy for Mucositis Induced by a Radio-chemotherapy in Head and Neck Cancer (LaserMucite). Study Start Date: October 2008. Primary Completion Date: October 2016. Responsible Party: Institut de Cancérologie de l’Ouest – Paul Papin. Principal Investigator: Eric Jadaud, M.D., Institut de Cancérologie de l’Ouest – Paul Papin. Funding: French Ministry of Health, French national funding scheme (PHRC 2008).

Efficacy of Photobiomodulation in the Treatment of Cancer Chemotherapy-Induced Oral Mucositis: A Meta-Analysis with Trial Sequential Analysis

“…The characteristics of the included studies are provided in Table 1 . A total of 6 trials [ 23 , 24 , 25 , 26 , 27 , 28 ] were included in the final meta-analysis, encompassing 398 participants. Two trials were conducted in Brazil [ 25 , 26 ], two in Italy [ 23 , 24 ] and one each in France [ 27 ] and Belgium [ 28 ].…”

“…A total of 6 trials [ 23 , 24 , 25 , 26 , 27 , 28 ] were included in the final meta-analysis, encompassing 398 participants. Two trials were conducted in Brazil [ 25 , 26 ], two in Italy [ 23 , 24 ] and one each in France [ 27 ] and Belgium [ 28 ]. With respect to the laser source, a diode laser was used in two trials [ 23 , 24 ], GaAIAs in two trials [ 25 , 26 ], He-Ne in one trial [ 27 ] and the LEL (low-energy laser) with a scanning laser combined with an infra-red laser in one trial [ 28 ].…”

“…The dose ranged from 2 J/cm 2 to 6 J/cm 2 . Evaluation of OM was performed by The World Health Organization criteria in three studies [ 23 , 24 , 27 ], the National Cancer Institute (version 2.0) in two studies [ 25 , 26 ] and the European Organization for Research and Treatment of Cancer Scale in one study [ 28 ].…”

“…Three studies were graded as low risk of bias [ 25 , 26 , 28 ] and three were graded as high risk of bias [ 23 , 24 , 27 ] ( Figure 2 ).…”

REVISIÓN: Patogenia y tratamiento de la mucositis asociada al tratamiento de Radioterapia y/o Quimioterapia en pacientes con cáncer de cabeza y cuello.

“…Los pacientes sometidos a LLLT mostraron un aumento en la sobrevida libre de progresión comparados con el grupo placebo (61.7% vs. 40.4%; p = 0.030; HR: 1: 93; IC 95%: 1.07-3.5) y una tendencia a mejor sobrevida global (57.4% vs. 40.4%; p = 0.90; HR: 1.64; IC 95%: 0.92-2.91). (21) En el año 2019 se publicó otro estudio fase III que comparaba el uso de LLLT con placebo, que demostró resultados similares en cuanto a la disminución de la mucositis, pero los resultados no fueron significativos y el estudio carece de poder estadístico (22) .…”