Head and Neck Cancer, Oral Complications of Chemotherapy and Head/Neck Radiation, Radiation-Induced Xerostomia, Radiation Toxicity
Conditions
Keywords
hypopharyngeal cancer, laryngeal cancer, lip and oral cavity cancer, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, salivary gland cancer, radiation toxicity, xerostomia, long-term effects of cancer treatment, oral complications of radiation therapy
Brief summary
This study is being done to find out what effects, good and/or bad, acupuncture has on participants and their xerostomia caused by radiation therapy for the treatment of the cancer.
Detailed description
Patients who have met all eligibility criteria will be randomized to standard oral hygiene, standard oral hygiene + true acupuncture twice weekly for 4 weeks, or standard oral hygiene + sham acupuncture twice weekly for 4 weeks by a form of adaptive randomization, called minimization, because simple randomization could result in covariate imbalances . The acupuncture points will be at three sites on each ear (Shenmen, Point Zero, Salivary Gland 2-prime), a site on the chin (CV24), a site on each forearm (Lu7), a site on each hand (LI 1-prime), a site on each leg (K6), and one placebo needle at Gb32 for a total of 14 sites. All sites will be applied for 20 minutes. For body points, standardized techniques for location will be utilized, which are based on anatomical landmarks as well as proportional measurements using the patient's own body. For example, finger breadth is based on each patient's middle finger, and the proportional unit of measure, the "cun," is defined as the distance between the two medial ends of the creases of the interphalangeal joints when the middle finger is flexed. Ear point locations will mimic standard practice and be identified by the acupuncturists.
Interventions
Oral hygiene care provided per individual institutions standard of care.
OTHERStandard Oral Hygiene + True Acupuncture
Oral hygiene care provided per individual institutions standard of care. 14 true acupoint sites will be selected and applied to each participant for 20 minutes at each session. There will be 2 sessions a week for 8 weeks.
OTHERStandard Oral Hygiene + Sham Acupuncture
Oral hygiene care provided per individual institutions standard of care. 14 sham acupoint sites will be selected and applied to each participant for 20 minutes at each session. There will be 2 sessions a week for 8 weeks.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be at least 18 years of age and able to give informed consent. * Must be able to read, write and understand English. * Must have a diagnosis of head/neck cancer. * Must have received bilateral radiation therapy, and subsequently developed grade 2 or 3 xerostomia, according to modified Radiation Therapy Oncology Group (RTOG) scale: * Grade 0 - None * Grade 1 - Slight dryness of mouth (good response on stimulation and no significant dietary alterations necessary) * Grade 2 - Moderate dryness of mouth (poor response on stimulation and altered oral intake required such as frequent water, oral lubricants, or soft-moist foods) * Grade 3 - Complete dryness of mouth (no response on stimulation and difficult oral alimentation; IV fluids, pureed diet or tube feedings may be required) * Grade 4 - Fibrosis * Must have received external beam radiation at a mean dose of at least 24 Gy to one of the parotid glands. The other gland can receive less than 24 Gy. * Must have completed radiotherapy at least 12 months prior to entry. * Must have anatomically intact parotid and submandibular glands. A focused (head/neck) history and exam conducted by a physician or dentist within the past year is required. * Must be acupuncture naïve. * Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Exclusion criteria
* History of xerostomia, Sjogren's disease or other illness known to affect salivation prior to head/neck radiation. * Suspected or known closure of salivary gland ducts on either side. (Patients addressed in inclusion criteria (i.e. those who have had one submandibular gland removed) are expected to have closure to the removed submandibular gland and will be exempt from this
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Xerostomia Questionnaire Scores | Baseline to 4, 8, 12, 26 weeks post acupuncture | Self reported Xerostomia questionnaire consists of eight items (scored on an 11-point scale; 0-10), has been validated in several cohorts, and is regarded as the gold-standard measure for xerostomia.The questions are equally divided into 4 items about oral dryness while eating or chewing and 4 items about dryness while not eating or chewing. Item scores are summed and transformed linearly to produce a final summary score between 0 and 80. Higher scores represent more xerostomia. Questionnaire is completed prior to randomization and at each time point week 4, week 8, week 12, and end of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Assessment of Cancer Therapy (FACT-G) Total | Baseline, 4 , 8 , 12, and 26 weeks | The FACT-G QOL instrument discriminates between individuals with metastatic and non-metastatic disease, as well as between patients at different stages of illness. The scale has good concurrent validity, high internal consistency (0.89), and good test-re-test reliability (0.82 to 0.88). The total score is reported, which is a combination of the subscales of physical, social/family, emotional, and functional well-being, with higher scores representing better QOL. Scale range 0-108 |
| The Acupuncture Expectancy Scale (AES) | Week 4 | The 4-item AES was used to ensure there were no baseline group differences in expectations related to the benefits of acupuncture on dry mouth and to assess aspects of blinding after the first 4 weeks of acupuncture for the TA and SA groups. The AES is reliable (α=0·82) and valid by positive correlation with patient self-reported efficacy and satisfaction. The scale has been further validated among cancer patients who were acupuncture naïve. Scale from 4-20. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSuzanne C Danhauer, PhD
Wake Forest University Health Sciences
Participant flow
Recruitment details
Study was designed with first enrollment July 29,2013 under the oversight of MD Anderson (MDA) Community Clinical Oncology Program (CCOP) Research Base (RB) (NCI Division of Cancer Prevention (DCP) #MDA 04-01; MDA Protocol #2010-0547). Twenty-eight participants recruited from multiple centers. After the MDA CCOP RB was closed, the trial transferred to Wake Forest (WF) NCI Community Oncology Research Program (NCORP) RB (2UG1CA189824) where the trial continued (WF-97115) from April 2016-June 2021.
Pre-assignment details
258 of 281 eligible screened participants enrolled and randomized into study. Reasons for the 23 which chose not to participate: 16 no reason given 5 Too busy 1 did not want randomization 1 distance.
Participants by arm
| Arm | Count |
|---|---|
| Standard Oral Hygiene All patients will receive standard oral hygiene patient teaching information that includes instructions regarding mouth rinses, use of lip balms, use of mild fluoride toothpaste, the importance of adequate oral hydration, and other standard advice. Each participating site determines the standard oral hygiene recommendations used at their site.
Standard Oral Hygiene: Oral hygiene care provided per individual institutions standard of care. | 86 |
| Standard Oral Hygiene + True Acupuncture All patients will receive standard oral hygiene patient teaching information that includes instructions regarding mouth rinses, use of lip balms, use of mild fluoride toothpaste, the importance of adequate oral hydration, and other standard advice. Each participating site determines the standard oral hygiene recommendations used at their site.
The True acupuncture points will be at 3 sites on each ear, a site on the chin, on each forearm, a site on each hand, a site on each leg, and one placebo needle for a total of 14 sites. All sites will be applied for 20 minutes.
Standard Oral Hygiene + True Acupuncture: Oral hygiene care provided per individual institutions standard of care.
14 true acupoint sites will be selected and applied to each participant for 20 minutes at each session. There will be 2 sessions a week for 8 weeks. | 86 |
| Standard Oral Hygiene + Sham Acupuncture All patients will receive standard oral hygiene patient teaching information that includes instructions regarding mouth rinses, use of lip balms, use of mild fluoride toothpaste, the importance of adequate oral hydration, and other standard advice. Each participating site determines the standard oral hygiene recommendations used at their site.
The Sham acupuncture points will be given according to the same schedule as the active acupuncture points, except the Sham needles will be placed below, above or between true active points.
Standard Oral Hygiene + Sham Acupuncture: Oral hygiene care provided per individual institutions standard of care.
14 sham acupoint sites will be selected and applied to each participant for 20 minutes at each session. There will be 2 sessions a week for 8 weeks. | 86 |
| Total | 258 |
Baseline characteristics
| Characteristic | Standard Oral Hygiene + Sham Acupuncture | Total | Standard Oral Hygiene | Standard Oral Hygiene + True Acupuncture |
|---|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 9.9 | 65.0 years STANDARD_DEVIATION 9.2 | 65.6 years STANDARD_DEVIATION 9.2 | 65.0 years STANDARD_DEVIATION 8.6 |
| Age, Customized Age Stratification (years) <= 40 years | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized Age Stratification (years) 41-55 years | 13 Participants | 43 Participants | 16 Participants | 14 Participants |
| Age, Customized Age Stratification (years) 56-70 years | 47 Participants | 143 Participants | 46 Participants | 50 Participants |
| Age, Customized Age Stratification (years) > 70 years | 24 Participants | 70 Participants | 24 Participants | 22 Participants |
| Baseline values for outcomes Acupuncture Expectancy Scale (AES) Score (scale 4-20) | 11.7 scoring on a scale STANDARD_DEVIATION 3.7 | 12.1 scoring on a scale STANDARD_DEVIATION 4 | 12.7 scoring on a scale STANDARD_DEVIATION 4.3 | 11.9 scoring on a scale STANDARD_DEVIATION 4.1 |
| Baseline values for outcomes FACT-G Total Score (scale 0-108) | 97.7 scoring on a scale STANDARD_DEVIATION 15.1 | 97.1 scoring on a scale STANDARD_DEVIATION 15.5 | 94.8 scoring on a scale STANDARD_DEVIATION 15.9 | 98.8 scoring on a scale STANDARD_DEVIATION 15.5 |
| Baseline values for outcomes Xerostomia Questionnaire (XQ) Score (scale 0-80) | 62.1 scoring on a scale STANDARD_DEVIATION 17.7 | 62.7 scoring on a scale STANDARD_DEVIATION 17.1 | 63.2 scoring on a scale STANDARD_DEVIATION 16.8 | 63.0 scoring on a scale STANDARD_DEVIATION 17.1 |
| Body Mass Index (BMI) | 26.5 kg/m^2 STANDARD_DEVIATION 5.7 | 26.7 kg/m^2 STANDARD_DEVIATION 5.5 | 27.6 kg/m^2 STANDARD_DEVIATION 6.2 | 26.0 kg/m^2 STANDARD_DEVIATION 4.3 |
| Education Advanced degree | 13 Participants | 34 Participants | 10 Participants | 11 Participants |
| Education College degree (BA/BS) | 16 Participants | 51 Participants | 15 Participants | 20 Participants |
| Education High School/GED | 17 Participants | 55 Participants | 20 Participants | 18 Participants |
| Education Some college/training | 30 Participants | 88 Participants | 31 Participants | 27 Participants |
| Education Unknown | 10 Participants | 30 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 16 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 238 Participants | 78 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Insurance - Medicaid | 5 Participants | 15 Participants | 8 Participants | 2 Participants |
| Insurance - Medicare | 35 Participants | 101 Participants | 34 Participants | 32 Participants |
| Insurance - None | 5 Participants | 13 Participants | 4 Participants | 4 Participants |
| Insurance - Private | 51 Participants | 154 Participants | 47 Participants | 56 Participants |
| Job Status Disabled - unable to work | 7 Participants | 22 Participants | 10 Participants | 5 Participants |
| Job Status Employed (FT/PT) | 26 Participants | 86 Participants | 31 Participants | 29 Participants |
| Job Status Other/Unknown | 25 Participants | 55 Participants | 15 Participants | 15 Participants |
| Job Status Retired | 28 Participants | 95 Participants | 30 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 13 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 77 Participants | 229 Participants | 75 Participants | 77 Participants |
| Region of Enrollment United States | 86 participants | 258 participants | 86 participants | 86 participants |
| Sex: Female, Male Female | 19 Participants | 57 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 67 Participants | 201 Participants | 66 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 86 | 0 / 86 | 1 / 86 |
| other Total, other adverse events | 0 / 86 | 3 / 86 | 3 / 86 |
| serious Total, serious adverse events | 0 / 86 | 0 / 86 | 0 / 86 |
Outcome results
Primary
Xerostomia Questionnaire Scores
Self reported Xerostomia questionnaire consists of eight items (scored on an 11-point scale; 0-10), has been validated in several cohorts, and is regarded as the gold-standard measure for xerostomia.The questions are equally divided into 4 items about oral dryness while eating or chewing and 4 items about dryness while not eating or chewing. Item scores are summed and transformed linearly to produce a final summary score between 0 and 80. Higher scores represent more xerostomia. Questionnaire is completed prior to randomization and at each time point week 4, week 8, week 12, and end of study.
Time frame: Baseline to 4, 8, 12, 26 weeks post acupuncture
Population: Intent to treat analysis. Considered and utilized all data available at each timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Standard Oral Hygiene | Xerostomia Questionnaire Scores | Week 26 | 54.4 score on a scale 0-80 |
| Standard Oral Hygiene | Xerostomia Questionnaire Scores | Week 12 | 54.8 score on a scale 0-80 |
| Standard Oral Hygiene | Xerostomia Questionnaire Scores | Week 8 | 55.2 score on a scale 0-80 |
| Standard Oral Hygiene | Xerostomia Questionnaire Scores | Week 4 | 57.3 score on a scale 0-80 |
| Standard Oral Hygiene + True Acupuncture | Xerostomia Questionnaire Scores | Week 4 | 50.6 score on a scale 0-80 |
| Standard Oral Hygiene + True Acupuncture | Xerostomia Questionnaire Scores | Week 26 | 49.2 score on a scale 0-80 |
| Standard Oral Hygiene + True Acupuncture | Xerostomia Questionnaire Scores | Week 8 | 48.3 score on a scale 0-80 |
| Standard Oral Hygiene + True Acupuncture | Xerostomia Questionnaire Scores | Week 12 | 48.9 score on a scale 0-80 |
| Standard Oral Hygiene + Sham Acupuncture | Xerostomia Questionnaire Scores | Week 26 | 47.4 score on a scale 0-80 |
| Standard Oral Hygiene + Sham Acupuncture | Xerostomia Questionnaire Scores | Week 4 | 55.0 score on a scale 0-80 |
| Standard Oral Hygiene + Sham Acupuncture | Xerostomia Questionnaire Scores | Week 12 | 49.9 score on a scale 0-80 |
| Standard Oral Hygiene + Sham Acupuncture | Xerostomia Questionnaire Scores | Week 8 | 51.2 score on a scale 0-80 |
Comparison: The primary endpoint was to determine whether true acupuncture (TA) was more effective than sham acupuncture (SA) or standard oral hygiene (SOH) at treating xerostomia as assessed by the xerostomia questionnaire (XQ) at Week 4. The study was powered to detect a difference of 10 points with an assumed standard deviation (SD)=16 between each pair of groups on XQ.This assumed a t-test with a two-sided significance level of 0·0133 and 84% power with 20% dropout.p-value: 0.0167ANCOVA
Secondary
Functional Assessment of Cancer Therapy (FACT-G) Total
The FACT-G QOL instrument discriminates between individuals with metastatic and non-metastatic disease, as well as between patients at different stages of illness. The scale has good concurrent validity, high internal consistency (0.89), and good test-re-test reliability (0.82 to 0.88). The total score is reported, which is a combination of the subscales of physical, social/family, emotional, and functional well-being, with higher scores representing better QOL. Scale range 0-108
Time frame: Baseline, 4 , 8 , 12, and 26 weeks
Population: Intent to treat analysis. Considered and utilized all data available at each timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Standard Oral Hygiene | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 12 | 97.4 score on a scale 0-108 |
| Standard Oral Hygiene | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 4 | 97.7 score on a scale 0-108 |
| Standard Oral Hygiene | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 26 | 98.7 score on a scale 0-108 |
| Standard Oral Hygiene | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 8 | 99.5 score on a scale 0-108 |
| Standard Oral Hygiene + True Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 12 | 102.1 score on a scale 0-108 |
| Standard Oral Hygiene + True Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 8 | 101.1 score on a scale 0-108 |
| Standard Oral Hygiene + True Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 26 | 100.5 score on a scale 0-108 |
| Standard Oral Hygiene + True Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 4 | 101.6 score on a scale 0-108 |
| Standard Oral Hygiene + Sham Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 26 | 100.1 score on a scale 0-108 |
| Standard Oral Hygiene + Sham Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 12 | 98.4 score on a scale 0-108 |
| Standard Oral Hygiene + Sham Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 4 | 100.1 score on a scale 0-108 |
| Standard Oral Hygiene + Sham Acupuncture | Functional Assessment of Cancer Therapy (FACT-G) Total | Week 8 | 100.1 score on a scale 0-108 |
Secondary
The Acupuncture Expectancy Scale (AES)
The 4-item AES was used to ensure there were no baseline group differences in expectations related to the benefits of acupuncture on dry mouth and to assess aspects of blinding after the first 4 weeks of acupuncture for the TA and SA groups. The AES is reliable (α=0·82) and valid by positive correlation with patient self-reported efficacy and satisfaction. The scale has been further validated among cancer patients who were acupuncture naïve. Scale from 4-20.
Time frame: Week 4
Population: Intent to treat analysis excluding standard oral hygiene group. Considered and utilized all data available at each timepoint. AES was not collected for the standard oral hygiene arm per protocol specifications. Standard oral hygiene participants were not to receive any form of acupuncture making this outcome not applicable for these participants and therefore not collected.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Standard Oral Hygiene | The Acupuncture Expectancy Scale (AES) | 10.8 score on a scale 4-20 |
| Standard Oral Hygiene + True Acupuncture | The Acupuncture Expectancy Scale (AES) | 10.7 score on a scale 4-20 |