Salivary Gland Surgery Before Radiation Therapy in Preventing Radiation-Caused Xerostomia in Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Moving a salivary gland out of the area that will undergo radiation therapy may protect the gland from side effects of radiation therapy and may prevent xerostomia (dry mouth). PURPOSE: Phase II trial to study the effectiveness of salivary gland surgery in preventing xerostomia in patients who are undergoing radiation therapy for head and neck cancer.

Detailed Description
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OBJECTIVES: Determine the reproducibility of the surgical technique of submandibular salivary gland transfer in patients with head and neck cancer. Determine the rate and severity of radiation-induced xerostomia after this surgery in these patients. Determine the pattern of recurrence, disease-free survival, and overall survival of patients treated with this surgery followed by radiotherapy. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo surgical transfer of the submandibular salivary gland to the submental space. Within 4-6 weeks after surgery, patients undergo radiotherapy once daily, 5 days a week for 5 ½ to 7 weeks in the absence of disease progression or unacceptable toxicity. Salivary scans are performed before surgery, at 2-3 weeks after surgery, and then at 6 months from the start of radiotherapy. Quality of life is assessed at baseline and at 3, 6, and 12 months from the start of radiotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years and then annually. PROJECTED ACCRUAL: A total of 11-48 patients will be accrued for this study within 1.6 years.

Official Title
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A Phase II Study Of Submandibular Salivary Gland Transfer To The Submental Space Prior To Start Of Radiation Treatment For Prevention Of Radiation-Induced Xerostomia In Head And Neck Cancer Patients

Conditions
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Head and Neck Cancer, Radiation Toxicity, Xerostomia

Intervention / Treatment
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* Procedure: salivary gland transfer
* Radiation: Post-operative radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following diagnoses: Histologically confirmed, previously untreated squamous cell carcinoma of the oropharynx, hypopharynx, or larynx Head and neck cancer of unknown primary with unilateral metastases to the neck nodes No N3 disease No carcinoma of the oral cavity or nasopharynx No bilateral neck node involvement No suspicious neck node on the contralateral neck or the side chosen for salivary gland transfer by CT scan or MRI No pre-epiglottic space involvement No involvement of level 1 nodes on either side of the neck No salivary gland malignancy No recurrent disease PATIENT CHARACTERISTICS: Age At least 18 years old Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Hemoglobin at least 10 g/dL Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No salivary gland disease (e.g., Sjögren's syndrome) No other malignancy within the past 3 years except basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 3 years since prior chemotherapy No prior or concurrent neoadjuvant chemotherapy Concurrent adjuvant chemoradiotherapy (in addition to study radiotherapy) allowed Endocrine therapy Not specified Radiotherapy See Chemotherapy No prior radiotherapy to the head and neck No concurrent intensity-modulated radiotherapy Surgery Not specified Other No concurrent cholinergic drugs No concurrent anti-cholinergic drugs No concurrent tricyclic drugs No concurrent prophylactic amifostine or pilocarpine during and for at least 3 months after completion of study radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery + Transfer + Radiation<br>Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy. | Procedure: salivary gland transfer<br>* Seikaly and Jha method of submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes on Day 1<br>Radiation: Post-operative radiation therapy<br>* Dose ranging from 54-70 Gy over 5.5-7 weeks, at 2.0 Gy/fraction. Starts within 4-6 weeks of surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed Per Protocol | Surgery will be scored as per protocol prescription if scored as such by both central reviewers- the Study Chair and the Radiation Therapy Oncology Group Head and Neck Committee Surgical Chair. If 21 or more of 43 subjects are scored as having surgery per protocol prescription, then the technique will be considered reproducible with 80% power and 5% type I error using Simon's two stage design with unacceptable/acceptable rates set at 60%/80%. | At the time of the submandibular salivary gland transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Acute Xerostomia | The proportion of patients who experience grade 2 or higher xerostomia or start amifostine and/or pilocarpine within 90 days of the start of radiation therapy. A proportion less than or equal to 51% would be considered acceptable based on the results of the U.S. Bioscience phase III amifostine trial (this trial preceded FDAAA requirements). | From start of treatment to 90 days | 
| Percentage of Patients With Normal Functioning Transferred Submandibular Gland | Salivary gland functioning classified as Non-functioning, Minimal function, Well-functioning but some impairment, Normal functioning, or Other is determined by central review of scintigraphy scans using sodium pertechnetate (Na-99mTcO4-) with a sialagogue (lemon juice) administered halfway through the study to determine if secretory function is maintained. | Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks) | 
| Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire | The University of Washington Head and Neck Symptom Questionnaire, also referred to as the University of Washington Health Related Quality of Life tool (UW-QOL) was modified for use by the Radiation Therapy Oncology Group (RTOG). The resulting UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The UW-QOL-RTOG modification consists of 15 items with response options ranging from 10-50, in multiples of 10. That is, the lowest symptom burden is rated as 10, while the highest symptom burden is rated as 50. The individual item scores are averaged to obtain the final score which also ranges from 10 to 50. This scoring results in a lower score indicating greater HR-QOL; and conversely, higher scores indicating lower health-related quality of life (HR-QOL). Change = baseline score - one year score, such that a positive change score indicates improvement. | Baseline and one year | 
| Percentage of Patients Experiencing Facial Edema Following Surgery | Facial edema was noted as present or absent following surgery. | From surgery to 30 days after surgery | 
| Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy | Adverse events are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v2.0. Grade refers to the severity of the toxicity by assigning Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. Acute refers to toxicities occurring less than or equal to 90 days from the start of radiation therapy. | From start of radiation therapy to 90 days | 
| Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy | Adverse events are graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v2.0. Grade refers to the severity of the toxicity by assigning Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. Late refers to toxicities occurring at least 91 days from the start of radiation therapy. | From 91 days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 5.6 years. | 
| Disease-free Survival Rate at 2 Years | Failure was defined as local, regional, or distant recurrence/progression, second primary tumor, or death due to any cause. Disease-free survival time is defined as time from registration to the the date of failure or last known follow-up (censored). Disease-free survival rate is estimated using the kaplan-meier method. | From registration to two years | 
| Overall Survival Rate at 2 Years | Failure was defined as death due to any cause. Survival time is defined as time from registration to the the date of failure or last known follow-up (censored). Survival rate is estimated using the kaplan-meier method. | From registration to two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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xerostomia, radiation toxicity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage I squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, untreated metastatic squamous neck cancer with occult primary, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the oropharynx