Paper 2/2012

Int J Radiat Oncol Biol Phys. 2010 Dec 14.

Oral Mucositis Prevention by Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study.

Gouvêa de Lima A, Villar RC, de Castro G Jr, Antequera R, Gil E, Rosalmeida MC, Federico MH, Snitcovsky IM.
Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.

PURPOSE: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions.

METHODS AND MATERIALS: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm^2 or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients.

RESULTS: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain.

CONCLUSIONS: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy.

Annal Comments:

The laser parameters of this study were: 660 nm, 10 mW, spot size 4 mm^2, 2.5 J/cm^2, 0.1 J per site. The original phase III study by Bensadoun [1] in 1999 used 2 J/cm^2 successfully, so why the negative outcome of the present study? The Bensadoun study used a HeNe laser of 60 mW, irradiating each point for 33 seconds. That makes an energy of 1.98 J. It is obvious that both the energy and the dose (J/cm^2, local intensity) need to be within the therapeutic window. The present study used only 0.1 J per point, which is in the homeopathic range. Further to that, the long length of coherence of the HeNe laser makes the energy requirement lower than that of a red diode laser. Probably the energy of a diode needs to be at least double that of a HeNe laser to obtain similar biological effect [2]. There are more than 30 studies in the area of laser therapy for mucositis. The only negative ones are the above study and the one by Cruz [3], also using very low energies.

The reason for the negative outcome of the above study is then obviously the use of very low energies.


1.   Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M, Dejou J, Tardieu C, Benezery K, Nguyen TD, Laudoyer Y, Dassonville O, Poissonnet G, Vallicioni J, Thyss A, Hamdi M, Chauvel P, Demard F. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer. 1999 Jul;7(4):244-52.

2.   Qadri T, Bohdanecka P, Tunér J, Miranda L, Altamash M, Gustafsson A. The importance of coherence length in laser phototherapy of gingival inflammation: a pilot study. Lasers Med Sci. 2007 Nov;22(4):245-51.

3.   Cruz LB, Ribeiro AS, Rech A, Rosa LG, Castro CG Jr, Brunetto AL. Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatr Blood Cancer. 2007 Apr;48(4):435-40.