Carcinomas, Squamous Cell, Dysphagia
Conditions
Keywords
acupuncture, dysphagia, chemoradiation related effects, squamous cell carcinoma of the head and neck, nasopharyngeal cancer, oropharynx cancer, hypopharynx cancer, larynx cancer
Brief summary
The current standard of care for advanced HNC is concurrent chemoradiation therapy (CRT), which has led to increased survival rates, but with significant acute and long-term toxicities. Dysphagia, or difficulty with swallowing, is a common and expected side effect during and following CRT. Dysphagia occurs in up to 50% of patients and significantly impairs the quality of life (QOL) of patients during delivery of and recovery from CRT. Clinical trials evaluating promising and innovative adjunctive approaches that could increase the rate and magnitude of recovery from dysphagia in HNC patients are needed. Acupuncture is a traditional Chinese medical technique that has been found to reduce symptoms and side effects associated with primary cancer therapy. This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture.
Detailed description
AIMS: Aim 1. To assess the feasibility of recruiting and retaining HNC patients with dysphagia into a randomized sham-controlled trial of acupuncture. Aim 2. To collect preliminary data on the efficacy of acupuncture in changing scores of HRQOL in post CRT head and neck cancer patients. Aim 3. (Exploratory) In a subset of HNC subjects treated with both active and sham acupuncture, to collect objective measures on swallowing functions using Videofluoroscopic swallowing study (VFSS); salivary flow production; and plasma Transforming Growth Factor (TGF)-β1, Interleukin 6 (IL-6), Tumor necrosis factor-alpha (TNF-α) and Interleukin 13 levels.
Interventions
DEVICEAcupuncture
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN) at stage II, III and IV, without evidence of distant metastasis. Stage I disease will also be permitted if the patient is receiving CRT; * Primary tumor sites eligible: nasopharyngeal, oropharynx, hypopharynx or larynx. Tumors of the nasal and paranasal cavities will also be included. Unknown primary squamous cell carcinoma (SCC) in the neck will also be eligible. SCC of the oral cavity will also be eligible with the approval of the treating staff; * Receiving chemoradiation; * Currently or recently undergoing swallowing therapy program with or without feeding tube use, with or without neck dissection; * Age ≥ 18 years; * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; * Adequate hematological function: neutrophil count \>1.0 x109/L, platelet count \>50x109/L * Signed informed consent.
Exclusion criteria
Patients with the following criteria will NOT be eligible for the study: * Unstable cardiac disease or myocardial infarction within 6 months prior to study entry; * Wearing a pacemaker or implantable cardioverter-defibrillator; * History of significant neurologic disorder that affects swallowing, including stroke, neurodegenerative disease, advanced dementia, or uncontrolled seizure disorder; * Active clinically significant uncontrolled infection; * Prior use of acupuncture for dysphagia;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Outcome Compliance Rate | Assessed at baseline and at 6 months post acupuncture treatment | Outcome compliance rate is the percentage of enrolled participants who completed the primary study assessments (at baseline and in long-term follow-up 6 months post acupuncture treatment). |
| Treatment Compliance Rate | Assessed throughout the 6 month treatment period (12 acupuncture treatments every 2 weeks) | Treatment compliance rate is the percentage of enrolled participants who completed at least 80% of treatment (10 of 12 acupuncture sessions). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MDADI Change From Baseline to 12 Months Post Chemoradiation Therapy (CRT) | Assessed at baseline and 6 months post acupuncture which parallels 12 months post-CRT | The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline. |
| MDADI Scores | Assessed at baseline, 20 weeks post chemoradiation therapy and 6 months post acupuncture | The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline. |
Countries
United States
Participant flow
Recruitment details
Patients were screened for potential enrollment from January 2009 through December 2011.
Pre-assignment details
Since one primary aim was to assess feasibility as measured by recruitment the screening non-randomized count is included in the participant flow.
Participants by arm
| Arm | Count |
|---|---|
| Active Acupuncture Both active and sham acupuncture were administered by 5 experienced staff acupuncturists employing a traditional Chinese medicine (TCM) style, once every 2 weeks for 24 weeks, starting 2 weeks into CRT and ending at 20 weeks after CRT. | 21 |
| Sham Acupuncture TBoth active and sham acupuncture were administered by 5 experienced staff acupuncturists employing a traditional Chinese medicine (TCM) style, once every 2 weeks for 24 weeks, starting 2 weeks into CRT and ending at 20 weeks after CRT. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Excluded due to time constraints | 0 | 0 | 24 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Not meet inclusion criteria | 0 | 0 | 7 |
| Overall Study | Refused to Participate | 0 | 0 | 123 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 0 |
Baseline characteristics
| Characteristic | Active Acupuncture | Sham Acupuncture | Total |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 12.8 | 59.1 years STANDARD_DEVIATION 8.3 | 58.2 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 21 Participants | 21 Participants | 42 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 34 Participants |
| Total IMRT dose (Gy) 58 Gy | 1 Participants | 0 Participants | 1 Participants |
| Total IMRT dose (Gy) 64 GY | 0 Participants | 3 Participants | 3 Participants |
| Total IMRT dose (Gy) 66 Gy | 1 Participants | 2 Participants | 3 Participants |
| Total IMRT dose (Gy) 70 Gy | 19 Participants | 16 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 1 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Outcome Compliance Rate
Outcome compliance rate is the percentage of enrolled participants who completed the primary study assessments (at baseline and in long-term follow-up 6 months post acupuncture treatment).
Time frame: Assessed at baseline and at 6 months post acupuncture treatment
Population: The analysis population is comprised of all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Acupuncture | Outcome Compliance Rate | 76.2 percentage of participants |
| Sham Acupuncture | Outcome Compliance Rate | 85.7 percentage of participants |
Primary
Treatment Compliance Rate
Treatment compliance rate is the percentage of enrolled participants who completed at least 80% of treatment (10 of 12 acupuncture sessions).
Time frame: Assessed throughout the 6 month treatment period (12 acupuncture treatments every 2 weeks)
Population: The analysis population is comprised of all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Acupuncture | Treatment Compliance Rate | 76.2 percentage of participants |
| Sham Acupuncture | Treatment Compliance Rate | 81.0 percentage of participants |
Secondary
MDADI Change From Baseline to 12 Months Post Chemoradiation Therapy (CRT)
The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline.
Time frame: Assessed at baseline and 6 months post acupuncture which parallels 12 months post-CRT
Population: The analysis population represents the subset of participants evaluable at baseline and 12 months post CRT/6 months post acupuncture
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Acupuncture | MDADI Change From Baseline to 12 Months Post Chemoradiation Therapy (CRT) | 7.9 units on a scale |
| Sham Acupuncture | MDADI Change From Baseline to 12 Months Post Chemoradiation Therapy (CRT) | 13.9 units on a scale |
p-value: 0.17Wilcoxon (Mann-Whitney)
Secondary
MDADI Scores
The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline.
Time frame: Assessed at baseline, 20 weeks post chemoradiation therapy and 6 months post acupuncture
Population: The analysis population is comprised of all randomized participants. At each timepoint, a subset of participants were evaluable for quality of life assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Acupuncture | MDADI Scores | Baseline | 60.3 units on a scale | Standard Deviation 14.7 |
| Active Acupuncture | MDADI Scores | 20 weeks post chemoradiation start | 68.7 units on a scale | Standard Deviation 13.3 |
| Active Acupuncture | MDADI Scores | 6 months post acupuncture start | 72.7 units on a scale | Standard Deviation 13.3 |
| Sham Acupuncture | MDADI Scores | Baseline | 69.2 units on a scale | Standard Deviation 15.5 |
| Sham Acupuncture | MDADI Scores | 20 weeks post chemoradiation start | 77.8 units on a scale | Standard Deviation 10.9 |
| Sham Acupuncture | MDADI Scores | 6 months post acupuncture start | 79.3 units on a scale | Standard Deviation 12.4 |