Aubrey A Carhill1, Danielle R Litofsky1, Douglas S Ross1, Jacqueline Jonklaas1, David S Cooper1, James D Brierley1, Paul W Ladenson1, Kenneth B Ain1, Henry G Fein1, Bryan R Haugen1, James Magner1, Monica C Skarulis1, David L Steward1, Mingxhao Xing1, Harry R Maxon1, Steven I Sherman1. 1. Department of Endocrine Neoplasia and Hormonal Disorders (A.A.C., D.R.L., S.I.S.), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030; Thyroid Unit (D.S.R.), Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology (J.J.), Department of Medicine, Georgetown University Medical Center, Washington, DC 20057; Division of Endocrinology and Metabolism (D.S.C., P.W.L., M.X.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Radiation Oncology (J.D.B.), Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada; Department of Internal Medicine (K.B.A.), Veterans Affairs Medical Center and University of Kentucky, Lexington, Kentucky 40502; Division of Endocrinology and Metabolism (H.G.F.), Sinai Hospital, Baltimore, Maryland 21215; Division of Endocrinology, Metabolism, and Diabetes (B.R.H.), University of Colorado School of Medicine, Aurora, Colorado 80045; Genzyme (J.M.), a Sanofi Company, Cambridge, Massachusetts 02142; Diabetes, Endocrinology, Obesity Branch (M.C.S.), National Institutes of Health, Bethesda, Maryland 20892; Departments of Head and Neck Surgery (D.L.S.) and Nuclear Medicine (H.R.M.), University of Cincinnati Medical Center, Cincinnati, Ohio 45219.
Abstract
CONTEXT: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer. OBJECTIVE: The objective was to examine effects of initial therapies on outcomes. DESIGN/ SETTING: This was a prospective multi-institutional registry. PATIENTS: A total of 4941 patients, median follow-up, 6 years, participated. INTERVENTION: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST). MAIN OUTCOME MEASURE: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses. RESULTS: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P = .04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P = .049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3. CONCLUSIONS: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.
CONTEXT: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer. OBJECTIVE: The objective was to examine effects of initial therapies on outcomes. DESIGN/ SETTING: This was a prospective multi-institutional registry. PATIENTS: A total of 4941 patients, median follow-up, 6 years, participated. INTERVENTION: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST). MAIN OUTCOME MEASURE: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses. RESULTS: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P = .04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P = .049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3. CONCLUSIONS: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.
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