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

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00068237
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 12
• Arm: 1
• Duration (Months): 160
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Radiation Toxicity; Xerostomia	Procedure: salivary gland transfer; Radiation: Post-operative radiation therapy	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed "Per Protocol" [At the time of the submandibular salivary gland transfer]

   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%.

Secondary Outcome Measures

1. Percentage of Patients With Acute Xerostomia [From start of treatment to 90 days]

   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).

2. Percentage of Patients With Normal Functioning Transferred Submandibular Gland [Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks)]

   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.

3. Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire [Baseline and one year]

   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.

4. Percentage of Patients Experiencing Facial Edema Following Surgery [From surgery to 30 days after surgery]

   Facial edema was noted as present or absent following surgery.

5. Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy [From start of radiation therapy to 90 days]

   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.

6. Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to 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.]

   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.

7. Disease-free Survival Rate at 2 Years [From registration to two 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.

8. Overall Survival Rate at 2 Years [From registration to two 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.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
2	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
3	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
4	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
5	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
6	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
7	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
8	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
9	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin	United States	53295
10	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
11	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
12	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Naresh Jha, MBBS, Cross Cancer Institute at University of Alberta

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00068237
• Other Study ID Numbers: RTOG-0244; CDR0000287213
• First Posted: Sep 11, 2003
• Last Update Posted: Feb 5, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Radiation Therapy Oncology Group: 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
• Additional relevant MeSH terms: Head and Neck Neoplasms; Xerostomia

Study Results

Participant Flow

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Period Title: Overall Study
STARTED	49
COMPLETED	44
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Overall Participants	44
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56.5
Sex: Female, Male (Count of Participants)
Female	8 18.2%
Male	36 81.8%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Scored as Having the Surgical Technique of Submandibular Salivary Gland Transfer Performed "Per Protocol"
Description	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%.
Time Frame	At the time of the submandibular salivary gland transfer

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment.

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	44
Number [participants]	34 77.3%

2. Secondary Outcome

Title	Percentage of Patients With Acute Xerostomia
Description	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).
Time Frame	From start of treatment to 90 days

Outcome Measure Data

Analysis Population Description

Eligible patients who started RT

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	25.6 58.2%

3. Secondary Outcome

Title	Percentage of Patients With Normal Functioning Transferred Submandibular Gland
Description	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.
Time Frame	Pre-surgery, post-surgery (4-6 weeks), post radiation therapy (10-13 weeks)

Outcome Measure Data

Analysis Population Description

Eligible patients with salivary scans submitted

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	37
Pre-surgery	70.3 159.8%
Post-surgery	16.7 38%
Post-radiotherapy	0.0 0%

4. Secondary Outcome

Title	Change From Baseline to One Year in Total Score on the Modified University of Washington Head and Neck Symptom Questionnaire
Description	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.
Time Frame	Baseline and one year

Outcome Measure Data

Analysis Population Description

Eligible patients with both baseline and 1-year questionnaire completed

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	22
Median (Inter-Quartile Range) [score on a scale]	13.6

5. Secondary Outcome

Title	Percentage of Patients Experiencing Facial Edema Following Surgery
Description	Facial edema was noted as present or absent following surgery.
Time Frame	From surgery to 30 days after surgery

Outcome Measure Data

Analysis Population Description

Eligible patients who received the procedure

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	44
Number (95% Confidence Interval) [percentage of participants]	13.6 30.9%

6. Secondary Outcome

Title	Percentage of Patients Experiencing Acute Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy or Chemotherapy
Description	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.
Time Frame	From start of radiation therapy to 90 days

Outcome Measure Data

Analysis Population Description

Eligible patients who started RT

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	34.9 79.3%

7. Secondary Outcome

Title	Percentage of Patients Experiencing Late Grade 3-4 Toxicity Definitely, Probably, or Possibly Related to Radiation Therapy
Description	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.
Time Frame	From 91 days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 5.6 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who started RT and had toxicity data at least 90 days from the end of RT

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	7.9 18%

8. Secondary Outcome

Title	Disease-free Survival Rate at 2 Years
Description	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.
Time Frame	From registration to two years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	44
Number (95% Confidence Interval) [percentage of participants]	71.7 163%

9. Secondary Outcome

Title	Overall Survival Rate at 2 Years
Description	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.
Time Frame	From registration to two years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
Measure Participants	44
Number (95% Confidence Interval) [percentage of participants]	76.4 173.6%

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE). Please note that different numbers of patients were at risk for different treatment-specific adverse events due to the timing and sequence of treatments.
Arm/Group Title	Surgery + Transfer + Radiation
Arm/Group Description	Submandibular salivary gland transfer at the time of surgery for the primary tumor and neck nodes followed by post-operative radiation therapy.
All Cause Mortality
	Surgery + Transfer + Radiation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Surgery + Transfer + Radiation
	Affected / at Risk (%)	# Events
Total	2/44 (4.5%)
Metabolism and nutrition disorders
Anorexia	1/43 (2.3%)
Psychiatric disorders
Confusion	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Apnoea	1/43 (2.3%)
Surgical and medical procedures
Acute Surgical Complication: Bleeding/hematoma	2/44 (4.5%)
Acute Surgical Complication: Cerebral embolism/CVA	1/44 (2.3%)
Acute Surgical Complication: Wound infection	2/44 (4.5%)
Other (Not Including Serious) Adverse Events
	Surgery + Transfer + Radiation
	Affected / at Risk (%)	# Events
Total	38/44 (86.4%)
Blood and lymphatic system disorders
Hemoglobin decreased	4/43 (9.3%)
Lymphatics-Other	1/43 (2.3%)
Ear and labyrinth disorders
Hearing impaired	2/43 (4.7%)
Hearing-Other	3/43 (7%)
Endocrine disorders
Hypothyroidism	1/43 (2.3%)
Gastrointestinal disorders
Constipation	2/43 (4.7%)
Diarrhea NOS	2/43 (4.7%)
Dry mouth	26/43 (60.5%)
Dysphagia	6/43 (14%)
Esophageal spasm	1/43 (2.3%)
Esophagitis NOS	6/43 (14%)
GI-other	3/43 (7%)
Gastric ulcer	1/43 (2.3%)
Nausea	10/43 (23.3%)
Radiation mucositis	14/43 (32.6%)
Salivary gland disorder NOS	18/43 (41.9%)
Stomatitis	3/43 (7%)
Vomiting NOS	7/43 (16.3%)
General disorders
Chest pain	1/43 (2.3%)
Fatigue	17/43 (39.5%)
Infection NOS	1/43 (2.3%)
Late RT Toxicity: Esophagus	4/38 (10.5%)
Late RT Toxicity: Joint	3/38 (7.9%)
Late RT Toxicity: Larynx	6/38 (15.8%)
Late RT Toxicity: Mucous Membrane	9/38 (23.7%)
Late RT Toxicity: Other	10/38 (26.3%)
Late RT Toxicity: Salivary Gland (xerostomia, taste impairme	22/38 (57.9%)
Late RT Toxicity: Skin (within XRT field)	6/38 (15.8%)
Late RT Toxicity: Subcutaneous Tissue (Within XRT field)	6/38 (15.8%)
Pain due to radiation	11/43 (25.6%)
Pain-other	8/43 (18.6%)
Pyrexia	2/43 (4.7%)
Rigors	1/43 (2.3%)
Immune system disorders
Allergy-Other	1/43 (2.3%)
Infections and infestations
Infection, Other	5/43 (11.6%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	12/43 (27.9%)
Investigations
Blood creatinine increased	1/43 (2.3%)
Leukopenia NOS	3/43 (7%)
Weight decreased	12/43 (27.9%)
Metabolism and nutrition disorders
Anorexia	7/43 (16.3%)
Blood albumin decreased	1/43 (2.3%)
Blood magnesium decreased	1/43 (2.3%)
Dehydration	5/43 (11.6%)
Hypokalemia	1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone-Other	5/43 (11.6%)
Muscle weakness NOS	1/43 (2.3%)
Nervous system disorders
Depressed level of consciousness	1/43 (2.3%)
Peripheral motor neuropathy	1/43 (2.3%)
Peripheral sensory neuropathy	1/43 (2.3%)
Taste disturbance	23/43 (53.5%)
Psychiatric disorders
Anxiety NEC	2/43 (4.7%)
Insomnia NEC	2/43 (4.7%)
Reproductive system and breast disorders
Sexual/reproductive function-Other	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	5/43 (11.6%)
Dysphonia	2/43 (4.7%)
Dyspnea NOS	5/43 (11.6%)
Hemoptysis	2/43 (4.7%)
Hypoxia	1/43 (2.3%)
Pulmonary-other	2/43 (4.7%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative NOS	6/43 (14%)
Erythema multiforme	1/43 (2.3%)
Skin discoloration	1/43 (2.3%)
Skin-Other	2/43 (4.7%)
Surgical and medical procedures
Acute Surgical Complication: Facial edema	6/44 (13.6%)
Acute Surgical Complication: Facial edema on the transfer si	6/44 (13.6%)
Acute Surgical Complication: Gland movement out of position	1/44 (2.3%)
Acute Surgical Complication: Neck numbness	3/44 (6.8%)
Acute Surgical Complication: Neck numbness on the transfer s	2/44 (4.5%)
Acute Surgical Complication: Nerve injury: hypoglossal	1/44 (2.3%)
Acute Surgical Complication: Nerve injury: hypoglossal on th	1/44 (2.3%)
Acute Surgical Complication: Nerve injury: lingual	1/44 (2.3%)
Acute Surgical Complication: Other	4/44 (9.1%)
Acute Surgical Complication: Shoulder weakness	2/44 (4.5%)
Acute Surgical Complication: Shoulder weakness on the transf	1/44 (2.3%)
Late Surgical Complication: Other	10/44 (22.7%)
Late Surgical Complication: Recurrent adenitis	1/44 (2.3%)
Late Surgical Complication: Submental fullness	8/44 (18.2%)
Vascular disorders
Edema NOS	3/43 (7%)
Hemorrhage-Other	1/43 (2.3%)
Lymphangiopathy NOS	2/43 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.