Thyrotropin Suppression and Disease Progression in Patients with Differentiated Thyroid Cancer: Results from the National Thyroid Cancer Treatment Cooperative Registry

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question

Prospective Multicenter Study of Thyroiscarcinoma Treatment: Initial Analysis of Staging and Outcome

BACKGROUND: A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with other available staging classifications.METHODS: Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation.RESULTS: Between 1987 and 1995, 1607 patients were registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were more likely to have high risk Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. Five-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage IV (P \u3c 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1%for Stage II, 77.8% for Stage III, and 24.6% for Stage IV). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type.CONCLUSIONS: The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma

Outcome After Treatment of High-risk Papillary and Non-Hürthle-cell Follicular Thyroid Carcinoma

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial.OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.DESIGN: Analysis of data from a multicenter study.SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry.PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma).MEASUREMENTS: Death, disease progression, and disease-free survival.RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival.CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma

E. Chester Ridgway, MD, MACP (1942-2014) in MEMORIAM

Univ Colorado, Sch Med, Aurora, CO 80045 USAUniv Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USAMass Gen Hosp, Boston, MA USAMassachusetts Gen Hosp, Boston, MA 02114 USAHarvard Univ, Sch Med, Boston, MA USAMassachusetts Gen Hosp, Partners HealthCare, Boston, MA 02114 USAMassachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USAMassachusetts Gen Hosp, Harvard Reprod Endocrine Unit, Boston, MA 02114 USATogus Vet Affairs Med Ctr, Endocrine Serv, Augusta, ME USAMedStar Washington Hosp Ctr, Washington, DC USAGeorgetown Univ, Sch Med, Washington, DC USAJohns Hopkins Univ, Sch Med, Baltimore, MD USAUniv Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90095 USAUniv Virginia, Sch Med, Charlottesville, VA 22908 USAOregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USAOregon Hlth & Sci Univ, Clin & Translat Res Ctr, Portland, OR 97201 USANagasaki Univ, Tokyo, JapanAOTA, Tokyo, JapanRadiat Effects Assoc, Tokyo, JapanUniv Siena, European Thyroid Assoc, I-53100 Siena, ItalyUniv Siena, Dept Endocrinol & Metab, I-53100 Siena, ItalyUniversidade Federal de São Paulo, Lab Mol & Translat Endocrinol, Div Endocrinol, Dept Med,Escola Paulista Med, São Paulo, BrazilUniv So Calif, Keck Sch Med, Los Angeles, CA 90033 USAUniversidade Federal de São Paulo, Lab Mol & Translat Endocrinol, Div Endocrinol, Dept Med,Escola Paulista Med, São Paulo, BrazilWeb of Scienc