Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

Phase 2

Completed

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

Interventions: Procedure: Thyroidectomy
Procedure: entral lymph node dissection (CLND)
Other: Quality-of-life assessment

Registration Number: NCT02138214

Lead Sponsor: University of Wisconsin, Madison

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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 117

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (CND)	Quality-of-life assessment	Patients undergo total thyroidectomy with ipsilateral prophylactic CND.
Arm I (no CND)	Thyroidectomy	Patients undergo total thyroidectomy alone.
Arm I (no CND)	Quality-of-life assessment	Patients undergo total thyroidectomy alone.
Arm II (CND)	Thyroidectomy	Patients undergo total thyroidectomy with ipsilateral prophylactic CND.
Arm II (CND)	entral lymph node dissection (CLND)	Patients undergo total thyroidectomy with ipsilateral prophylactic CND.
Arm III (SOC)	Quality-of-life assessment	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

Primary Outcome Measures

Name	Time	Method
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
Post-operative Serum PTH (pg/ml) at Month 6	At Month 6
Post-operative Serum Calcium (mg/dL) at Day 12	At day 12	Post-operative serum calcium (mg/dL) at Day 12
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.
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).
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)
Post-operative Serum Calcium Level at Month 6	At Month 6	Post-operative serum calcium (mg/dL) at Month 6
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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.