Photobiomodulation Protocols in the Analgesia of Chemotherapy-induced Oral Mucositis in Children

• LLLT applied every other day (Radiation): Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied every other day
• LLLT applied daily (Radiation): Low-level laser therapy (LLLT) protocol combining red and infrared wavelengths applied daily

Primary outcomes

• Session evaluation [Throught treatment period up to 1 month]: Duration (in days) from the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM related pain at 2 consecutive measurements before the next scheduled PBM session (either active laser application or matching placebo application)

Secondary outcomes

• Production costs evaluation [2 months]: Production costs from the hospital perspective and efficacy (i.e. number of days after which a child has no longer mucositis related pain as described in the primary endpoint section) to build Incremental Cost-Effectiveness Ratio (ICER) comparing every other day LLLT application versus with daily LLLT application.
• Health insurance evaluation [2 months]: Costs of inpatient hospital stays from the French health insurance perspective.
• OM duration evaluation [Throught treatment period up to 1 month]: Duration (in days) of chemotherapy-induced OM of WHO grade 2 or higher between the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM at 2 consecutive measurements before the next scheduled PBM session (either every other day application or daily application).
• OM occurrence [2 months]: Occurrence of chemotherapy-induced OM of WHO grade 3 or 4 (deterioration of the clinical situation).
• Feed evaluation [2 months]: Occurrence of enteral feeding.
• Analgesic consumption [2 months]: Duration (in days) of consumption of step 2 and step 3 analgesics during chemotherapy-induced OM of WHO grade 2 or higher.
• PBM evaluation [Through treatment period up to 1 month]: Duration (in days) from the day of first PBM session up to the day of first measurement when patient has no longer WHO grade 2 or higher chemotherapy-induced OM related pain at 2 consecutive measurements before the next scheduled PBM session (either active laser application or matching placebo application) as evaluated, regardless of patient's age, with the ChIMES scale and use of step 3 analgesics.
• Pain change evaluation [From baseline to each day of PBM session]: Change over time in WHO grade 2 or higher chemotherapy-induced OM related pain, as assessed by pain scales (HEDEN (Hétero Evaluation Douleur Enfant) mucositis scale (5 items ranging from 0 to 2) or VAS (ranging from 0 to 10)depending on patient's age category, and Children's International Mucositis Evaluation Scale (4 items ranging from 0 to 5) whatever patient's age category)
• Adverse events occurrence [2 months]: Occurrence of adverse events reported according to descriptions and grading scale found in NCI CTCAE version 5.0.
• thyroid-stimulating hormone (TSH) evolution [From baseline to 2 months]: TSH shift from baseline value classified according to the following three categories: "< 0.4 IU/mL", "\[0.4 - 10\] IU/mL", "> 10 IU/mL", to value at D14-31 after end of WHO grade 2 or higher chemotherapy-induced OM classified according to the same three categories.

Sex: All, ages: 3 Years to 17 Years

Inclusion Criteria:

1. Male or female children aged ≥ 3 years and < 18 years.
2. Hospitalization in an oncology or hematology department in the participating centres.
3. Patients with oropharyngeal mucositis of grade 2 or higher (WHO grading system) related to cancer chemotherapy, including conditioning for Hematopoietic Stem Cell Transplantation (HSCT).
4. Written informed consent of both patient's holders of parental authority, and patient's assent when applicable.
5. Patients affiliated to a French Social Security insurance or equivalent social protection.
6. Absence of any physical or psychological disability that may interfere with the LLLT application.

Exclusion Criteria:

1. Patients with a solid cancer lesion in the area of low-level laser application.
2. History of cervicofacial radiotherapy.
3. Application of low-level laser therapy for oral mucositis within 2 weeks prior to randomization.
4. Hyperthyroidism defined by TSH < 0.4 IU/mL at inclusion.
5. Patients susceptible to epilepsy seizure.
6. Patients with pacemaker.
7. Patients refusing to wear retinal goggles during low-level laser 1. Patients with a solid cancer lesion in the area of low-level laser application.
8. Patients protected by law (guardianship and safeguarding of justice).
9. Pregnant female patients as determined by positive serum pregnancy test at screening.
10. Lactating female patients who are actively breast feeding.
11. Participation in another clinical trial involving oral care.

• Marlène PASQUET, Principal investigator, University Hospital, Toulouse