Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT02138214
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 117
• Location: 1
• Arms: 3
• Actual Duration (Months): 76.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This phase II trial studies how well thyroid gland removal with or without central lymph node dissection works in treating patients with thyroid cancer or suspected thyroid cancer that has not spread to the lymph nodes (randomized into Arms I and II). Arms I and II are compared to a standard of care (SOC) Arm III to enable comparison of quality of life among various surgical treatments. Currently, the standard treatment for thyroid cancer is total thyroidectomy, or complete removal of the thyroid. The lymph nodes in the central part of the neck may also be surgically removed, called central lymph node dissection. Prophylactic removal of the lymph nodes may increase the risk of life-threatening complications, and may reduce post-surgery quality of life. It may also prevent the cancer from returning and reduce the need for additional surgery. It is not yet known whether recurrence rates and complication levels are lower after thyroid gland removal alone or with central lymph node dissection.

Condition or Disease	Intervention/Treatment	Phase
Stage I Papillary Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage III Papillary Thyroid Cancer	Procedure: Thyroidectomy; Procedure: entral lymph node dissection (CLND); Other: Quality-of-life assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the rate of transient and permanent hypocalcemia

SECONDARY OBJECTIVES:

1. To determine the rate of voice and swallowing problems.

2. To determine the degree to which quality of life (QOL) is compromised.

3. To determine the degree to which accurate quality of life measures can be extracted from patient interview narratives using natural language processing techniques.

4. To determine clinical recurrence rates.

OUTLINE: Patients are randomized to 1 of 2 treatment arms, if ineligible into a SOC arm.

Arm I: Patients undergo total thyroidectomy alone.

Arm II: Patients undergo total thyroidectomy with ipsilateral prophylactic central neck dissection (CND).

Arm III: Patients ineligible to be randomized into Arm I or II, Standard of Care (SOC) comparator receiving same follow up.

After completion of study treatment, patients are followed up at day 1, 2 and 6 weeks, and 6 and 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Thyroid Gland Removal With or Without Central Lymph Node Dissection in Treating Patients With Node Negative Thyroid Cancer
• Actual Study Start Date: Jun 6, 2014
• Actual Primary Completion Date: Oct 30, 2019
• Actual Study Completion Date: Oct 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (no CND) Patients undergo total thyroidectomy alone.	Procedure: Thyroidectomy; Undergo total thyroidectomy; Other: Quality-of-life assessment; Voice evaluation, interviews, ancillary studies
Experimental: Arm II (CND) Patients undergo total thyroidectomy with ipsilateral prophylactic CND.	Procedure: Thyroidectomy; Undergo total thyroidectomy; Procedure: entral lymph node dissection (CLND); Undergo total thyroidectomy with ipsilateral prophylactic CND; Other: Quality-of-life assessment; Voice evaluation, interviews, ancillary studies
Active Comparator: Arm III (SOC) Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference	Other: Quality-of-life assessment; Voice evaluation, interviews, ancillary studies

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml [Post-operative day 1]

   Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml.

2. Post-operative Serum Calcium (mg/dL) at Day 12 [At day 12]

   Post-operative serum calcium (mg/dL) at Day 12

3. Total Calcium Consumption in First 2 Weeks [2 weeks after surgery]

   Total calcium consumption in first 2 weeks (total mg). Participants were given calcium symptom logs in which to record their calcium consumption between surgery and their first preoperative follow up appointment, approximately two week.

4. Number of Participants With Hypocalcemia Symptoms in First 2 Weeks [2 weeks]

   Number of participants with hypocalcemia symptoms and symptom severity in first two weeks, as defined by presence of clinically significant symptoms of hypocalcemia. Clinically significant symptoms defined as 1 or more episodes of symptoms of hypocalcemia per day for multiple days, symptoms leading to calls to provider for assistance with managing and/or symptoms leading to escalation of dosage of prescribed medications to treat symptoms of hypocalcemia

5. Hypocalcemia Symptom Severity Scale (Range of 1-5) [2 weeks post surgery]

   Mean number of occurrences of mild (severity 1 - 2) and severe (severity 3 - 5) hypocalcemia symptoms. Participants were asked to record hypocalcemia symptoms between surgery and first postoperative follow-up at approximately two weeks in their provided calcium symptom logs and rank severity on scale of 1 (mild) to 5 (severe).

6. Percentage of Participants That Required Calcium and Calcitriol at Month 6 [At Month 6]

   Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH <15 pg/ml)

7. Post-operative Serum PTH (pg/ml) at Month 6 [At Month 6]

8. Post-operative Serum Calcium Level at Month 6 [At Month 6]

   Post-operative serum calcium (mg/dL) at Month 6

Secondary Outcome Measures

1. Rate of Transient and Permanent Hypocalcemia [Post-operative day 1 - Month 6]

   The rate of transient and permanent hypocalcemia will be determined by assessing the following: I. Post-operative serum calcium (mg/dl) and PTH (pg/ml) at Day 12 and Month 6 II. Total calcium consumption in first 2 weeks (total gm) III. Hypocalcemia symptoms in first 2 weeks (average episodes/day) IV. Hypocalcemia symptom severity scale (range 1-5) V. Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH < 15 pg/ml Data will be analyzed using the methods described above.

2. Rate of Voice and Swallowing Problems [Post operative day 1 - up to 1 year]

   The rate of voice and swallowing problems will be determined by assessing the following: I. Phonation threshold pressure, in centimeters of water II. Dysphonia severity index (DSI) score (+5 to -5) III. Grade Roughness Breathiness Asthenia Strain (GRBAS) score (0-3) IV. Voice quality parameters as measured by Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) (0-100 on visual analog scale) V. Vocal fold vibratory and movement parameters as measured by stroboscopy assessment (1-4) VI. Glottal function index score VII. Penetration-Aspiration score as measured by videofluoroscopic swallow study (0-8) Data will be analyzed using the methods described above.

3. Degree to Which Quality of Life (QOL) is Compromised [Post-operative day 1 - up to 1 year]

   The degree to which quality (QOL) is compromised will be determined by assessing the following: I. Short Form Health Survey (SF-12) Mental Composite Scale (MCS) score II. Short Form Health Survey (SF-12) Physical Composite Scale (PCS) score III. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core-30 (C30) score IV. Thyroid Cancer Specific Quality of Life (ThyCA-QOL) score V. 10-item Eating Assessment Tool (EAT-10) dysphagia inventory score VI. Voice Handicap Index (VHI) score VII. Themes and codes from interview transcripts assessed using qualitative research methods Data will be analyzed using the methods described above.

4. Clinical Recurrence Rates [Week 6 - up to 5 years]

   Clinical recurrence rates will be determined by assessing the following: I. Percent of patients with a recombinant thyroid-stimulating hormone (rTSH) stimulated thyroglobulin level < 1 ng/ml one year after surgery II. Unstimulated thyroglobulin level prior to beginning week 6 radioactive iodine treatment III. Stimulated thyroglobulin at the time of week 6 radioactive iodine treatment IV. Incidence of unstimulated thyroglobulin > 1 ng/mL at 6 months V. Incidence of stimulated thyroglobulin > 2 ng/mL at 1 year VI. Incidence of biopsy-proven disease identification on neck ultrasound or iodine-131 (I-131) uptake up to 5 years post-surgery Data will be analyzed using the methods described above.

5. Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques [Post-operative day 1 - up to 1 year]

   The degree to which accurate quality of life (QOL) measures can be extracted from patient interview narratives using natural language process techniques will allow for the development of computer algorithms that convert patient narrative text into simple quality of life measures. Data will be analyzed using the methods described above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 73 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pre-operative diagnosis or suspicion of papillary thyroid cancer, usually by fine needle aspiration (FNA)

• No pre-operative evidence of cervical lymph node metastases on neck ultrasound (randomization arms only)

• No evidence of distant metastases

• Ability to read and write in English

Exclusion Criteria:

• Largest papillary thyroid carcinoma < 1 cm in size on ultrasound

• Previous thyroid surgery

• Concurrent active malignancy of another type

• Inability to give informed consent or lacks decision making capacity

• T4 tumor

• Pre-existing vocal cord paralysis

• Chronic neurologic condition which affects voice or swallow (for instance, multiple sclerosis or Parkinson disease)

• Baseline laryngeal pathology that would warrant intervention that could affect voice or swallow function

• Becomes pregnant before surgery or at any time while on study

INTRA-OPERATION EXCLUSION CRITERIA (randomization arms only)

• Evidence of nodal involvement identified in the operating room (OR)

• Failure to confirm diagnosis of cancer in participant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rebecca Sippel, University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 17, 2020

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center Homepage

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT02138214
• Other Study ID Numbers: UW13115; NCI-2014-00833; UW13115; R01CA176911; 2014-0391; A539700; SMPH\SURGERY\SURGERY
• First Posted: May 14, 2014
• Last Update Posted: Dec 21, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroid Diseases

Study Results

Participant Flow

Pre-assignment Detail	117 participants consented. 27 participants were excluded from the study before assignment to arms (15 participants withdrew before surgery, 12 participants did not meet intraoperative inclusion criteria). 90 participants were allocated in 3 arms

Arm/Group Title	Arm I (no CND)	Arm II (CND)	Arm III (SOC)
Arm/Group Description	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Period Title: Overall Study
STARTED	30	30	30
Analyzed for Baseline Measures	30	29	30
COMPLETED	30	26	26
NOT COMPLETED	0	4	4

Baseline Characteristics

Arm/Group Title	Arm I (no CND)	Arm II (CND)	Arm III (SOC)	Total
Arm/Group Description	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Total of all reporting groups
Overall Participants	30	29	30	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.10 (1.47)	50.07 (2.38)	43.17 (2.68)	46.40 (1.47)
Sex: Female, Male (Count of Participants)
Female	23 76.7%	21 72.4%	27 90%	71 79.8%
Male	7 23.3%	8 27.6%	3 10%	18 20.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.3%	0 0%	2 6.7%	3 3.4%
Not Hispanic or Latino	29 96.7%	29 100%	28 93.3%	86 96.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	2 6.7%	2 2.2%
Asian	0 0%	1 3.4%	0 0%	1 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	30 100%	28 96.6%	27 90%	85 95.5%
More than one race	0 0%	0 0%	1 3.3%	1 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%	29 100%	30 100%	89 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml
Description	Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml.
Time Frame	Post-operative day 1

Outcome Measure Data

Analysis Population Description

1 participant in the Arm II(CND) was a screen failure. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	29	30
Number [percentage of participants]	24.1 80.3%	33.3 114.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.567
	Comments	p-value threshold for statistical significance is 0.05
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Post-operative Serum Calcium (mg/dL) at Day 12
Description	Post-operative serum calcium (mg/dL) at Day 12
Time Frame	At day 12

Outcome Measure Data

Analysis Population Description

1 participant in the Arm II(CND) was a screen failure. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	29	30
Mean (Standard Error) [mg/dL]	9.39 (0.12)	9.13 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	Total Calcium Consumption in First 2 Weeks
Description	Total calcium consumption in first 2 weeks (total mg). Participants were given calcium symptom logs in which to record their calcium consumption between surgery and their first preoperative follow up appointment, approximately two week.
Time Frame	2 weeks after surgery

Outcome Measure Data

Analysis Population Description

19 participants in CND arm, 22 in 'no CND' arm returned their calcium symptom log to study staff at the end of the postoperative follow-up period. Missing data is due to participants losing/forgetting to return their calcium symptom logs/lack of clarity in their handwritten log entries. This may also have led to limited reliability/accuracy of the data we were able to collect. SOC arm data was not collected as outcome is a comparison of complication rates between TT and CND arms, N/A to SOC arm.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	19	22
Mean (Standard Error) [mg]	21876.63 (6353.42)	25470.19 (6592.60)

4. Primary Outcome

Title	Number of Participants With Hypocalcemia Symptoms in First 2 Weeks
Description	Number of participants with hypocalcemia symptoms and symptom severity in first two weeks, as defined by presence of clinically significant symptoms of hypocalcemia. Clinically significant symptoms defined as 1 or more episodes of symptoms of hypocalcemia per day for multiple days, symptoms leading to calls to provider for assistance with managing and/or symptoms leading to escalation of dosage of prescribed medications to treat symptoms of hypocalcemia
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	28	30
Number [participants]	8 26.7%	6 20.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.758
	Comments
	Method	Fisher Exact
	Comments

5. Primary Outcome

Title	Hypocalcemia Symptom Severity Scale (Range of 1-5)
Description	Mean number of occurrences of mild (severity 1 - 2) and severe (severity 3 - 5) hypocalcemia symptoms. Participants were asked to record hypocalcemia symptoms between surgery and first postoperative follow-up at approximately two weeks in their provided calcium symptom logs and rank severity on scale of 1 (mild) to 5 (severe).
Time Frame	2 weeks post surgery

Outcome Measure Data

Analysis Population Description

Missing data is due to participants losing/forgetting to return their calcium symptom logs/lack of clarity in their handwritten log entries. This may also have led to limited reliability/accuracy of the data we were able to collect. SOC arm data was not collected as outcome is a comparison of complication rates between TT and CND arms, not applicable (N/A) to SOC arm.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	13	19
mild symptoms (severity 1 - 2)	3 (1.49)	2.50 (0.81)
severe symptoms (severity 3 - 5)	3.36 (1.59)	1.42 (0.73)

6. Primary Outcome

Title	Percentage of Participants That Required Calcium and Calcitriol at Month 6
Description	Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH <15 pg/ml)
Time Frame	At Month 6

Outcome Measure Data

Analysis Population Description

In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	27	30
Count of Participants [Participants]	0 0%	3 10.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.236
	Comments
	Method	Fisher Exact
	Comments

7. Primary Outcome

Title	Post-operative Serum PTH (pg/ml) at Month 6
Time Frame	At Month 6

Outcome Measure Data

Analysis Population Description

In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	27	30
Mean (Standard Error) [pg/mL]	45.62 (4.6)	44.24 (4.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.759
	Comments
	Method	t-test, 2 sided
	Comments

8. Primary Outcome

Title	Post-operative Serum Calcium Level at Month 6
Description	Post-operative serum calcium (mg/dL) at Month 6
Time Frame	At Month 6

Outcome Measure Data

Analysis Population Description

In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Arm/Group Title	Arm II (CND)	Arm I (no CND)
Arm/Group Description	Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Measure Participants	27	30
Mean (Standard Error) [mg/dL]	9.12 (0.08)	8.98 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (CND), Arm I (no CND)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.400
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Rate of Transient and Permanent Hypocalcemia
Description	The rate of transient and permanent hypocalcemia will be determined by assessing the following: I. Post-operative serum calcium (mg/dl) and PTH (pg/ml) at Day 12 and Month 6 II. Total calcium consumption in first 2 weeks (total gm) III. Hypocalcemia symptoms in first 2 weeks (average episodes/day) IV. Hypocalcemia symptom severity scale (range 1-5) V. Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH < 15 pg/ml Data will be analyzed using the methods described above.
Time Frame	Post-operative day 1 - Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Rate of Voice and Swallowing Problems
Description	The rate of voice and swallowing problems will be determined by assessing the following: I. Phonation threshold pressure, in centimeters of water II. Dysphonia severity index (DSI) score (+5 to -5) III. Grade Roughness Breathiness Asthenia Strain (GRBAS) score (0-3) IV. Voice quality parameters as measured by Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) (0-100 on visual analog scale) V. Vocal fold vibratory and movement parameters as measured by stroboscopy assessment (1-4) VI. Glottal function index score VII. Penetration-Aspiration score as measured by videofluoroscopic swallow study (0-8) Data will be analyzed using the methods described above.
Time Frame	Post operative day 1 - up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Degree to Which Quality of Life (QOL) is Compromised
Description	The degree to which quality (QOL) is compromised will be determined by assessing the following: I. Short Form Health Survey (SF-12) Mental Composite Scale (MCS) score II. Short Form Health Survey (SF-12) Physical Composite Scale (PCS) score III. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core-30 (C30) score IV. Thyroid Cancer Specific Quality of Life (ThyCA-QOL) score V. 10-item Eating Assessment Tool (EAT-10) dysphagia inventory score VI. Voice Handicap Index (VHI) score VII. Themes and codes from interview transcripts assessed using qualitative research methods Data will be analyzed using the methods described above.
Time Frame	Post-operative day 1 - up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Clinical Recurrence Rates
Description	Clinical recurrence rates will be determined by assessing the following: I. Percent of patients with a recombinant thyroid-stimulating hormone (rTSH) stimulated thyroglobulin level < 1 ng/ml one year after surgery II. Unstimulated thyroglobulin level prior to beginning week 6 radioactive iodine treatment III. Stimulated thyroglobulin at the time of week 6 radioactive iodine treatment IV. Incidence of unstimulated thyroglobulin > 1 ng/mL at 6 months V. Incidence of stimulated thyroglobulin > 2 ng/mL at 1 year VI. Incidence of biopsy-proven disease identification on neck ultrasound or iodine-131 (I-131) uptake up to 5 years post-surgery Data will be analyzed using the methods described above.
Time Frame	Week 6 - up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques
Description	The degree to which accurate quality of life (QOL) measures can be extracted from patient interview narratives using natural language process techniques will allow for the development of computer algorithms that convert patient narrative text into simple quality of life measures. Data will be analyzed using the methods described above.
Time Frame	Post-operative day 1 - up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year
Arm/Group Title	Arm I (no CND)		Arm II (CND)		Arm III (SOC)
Arm/Group Description	Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies		Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies		Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
All Cause Mortality
	Arm I (no CND)		Arm II (CND)		Arm III (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/29 (0%)		0/30 (0%)
Serious Adverse Events
	Arm I (no CND)		Arm II (CND)		Arm III (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/29 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (no CND)		Arm II (CND)		Arm III (SOC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)		25/29 (86.2%)		9/30 (30%)
Injury, poisoning and procedural complications
biochemical hypopcalcemia	2/30 (6.7%)	2	0/29 (0%)	0	1/30 (3.3%)	1
symptomatic hypoparathyroidism	2/30 (6.7%)	2	4/29 (13.8%)	4	1/30 (3.3%)	1
nerve injury	12/30 (40%)	12	7/29 (24.1%)	7	3/30 (10%)	3
significant voice changes not otherwise characterized	11/30 (36.7%)	11	7/29 (24.1%)	7	2/30 (6.7%)	2
biochemical hypoparathyroidism	9/30 (30%)	9	8/29 (27.6%)	8	3/30 (10%)	3
symptomatic hypocalcemia	4/30 (13.3%)	4	6/29 (20.7%)	6	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.