Low-Level Laser Therapy for Prevention of Oral Mucositis

• Sponsor: David A. Clump, MD, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT02682992
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Arm: 1
• Duration (Months): 53
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The overall purpose of this study is to examine the efficacy of prophylactic low-level laser therapy (LLLT) to reduce the incidence of oral mucositis and adverse events in patients receiving combined modality therapy consisting of chemotherapy and radiation therapy for head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Mucositis	Device: Low Level Laser Therapy	N/A

Detailed Description

A phase II, single-arm trial to examine the efficacy of prophylactic low-level laser therapy (LLLT) to reduce the incidence of oral mucositis and adverse events in patients receiving combined modality therapy consisting of chemotherapy and radiation therapy for head and neck cancer.

Patients meeting the eligibility criteria will be enrolled to receive prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices.

Patients will receive LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam will be performed to identify any areas of mucositis. If the patient should develop intraoral lesions they will be targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings to be used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.

Patients will be evaluated prior to therapy, weekly during therapy, two weeks after the completion of therapy, and three months after the completion of therapy. During each assessment, the following toxicities will be assessed: pain, mucositis, dysphagia, xerostomia, dysgeusia, dermatitis, trismus, and quality of life.

Previous studies indicate that approximately 40% of patients will experience severe mucositis with radiation and concurrent chemotherapy. The hypothesis in this trial is that the addition of LLLT to this treatment regimen will decrease the rate of severe acute OM to 20%. We plan to enroll 50 patients at our institution.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Prospective Trial of Low-Level Laser Therapy for Prevention of Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Nov 1, 2020
• Actual Study Completion Date: Nov 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Low Level Laser Therapy Patients meeting the eligibility criteria will be enrolled to receive prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices.

Device: Low Level Laser Therapy; Patients will receive LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam will be performed to identify any areas of mucositis. If the patient should develop intraoral lesions they will be targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings to be used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Severe (WHO Grade 3-4) Oral Mucositis [Up to 1 year]

   Percentage of participants with severe oral mucositis per the World Health Organization (WHO grade 3-4) (ulcerative lesions of the oral mucosa) in patients treated to a cumulative radiation dose of at least 5000 cGy.

2. Percentage of Participants With Severe (CTCAE v. 4.0 Grade 3-5) Oral Mucositis [Up to 1 year]

   The Percentage of participants with severe Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0 grade 3-5) oral mucositis in patients treated to a cumulative radiation dose of at least 5000 cGy.

Secondary Outcome Measures

1. Time to Onset of Oral Mucositis [Up to 1 year]

   Time to onset of severe oral mucositis following the initiation of radiotherapy. per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4) oral mucositis following the initiation of radiotherapy.

2. Mean Cumulative Radiation Dose [Up to 1 year]

   Mean cumulative radiation dose at time of onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4)

3. Duration of Oral Mucositis [Up to 1 year]

   Time from onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4). The duration of SOM is calculated as the time in days between the onset of SOM to the time when the patient is first found to recover from SOM. If the patient do not recover from SOM, the duration is censored at the last observation time.

4. Percentage of Participants With Feeding Tube Replacement [Up to 1 year]

   Percentage of participants who require feeding tube placement during treatment.

5. Percentage of Participants With Trismus [Up to 1 year]

   Percentage of Participants with trismus (reduced opening of the jaws determined via measurement of interincisal distance). The interincisal distance will be measured in millimeters at the patient's maximum comfortable extent of mouth opening.

6. Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire [Up to 1 year]

   This measure is based on a self-administered questionnaire. Responses to each item were on a Likert scale score ranging from 0 to 4. The individual responses were summed to compute subscale scores, and the subscales to compute overall total scores, with higher scores indicating better Quality of Life. FACT-HN includes 2 parts - FACT-G and FACT-HN. The basic FACT-G (general) is comprised of 27 items (0-108). Subscales include Physical Well-Being (0-28), Social/Family Well-Being (0-28), Emotional Well-Being (0-24), and Functional Well-Being, (0-28). Two "Relationship with physician" items (subscale score min/max = 0-8) were added to the FACT-G in this trial, for a total of 29 FACT-G items (total min/max = 0-116). The FACT-HN is comprised of 12 head and neck specific items (0-48). Thus, the overall total possible score range was 0-164. The FACT Head & Neck Trial Outcome Index is a composite score which includes only physical, functional, and FACT-HN, thus a score range from 0-104.

7. Percentage of Participants With Oral Mucositis [Up to 1 year]

   The percentage of participants with oral mucositis Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 - all grades) in patients treated to a cumulative radiation dose of at least 5000 cGy.

8. Percentage of Participants With Dysphagia [Up to 1 year]

   Percentage of participants with dysphagia per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) and via diet assessment.

9. Percentage of Participants With Xerostomia [Up to 1 year]

   Percentage of participants with xerostomia (oral dryness) per Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v. 4.0.

10. Percentage of Participants With Dysgeusia [Up to 1 year]

    Percentage of participants with dysgeusia (altered taste with/without change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).

11. Percentage of Participants With Radiodermatitis [Up to 1 year]

    Percentage of participants with radiodermatitis (skin response to ionizing radiation exposure/therapy ranging from erythematous rash to desquamation and necrosis) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).

12. Percentage of Participants With Mouth Pain [Up to 1 year]

    Percentage of participants with mouth pain. Mouth pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.

13. Percentage of Participants With Throat Pain [Up to 1 year]

    Percentage of participants with throat pain. Throat pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.

14. Narcotic Analgesia Use [Up to 2 years]

    Percentage of patients using narcotic analgesia during treatment.

15. Breaks in Chemoradiotherapy [Up to 2 years]

    Mean number of breaks in chemoradiotherapy with LLLT use.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to understand and sign informed consent form approved by the HRPO.

• Males or females greater than or equal to 18 years old.

• Biopsy-proven HNC including cancers of the nasopharynx, oropharynx, larynx, hypopharynx, or HNC of unknown primary origin amenable to therapy with radiation and concurrent chemotherapy.

• Patients who are planned to receive definitive or adjuvant radiotherapy with concurrent platinum-based chemotherapy.

• Patients whose clinical treatment plans include a continuous course of external beam radiotherapy by intensity-modulated radiation therapy (IMRT) and/or image-guided radiation therapy (IGRT), given as a cumulative dose of 5000 - 7000 cGy in single daily fractions of 180 - 200 cGy, combined with a concurrent course of weekly or tri-weekly cisplatin or carboplatin chemotherapy.

• Karnofsky performance status score >60.

• Female subjects of child-bearing potential must have a negative pregnancy test prior to enrollment.

Exclusion Criteria:

• Subject has evidence of current mucositis, mucosal ulceration, or unhealed surgical wounds from surgical resection or biopsy.

• Prior radiation to the head and neck.

• Patients with gross tumor involvement of the oral cavity or oral mucosa.

• Subjects planned to receive altered fractionation radiotherapy or multiple fractions per day

• Subject is using a pre-existing feeding tube for nutritional support at the time of study entry.

• Women who are pregnant or breast-feeding.

• Subject plans to receive concurrent chemotherapy, other than the regimens specified in the inclusion criteria.

• Patients who have chronic immunosuppression or are on current immunosuppressive therapies.

• Patients who have a contraindication to radiation therapy.

• Patients enrolled on another investigational trial for oral mucositis prevention.

• Life expectancy of less than 3 months.

• Unable or unwilling to adhere to study-specified procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Shadyside Department of Radiation Oncology	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• David A. Clump, MD, PhD

Investigators

• Principal Investigator: David A Clump, MD, PhD, UPMC Department of Radiation Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 3, 2015

More Information

Publications

None provided.

• Responsible Party: David A. Clump, MD, PhD, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02682992
• Other Study ID Numbers: 18-127
• First Posted: Feb 17, 2016
• Last Update Posted: Apr 13, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Mucositis; Stomatitis

Study Results

Participant Flow

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Period Title: Overall Study
STARTED	47
COMPLETED	47
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Overall Participants	47
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	60.5
Sex: Female, Male (Count of Participants)
Female	6 12.8%
Male	41 87.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 10.6%
White	40 85.1%
More than one race	0 0%
Unknown or Not Reported	2 4.3%
Head Neck Origin (Count of Participants)
Hypopharynx	1 2.1%
Larynx	8 17%
Nasopharynx	3 6.4%
Oropharynx	33 70.2%
Unknown	2 4.3%
Tobacco History (Count of Participants)
Tobacco use - No	25 53.2%
Tobacco use - Yes	22 46.8%
Alcohol History (Count of Participants)
Alcohol use - No	18 38.3%
Alcohol use - Yes	29 61.7%
Positive Karnofsky Performance Status (participants) [Number]
Number [participants]	47 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Severe (WHO Grade 3-4) Oral Mucositis
Description	Percentage of participants with severe oral mucositis per the World Health Organization (WHO grade 3-4) (ulcerative lesions of the oral mucosa) in patients treated to a cumulative radiation dose of at least 5000 cGy.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing severe oral mucositis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	23 48.9%

2. Primary Outcome

Title	Percentage of Participants With Severe (CTCAE v. 4.0 Grade 3-5) Oral Mucositis
Description	The Percentage of participants with severe Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0 grade 3-5) oral mucositis in patients treated to a cumulative radiation dose of at least 5000 cGy.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing severe oral mucositis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	23 48.9%

3. Secondary Outcome

Title	Time to Onset of Oral Mucositis
Description	Time to onset of severe oral mucositis following the initiation of radiotherapy. per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4) oral mucositis following the initiation of radiotherapy.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Includes only treated patients experiencing severe oral mucositis

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	11
Median (95% Confidence Interval) [days]	NA

4. Secondary Outcome

Title	Mean Cumulative Radiation Dose
Description	Mean cumulative radiation dose at time of onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4)
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Includes only treated patients experiencing severe oral mucositis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	11
Mean (Standard Deviation) [Gy]	56 (12.8624)

5. Secondary Outcome

Title	Duration of Oral Mucositis
Description	Time from onset of severe oral mucositis per Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 grade 3-4). The duration of SOM is calculated as the time in days between the onset of SOM to the time when the patient is first found to recover from SOM. If the patient do not recover from SOM, the duration is censored at the last observation time.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Includes only treated patients experiencing severe oral mucositis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	11
Median (95% Confidence Interval) [days]	24

6. Secondary Outcome

Title	Percentage of Participants With Feeding Tube Replacement
Description	Percentage of participants who require feeding tube placement during treatment.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients who required feeding tube placement.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	36 76.6%

7. Secondary Outcome

Title	Percentage of Participants With Trismus
Description	Percentage of Participants with trismus (reduced opening of the jaws determined via measurement of interincisal distance). The interincisal distance will be measured in millimeters at the patient's maximum comfortable extent of mouth opening.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing trismus.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	26 55.3%

8. Secondary Outcome

Title	Quality of Life Via Functional Assessment of Cancer Therapy Head & Neck Cancer (FACT-HN) Questionnaire
Description	This measure is based on a self-administered questionnaire. Responses to each item were on a Likert scale score ranging from 0 to 4. The individual responses were summed to compute subscale scores, and the subscales to compute overall total scores, with higher scores indicating better Quality of Life. FACT-HN includes 2 parts - FACT-G and FACT-HN. The basic FACT-G (general) is comprised of 27 items (0-108). Subscales include Physical Well-Being (0-28), Social/Family Well-Being (0-28), Emotional Well-Being (0-24), and Functional Well-Being, (0-28). Two "Relationship with physician" items (subscale score min/max = 0-8) were added to the FACT-G in this trial, for a total of 29 FACT-G items (total min/max = 0-116). The FACT-HN is comprised of 12 head and neck specific items (0-48). Thus, the overall total possible score range was 0-164. The FACT Head & Neck Trial Outcome Index is a composite score which includes only physical, functional, and FACT-HN, thus a score range from 0-104.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients that completed Fact QoL assessments.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	36
PHYSICAL WELL BEING (PWB)	21.5417
SOCIAL/FAMILY WELL BEING (SWB)	24.3654
EMOTIONAL WELL BEING (EWB)	20.9167
FUNCTIONAL WELL BEING (FWB)	18.7708
FACT-G total score (FACTG)	84.9028
FACT HN	21.7035
FACT-G with FACT HN total score	107.403
FACT Head & Neck Trial Outcome Index	62.4470

9. Secondary Outcome

Title	Percentage of Participants With Oral Mucositis
Description	The percentage of participants with oral mucositis Common Terminology Criteria for Adverse Events (CTCAE v. 4.0 - all grades) in patients treated to a cumulative radiation dose of at least 5000 cGy.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing oral mucositis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	96 204.3%

10. Secondary Outcome

Title	Percentage of Participants With Dysphagia
Description	Percentage of participants with dysphagia per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) and via diet assessment.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	100 212.8%

11. Secondary Outcome

Title	Percentage of Participants With Xerostomia
Description	Percentage of participants with xerostomia (oral dryness) per Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v. 4.0.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing xerostomia.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	100 212.8%

12. Secondary Outcome

Title	Percentage of Participants With Dysgeusia
Description	Percentage of participants with dysgeusia (altered taste with/without change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing dysgeusia.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	100 212.8%

13. Secondary Outcome

Title	Percentage of Participants With Radiodermatitis
Description	Percentage of participants with radiodermatitis (skin response to ionizing radiation exposure/therapy ranging from erythematous rash to desquamation and necrosis) per Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing radiodermatitis.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	100 212.8%

14. Secondary Outcome

Title	Percentage of Participants With Mouth Pain
Description	Percentage of participants with mouth pain. Mouth pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing mouth pain.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	94 200%

15. Secondary Outcome

Title	Percentage of Participants With Throat Pain
Description	Percentage of participants with throat pain. Throat pain severity will be assessed using a standard 0-10 scale, with higher scores indicating greater pain.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Treated patients experiencing throat pain.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (90% Confidence Interval) [percentage of participants]	96 204.3%

16. Secondary Outcome

Title	Narcotic Analgesia Use
Description	Percentage of patients using narcotic analgesia during treatment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Treated patients that used a narcotic analgesic.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	47
Number (95% Confidence Interval) [percentage of participants]	55 117%

17. Secondary Outcome

Title	Breaks in Chemoradiotherapy
Description	Mean number of breaks in chemoradiotherapy with LLLT use.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Treated patients that experienced breaks in chemoradiotherapy.

Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
Measure Participants	38
Mean (Standard Deviation) [events]	47.7368 (5.19191)

Adverse Events

Time Frame	Adverse Events monitored up to 24 months, All-Cause Mortality monitored up to 36 months
Adverse Event Reporting Description	Adverse Events: Grade 1 and Grade 2 events per CTCAE v4.0 Serious Adverse Events: Grade 3 and Grade 4 events per CTCAE v4.0
Arm/Group Title	Low Level Laser Therapy
Arm/Group Description	Patients that received prophylactic LLLT in addition to standard of care measures for oral mucositis or other toxicity of therapy. The radiation and chemotherapy dose, schedule, modality, technique, and any required adjustments will not be influenced by this protocol and will follow standard existing institutional practices. Low Level Laser Therapy: LLLT three times per week concurrently with chemoradiotherapy. LLLT may be delivered either immediately prior to or after the patient's daily fraction of radiotherapy. Patients will be treated extra-orally with a THOR® LED cluster for one minute along the buccal mucosa on each side and intraorally for one minute to the tongue and soft palate. During each LLLT treatment session a thorough oral exam performed to identify any areas of mucositis. Patients that develop intraoral lesions are targeted directly with the intraoral probe for one minute to each site of mucositis. The laser settings used are as follows: frequency 2.5 Hz; wavelength 660 nm; and power 75 mW, for an energy of 4.5 J.
All Cause Mortality
	Low Level Laser Therapy
	Affected / at Risk (%)	# Events
Total	7/47 (14.9%)
Serious Adverse Events
	Low Level Laser Therapy
	Affected / at Risk (%)	# Events
Total	18/47 (38.3%)
Gastrointestinal disorders
Oral Mucositis	11/47 (23.4%)
dysphagia	18/47 (38.3%)
dry mouth	1/47 (2.1%)
Injury, poisoning and procedural complications
dermatitis	2/47 (4.3%)
Other (Not Including Serious) Adverse Events
	Low Level Laser Therapy
	Affected / at Risk (%)	# Events
Total	47/47 (100%)
Gastrointestinal disorders
Oral Mucositis	34/47 (72.3%)
dysphagia	29/47 (61.7%)
dry mouth	46/47 (97.9%)
oral pain	44/47 (93.6%)
Injury, poisoning and procedural complications
dermatitis	45/47 (95.7%)
Nervous system disorders
dysgeusia	47/47 (100%)
Respiratory, thoracic and mediastinal disorders
sore throat	45/47 (95.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.