Polina Zmijewski, MD

Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and MV-NIS infected MSC (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo ECHO or MUGA prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or MRI throughout the study.

Laboratory Biomarker Analysis

Mesenchymal Stem Cell Transplantation

Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Echocardiography

Multigated Acquisition Scan

Biospecimen Collection

Chest Radiography

Single Photon Tomography and Computed Tomography Scan

Computed Tomography

Magnetic Resonance Imaging

Parathyroid Allotransplant to treat hypoparathyroidism

Parathyroid Allotransplant

Participants undergo adenoma removal guided by PTS imaging, with deliberate preservation of the NIR-autofluorescent rim of normal parathyroid tissue.

FDA-cleared imager (e.g., Fluobeam LX/PTeye) providing real-time autofluorescence to identify parathyroid tissue during surgery; no dye or radiation.

Near-Infrared Parathyroid Tissue Sensor Imaging (PTS)

Surgical excision of adenoma while leaving the NIRAF-positive rim of normal parathyroid tissue in situ; minimal defatting to ensure perfusion.

Rim-Preservation Technique

Participants undergo PTS-guided en-bloc excision of the adenoma plus its NIR-positive rim; parathyroid autotransplantation performed when indicated.

Surgical excision of adenoma together with the surrounding NIRAF-positive rim; autotransplant fragment if \< 2 normal glands remain in neck.

En-bloc Resection Technique

Bo Wang Porfessor, MD

Bo Wang MD, Principal Investigator

For patients assigned to the study arm, the surgeon will use the PTeye as an intraoperative tool to identify if a suspect tissue is a parathyroid or not, during the parathyroid surgery.

Parathyroid Eye (PTeye)

The surgeon will proceed with the parathyroid surgery as usual, while relying solely on her/his surgical experience in identifying the parathyroid glands during the operations.

Combination therapy with desiccated thyroid extract and levothyroxine (DTE + L-T4) as the TSH-suppressive regimen.

Desiccated thyroid extract (DTE) is a dry preparation obtained from animal thyroid glands that contains both thyroxine (T4) and triiodothyronine (T3) in an approximately 4:1 ratio, closely matching the physiological hormone profile secreted by the human thyroid. Combining DTE with levothyroxine (L-T4) may overcome current therapeutic bottlenecks. First, L-T4 given in adequate doses provides the major T4-mediated TSH suppression, while the small amount of T3 supplied by DTE acts directly on pituitary thyrotrophs, bypassing impaired DIO2 conversion; this pharmacodynamic synergy yields tighter TSH control, steadier serum levels, and fewer thyrotoxic side-effects. Second, because thyroid-hormone receptor isoforms are differentially expressed across tissues and display distinct T4/T3 affinities, the combination allows finer tuning of thyroid hormone signaling-maintaining adequate tumor suppression while attenuating adverse cardiac and skeletal effects.

desiccated thyroid extract (DTE)+levothyroxine (L-T4)

Levothyroxine (L-T4) monotherapy as the TSH-suppressive regimen.

하시모토 갑상선염 환자를 대상으로 글루텐 프리 식단이 염증과 자가면역 반응을 줄이는 데 효과가 있는지 살펴보는 시험입니다.

Gluten Free Diet in patients with Hashimoto's Hypothyroidism

Gluten Free Diet in Hashimoto's Hypothyroidism

하시모토 갑상선 기능 저하증 환자의 글루텐 프리 식단

Shannon Downie

All enrolled patients for thyroid surgery, once the thyroid gland is removed the device will be used to identify the parathyroid glands.

Parathyroid auto-fluorescence imaging

For a select group of patients when deemed necessary by the surgeon, and when one or more parathyroid gland appear to be de vascularized ICG will be administered, A dosage of 5 mg will be injected into a peripheral IV line, followed by fluorescence imaging to determine the perfusion status of the gland.

Indocyanine green

Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality-of-Life Assessment

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15, or paclitaxel IV over 1 hour on days 1, 8, and 15. Patients may also receive bevacizumab IV over 30-90 minutes on days 1 and 15 with pegylated liposomal doxorubicin hydrochloride, topotecan hydrochloride, or paclitaxel. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Bevacizumab

Gemcitabine Hydrochloride

Paclitaxel

Pegylated Liposomal Doxorubicin Hydrochloride

Topotecan Hydrochloride

Patients receive vemurafenib PO BID for 6 weeks and cobimetinib PO QD for 3 weeks, followed by 1 week off, and then continuing for 2 weeks. Patients then receive iodine 131 PO followed by 3 additional days of vemurafenib PO BID and cobimetinib PO QD. Patients receive thyrogen IM daily for 2 days followed by I-123 diagnostic scan during screening and on study. Patients also undergo MRI during screening, PET scan or CT scan and blood sample collection throughout the study and ultrasound imaging and I-131 whole body scan during follow up.

Cobimetinib

Diagnostic Imaging

I-131 Uptake Test

Iodine I-131

Positron Emission Tomography

Recombinant Thyrotropin Alfa

Ultrasound Imaging

Vemurafenib

Sasan Fazeli

Patients randomised to this arm will undergo total thyroidectomy with bilateral central compartment (level VI) neck dissection

Total Thyroidectomy with bilateral central compartment (level VI) neck dissection - surgical removal of entire thyroid gland and perform bilateral Level VI neck dissection. This is the standard treatment recommended by the Chinese Guidelines for the Diagnosis and Management of Thyroid Nodules and Differentiated Thyroid Cancer (2nd Edition).

The participating surgeons all routinely perform complete central neck dissections. They were selected for this study due to their standardized technique, which ensures a consistent surgical approach.

Total thyroidectomy

Patients randomised to this arm will undergo extended isthmusectomy (ensure R0 resection) with bilateral central compartment (level VI) neck dissection

Extended isthmusectomy with bilateral central compartment (level VI) neck dissection : Completely resect the isthmus and portions of the bilateral thyroid gland adjacent to the isthmus, ensuring an R0 resection margin for the tumor, while preserving at least more than half of the bilateral thyroid lobes.

Extended isthmusectomy

Second Affiliated Hospital, School of Medicine, Zhejiang University

124I PET/CT scan after preparation with human recombinant TSH

intramuscular injection administered once/day for 2 consecutive days at Week 3; then once annually for subjects who meet criteria.

Thyrogen

therapeutic dose administered orally to treat thyroid cancer at Week 8. 5-7 days later, the post-treatment I-131 Whole Body scan w/ SPECT is performed; then administered once annually, if the patient needs to be re-treated

I-131

one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.

I-124

124I PET/CT scan after preparation with thyroid hormone withdrawal

withdrawal of thyroid hormone during weeks 4 through 8

Thyroid hormone withdrawal

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Randomization Protocol

Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further.

Peri-operative Protocol

Thyroid Lobectomy Patients undergoing thyroid lobectomy will have the thyroid lobe containing the cancer removed in the standard surgical technique. These operations will be performed at either the UCLA Health Westwood Ambulatory Surgery Center, UCLA Ronald Reagan Medical Center, or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

Protocol for Operative Management based on Molecular Risk Classifier

Patients will have a televisit (i.e. video-visit) with us in 2 weeks once the ThyroSeq molecular analysis results. In that visit, we will discuss the operation the patient will receive, including the risks and benefits of the operation. Operative management will be dictated by the molecular results listed below:

* Low molecular-risk: thyroid lobectomy
* High molecular-risk: total thyroidectomy
* Intermediate molecular-risk: randomization to thyroid lobectomy or total thyroidectomy

Of note, the respective operations for the low and high molecular-risk groups are standard of care.

Molecular Analysis for Thyroid Resection

Randomization Protocol

Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further.

Total Thyroidectomy and Completion Thyroidectomy

Patients undergoing total thyroidectomy will have their whole thyroid gland removed in the standard surgical technique. Patients undergoing a completion thyroidectomy will have their remaining thyroid lobe removed. These operations will be performed at UCLA Ronald Reagan Medical Center or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

부갑상선 동종이식

부갑상선 동종이식

근적외선 부갑상선 조직 센서 영상(PTS), 림 보존 기술, 일괄 절제 기술

부갑상선안(PTeye)

건조갑상선추출물(DTE)+레보티록신(L-T4)

하시모토 갑상선 기능 저하증 환자의 글루텐 프리 식단

부갑상선 자가형광 영상, 인도시아닌 그린

베바시주맙, 젬시타빈 염산염, 임상 생체지표 분석, 갑상선 요오드화나트륨 수송체를 암호화하는 용해성 홍역 바이러스, 파클리탁셀, 페길화 리포솜 독소루비신 염산염, 삶의 질 평가, 토포테칸 염산염

생체 시료 채취, 코비메티닙, 컴퓨터 단층 촬영, 진단 영상, I-131 섭취 검사, 요오드 I-131, 자기 공명 영상, 양전자 방출 단층 촬영, 재조합 갑상선 자극 호르몬 알파, 초음파 영상, 베무라페닙

전체 갑상선 절제술, 확장 협부 절제술

티로겐, I-131, I-124, 갑상선 호르몬 결핍

갑상선 절제술을 위한 분자 분석