Head and Neck Cancer
Conditions
Brief summary
The main objective of this study is to determine the feasibility of optimizing the IMRT treatment plan based on dosimeter measurements of mucosal radiation dose adjacent to the dental fillings to reduce such dose to \< 35 Gy without compromising tumor coverage and/or increasing the dose to the remaining oral cavity or nearby parotid glands.
Detailed description
Using radiation dosimeter, we will perform measurement of the doses received by the mucosa adjacent to the dental fillings in patients receiving IMRT for head and neck cancer. If the mucosa dose is estimated to be greater than 35 Gy for the entire radiation course, we will generate and implement a filling optimized IMRT plan, provided that this new plan does not compromise tumor coverage or increase dose to the rest of the oral mucosa or parotid glands. Dosimeter will be used to measure the mucosal dose delivered by this new IMRT plan. Patient's mucositis grade, narcotic use and self-reported mouth and throat soreness scores will be recorded and correlated to mucosal dose. We hypothesize that modulation of an IMRT plan to reduce the dose delivered to adjacent normal mucosa surrounding the dental filling can decrease the severity and duration of radiation-related oral mucositis. Here we propose to use thermoluminescent dosimeter (TLD) to measure the mucosal dose adjacent to the dental fillings in a standard, non-filling optimized IMRT plan that is normally delivered in the clinic.
Interventions
RADIATIONIntensity Modulated Radiation Therapy
We are using thermoluminescent dosimeter (TLD) to measure the mucosal dose adjacent to the dental fillings in a standard, non-filling optimized IMRT (intensity modulated radiotherapy treatment) plan that is normally delivered in the clinic. If the measured mucosal dose exceeds 35 Gy, we will generate a filling optimized IMRT plan to reduce it to \< 35 Gy. The new plan will be deemed acceptable and implemented only if it does not (1) compromise the tumor coverage, (2) increase the dose to either the remaining oral cavity or the spared parotid gland(s).
Sponsors
Varian Medical Systems
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with HNC undergoing radiation therapy +/- chemotherapy at Stanford University * At least 18 years old * Metallic filling present * Planned radiation dose to the tumor \> 60 Gy at 1.8 to 2.2 Gy/fx * Able to understand and sign a written informed consent document.
Exclusion criteria
* Pregnant * Nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Until the Maximum Oral Mucositis Measured From the Start of Radiation Treatment. | 3 years | The time to onset of oral mucositis was measured from the start of radiation treatment until oral mucositis was visual observed by a clinician during the weekly checkup for the first time. Analysis done by Kaplan-Meier. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version (V) 4.0. Medical doctor performed evaluation and grading of clinical and functional mucositis for the measured site weekly during the radiation treatment course and biweekly after completion of radiation until oral mucositis was \< grade 2. A pain medication assessment was done for each mucositis time point. Patients completed the Oral Mucositis Weekly Questionnaire-Head and Neck cancer (OMWQ-HN) during and after treatment until oral mucositis is \< grade 2. |
| Duration of Grade 2 or Higher Oral Mucositis After First Oral Mucositis Was Observed. | 3 years | The duration of grade 2 or higher oral mucositis was measured as the time from the first time oral mucositis was observed by a clinician at the weekly checkup until the oral mucositis was resolved. The data was analyzed in a mixed effects model to account for the within subject correlation, since each patient contributed two measurements to the data set. The model was limited to those subjects who had experienced mucositis and then the outcome was the duration of grade 2 or higher mucositis. This allowed us to model the data in a mixed effects model with the continuous outcome of duration of grade 2 or higher mucositis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between the Measured Lateral Tongue Mucosal Dose and the Amount of Narcotic Use | 3 years | The narcotics use was a patient reported measurement that was documented in the medical note in the patient chart. Patient self reported measurements are generally known to be unreliable. |
| How Does Increase in Soreness Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose | 3 years | The quality of life questionnaire was the HNC adaptation of the Oral Mucositis Daily Questionnaire (OMWQ). It is designed to assess the severity and impact of the oral mucositis by evaluating mouth and throat soreness and the degree to which the mouth and throat soreness interferes with activities of daily life such as eating, swallowing, drinking, talking and sleeping. This outcome measures soreness in both the mouth and throat. This outcome is not a combination of several sub-scales. This outcome was the response to the single question: On a scale from 0 to 10, how would you rate your OVERALL MOUTH AND THROAT SORENESS during the past 24 hours? Mouth and throat soreness was measured as a single scale from 0 (no soreness) to 10 (worst soreness possible). |
| How Does Increase in Pain Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose? | 3 years | The quality of life questionnaire was the HNC adaptation of the Oral Mucositis Daily Questionnaire (OMDQ). It is designed to assess the severity and impact of the oral mucositis by evaluating mouth and throat soreness and the degree to which the mouth and throat soreness interferes with activities of daily life such as eating, swallowing, drinking, talking and sleeping. This outcome measures pain in the mouth only. This outcome is not a combination of several sub-scales. This outcome was the response to a single question: On a scale from 0 to 10, what number best describes the MOUTH PAIN that you experienced in the past 24 hours? Mouth pain scale was measured as a single scale from 0 (no pain) to 10 (worst pain imaginable). |
Countries
United States
Participant flow
Recruitment details
The study took place at Stanford University. The study started in July 2011 and it ended July 2014.
Pre-assignment details
No pre-assignment details as the patients were recruited and placed directly in the study.
Participants by arm
| Arm | Count |
|---|---|
| Intensity Modulated RT Treatment Radiation dose to the tumor is \> 60 Gy at 1.8-2.2 Gy/fx.
intensity modulated radiotherapy treatment | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Intensity Modulated RT Treatment |
|---|---|
| Age, Continuous | 61.5 years |
| Primary Tumor location Oral Cavity | 7 Participants |
| Primary Tumor location Pharynx | 23 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 25 Participants |
| Tongue dose | 30.5 Gy |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 11 / 30 |
Outcome results
Primary
Duration of Grade 2 or Higher Oral Mucositis After First Oral Mucositis Was Observed.
The duration of grade 2 or higher oral mucositis was measured as the time from the first time oral mucositis was observed by a clinician at the weekly checkup until the oral mucositis was resolved. The data was analyzed in a mixed effects model to account for the within subject correlation, since each patient contributed two measurements to the data set. The model was limited to those subjects who had experienced mucositis and then the outcome was the duration of grade 2 or higher mucositis. This allowed us to model the data in a mixed effects model with the continuous outcome of duration of grade 2 or higher mucositis.
Time frame: 3 years
Population: For each subject, both left and right sides were included as two measurements from the same individual.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intensity Modulated Radiotherapy Treatment | Duration of Grade 2 or Higher Oral Mucositis After First Oral Mucositis Was Observed. | dose < 30 Gy | 25.722 Days |
| Intensity Modulated Radiotherapy Treatment | Duration of Grade 2 or Higher Oral Mucositis After First Oral Mucositis Was Observed. | dose >= 30 Gy | 27.917 Days |
p-value: 0.120995% CI: [-0.077, 0.634]Regression, Linear
Primary
Time Until the Maximum Oral Mucositis Measured From the Start of Radiation Treatment.
The time to onset of oral mucositis was measured from the start of radiation treatment until oral mucositis was visual observed by a clinician during the weekly checkup for the first time. Analysis done by Kaplan-Meier. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version (V) 4.0. Medical doctor performed evaluation and grading of clinical and functional mucositis for the measured site weekly during the radiation treatment course and biweekly after completion of radiation until oral mucositis was \< grade 2. A pain medication assessment was done for each mucositis time point. Patients completed the Oral Mucositis Weekly Questionnaire-Head and Neck cancer (OMWQ-HN) during and after treatment until oral mucositis is \< grade 2.
Time frame: 3 years
Population: The entire cohort was analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intensity Modulated Radiotherapy Treatment | Time Until the Maximum Oral Mucositis Measured From the Start of Radiation Treatment. | Dose <30 Gy | 34 Days |
| Intensity Modulated Radiotherapy Treatment | Time Until the Maximum Oral Mucositis Measured From the Start of Radiation Treatment. | Dose >= 30 Gy | 29 Days |
p-value: 0.990695% CI: [0.979, 1.022]Regression, Cox
Secondary
How Does Increase in Pain Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose?
The quality of life questionnaire was the HNC adaptation of the Oral Mucositis Daily Questionnaire (OMDQ). It is designed to assess the severity and impact of the oral mucositis by evaluating mouth and throat soreness and the degree to which the mouth and throat soreness interferes with activities of daily life such as eating, swallowing, drinking, talking and sleeping. This outcome measures pain in the mouth only. This outcome is not a combination of several sub-scales. This outcome was the response to a single question: On a scale from 0 to 10, what number best describes the MOUTH PAIN that you experienced in the past 24 hours? Mouth pain scale was measured as a single scale from 0 (no pain) to 10 (worst pain imaginable).
Time frame: 3 years
Population: Only 29 out of the 30 subjects filled out the pain surveys
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intensity Modulated Radiotherapy Treatment | How Does Increase in Pain Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose? | dose < 30 Gy | 2.28 units on pain scale |
| Intensity Modulated Radiotherapy Treatment | How Does Increase in Pain Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose? | dose >= 30 Gy | 3.292 units on pain scale |
p-value: 0.003995% CI: [0.0199, 0.0935]Mixed Models Analysis
Secondary
How Does Increase in Soreness Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose
The quality of life questionnaire was the HNC adaptation of the Oral Mucositis Daily Questionnaire (OMWQ). It is designed to assess the severity and impact of the oral mucositis by evaluating mouth and throat soreness and the degree to which the mouth and throat soreness interferes with activities of daily life such as eating, swallowing, drinking, talking and sleeping. This outcome measures soreness in both the mouth and throat. This outcome is not a combination of several sub-scales. This outcome was the response to the single question: On a scale from 0 to 10, how would you rate your OVERALL MOUTH AND THROAT SORENESS during the past 24 hours? Mouth and throat soreness was measured as a single scale from 0 (no soreness) to 10 (worst soreness possible).
Time frame: 3 years
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intensity Modulated Radiotherapy Treatment | How Does Increase in Soreness Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose | dose < 30 Gy | 2.908 units on soreness scale |
| Intensity Modulated Radiotherapy Treatment | How Does Increase in Soreness Scores Affect Quality of Life Questionnaire While Adjusting for the Measured Lateral Tongue Mucosal Dose | dose >= 30 Gy | 3.689 units on soreness scale |
p-value: 0.026395% CI: [0.00483, 0.071]Mixed Models Analysis
Secondary
Relationship Between the Measured Lateral Tongue Mucosal Dose and the Amount of Narcotic Use
The narcotics use was a patient reported measurement that was documented in the medical note in the patient chart. Patient self reported measurements are generally known to be unreliable.
Time frame: 3 years
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intensity Modulated Radiotherapy Treatment | Relationship Between the Measured Lateral Tongue Mucosal Dose and the Amount of Narcotic Use | dose < 30 Gy | 917.5 mg |
| Intensity Modulated Radiotherapy Treatment | Relationship Between the Measured Lateral Tongue Mucosal Dose and the Amount of Narcotic Use | dose >= 30 Gy | 1214.3 mg |
p-value: 0.983295% CI: [-27.28, 26.71]Regression, Linear