Antunes, H.S., Herchenhorn, D., Small, I.A., Araujo, C. M., Viegas, C.M.P., de Assis Ramos, G., . . . Ferreira, C.G. (2017). Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis. Oral Oncology, 71, 11–15.

To compare between LLLT and placebo for overall disease-free survival (DFS) and progression-free survival (PFS) of patients with head and neck cancer who received chemoradiation therapy. Randomized double-blinded placebo controlled phase III trial

Patients received low-level laser therapy or placebo; LLLT with an InGaAIP diod (660 nm to 100 mW-1 J-4J/cmsq, and a spot size of 0.24 cm² five days a week before radiotherapy. contact with the mucosa on nine points per region for 10 seconds per point, totaling 12 minutes per patient for LLLT.

• N: 94; laser group = 47, placebo group = 47    
• AGE: Mean age of LG = 53.5, PG = 55.7; non-significant
• MALES: LG male, 89.4%; PG male, 85.1%    
• FEMALES: LG female, 10.6 %; PG female, 14.9%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (nasopharynx, oropharynx, and hypopharynx cancer)

• SITE: Not stated/unknown Instituto Nacional de Câncer (INCA)
• SETTING TYPE: Not specified    
• LOCATION: Rio de Janeiro Brazil

PHASE OF CARE: Active anti-tumor treatment

Randomized phase III trial of patients with head and neck cancer. Details of randomization not provided.  

Both group received treatments of chemotherapy (cisplatin 100 mg/m² at day 1, 22, and 43) and radiotherapy according to tumor localization, using megavoltage radiotherapy with 2D and 3D techniques. A total dose of 70.2 Gy daily in 39 fractions, five days a week, using a cobalt-60 and a linear accelerator unit.

The adverse effects were evaluated daily, according to the Common Toxicity Criteria, version 3.0, from the National Cancer Institute (NCI-CTC) [16]. Oral mucositis was evaluated every day during the treatment period, according to the OMS and OMAS scales. The modified visual analog scale was used to evaluate pain. Body weight (body mass index) was measured every week. Patients were evaluated by a complete physical examination, oroscopy, nasopharyngoscopy, hematologic and biochemical profiles, chest radiography, and CT/MRI performed every four months for the first two years, every six months from the third to the fifth year, and then annually according to the RECIST criteria.

• Overall survival: LG 57.4% versus PG 40.4%; p = 0.9 NS; HR = 1.64; 95% CI [0.92, 2.91]
• DFS: PG 65.9% versus 58.6%; p = 0.659 NS; HR = 1.19; 95% CI [0.55, 2.57]
• PFS*: 61.7% versus 40.4%; p = 0.03; HR = 1.93; 95% CI [1.07, 3.5] 
• OM stage 3-4*: LG 6.3% versus PG 48% (p < 0.001)
• Gastrostomies*: LG 14.9% versus PG 38.3%; RRR = 0.39 (95% CI [0.18, 0.84]), p = 0.01
• Complete chemotherapy interruption: LG 12.8% versus PG 19.1%
• Chemotherapy dose reduction: LG 2.1% versus PG 6.4%
• Opioid use*: LG = 31.9% versus PG = 85.1; RRR = 0.38 (95% CI [0.24, 0.58]; p < 0.001
• Temporary radiotherapy interruption due to radiodermatitis: LG 14.9% versus PG 8.5%

* statistically significant findings.

Laser group had better progression-free survival and complete response, however this did not carry over to overall survival significance. Oral mucositis severity was statistically significantly lower in LLLT group.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Limited information in article regarding original study, so do not have many details that would be helpful

LLLT was beneficial to reduce oral mucositis. No statistically significant results for overall survival is likely affected by type II error (small sample size), and larger sample size study is needed. This study found statistically significant improvement for progression-free survival and LLLT may improve not only mucositis occurrence/severity but also patients’ survival.