Efficacy of Organoid-Based Chemotherapy Drug Precision Screening to Guide Treatment for Thyroid Cancer

Inclusion Criteria

• •1. At least 18 years of age on the day of signing informed consent
• •2. Cytologically confirmed thyroid neoplasm, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC), medullary thyroid carcinoma (MTC), anaplastic thyroid carcinoma (ATC)
• •3. Patients defined as poorly differentiated iodine-refractory thyroid tumors with inoperable locally advanced disease or metastases. The primary tumor may or may not be removed, but the risk of aerodigestive compression or bleeding should be excluded.
• •4. Evidence of extrathyroidal extension and/or locally invasive disease and deemed at risk for R2 resection by treating team on clinical and/or fiberoptic examination and/or radiographic evaluation in the primary or recurrent setting. Evidence of "at risk for R2 resection" includes:
• •1. Vocal cord paralysis by fiberoptic examination
• •2. Extrathyroid and/or extranodal extension on CT or MRI, including tracheal and/or laryngeal cartilage invasion, esophageal involvement, and/or involvement of perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor muscles) or bone involvement
• •3. Extension into the mediastinum with visceral and/or vascular involvement
• •4. Involvement of the carotid artery or other major vessel by 180 degrees or more (exclusive of complete encasement)
• •5. Other factors that make the participant to be "at risk for R2 resection" may be allowed, after discussion with the study's principal investigator
• •5. At least one measurable lesion as defined by RECIST v1.1
• •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no medical contraindication to surgery
• •7. Surgical morbidity/complexity score of 1 to 4 (moderate, severe, very severe, or unresectable)
• •8. The expected survival time was more than 2 months
• •9. Adequate end-organ function (including bone marrow, coagulation, renal, liver and cardiac) 28 days prior to the study registration as defined below:
• •1. leukocytes ≥3,000/mcL
• •2. absolute neutrophil count ≥1,500/mcL
• •3. platelets ≥100,000/mcL
• •4. hemoglobin ≥ 9 g/dL (5.58 mmol/L)
• •5. total bilirubin ≤1.5 x institutional upper limit of normal, unless attributed to Gilberts syndrome
• •6. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) \< 2.5 x institutional upper limit of normal
• •7. INR ≤1.5 x institutional upper limit of normal
• •8. creatinine within normal institutional limits OR
• •9. creatinine clearance ≥30 mL/min per Cockcroft-Gault formulation
• •10. normal serum potassium, calcium, and magnesium levels (may be receiving supplements). Grade 1 hypocalcemia (corrected serum calcium \> 8) is acceptable
• •10. Willing to undergo tumor biopsy prior to trial treatment, unless in the opinion of the treating physician, a biopsy is not feasible or safe. Subjects must be willing to ultimately undergo surgery if their tumor becomes surgically resectable
• •11. Ability to comply with outpatient treatment, laboratory monitoring, and require clinic visits for the duration of study participation
• •12. Willing and able to provide written informed consent signed by study patient (or legally acceptable representative if applicable)
• •13. Willingness of patients with partners of childbearing potential to use a highly effective contraceptive method during treatment with study drug and for 3 months following the last dose of study drug
• •16. Patients with incomplete clinical data
• •17. History of significant neurological or mental disorder, including seizures or dementia, which would interfere compliance and sign of consent inform
• •18. Patients deemed unsuitable for inclusion by the investigators