Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the rate of transient and permanent hypocalcemia SECONDARY OBJECTIVES: I. To determine the rate of voice and swallowing problems. II. To determine the degree to which quality of life (QOL) is compromised. III. To determine the degree to which accurate quality of life measures can be extracted from patient interview narratives using natural language processing techniques. IV. 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.

Official Title
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Thyroid Gland Removal With or Without Central Lymph Node Dissection in Treating Patients With Node Negative Thyroid Cancer

Conditions
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Stage I Papillary Thyroid Cancer, Stage II Papillary Thyroid Cancer, Stage III Papillary Thyroid Cancer

Intervention / Treatment
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* Procedure: Thyroidectomy
* Procedure: entral lymph node dissection (CLND)
* Other: Quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 73 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (no CND)<br>Patients undergo total thyroidectomy alone. | Procedure: Thyroidectomy<br>* Undergo total thyroidectomy<br>Other: Quality-of-life assessment<br>* Voice evaluation, interviews, ancillary studies<br>|
| Experimental: Arm II (CND)<br>Patients undergo total thyroidectomy with ipsilateral prophylactic CND. | Procedure: Thyroidectomy<br>* Undergo total thyroidectomy<br>Procedure: entral lymph node dissection (CLND)<br>* Undergo total thyroidectomy with ipsilateral prophylactic CND<br>Other: Quality-of-life assessment<br>* Voice evaluation, interviews, ancillary studies<br>|
| Active Comparator: Arm III (SOC)<br>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<br>* Voice evaluation, interviews, ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml | Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml. | Post-operative day 1 | 
| Post-operative Serum Calcium (mg/dL) at Day 12 | Post-operative serum calcium (mg/dL) at Day 12 | At day 12 | 
| Total Calcium Consumption in First 2 Weeks | 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. | 2 weeks after surgery | 
| Number of Participants With Hypocalcemia Symptoms in First 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 | 2 weeks | 
| Hypocalcemia Symptom Severity Scale (Range of 1-5) | 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). | 2 weeks post surgery | 
| Percentage of Participants That Required Calcium and Calcitriol 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) | At Month 6 | 
| Post-operative Serum PTH (pg/ml) at Month 6 |  | At Month 6 | 
| Post-operative Serum Calcium Level at Month 6 | Post-operative serum calcium (mg/dL) at Month 6 | At Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Transient and Permanent Hypocalcemia | 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. | Post-operative day 1 - Month 6 | 
| Rate of Voice and Swallowing Problems | 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. | Post operative day 1 - up to 1 year | 
| Degree to Which Quality of Life (QOL) is Compromised | 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. | Post-operative day 1 - up to 1 year | 
| Clinical Recurrence Rates | 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. | Week 6 - up to 5 years | 
| Degree to Which Accurate Quality of Life (QOL) Measures Can be Extracted From Patient Interview Narratives Using Natural Language Processing Techniques | 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. | Post-operative day 1 - up to 1 year |