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/cm².

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/cm² 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).

Keywords: Chemoradiotherapy; Head and neck cancer; Lasertherapy; Oral mucositis; Supportive care.

Fig. 1

Flowchart. CRT: Chemoradiotherapy, LLLT: Low-Level Laser Therapy, OM: Oral Mucositis, Reasons of exclusion: - Patients without complete chemoradiotherapy, - Patients with exclusion criteria. Randomisation was still well balanced despite the exclusion of 14 patients. Only 51 patients were treated by lasertherapy (active or inactive): no imbalance was observed between the LLLT groups

Fig. 2

a: Time to first occurrence of OM grade ≥ 3 – Modified intention to treat analysis. b: Time to first occurrence of OM grade ≥ 3 – Per protocol analysis. Arm A: active Lasertherapy arm - Arm B: control placebo, arm (Laser-off treatment), OM: Oral mucositis

Fig. 3

Pain assesment – at the first and at the last lasertherapy session - Per protocol analysis. Arm A: active Lasertherapy arm - Arm B: control placebo arm (Laser-off treatment), VAS: Visual Analogue Scale: A numeric pain rating scale was used (0: ‘No pain’ to 10: ‘Worst pain possible’)