Low Level Laser Therapy in Patients Receiving Chemotherapy

To assess the effectiveness of interventions for treatment of oral mucositis or its associated pain for patients receiving chemotherapy or radiation therapy

Databases searched were MEDLINE, CancerLIT, EMBASE, CINAHL, LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Oral Health Group and PaPaS Trials Registers, Cochrane Central Register of Controlled Trials (CENTRAL), OpenSIGLE, and Current Controlled Trials. Handsearching carried out by the Cochrane Collaboration was included. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.

Search keywords were (neoplasm* OR leukemia OR leukaemia OR lymphoma* OR plasmacytoma OR “histiocytosis malignant” OR reticuloendotherliosis OR “sarcoma mast cell” OR “LettererSiwe disease” OR “immunoproliferative small intestine disease” OR “Hodkin disease”  OR “bone marrow transplant*” OR cancer* OR tumor* OR malignan* OR netropeni* OR carino* or Adenocarcinoma* OR radioth* OR radiat* OR radiochemo* OR irradiat* OR chemo*) AND (stomatitis OR “Stevnes Johnson syndrome” OR “candidiasis oral” OR mucositis OR (oral AND (cand* OR mucos* OR fung*)) OR mycosis OR mycotic OR thrush. Extensive appendices are provided with specific search strategies used for each database. 

Studies were included in the review if they  

• Were randomized controlled trials using placebo, no treatment, or another active intervention.
• Involved patients with cancer receiving chemotherapy or radiotherapy and experiencing oral mucositis.
• Involved any intervention for the treatment of oral mucositis or its associated pain.
• Written in any languages. Papers not in English were translated by members of the Cochrane collaboration.

The final assessment incorporated 32 studies. Out of an initial 95 eligible studies, 64 were excluded because of study design issues, protocol violations, lack of useable data, or no relevant outcomes.

• The final set of studies involved a total of 1,505 patients; 1,023 patients were involved in trials investigating the effectiveness of agents to treat mucositis, and 718 patients were involved in trials evaluating pain relief. 
• Sample sizes ranged from 6–71 patients per treatment or control group.
• Twenty-eight trials included only adult patients, and four included only children.
• Trials included patients treated for a combination of leukemia and solid tumors (n = 14), patients with head and neck cancer (n = 8), and patients who had received bone marrow or stem call transplant (n = 11).

Treatment of mucositis

Summary of data from single trials showed the following interventions to demonstrate statistically significant benefit (p < 0.05).

• Allopurinal mouthwash resulted in improvement in mucositis, eradication of mucositis in some cases, and reduction in time to healing.
• Granulocyte macrophage-colony stimulating factor (GM-CSF) demonstrated mixed results, with two trials showing improved time to healing versus use of providone iodine and antimycotic mouthwash and one trial showing improvement in mucositis by the end of radiotherapy.
• Human placental extract demonstrated improvement in mucositis in one trial.
• Phenytoin mouthrinse was associated with better quality of life than placebo in one trial, but no benefit for pain was found and healing was not evaluated.
• Polyvariant intramuscular immunoglobulin was associated with improvement in mucositis versus placebo in one trial.
• Topical vitamin E was associated with improvement in mucositis and eradication of mucositis compared to systemic vitamin E in one trial.
• Debridement was associated with fewer days to clinical resolution and decreased severity of mucositis, when compared to no debridement.
• Laser treatment was beneficial in management of mild to moderate mucositis compared to sham treatment.

Other interventions for treatment of mucositis evaluated included chlorhexadine versus salt and soda, Gelclair verus sucralfate and mucaine,”Magic” mouthwash versus salt and soda, sucralfate versus placebo and versus salt and soda, and tetrachlorodecaoxide.

Management of pain with mucositis

The following interventions demonstrated statistically significant benefit in managing pain (p < 0.05).

• Opiod use was associated with lower average pain scores when compared to antidepressant use.
• Morphine pharmacokinetically patient controlled analgesia (PKPCA) was associated with lower average pain score than morphine standard patient controlled analgesia (PCA).
• When morphine PCA was compared to continuous morphine infusion, meta-analysis showed no difference in mean pain scores; however, mean opiate intake was reduced with PCA, and PCA was associated with fewer days of pain.

Other findings

• Interventions reviewed that showed no statistical benefit for treatment of mucositis included chlorhexadine, Gelclair, “Magic” mouthwash, and sucralfate.
• Interventions reviewed for management of associated pain that demonstrated no statistical benefit included hydromorphone PCA versus morphine, Alfentanil versus morphine, Dicofenic versus placebo, PCA versus staff controlled, hypnosis, relaxation, and imagery.
• Out of 27 different interventions evaluated for treatment of mucositis, only one comparison was significant for one outcome: low level laser treatment reduced the severity of mucositis.
• No evidence was found to suggest a difference in pain control between continuous infusion and PCA; however, the PCA group required less morphine, and the pain lasted two less days.

• Some evidence exists that low level laser treatment may help reduce severity of mucositis.
• No evidence suggests that PCA is more effective than continuous infusion for controlling pain. Weak evidence is available to support that PCA is associated with less opiate used per hour and that the duration of pain may be reduced.
• No clear benefit appears to be associated with antimicrobial use and GM-CSF for prevention or management of mucositis.
• This review demonstrated weak and unreliable evidence of benefit for interventions for mucositis.

The lack of independent duplication of studies investigating the same intervention limits the strength of evidence and ability to generalize results.

Most studies reviewed had small sample sizes and may have been underpowered to demonstrate significant differences in outcomes.

Different scoring systems for mucositis were used, and, in some studies, the method of scoring was not defined.

The need for further well-designed trials to evaluate the effectiveness of interventions continues.

Adoption of standard clinical outcome measures should be considered, including patient-based measures and inclusion of the cost of interventions.

STUDY PURPOSE: To assess the effect of low level laser therapy (LLLT) for oral mucositis

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 24
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,383
• SAMPLE RANGE ACROSS STUDIES: 1–221 patients
• KEY SAMPLE CHARACTERISTICS: Patients who have had hematopoietic cell transplantation (HCT), patients with head and neck cancer receiving chemotherapy and radiation therapy, patients with other tumor types receiving chemotherapy, and two studies including pediatric cases

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics

Most evidence showed a positive effect of LLLT on oral mucositis in delayed time of onset, lower peak severity, and shortened duration. One study in children showed no benefit of LLLT when optimal dental and oral care were provided.

LLLT is beneficial for the management of oral mucositis; however, ideal wavelengths, timing, and frequency of treatment are unclear.

• Limited search
• No study quality evaluation

LLLT has been shown to be effective in reducing the symptoms of oral mucositis in patients undergoing transplantation and those receiving treatment for head and neck cancer. The specifics for optimal LLLT timing, duration, and so forth have not been determined. Further research on these aspects is needed.

• STUDY PURPOSE: To evaluate effect of prophylactic and therapeutic low-level laser therapy (LLLT) in pediatric and young patients with cancer or undergoing HSCT.
• TYPE OF STUDY: Meta analysis and systematic review

• DATABASES USED: Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), Wanfang Database, and China National Knowledge Infrastructure (CNKI)
• YEARS INCLUDED: (overall for all databases) Years searched was unclear. Included articles were as old as 2007. The newest study was from 2017.
• INCLUSION CRITERIA: The randomized controlled trials and clinical controlled trials. Study participants were younger than age 23 years at diagnosis of any type of childhood cancer or undergoing HSCT. Both prophylaxis and therapeutic use of LLLT were included.  
• EXCLUSION CRITERIA: Not specified, but can assume studies that do not fit inclusion criteria were excluded.

• TOTAL REFERENCES RETRIEVED: 202
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The authors made reasonable effort to evaluate articles. The authors also used Cochrane Collaboration’s tool for assessing potential risk of bias for each article.

• FINAL NUMBER STUDIES INCLUDED: 8 
• TOTAL PATIENTS INCLUDED IN REVIEW: Occurrence of OM after prophylactic LLLT = 213 (ex, 106; con, 107);  grade 3 or higher OM after prophylactic LLLT = 173 (ex, 86; con, 87); OM severity after prophylactic LLLT = 96(ex, 44; con, 52); OM severity after therapeutic LLLT = 160 (ex, 79; con, 81); oral pain after therapeutic LLLT = 139 (ex, 70; con 69) 
• SAMPLE RANGE ACROSS STUDIES: 16-123 
• KEY SAMPLE CHARACTERISTICS: Patients with various solid tumors or lymphoma and leukemia who underwent HSCT

• PHASE OF CARE: Active anti-tumor treatment     
• APPLICATIONS: Pediatrics

• After prophylactic LLLT, the OR for developing OM was significantly lower compared with placebo (OR = 0.5, 95% CI [0.29, 0.87], p = 0.01) 
• The OR for developing grade III OM or worse was statistically significantly lower compared with placebo (OR = 0.3, 95% CI [0.1, 0.9], p = 0.03) 
• The OM severity was statistically significantly lower compared with placebo (SMD = −0.56, 95% CI [−0.98, −0.14], p = 0.009) 
• For therapeutic LLLT, the OM severity was significantly reduced compared to routine care (SMD = −1.18, 95% CI [−1.52, −0.84], p < 0.00001) 
• Oral pain was also reduced after LLLT over routine care (MD = −0.73, 95% CI [−1.36, −0.11], p = 0.02)

• Prophylactic LLLT reduces mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients with cancer.
• Therapeutic LLLT also reduces the average severity of oral mucositis and oral pain.

Low sample sizes

LLLT is effective to reduce mucositis and associated pain in pediatric patients with cancer overall. Despite of the deliveries of LLLT vary among the studies, it has been consistent to show the reduction of mucositis in pediatric population.

To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children

Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.

Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.

Studies were included in the search if they

• Involved English-speaking children.
• Were clinical trials conducted on the prevention of oral mucositis during cancer therapy.

Studies were excluded if they

• Were not in English
• Did not involve children
• Involved only gastrointestinal mucositis.
• Involved treatment of mucositis rather than prevention.
• Were case studies or pilot studies.
• Were commentaries or letters to the editor.
• Involved sample sizes of less than 20 patients.

• The total number of references retrieved was 16,471.
• The authors evaluated the references using the Canadian Task Force on Preventive Health Care evidence-based guidelines.

• The final number of studies was 27. The sample range across studies was not reported.
• Other than inclusion of pediatric cases, no other characteristics were described.

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

• The studies involved the following interventions.
  • Oral care protocols (n = 5)
  • Chlorhexidine mouthwash (n = 7) 
  • Benzydamine mouthwash (n = 1)
  • Iseganan mouthwash (n = 1),
  • Granulocyte macrophage-colony stimulating factor (GM-CSF) mouthwash (n = 2)
  • Oral glutamine (n = 2)
  • Enteral glutamine (n = 1)
  • Oral propantheline and cryotherapy (n = 1)
  • Oral cryotherapy (n = 1)
  • Oral sucralfate suspension (n = 1)
  • Prostaglandin E2 tablets (n = 1)
  • Chewing gum (n = 1)
  • Laser therapy (n = 3). 
• Good evidential support was found for the use of oral care protocols. Fair support was found for the use of chlorhexidine with some mixed results.
• Only one article was found that studied benzydamine, CSF, and iseganan. The evidence was deemed insufficient to make a recommendation. 
• Good evidential support was found against the use of sucralfate and prostaglandin E2 tablets.
• Evidence regarding laser use and oral and enteral glutamine were mixed.

The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.

• No disease or treatment factors were reported or considered in the analysis. 
• Some interventions were evaluated in only one study.
• The quality of the evidence in general was highly variable.
• No information was provided on how the outcome for mucositis was measured in the included studies.
• The authors recommendations suggest no use of a specific intervention if findings were conflicting, which assumes that insufficient evidence of effectiveness is equivalent to ineffectiveness.

Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.

To evaluate the evidence for prophylactic agents in management of oral mucositis in patients with cancer receiving treatment

Databases searched were MEDLINE, CANCERLIT, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature (LILACS), System for Information on Grey Literature in Europe (SIGLE), and the Cochrane Database.

An extensive list of search terms and strategies used per database was provided in the article.

Studies were included in the review if they

• Were randomized controlled trials (RCTs).
• Compared an intervention to a placebo or no treatment.

A total of 383 references were retrieved. Risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions. Studies were categorized as low, unclear, or high risk of bias. Studies were labeled using the GRADES system for evaluating quality of evidence.

• The final number of studies included in the review was 131.
• The total sample size across all studies was 10,514 with an across-study sample range of 12–301. 
• Studies involved a variety of cancers and patients receiving chemotherapy, radiation therapy, or both.

• Patients were in the active antitumor treatment phase of care.
• This study has clinical applicability to pediatrics.

• Only 8% of studies included were seen to have a low risk of bias. 
• Studies included a variety of treatments such as acyclovir, allopurinol rinse, aloe vera, amifostine, antibiotic paste, systemic antibiotics, axulene, benzydamine, beta carotene, chamomile, chewing gum, Chinese herbs, chlorhezidine, cryotherapy, epidermal growth factor, glutamine, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), histamine gel, honey, hydrolytic enymes, indigo wood root, intestinal trefoil factor, keratinocyte growth factor, laser, anti-inflammatory drugs, oral care, pentoxifylline, pilocarpine, polymixin/tobramycin/amphotericin (PTA), traumeel, sucralfate, zinc sulphate, and povidone iodine. 
• From all analyses, at least moderately strong evidence of benefit was found for cryotherapy (RR = 0.74, 95% confidence interval [CI] 0.57–0.95, p = 0.02) for any mucositis and for keratinocyte growth factor (RR = 0.82, 95% CI 0.71–0.94, p = .0005) for any mucositis. 
• Weak and unreliable evidence for potential benefit was found with aloe vera, amifostine, glutamine, G-CSF, honey, laser, polymixin/tobramycin, amphotericin lozenges, and sucralfate.
• A substantial body of evidence showed no benefit of chlorhexidine.

Findings support the benefits of cryotherapy and keratinocyte growth factor. The low quality of evidence in most of the other interventions points to the need for ongoing, well-designed research in this area. The presentation of findings in many publications made meta-analysis impossible.

The rationale for the authors' summaries of findings was not entirely clear. Similar RR ratio results with similar evidence quality levels were identified differently in terms of potential benefit. Although the review was inclusive and extensive, interpretation of results was inconsistent. High heterogeneity existed in most interventions, and most studies were either at high or unclear risk of bias with low GRADES scoring. Studies did not always differentiate between mucositis and candidiasis, which would affect recommendations.

This article suggests strong support for use of cryotherapy and keratinocyte growth factor for mucositis prevention. It suggests possible benefit from aloe vera, amifostine, IV glutamine, G-CSF, honey, laser, and antibiotic lozenges. Sucralfate may reduce the severity of mucositis. These findings should be interpreted with caution, given the relatively low quality of overall evidence and high heterogeneity across studies included in meta-analysis, as well as the fact that treatments and sample characteristics were highly varied.

To evaluate the efficacy of low-level laser therapy (LLLT) to reduce the severity of chemotherapy-related oral mucositis in children

Patients were randomized to receive LLLT or sham control interventions. Therapy began on day 1 of diagnosis of oral mucositis and was continued daily for the next three days. Study assessments were done immediately before beginning laser therapy, on day 4 after completion of laser therapy, and on day 7. Individuals who applied the laser treatment were not involved in mucositis data collection.

• N = 123   
• MEAN AGE = 9.54 years
• MALES: 45.5%, FEMALES: 54.5%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Thirty percent were undergoing hematopoietic cell transplantation (HCT), and the majority were being treated for leukemia or lymphoma.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment

• Double-blind, sham-controlled, randomized controlled trial

• World Health Organization (WHO) Toxicity Scale 
• Visual analog scale (VAS) faces scale for pain severity
• Analgesics used

Progressive decline in mucositis severity occurred in both groups, and no significant difference in grading existed between groups. Pain scores were lower in those treated with laser therapy (p < 0.05), and those getting LLLT required less analgesia.

The findings suggested that LLLT may help the management of pain from oral mucositis among children receiving chemotherapy.

• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• No subgroup analysis was conducted according to the type of analgesia consumed—some were getting morphine and some were getting Tylenol. No subgroup analysis according to disease type or chemotherapeutic agents was received. No information was provided on chemotherapy used.

The findings did not show the efficacy of LLLT among children to reduce the severity of oral mucositis. Further well-designed research is needed to determine if a role exists for LLLT in children receiving chemotherapy.

To evaluate the efficacy of low-level laser therapy for prevention of chemotherapy-induced mucositis and xerostomia

Patients were randomized to receive the laser or sham procedure. The laser group had laser therapy prior to each episode of chemotherapy with a 630-nm laser with a dose of 5 J/cm². Patients in the sham control group underwent procedures with the laser unit turned off. All patients received the same instruction for ongoing oral care and underwent mucous and salivary health assessment by an oral medicine specialist prior to beginning chemotherapy, after two weeks, and then every two weeks until the end of chemotherapy treatment. Severity of pain, mucositis, and xerostomia was assessed at these times, and observers were blinded to patients’ study group assignments. Data were collected for 14 weeks.

• The study reported on 48 patients.
• The mean patient age was 45.6 years, with a range of 17-79 years.
• The sample was 50% male and 50% female.
• Cancer diagnoses were lung, lymphoma, gastrointestinal (GI), skin and breast. Patients with head and neck cancer were excluded.

This was a single-site, outpatient study conducted in Iran.

Patients were undergoing the active antitumor treatment phase of care.

This was a randomized, double-blind, sham-controlled study.

• The World Health Organization (WHO) mucositis grading was used.
• A late effects of normal tissues subjective, objective, management, and analytic (LENT-SOMA) four-point scale was used to measure xerostomia.
• A visual analog scale (VAS) was used to measure pain.

In the laser group, over the course of the study, 8.3% of patients experienced grade 2 mucositis and none experienced a higher grade of mucositis, compared to 91.6% of patients in the control group who developed grade 2 or higher mucositis (p = 0.001). By week two, xerostomia intensity was significantly lower in the laser group than the control group (p < 0.005). Across all time points, pain intensity in the laser group was significantly lower (p = 0.001). Difference in pain was substantial, with a mean of 0.7 in the laser group compared to 6.8 in the control group at week 2. The magnitude of these differences in pain intensity was large at all study assessment times.

Findings showed that provision of low-level laser treatment was effective in preventing chemotherapy-induced mucositis, xerostomia, and associated pain.

• The sample size was small with fewer than 100 patients.
• The chemotherapy agents used and the schedule given were not described. 
• Laser treatment was done prior to each chemotherapy administration, and the actual number of treatments given was not clear.
• The actual risk of mucositis development in both groups was not clear.

The results here support the effectiveness of low-level laser treatment for prevention of chemotherapy-induced mucositis. The actual number of laser treatments given was not clear. One of the difficulties in evaluating laser evidence for prevention of mucositis is the different treatment schedules and doses used in the research. Further research to identify the most effective laser dosages and schedules would be helpful to facilitate clinical translation of this evidence.

To study the capacity of pain relief and wound healing of low-level laser therapy (LLLT) in chemotherapy-induced oral mucositis in a pediatric population

Children were treated using a GaAIAs diode laser with 830 nm continuous wavelength an output of 150 mW. Laser was applied every 48 hours until complete healing of the lesion occurred.

• The study reported on 16 patients with a mean age of 9.4 years.
• The sample was 50% male and 50% female.
• Patients had been diagnosed with leukemia and lymphoma (n = 12), neuroblastoma (n = 1), osteosarcoma (n = 1), Ewing’s sarcoma (n = 1), and germ cell tumor (n = 1).
• All patients were receiving chemotherapy.

The study was conducted at a single site in Belgium.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for pediatrics.

The study used a convenience sample.

• The Modified Faces Pain Scale was used.
• A visual analogue scale was used.
• The World Health Organization (WHO) Oral Toxicity Scale was used.

Fifty episodes of oral mucositis were included. Pain scores improved after each session with only one exception.

The LLLT appeared to be effective for pain relief in this population.

• The study sample size was small with fewer than 30 patients.
• No control group was included.
• Wound healing measures could have been used, as these are more objective.

To evaluate the influence of low-level laser therapy (LLLT) on the prevention and treatment of oral mucositis (OM)

Patients were distributed by convenience sampling into two groups (A and B) based on the order in which they were hospitalized. Group A was composed of patients who received preventive laser (red or infrared subgroups A1 [n = 10] and A2 [n = 10], respectively) for five days, beginning on the first day of chemotherapy. Group B was composed of patients who did not receive any preventive intervention, and those who developed post-chemotherapy mucositis were subjected to therapeutic laser (red or infrared subgroups B1 [n = 10] and B2 [n = 10]) until full remission of the lesions.

• N = 40  
• AGE = 1–18 years
• MALES: 67.5 %, FEMALES: 32.5%
• KEY DISEASE CHARACTERISTICS: Pediatric population with acute lymphoblastic leukemia who received high-dose methotrexate

• SITE: Single site  
• SETTING TYPE: Inpatient   
• LOCATION: Instituto de Medicina Integral Professor Fernano Figueira

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

The patients were distributed by convenience sampling into two groups (A and B) based on the order in which they were hospitalized. Group A received preventive laser, and Group B received therapeutic laser.

Evaluations were done by daily use of the World Health Organization (WHO) scale grade 0–IV, and patient self-assessed pain was measured by means of the visual analog scale (VAS) (0–10). This assessment was made before each LLLT session.

The overall incidence of OM was 57.5% up to the age of 8 years; the degree of mucositis was significantly higher than that observed among patients older than 8 years. Generally in group A, 40% of patients developed OM, and in Group B, 75% of patients developed OM. In subgroup A1, 30% had mucositis, and in subgroup A2, 50% had mucositis. In subgroup B1, 70% had mucositis, and in subgroup B2, 80% had mucositis. In both groups, 75% did not develop pain symptoms. The Mann-Whitney test showed that there were statistically significant differences between the type of laser with the number of days with pain and severity of mucositis.

This study validates that there are positive results with the use of LLLT in reducing the incidence and severity of OM in patients undergoing anticancer treatment. The study confirmed that there is a reduction in the average duration of OM that occurred in both groups.

• Small sample (< 100)
• Findings not generalizable
• Intervention expensive, impractical, or training needs

Among the pediatric population receiving consolidation chemotherapy with methoexate, the study showed that prophylactic laser (with red laser 660nm) produced a better outcome than when patients did not receive any preventive intervention for OM. For nursing, this is another option to help reduce the severity and duration of OM. It is likely that nurses would need to work in a multidisciplinary setting to provide the patient population with this intervention. The study does not provide information about the professional who is trained and able to provide the LLLT.

A prospective study to compare the effect of an established laser therapy protocol with a potential therapy utilizing LED (light-emitting diode) on chemotherapy-induced oral mucositis

1. Physical examination was done on all patients and oral hygiene instructions were given to patients at the start of treatment.
2. Oral examinations were conducted during irradiation sessions and the degree of mucositis and pain were recorded daily.
3. Two different phototherapeutic protocols were used randomly from the time of the patient’s registration to 12–15 days later.
4. Patients received 10 consecutive days of irradiation, except for weekends.
5. Patients in group 1 received one laser phototherapy protocol of InGaAIP diode laser with a wavelength of 660 nm. Irradiation time was six seconds per point based on the laser beam spot size of 0.036 cm². Irradiations were performed intraorally: 12 points on each buccal mucosa, 8 on the superior and inferior labial mucosa, 12 on the hard palate, 4 on the soft palate, 12 on the lingual dorsum, 6 on the lateral edge of the tongue bilaterally, 2 on the right and left pillar of the tongue, 4 on the floor of the mouth, and 1 on the labial commissure bilaterally.
6. Patients in group 2 received one LED phototherapy protocol. The dentists were trained to perform LED irradiation in a standardized manner.
7. Irradiations were performed daily for 10 consecutive days, except for weekends, with a wavelength of 630 nm and with the same energy per point as was used in in laser protocol. Laser power was 40 mW, energy density of 6.6J/cm², power density of 1.1W/cm², and energy per point of 0.24J. Irridation was punctual, in contact, and perpendicular to the oral mucosa. Irradiations were performed intraorally in the same manner as for group 1.
8. For both radiation protocols before and after each session, power output was checked using a power meter.
9. Patient self-assessed pain was measured using a visual analog scale (VAS) for pain from 0 to 10 and was done prior to each laser/LED session.

• N = 4
• AGE RANGE: Group 1: 50.5 (+/– 14.7) years, Group 2: 57.4 (+/– 11.3) years 
• MALES: Group 1: 10 (44%), Group 2: 5 (29%) 
• FEMALES: Group 1: 13 (56%), Group 2: 12 (71%) 
• KEY DISEASE CHARACTERISTICS: Patients with chemotherapy-induced oral mucositis grades I, II, or III. Breast cancer was the most common cancer in both groups. A wide variety of chemotherapy were treatments used.

• LOCATION: Sao Paulo, Brazil

• PHASE OF CARE: Treatment
• APPLICATIONS: Patients with chemotherapy-induced oral mucositis grades I, II, and III

• Prospective trial

• World Health Organization (WHO) criteria for oral mucositis
• Visual analog scale (VAS) for pain (0 to 10)

• Beginning grade of mucositis did not differ between groups (p < 0.05).
• In the LED group, within-group analysis showed a significant decrease in mucositis from day 1 to days 7, 8, 9, and 10 (p < 0.05).
• In the laser group, within-group analysis showed a significant decrease in mucositis from day 1 compared to day 10 (p < 0.05).
• A trend was seen for both treatment groups. The higher the initial mucositis score, the more treatment that was required to improve mucositis. The trend was not statistically significant.
• Comparing the mucositis scores between the laser and LED groups according to patients initial mucositis grade, only in those patients with the initial mucositis score III (p = 0.028) was the LED treatment more effective in healing oral lesions than the laser treatment.
• Comparing the mean of VAS scores for laser and LED, according to the patients' initial mucositis scores, the LED treatment was more effective for patients with initial the mucositis scores I and II (p = 0.012 and p = 0.022).

Both therapies analyzed in this study were efficient in preventing breaks in treatment.

• The groups were not evenly matched for men and women.
• Risk of bias (no control group)
• Unsure how the randomization process was achieved; not stated in report
• Dentists were taught how to do WHO mucositis assessments, but the article did not speak to the training received.
• The LED power was twice as strong as the laser power, resulting in three and six seconds of irradiation per point, respectively. One advantage of the LED phototherapy protocol over the Laser protocol is that much less time is required to irradiate through the oral cavity.

LED phototherapy may be a viable alternative to traditional laser therapy to treat oral mucositis. This study, however, is small and has several flaws. Nurses should educate patients on proper oral hygiene to be used in combination with LED and laser therapy to promote optimal healing.

100 mW laser was delivered to tissues with a 1.2 mm spot size. Treatment areas included inferior and superior lips, right and left cheeks, right and left tongue, palate and velum palate, right and left gums, and tongue frenulum.

Average energy was 2 J/cm² on all sites, with a calculated mean duration of 33 seconds per site; each treatment lasted six minutes.

1. Three sessions per week
2. Started within 24 hours of diagnosis and given every other work day

(1) Patients with various solid tumors treated with chemotherapy; previous oral mucositis of 2 or higher

26 patients for 90% power

Patients with concomitant RT and those \"expected to be poor compliers to the treatment schedule\" were excluded.

Mean age 51 was years (range = 32–73 years).
20 women; 6 men

(2) Randomized trial for patients with hematologic malignancies who developed mucositis receiving radiochemotherapy prior to HSCT. Therapy started 24 hours after diagnosis of mucositis. Sham laser control was used.
20 patients were needed in each arm for 90% power.

n = 36 (18 patients in each arm)
 

Grade of mucositis using EORTC scale

Grading was performed by a nurse prior to each treatment session and afterward once a week by an independent blinded professional observer.

All treated areas were examined.
 

1. 21 of 26 patients were considered to have prevented mucositis (81%, 95% CI = 61%–93%); 4 with no mucositis, and 17 with grade I. Five patients had grade 2 or higher; median duration was 10 days (range = 8–14 days).

2. Grade 3 mucositis was observed in 16 patients in the sham group and in 3 LEL treated patients (p = 0.001). Overall success rate was 15 of 18 (83%, 95% CI = 59%–96%) and 2 of 18 in the control group (11%, 95% CI = 1–35).Time to grade 3 mucositis was calculated (p < 0.0001).

Of 16 patients in the control arm who developed grade 3–4, eight later received laser treatment; regression to grade 1 mucositis was three days in this group and four days in those who did not receive LEL.
 

Limited sample size, although the prevention trial (1) achieved 90% power.

The heterogeneous population in the prevention trial makes the results difficult to generalize. Oral care and other factors were not reported.

 

Laser energy 35 J/cm² once a day for five days after the development of chemotherapy-induced \"moderate\" mucositis.

Laser has an 830 nm wavelength with a potency of 250 mW.  
 

Each patient was informed of the oral hygiene protocol:       
Avoid spicy food acid fruits, alcohol, and food and drinks with high temperature.
Use a soft toothbrush and avoid dental floss.
Only use mouth solution provided by health personnel (3% bicarbonate).
Do not smoke.       

The study was conducted March-August 2002.

Thirteen individuals were treated. Convenience sample for chemo-induced mucositis-related pain.
Mucositis was determined using the Brown methodology. Patients determined to have moderate mucositis (score 13-18) were included in the study.

Non-parametric study

VAS pain scale

Brown methodology for classification of mucositis.
 

Significantly lower pain (p = 0.007) after each treatment. Average pain reduction was 67%. Pain reduction across the five days of treatment was also significant (p = 0.000).

Authors note that after five days, pain is usually reduced to such an extent not to require further treatment.

 Limited sample size, short study – no control

Other factors may have contributed to pain reduction, including normal healing and placebo effect.

Optimal energy level is not determined.

Cost is high, and treatment is not available at most centers.

Main focus of study was on pain .
 

To evaluate the effect of low-level laser therapy (LLLT) on the severity of oral mucositis (OM) and the release of salivary molecules (TNF~a, IL-1b, IL6, IL10, TGF-b, EGF< FGF< VEGF< MMP2/TIMP2, and MMP9/TIMP2) during chemoradiation in patients with head and neck cancer

• N = 25  
• AGE = 10 were aged greater than 60 years, and 15 were aged less than 60 years
• MALES: 84%, FEMALES: 16%
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (nine oral cavity, seven pharynx, and nine oropharynx)
• OTHER KEY SAMPLE CHARACTERISTICS: In the laser group, three patients died during the course of the study, two from pneumonia and one from hemorrhagic complications (not explained). In the control group, two patients dropped out of treatment. The sample started with 30 patients, and only 25 completed treatment.

• SITE: Single site  
• SETTING TYPE: Unknown
• LOCATION: Brazil

• PHASE OF CARE: Active treatment

Randomized, double-blinded, placebo-controlled clinical trial

• The severity of OM was rated according to the National Cancer Institute (NCI) and World Health Organization (WHO) mucositis grading scales.

LLLT reduced OM in the experimental group when compared to the control group. This study added to the growing body of literature demonstrating that LLLT is an effective intervention for OM in patients receiving treatment for cancer.

• Small sample (< 30)
• Key sample group differences that could influence results
• Other limitations/explanation: Six patients in the laser group had T3 or T4 disease while 10 patients in the control group had T3 or T4 disease. There was no mention of comorbid conditions such as diabetes, which might affect healing time and salivary concentrations. There were no limits on medications taken by the participants, which could have affected the outcomes.

Reducing OM can have a distinct impact on patients' quality of life, pain control, and ability to complete chemoradiation in a timely manner. Nurses have daily interactions with patients to assist them through the completion of therapy. This study contributed to the growing body of literature demonstrating that LLLT is an effective intervention for OM.