Low Level Laser Therapy in Patients With Head and Neck Cancer

Review the effects of low level laser therapy (LLLT) in prevention and treatment of oral mucositis induced by cancer therapy. Meta-analysis was done, and all results are provided.

Databases searched were Medline, EMBASE, CINAHL, PedRo, and Cochrane Controlled Trial Register. Hand searching in physiotherapy and medical journals from several countries also were used.

Search keywords were low level laser therapy, low intensity laser therapy, low energy laser therapy, phototherapy, oral mucositis, cancer, chemotherapy, radiation therapy, and specific laser types.

Studies were included if they

• Involved patients with cancer who had been diagnoses with oral mucositis after chemotherapy or radiation therapy.
• Used treatment with laser therapy with wavelengths of 632–1064 nm.
• Incorporated a randomized parallel group or crossover design, with blinding and placebo control with identical placebo laser.

A total of 149 papers were initially retrieved. Literature was evaluated using the Jadad checklist and inclusion of study funding sources.

A final sample of 11 trials published from 1997–2009 included 415 patients. Samples ranged from 21–70 subjects and included those receiving chemotherapy, radiation therapy, combined therapy, and transplant cases. One study was done in children.

• Six trials involved prevention of OM. The overall effect size was 2.31 in favor of laser (p = 0.02). In one trial, which used less than 1 joule, results did not favor laser use. Subgroup analysis showed positive results with laser whether done before cancer therapy, before and during therapy, or during therapy.
• Five trials assessed duration of OM. Overall effect size was 8.35 in favor of laser therapy (p < 0.00001).
• Seven trials assessed severity of OM. Overall effect size was 4.01 in favor of laser (p < 0.00001). Subgroup analysis showed there was no significant difference in these findings with different wavelengths of infrared LLLT.
• Three trials studied the effect on pain. Effect size was 4.97 in favor of laser (p < 0.00001).
• All analyses showed substantial heterogeneity. LLLT was well tolerated with no serious incidents or withdrawals because of the LLLT treatment.

Moderate to strong evidence was found for effectiveness of LLLT in the prevention of OM, reduced duration and severity of OM, and reduced pain with doses of 1–6 joules per point. Trials aimed at prevention started LLLT seven days before cancer treatment regimens, and effective dosing seen ranged from 1–6 joules. This meta-analysis supported the effectiveness of LLLT in the dosage ranges reported here for the prevention and management of oral mucositis.

The quality of studies was determined to be high; however, substantial variation existed in the actual treatment procedures, number of treatments, timing of treatments, and heterogeneity in the overall findings.

STUDY PURPOSE: To conduct a meta-analysis and systematic review to determine if laser therapy (LT) is effective in preventing oral mucositis (OM) during oncotherapy

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: LILACS, MEDLINE, Cochrane electronic

KEYWORDS: “laser therapy”, “oral mucositis” used in all databases

INCLUSION CRITERIA: Oncotherapy-induced and diagnosed OM, low-intensity laser was the form of treatment with specific wavelength between 632 and 1,064 nm, randomized trial with control group

EXCLUSION CRITERIA: No specific exclusion criteria referenced; however, OM grade ≥ 3 was used as a cutoff in all the scales to properly evaluate the preventative value of LT.

TOTAL REFERENCES RETRIEVED: 12 prospective, randomized studies met criteria out of 149 initial retrieved studies

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Jadad scale was used to evaluate the methodology of the studies included. BioEstat 5.0 was used for the meta-analysis. Literature was further evaluated using a standardized form that included study design, country of origin, year of publication, and authors. The patients’ data were analyzed for gender and age, type of cancer treatment, control group treatment, and LT specifics (e.g., wavelength, power, dose, irradiation time, and number of sessions per week).

FINAL NUMBER STUDIES INCLUDED =  12

SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Total sample of 527 patients; 276 of these patients underwent LT, and 251 patients were in the control group. Final meta-analysis resulted in a total sample of 293 patients.

KEY SAMPLE CHARACTERISTICS: 53% of the patients had hematologic malignancy; 47% had head and neck cancer.

PHASE OF CARE: Multiple phases of care

Out of the 12 studies included for review, 7 of them showed (through meta-analysis) that LT is almost 10 times more effective in preventing OM ≥ grade 3 than treatment without the use of LT.

The authors determined that the data supported the effectiveness of LT in the prevention of OM ≥ grade 3. They note that additional studies with larger sample sizes are still required to fully evaluate the total effectiveness of this intervention.

Age range was not listed in this review, nor was prior radiation or chemotherapy exposure. Dental health and evaluation prior to oncotherapy and LT were not referenced in this review. Due to multiple variances in the control group's non-LT prevention measures, the number of studies was much smaller than the number the initial search results returned.

This study, even with the limitations of its size and characteristics, is a good starting point for further investigation into LT to prevent severe OM in patients with cancer undergoing chemotherapy, radiation, or both. LT appears to be a promising intervention. If severe OM can be prevented, then pain and infection, which quickly result from OM, can be prevented, too. Thus, this study has larger implications in overall care and quality of life in patients with cancer. Nurses can begin to address the study and the use of LT in their own institutions.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics, elder care

The primary outcome (overall severity of oral mucositis) of this analysis was that prophylactic LLLT reduced the overall risk of severe mucositis when compared to a placebo or no therapy (RR = .37, 95%, CI = .18–.67, p = .001). The absolute risk reduction was -.35 (95%, CI = -.48– -.2, p < .0001). Secondary outcomes included a decreased risk of severe mucositis at the time of expected worst severity with prophylactic LLLT (RR = .34, 95%, CI = .20–.59, p = .0001). Overall mean grade of mucositis: standardized mean difference = -1.49, 95%, CI = -2– -.95;=, p < .0001. Duration of severe (grade 3 or 4) mucositis: weighted mean difference = -5.32, 95%, CI = -9.45– -1.19, p = .01. Incidence of pain: RR = .89, 95%, CI = .76–1.04, p = .15. Incidence of severe pain: RR = .26, 95%, CI = .18–.37, p < .0001. Overall mean pain score: WMD = -2.46, 95%, CI = -4.4– -.77, p = .004. Number of patients needing opioid analgesia: RR = .47, 95%, CI = .37–.60, p < .0001. Unplanned interruption in radiation (from mucositis in patients with head and neck cancer): RR = .23, 95%, CI = .12–.44, p < .0001.

The overall risk of severe mucositis is decreased by the use of low-level laser therapy. The duration of mucositis, the risk of severe pain, the need for opioid analgesia, and radiation treatment interruption also is positively impacted by LLLT.

There is heterogeneity to the laser schedules, mucositis assessment scales, laser parameters, intervals, and time points for assessment and outcome reporting (per the authors). It is difficult to generalize this study to the pediatric population. The feasibility of using laser therapy continues to be an issue in nursing.

Prophylactic LLLT shows benefit in the prevention of oral mucositis. Additional research to delineate the feasibility of this intervention and define best practice is needed.

• STUDY PURPOSE: To optimize the prophylactic treatment for radiotherapy-induced oral mucositis in patients with head and neck cancer receiving postoperative or definitive radiotherapy with or without chemotherapy
• TYPE OF STUDY: Network meta analysis and systematic review

• DATABASES USED: PubMed, Web of Science, Cochrane Library, and Chinese databases (WangFang, National Knowledge Infrastructure) 
• YEARS INCLUDED: (Overall for all databases) Authors stated the search was up to May 1, 2017. Supplemental material shows the oldest study included was 1989.  
• INCLUSION CRITERIA: Head and neck cancer or carcinoma or neoplasm, nasopharyngeal carcinoma or cancer or neoplasm, radiotherapy and mucositis 
• EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: 112 randomized clinical trials were identified. 10 excluded that did not adopt the required criteria to evaluate oral mucositis, 28 studies or conference abstracts that did not provide a detailed number of responders and non-responders, 2 trials that recruited patients with previous chemotherapy, 5 studies that only evaluated mucositis-related pain, and 10 studies with the intention of treatment. 57 studies were eligible. 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Randomization procedure, establishment of sample size, adoption of blinding in the study design, allocation of concealment if intention-to-treat analysis was followed, loss to follow-up, and dropout. Used the revised Jadad/Oxford quality scoring system to quantify study quality.

• FINAL NUMBER STUDIES INCLUDED: 57
• TOTAL PATIENTS INCLUDED IN REVIEW: 5,261 patients randomly assigned 
• SAMPLE RANGE ACROSS STUDIES: Not specified in this version of article.  
• KEY SAMPLE CHARACTERISTICS: Not specified in this version of article

PHASE OF CARE: Active anti-tumor treatment

• Direct meta analysis findings for grade 0–2 oral mucositis: Abs: SOC, AIS: PS, AVS: PS, CHS: PS, GFS: PS, GS: PS, GS: SOC, HS: SOC, LS: PS, LS: SOC, PS: SOC
• SOC and PS had worse effects and LS had better effects than most of the other treatments; details in supplementary materials
• In the network of 12 treatment arms, LS ranked as best and SOC as least effective in preventing grade 3 and 4 mucositis 

Abbreviations: SOC–standard oral care; ABS–antibiotics + SOC; AIS–anti-inflammatory + SOC; AVS–aloe vera + SOC, CAS–coating agents + SOC, CHS–Chinese herbs + SOC, GCS–granulocyte-macrophage colony–stimulating factor + SOC, GFS–growth factor + SOC, GS–glutamine + SOC, HS–honey + SOC, LS–laser + SOC, PS–placebo + SOC; NMT–non-medication treatment

Radiotherapy-induced oral mucositis in patients with head and neck cancer can be debilitating. This network meta-analysis compared prophylactic treatments in patients receiving postoperative radiation with or without chemotherapy. Low-level laser therapy in addition to standard of care may be more effective in reducing oral mucositis than standard care alone.

Limited information provided in the printed lack of control for or limit use of chemotherapy; not clear what constituted low-level laser therapy or the details regarding the other treatments.

Oral mucositis has been identified as a complex process; nurses should remain astute to changes in the oral cavity with the various treatments for cancer as well as changes over time. Interventions effective with a specific cancer treatment may not be universally effective. Study results should be read with a critical review process

To assess the efficacy of preventive low-laser therapy to reduce grade 3 and 4 oral mucositis (OM) in patients receiving chemoradiation

Both groups received cisplat 100 mg/m² for three cycles every three weeks, radiation 70.2 Gy (1.8 Gy per day five times per week), and the same oral hygiene. The intervention group received low-level laser therapy five times per week before every fraction of radiation. The energy and energy density were the same for each patient. A dentist applied the laser tip to the mucosa of the lips, the right and left buccal mucosa, the left and right lateral tongue border, the buccal floor, and the ventral tongue. The placebo group had the laser tip touched to the same sites, but there was no laser light.

• N = 94   
• AGE: 10–18 years
• MALES: Laser group: 89%, placebo: 85%; FEMALES: Laser group: 11%, placebo: 15%
• KEY DISEASE CHARACTERISTICS: Patients with squamous cell carcinoma of the head and neck
• OTHER KEY SAMPLE CHARACTERISTICS: Had to be ineligible for surgery, be able to tolerate chemo/radiation, have Eastern Cooperative Oncology Group status of 0 or 1, have had an intact oral mucosa at the start of the study

• SITE: Single site  
• SETTING TYPE: Outpatient   
• LOCATION: Brazilian National Cancer Institute in Rio de Janeiro

• PHASE OF CARE: Active antitumor treatment

• Prospective, randomized, double-blind, placebo-controlled, phase III trial

• World Health Organization Oral Mucositis Scale
• Oral Mucositis Assessment Scale
• Visual analog scale for pain
• The European Organization for Research and Treatment of Cancer QLQ-C30

A significant decrease was seen in the rate of grades 3 and 4 OM in the treatment group. Relative risk ratio (6.4% with laser versus 40.5% control) 0.158 (CI 95%). The treatment group reported better physical, emotional, fatigue, and pain scores and had less pain, fewer problems swallowing, and less trouble with social eating.

Low-level laser light therapy is effective in reducing grades 3 and 4 OM in patients with squamous cell carcinoma of the head and neck undergoing concurrent chemotherapy and radiation.

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

Nurses who work in facilities with access to low-level laser light therapy should advocate for the use of it for their patients with head and neck cancer undergoing radiation and chemotherapy. There may be a role for nurses in learning to administer low-level laser light therapy.

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.

To evaluate the efficacy of low level laser therapy (LLLT) for the prevention and treatment of radiotherapy-induced oral mucositis in patients with oral cancer

Patients with primary oral cancer were randomized to the laser group or a control group. All patients had oral prophylaxis before starting radiation therapy, and all had the same oral care during treatment. All patients were evaluated daily for pain severity, functional impairment, and oral mucositis. The clinical exams were performed by a single examiner. All the laser treatments were administered by one operator. The treatment consisted of use of a laser scanner for the first eight days followed by treatment to six areas on the right and left sides of the oral cavity for 25 days.

• The study reported on 24 patients, ages 55–59 years old.
• The sample was 50% female and 50% male.
• Patients were newly diagnosed with primary oral cancer limited to the oral cavity
• Patients received 66 Gy in 33 fractions, 5 days per week for 6.5 weeks. No patients experiencing treatment delays were included in the study.

This was a single site, inpatient and outpatient study conducted at Kasturba Medical College of Manipal University in Karnataka, India.

This was a randomized controlled trial.

• A numeric rating scale was used to measure severity of oral pain.
• To evaluate patient need for supplemental analgesics, the World Health Organization (WHO) analgesic ladder, date of initiation, and  duration of analgesic use were recorded.
• Functional impairment was recorded.
• A scale was used to assess severity of dysphagia.
• Mucositis severity was assessed daily by one examiner using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system.

Pain increased gradually and was the greatest at the end of seven weeks. The laser group had a statistically significant lower level of pain than did the control group (p < 0.03). In week 3, the laser group had grade I functional impairment, while the control group progressed to grade II and III functional impairment, with one individual having grade IV impairment. Overall, the laser group had lower mucositis severity than the control group (p = 0.033).

Prophylactic laser therapy during radiation therapy can reduce the severity of mucositis, as well as the severity of functional impairment and pain.

• The control group had a small sample size of fewer than 30 patients.
• The article did not state what the control group procedure involved (e.g., sham treatment).

This form of laser therapy is effective in the prevention of severe mucositis, but it is very high tech and requires special equipment and highly trained personnel.

To determine the efficacy of low‐level laser treatment (LLLT) in the prevention and treatment of radioinduced oral mucositis in patients with oral and oropharynx cancer

Patients were randomized into two groups. Group 1 received 660 nm/15 mW/3.8 J/cm² spot size 4 mm² LLLT, and Group 2 received 660 nm/5 mW/1.3 J/cm² spot size 4 mm² LLLT, both beginning on the first day of radiation. In both groups, LLLT application was done daily for five consecutive days per week starting on the first day of radiation therapy. Prior to the study, all patients underwent oral care, including an oral examination, preventive dental treatment, instructions for oral care during radiation therapy, and prescription mouthwashes and fluoride treatment. Randomized sample selection was based on the eligibility criteria that each patient was diagnosed with cancer of the oral cavity or oropharynx and treated with radiation therapy.

• The study reported on a sample of 54 patients.
  • The mean patient age in group 1 was 57.1 (SD = 12.8) with a range of 22–94 years.
  • The mean patient age in group 2 was 58.1 (SD = 10.9) with a range of 35–79 years.
• The sample was 66% male and 34% female.
• Patients were included in the study if they received conventional, three-dimensional conformal radiotherapy or intensity-modulated radiation therapy with doses in facial fields equal to or greater than 4,000 cGy exclusively or associated with chemotherapy.

This was a single-site study conducted in an inpatient setting at Hospital A.C. Camargo, Sao Paulo Brazil.

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized, double-blind study.

• The National Cancer Institute (NCI) classification criteria for oral mucositis was used.
• The World Health Organization (WHO) classification criteria for oral mucositis was used.
• A visual analog scale was used for pain evaluation, with 0 equal to no pain and 10 equal to maximum pain.

Group 1 had a delay in presentation with oral mucositis compared to Group 2 (13.5 days to 9.8 days, respectively). Group 2 presented with a higher grade of mucositis as compared to Group 1, and Group 2 reported higher overall pain scores.

This study reported a delay in development of mucositis, a decrease in severity of mucositis, and a decrease in pain scores with the group that received the higher dose of LLLT during treatment for oral or oropharynx cancer.

• The sample size was small, with fewer than 100 patients.
• Other limitations of the study included the fact that the incidence of oral mucositis may be affected by the location of primary tumors in different sites of the oral cavity and oropharynx.
• The study also did not take into account that some patients are reluctant to report pain symptoms, and no differences were found between the two groups in the reduction of analgesic administration.

Further studies are necessary to define dose, application time, and number of sessions needed for laser therapy in prevention and management of oral mucositis.

To evaluate the therapeutic effects of a low level He-Ne laser on chemoradiation (CRT) -induced oral mucositis (OM), associated severe pain, and use of total parenteral nutrition (TPN) in patients with oral cancer

Block randomization was done using a computerized program taking primary oral cancer stage as a matching variable of 121 primary patients with oral cancer scheduled to undergo CRT (RT dosage = 66 Gray/33 fractions for five days per week and chemotherapy was three weeks cisplatin). Patients were randomized to either laser (n = 60) or placebo (n = 61). Both groups received standard oral care and hygiene. Patients and outcomes assessor were kept blinded for the laser intervention. OM, its associated pain, and TPN were assessed every week by a blinded assessor. Opioid analgesic use, weight loss, and any CRT breaks were recorded.   

Laser treatments used He-Ne 632.8 nm, power output of 24 mW, beam spot diameter of 0.6 mm, noncontact method (Technomed Electronics, Advanced Laser Therapy 1000, Chennai, India). This was applied to the anatomical sites in the oral cavity (buccal mucosa, lateral and ventral tongue, labial mucosa, floor of the mouth and palate), excluding cancer site daily just before radiation session for 6.5 weeks.

The placebo group received sham therapy (the probe was kept off, and there was only a beep sound) just before radiation for 6.5 weeks. 

• The study reported on 121 patients with cancer of the oral cavity.
• The mean age of patients in the laser group was 51.71 years, and the mean age of patients in the placebo group was 52.60 years.
• The sample was 91% male and 9% female.

This was a single-site study in a nonspecified setting in India.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for end of life and palliative care.

This was a prospective double blinded, randomized controlled trial.

• An experienced radiology oncologist who was blinded for the intervention group performed the assessment of the oral mucositis using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system (grade 0–4).
• The need for TPN was recorded at the end of every week.
• Opioid analgesics use, weight less, CRT break during severe oral mucositis (grade > 2), and pain severity (using a visual analog scale [VAS]) of greater than 7 were recorded.

During the last weeks of CRT, incidence of mucositis greater than grade 2 was less in the laser group than in the placebo group (p < 0.0001). The mean duration of severe grades of OM was less than in the placebo group.

At the third week of CRT, no statistical difference was found between groups for incidence of OM, severe pain, TPN, and weight loss.

The laser group had less need for opioid use (p < 0.001). None of the patients in the laser group required a break in CRT, but 9% of patients in the placebo group required a break in CRT.

OM progressed at a slower rate in the laser group than in the placebo group. Pain was less severe as rated by pain scores, and TPN was significantly less in the laser group than in the placebo group.

Low level He-Ne laser was found to decrease the incidence of CRT-induced, severe OM and its associated pain; opioid analgesic use; and TPN for patients with oral cancer.

Low level helium neon laser therapy for the reduction of chemotherapy-induced OM in patients with oral cancer appears to be helpful, but the therapy is limited because of the need for the laser and an experienced laser therapist. The laser therapy in this study included standard oral care and hygiene; therefore, laser therapy does not eliminate this need.

Long-term follow-up on the effects of laser on OM is recommended to understand the carryover effects of laser in these patients. Studies explaining the exact mechanisms of action of laser also are recommended.

To evaluate the effects of low level laser therapy (LLLT) for the prevention and treatment of radiation-induced oral mucositis (OM) in older adult patients with head and neck cancer (HNC)

• N = 46  
• AGE = Older than 60 years
• MALES: 20 (90.9%) in the laser group and 19 (79.2%) in the placebo group, FEMALES: 2 (9.1%) in the laser group and 5 (20.8%) in the placebo group
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Primary HNC
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with lock jaw, any medical condition affecting healing mechanisms like diabetes, and who had prior radiation for HNC or were receiving any chemosensitizer were excluded.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Not specified

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

• Randomized, placebo controlled trial

• Radiation Therapy Oncology Group/European Organization for Research and Treatment for Cancer (RTOG/EORTC) scoring system for OM
• Visual Analog Scale (VAS) for pain and weight loss
• Weight changes
• Data analysis was done using descriptive statistics.
• ANOVA tests of repeated measures
• Shapiro-Wilk test to test the normality of the data

LLLT seems to be an effective intervention in preventing OM in older adult patients with HNC. Larger, multisite trials are needed for validation.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%  
• Patients all were said to have been kept on “standard oral care,” but that was never defined.
• Lack of inter-rater reliability in using the scales, no mention of training or consistency in using the scales between the radiation oncologists
• No mention of the calibration of the scales used to measure weight or mention of who weighed the patients

Nurses are vital in educating patients on good oral hygiene both before and during radiation treatments. Nurses see patients weekly, sometimes daily, and are essential to managing OM while patients undergo treatment, in combination with other methods such as LLLT investigated in this study. Reducing OM allows more patients to finish treatment.

To examine the efficacy of low level laser therapy (LLLT) in patients with head and neck cancer receiving chemotherapy and radiation therapy (RT)

Patients were randomly assigned to receive LLLT or sham treatment. Both groups received standard oral care and oral hygiene protocol, including frequent mouth washes with sodium bicarbonate. Patients in the LLLT group were treated with helium neon laser in 15–20 minute sessions, five sessions per week, at six anatomical sites in the oral cavity. Treatment was done daily prior to RT for 45 days. Patients, outcomes assessors, and statisticians were blinded to patient group assignment. Oral mucositis was assessed and graded daily.

• The study reported on 221 patients with a mean age of 55.4 years (SD = 11.4 years).
• The sample was 85.5% male and 14.5% female.
• All patients were newly diagnosed and receiving 100 m/m² cisplatin on days 1, 22, and 43 and 66 Gy radiation in 33 fractions, five days per week.
• All had stage 3 or 4 disease.  

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

Patients were undergoing the active antitumor treatment phase of care.

The study design was a randomized triple-blind sham-controlled randomized clinical trial.

• The European Organization for Research and Treatment of Cancer (EORTC) mucositis scoring system was used.
• The need for supplemental analgesics and parenteral nutrition was recorded.
• A visual analog scale was used to measure pain.

• Oral mucositis increased in both groups over time, but progressed more slowly in the laser group (p < 0.0001).
• At the end of treatment, incidence of grade 3–4 mucositis was about three times lower in the laser group.
• Duration of severe mucositis was less with the laser group.
• The average number of RT fractions after which severe mucositis developed was higher in the laser group. 
• Average pain scores were consistently lower in the laser group (p < 0.00001).
• The need for total parenteral nutrition was lower in the laser group (p < 0.00001). 
• Fewer patients in the laser group required any treatment delays.

Prophylactic LLLT in patients with head and neck cancer receiving concomitant radiation and chemotherapy was effective in reducing the incidence of severe oral mucositis.

Without a longer-term follow up, long-term effects of LLT are not known.

Prophylactic use of LLLT was able to prevent and treat severe oral mucositis in this group of patients. This study adds to the growing body of evidence supporting the effectiveness of LLLT in patients with head and neck cancer receiving treatment, particularly in patients receiving chemotherapy with RT. Nurses can advocate for the use of LLLT in this patient population.

To evaluate the efficacy of low-level laser therapy (LLLT) to decrease severe oral mucositis and reduce radiation therapy (RT) interruptions

 Patients received either gallium aluminum arsenide LLLT 2.5 J/cm² or placebo laser before each radiation fraction.

• The study reported on 75 patients with a median age of 55 years.
• The sample was 76% male and 24% female. 
• Patients had head and neck cancer, which was primarily squamous cell carcinoma.
• All patients underwent conventionally fractionated RT s-GY daily fractions, five times per week.

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

Patients were undergoing the active treatment phase of care.

This was a randomized, double-blind, phase III study.

• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 2, was used.
• A visual analog scale was used.

• Appearance of grade 3 mucositis was delayed in the patients treated with LLLT.
• Unplanned RT interruptions because of severe mucositis were necessary for six patients in the placebo arm and none in the LLLT arm.
• Pain scores and analgesic medication use were similar in the two arms.
• No significant differences were found between groups.

LLLT benefit was limited to fewer interruptions in RT.

• The sample size was small with fewer than 100 patients.
• Another dosage or a specific type of LLLT may be more effective.

LLLT dosage, schedule, specific laser type, and availability all need to be addressed.

To evaluate the use of low level laser therapy (LLLT) and aluminum hydroxide for the prevention of oral mucositis in patients with head and neck cancer, and to evaluate the impact of LLLT on pain scores.

Group 1 was given LLLT at 830 nm daily since first day of radiotherapy (RT) to end of therapy prior to RT (RT days only). It was applied to 12 areas of the oral cavity. Group 2 received aluminum hydroxide (AH) suspension (310 mg/5 mL) starting on first day of RT and continued throughout, including weekends. Patients used 10 mL of AH 4 times a day and swallowed and had to avoid eating during the first hour after treatment.

• The sample consisted of 22 patients with an age range of 33–80 years.
• The sample was 91% male and 9% female.
• The majority of head and neck cancer (77.27%) was diagnosed as squamous cell.

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

Patients were undergoing the active treatment phase of care.

The study was prospective, comparative, and nonrandomized.

• The National Cancer Institute (NCI) oral toxicity scale was used to evaluate oral mucositis.
• A visual analog scale (VAS) was used to evaluate pain.
• European Organization for Research and Treatment of Cancer's Quality-of-Life Questionnaires (QLQ) (QLQ-c30 and QLQ-H&N35) were used.

Lower oral mucositis (OM) scores were observed in the LLLT group (p = 0.061). More grade III OM was seen in the AH group, and severe OM was delayed in the LLLT group. LLLT pain scores were lower but not statistically significant overall. Quality-of-life (QOL) scores were all higher (i.e., more symptoms) in the AH group.

LLLT was found to be more effective than AH in delaying severe OM; however, more trials are needed.

• The sample size was small with fewer than 30 years.
• No appropriate control group was included. 

Although LLLT was found to be more effective than AH in delaying severe OM, questions exist regrding the best protocols and dosing, as well as how this evidence correlates to other disease types. Additionally, availability of equipment may be an issue.

He-Ne wavelength 632.8 nm and output of 10 mW was administered for three minutes five days a week until completion of radiation.
Control group received  oral analgesics, anesthetics, 0.9% saline, and ovidine wash.

Physician was blinded to the type of treatment.
 

Patients with cancer of the oral cavity stages 2–4 receiving radiation 66 Gy in 33 fractions over six weeks

Computer randomization; 25 patients receiving laser treatment, 25 patients in the control group
 
Mean age of study group was 54 years (+/– 1 year); mean age of the control group was 53 years (+/–1 year).
 
Ratio of men to women was 2:1.
 

WHO mucosiis

VAS for pain

Recorded weekly
 

At the end of week 6 of RT, pain rank in the study group significantly decreased (p < 0.001) as compared to the control group (13 versus 38).

Mean pain score in the study group was 2.6 (+/– 0.64); the control group score was 6.68 (+/– 1.44) (p < 0.001).

At the end of radiation,  mucositis grade in the study group was 1.72 (+/–  0.67); the grade was 3.32 (+/–0.09) in the control group  (p < 0.001).

18 patients in the study group had grade 1, and 7 had grade 2 mucositis;
14 patients in the control group had grade 3, and 11 had grade 4.
 

Small sample size, but findings were significant at the end of radiation.

Did not report data during treatment
 

To analyze the effect of different protocols of laser phototherapy (LPT) on the grade of mucositis and the degree of pain in patients undergoing radiation therapy

Patients were divided into three groups. One group was treated with low-dose laser therapy three times per week. Group 2 received combined high and low powered lasers used three times per week. The third group received low-level laser therapy (LLLT) once weekly. Oral mucositis and pain were assessed at the first visit and at each LPT visit.

• The study consisted of 39 patients whose ages ranged from 15–79 years.
• The sample was 38% female and 62% male.
• Patients had been diagnosed with head and neck cancer and were receiving radiation therapy, chemotherapy, or both.

This was a single-site study conducted at the Cancer Hospital of Mato-Grasso, Brazil.

This was a prospective clinical trial.

• A visual analog scale (VAS) was used to measure severity of oral pain.
• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) for radiation-induced oral mucositis scale was used.

No differences were found between groups in overall grades of mucositis. Pain increased in the patients that received LPT weekly (p = 0.01), while pain severity remained about the same over time in other groups. Patients who received combined high and low power laser took significantly more time to heal (p = 0.04).

LPT using low power laser alone or in combination with high powered lasers when applied three times weekly maintained the mucositis grades at levels I and II and prevented increased pain. Combination low and high power laser treatment was associated with a longer time to healing mucositis.

• The sample size was small with fewer than 100 patients.
• No control group was included.

This study provides an initial look at differences in outcomes with LPT based on different dosages and types of LPT treatment. Further research in this area, as well as studies looking at timing differences in the phase of care, are necessary to determine the most effective use of this treatment modality.

To evaluate the qualitative and quantitative effects of the 660-nm diode laser in the prevention and treatment of oral mucositis in patients with head and neck cancer being treated with chemotherapy and radiation

Seventy-two patients were divided into two groups. One group was the control, and the other group received low-level laser therapy twice weekly. Teeth were protected using a silicone tray containing neutral fluoride gel. Daily physical intraoral evaluations were performed. Patients were followed for seven weeks during radiation treatment.

• The study reported on 72 patients with head and neck cancer receiving treatment that included 1.8 gy radiation and 70 mg/m² cisplatin weekly.
• The sample had an age range of 34–80 years.
• The sample was 83% male and 17% female.

This was a single-site study conducted at the Cancer Hospital of Mato-Grasso, Cuiaba, MT, Brazil.

The study was a prospective clinical trial.

• A visual analog scale (VAS) was used to measure severity of oral pain.
• The Brown scale was used to evaluate incidence of oral mucositis.
• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) was used.
• Patients received daily physical intraoral exams.

• Patients in the laser group had significantly lower NCI mucositis scores throughout the study period (p < 0.001).
• Patients in the laser groups reported absence of pain during treatment, and controls reported increasing pain from weeks 1–4. Overall differences were significant (p = 0.05).

This study found that 660-nm diode laser therapy was effective in the prevention and treatment of oral mucositis in patients being treated with chemotherapy and radiation for head and neck carcinoma.

• The sample size was small with fewer than 100 patients.
• The control group was not adequately described, including whether they received sham treatment.
• A risk of bias exists because the patients were not randomly assigned to groups. Addtionally, the study was not blinded.
• The report did not include a discussion of other oral care or medications used.

Low level laser therapy may be effective in the prevention of mucositis. However, this treatment is highly technical and requires special equipment and highly trained personnel.

To review available literature to develop guidelines for the use of laser and other light therapies in patients with cancer

• This review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO).
• Database searched was MEDLINE.
• Search keywords were oral mucositis OR stomatitis AND lasers, laser, low level laser therapy (LLLT), light therapy, phototherapy, light-emitting dioide, visible light, and infrared.

• Patients were in the active antitumor treatment phase of care.
• The study has clinical applicability for pediatric applications.

A total of 692 papers initially were identified, and 24 clinical trials were included in the final review.

• Recommendations were laser therapy in a wavelength around 650 nm, intensity of 40 mW, and treatment of each square cm to tissue energy dose of 2 J/cm³ for prevention of oral mucositis in patients undergoing hematopoietic cell transplantation (HCT). For laser therapy as treatment, no guideline was possible because of insufficient evidence.
• No guidelines for LED and other light sources were provided because of insufficient evidence at the time, but promising findings noted that LED and visible light therapy appeared to interact with human tissue in the same way as LLLT.
• Laser therapy was recommended for prevention of radiation-induced oral mucositis in patients without concomitant chemotherapy with head and neck cancer.
• No guidelines were possible for combination radiation and chemotherapy because of inconsistent findings.
• No guideline were possible for other groups of patients.

• Multiple sources of evidence were relatively flawed studies.
• The authors noted later-breaking evidence that is promising in other groups but not fully included in the review.
• The review included articles through 2010 only.

Guidelines support use of LLLT for the prevention of oral mucositis in patients undergoing HCT and in patients with head and neck cancer receiving radiotherapy. The research in this area involves a variety of laser devices, protocols, and dosage, making it difficult to identify a specific protocol for clinical application. The most effective wavelengths and dosages are not yet clear. Most protocols examined have involved daily and long treatment times.  Based on accumulating evidence, LLLT or other forms of light therapy have the potential to become part of routine treatment.