Oral Mucositis and Laser Therapy Associated With Photodynamic Therapy
Condition: Oral Mucositis
MeSH terms: Mucositis; Stomatitis
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of the study was to evaluate the therapeutic action through the diameter of the
      lesion, of low level laser (LLL) associated to photodynamic therapy (PDT) in oral mucositis
      (OM) lesions, in young patients. A randomized clinical trial blinded, split-mouth was
      performed. The study sample consisted of 15 cancer patients (3-16 years old) of Aldenora
      Bello Hospital (São Luís, Maranhão, Brazil). Random allocation by lot of treatments (PDT +
      LLL and LLL) to quadrants of the oral cavity was performed, and the patient was his own
      control. Patients were masked about therapy performed on each side of the arch. The
      evaluation period of both therapeutic regimens was 8 days, and the outcome assessed was the
      lesion size (measured in cm²). Friedman and Wilcoxon tests were applied and the effect
      magnitude calculated. The significance level was 5%. Statistically significant difference was
      observed between the groups for the lesion diameter of the 6th to the 8th day (greater
      regression of lesion size for the PDT + LLL group), which was confirmed by a difference
      magnitude moderated. Based on the findings, it is concluded that PDT + LLL showed greater
      therapeutic effect when compared to LLL in reducing the severity of OM lesions.
    

Detailed description: 
      The blind randomized clinical trial included 18 young patients, between 3 and 16 years old,
      undergoing chemotherapy or chemo/radiological the pediatric ward of Aldenora Bello Hospital
      in São Luís (Maranhão, Brazil). The study was conducted from October/2014 to January/2015. It
      was adopted as inclusion criteria patients between 3 and 18 years old, in the inductive phase
      of chemotherapy, with oral mucositis (OM) and bilateral lesions.

      A mouth split model was conducted, and the patients were their own controls. The entry of the
      patients in the study occurred consecutively. To each patient, the operator/examiner drafted
      an envelope containing treatments to either side, being masked patient about the treatment of
      each side: PDT (photosensitized and low level laser) + low level laser; Low level laser].

      The following parameters were used for the calculation of sample size: 95% confidence level,
      80% statistical power and minimal difference of 0.82 point in the lesions diameter detected
      between paired samples. A "n" sample minimum of 14 was determined for each treatment. In
      order to compensate for possible losses, 18 patients were treated.

      The treatments (PDT and low level laser; Low level laser) were performed in a hospital bed.
      Prior to treatment, the OM lesions were evaluated and a lesion on each side was chosen.
      Lesions should be located at the same site on both sides. The chosen site was the lip mucosa.
      Before the procedure, the patient was instructed as to brushing and not using mouthwashes,
      followed by cleaning of the oral cavity with gauze and distilled water. Two days before the
      laser treatment, the side of the oral cavity chosen for the experimental treatment (PDT and
      low level laser) was pigmented with the photosensitizer (aqueous solution of 0.005% methylene
      blue). A ball of sterile cotton was soaked in the dye solution and placed in the center of
      the lesion. Photosensitizer remained in the place for 5 minutes (pre-irradiation period).
      Then, to activate the dye, the lesion was irradiated with red light (InGaAlP / phosphide and
      Indium, Gallium and potassium) (Flash Laser III, DMC, São Carlos, São Paulo, Brazil), with a
      wavelength of 660 nm, for a period 90 seconds, with a power of 100mW, to 1cm away, according
      to the manufacturer's specifications. The lesion on the opposite side was treated with ball
      of sterile cotton soaked in distilled water and the laser unit placed on the lesion without
      activation of the light. This procedure aimed to mask the patient about the side that
      received the experimental therapy (PDT and low level laser). This masking was possible
      because the experimental solution is insipid, very soluble and thus leaves no residue.

      From the 3rd to the 10th day (total of 8 days) was carried out only laser therapy on both
      sides. Lesions were evaluated until the 8th day. After the 8th day of assessment, the lesions
      were only treated to a complete remission as well as other lesions present in the oral
      cavity. For laser therapy was first used infrared emitter laser unit with active medium
      AsGaAl (Gallium Arsenide and Aluminium), with wavelength of 808nm, for analgesia. Then, the
      investigators used the red emitter, whose active medium was the InGaAlP (phosphide and
      Indium, Gallium and Potassium), with wavelength of 660nm to photobiomodulation. For both
      units emitting laser, the tip of the device was closed against the edges of the lesion,
      perpendicular to the tissue. A irradiation was continuous and the application punctual (10
      seconds). The distance between the points of irradiation was about 1cm. The energy delivered
      was 4J per point of application. The interval between sessions was 24 hours.

      The tip of the laser was disinfected with 70% alcohol solution and wrapped with a plastic
      film. Patients and operators wore glasses for eye protection.

      A questionnaire containing demographic, socioeconomic and type of treatment for cancer was
      applied to parents and children. White blood cell count and platelets (beginning and end of
      the inductive phase of QT) were extracted from medical records.

      The assessed outcome measure was the diameter of the lesion (in cm2). The areas of the
      lesions were measured with a flexible ruler (record made in cm2) by the operator/examiner
      from the start of treatment with exclusive laser therapy (3rd day). This procedure was
      repeated on subsequent days until the 8th day of laser treatment. The measurement of the
      lesions occurred prior to laser therapy applications.

      The Friedman test was used for multiple comparisons within groups (different times of
      treatment). Paired evaluation between each two moments was evaluated using the Wilcoxon test,
      with significance corrected by Bonferroni test (p = 0.0071). The Wilcoxon test was used to
      compare the diameter of the lesion, every day, between the PDT + Low level laser and Low
      level laser groups (dependent samples/split-mouth). It calculated the effect magnitude (d) of
      standardized differences between averages of two groups. The level of significance for
      analysis was 5%.
    

Intervention name(s): PDT + Low level laser; Low level laser
Intervention type(s): Other; Radiation
Intervention description(s): Two days before the laser treatment, the side of the oral cavity chosen for the experimental treatment was pigmented with aqueous solution of 0.005% methylene blue. A ball of sterile cotton was soaked in the dye solution and placed in the center of the lesion. Photosensitizer remained in the place for 5 minutes (pre-irradiation period). Then, to activate the dye, the lesion was irradiated with red light (InGaAlP / phosphide and Indium, Gallium and potassium).
From the 3rd to the 10th day was carried out only laser therapy. For laser therapy was first used infrared emitter laser unit with active medium AsGaAl (Gallium Arsenide and Aluminium). Then, we used the red emitter, whose active medium was the InGaAlP (phosphide and Indium, Gallium and Potassium).; Two days before the laser treatment, the lesion of the side of the oral cavity chosen for the control treatment was treated with ball of sterile cotton soaked in distilled water and the laser unit placed on the lesion without activation of the light. From the 3rd to the 10th day was carried out laser therapy. For laser therapy was first used infrared emitter laser unit with active medium AsGaAl (Gallium Arsenide and Aluminium). Then, we used the red emitter, whose active medium was the InGaAlP (phosphide and Indium, Gallium and Potassium).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: children; cancer; stomatitis; clinical trial; laser therapy, low-level; methylene blue; photochemotherapy