Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with Differentiated Thyroid Cancer.

INTRODUCTION: Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC. METHODS: A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs. >4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models. RESULTS: There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors >4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE] HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS, regardless of the presence of mETE within each size category (group 2 [≤4 cm with mETE] vs. group 1 [≤4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4 [>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For LRF and DMF, size but not mETE was also an independent risk factor. CONCLUSION: Tumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.

Prognostic Scoring System to Risk Stratify Parathyroid Carcinoma.

BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that lacks an established system for risk categorization. This study evaluated a prognostic scoring system for recurrence-free survival (RFS) of patients with parathyroid carcinoma. STUDY DESIGN: Patients diagnosed and confirmed to have parathyroid carcinoma and who were treated between 1980 and 2016 at The University of Texas MD Anderson Cancer Center were studied retrospectively. Univariate and multivariate Cox proportional hazards regression analyses of RFS were conducted. A prognostic scoring system was created based on multivariate analysis. RESULTS: Sixty-eight patients were evaluated. After a median follow-up of 4.6 years, 26 patients experienced a recurrence. The Kaplan-Meier RFS rates were 85% at 1 year (95% CI 77% to 95%), 67% at 2 years (95% CI 55% to 81%), and 51% at 10 years (95% CI 36% to 72%) after initial operation. Multivariate analysis demonstrated that age older than 65 years, serum calcium level >15 mg/dL, and vascular invasion were negatively correlated with RFS rate. Combining these adverse variables into a prognostic scoring system, we stratified patients into 3 risk groups: low (0 variable; 2-year RFS rate, 93%), moderate (1 variable; 2-year RFS rate, 72%), and high (2 variables; 2-year RFS rate, 27%) (p = 0.001 [log-rank test]; concordance index, 0.70; 95% CI 0.47 to 0.92). CONCLUSIONS: A prognostic scoring system using vascular invasion, age, and serum calcium level at initial parathyroidectomy can be used to predict RFS. This categorization might be helpful for clinical decisions relative to the timing and use of adjuvant therapy. Comprehensive validation using multiple cohorts will be needed to confirm applicability.

Facilitating anaplastic thyroid cancer specialized treatment: A model for improving access to multidisciplinary care for patients with anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Several treatment trials are available, but the number of eligible patients to participate is very low because of the rarity and aggressiveness of the disease. METHODS: Facilitating Anaplastic Thyroid Cancer Specialized Treatment (FAST) is a quality improvement project aimed at decreasing time from referral to disposition (scheduling of first appointment) to our institution. After identifying reasons for delays, we created a new process flow specifically for patients with ATC allowing patients to be scheduled immediately. RESULTS: Historical data revealed a mean referral to disposition time for patients with ATC of 8.7 days before our intervention. After the intervention, the mean referral to disposition time was reduced to 0.5 days. Participation in treatment trials for all patients with ATC was 34%. CONCLUSION: Since the implementation of FAST, the access time has decreased and the number of successful referrals for ATC has increased significantly.

Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience.

OBJECTIVES: Until recently, treatment options for patients with progressive, radioactive iodine-resistant differentiated thyroid cancer (DTC) have been limited. In our clinical practice, we have begun to use sorafenib and sunitinib for patients with progressive DTC who are not able or willing to participate in clinical trials. In this paper, we describe the University of Texas M. D. Anderson Cancer Center's experience with the off-label use of these tyrosine kinase inhibitors for DTC. METHODS: Adult patients were included if they had a diagnosis of radioactive iodine-refractory DTC, were treated with single agent sorafenib or sunitinib, and had both baseline and at least one follow-up scan for restaging purposes. All imaging data were collected, as well as the TSH-suppressed thyroglobulin (Tg) levels corresponding to each scan date. The primary endpoints were radiographic response and progression-free survival (PFS). Secondary objectives were tissue-specific radiographic responses and correlation of Tg with overall response. RESULTS: We identified 33 patients from our clinical database. Fifteen patients (nine women, six men) met inclusion criteria, with a median age of 61 yr (range, 38-83 yr). Eight patients had papillary and seven had follicular thyroid carcinoma. Sorafenib was used in 13 and sunitinib in two, including one patient who failed prior sorafenib therapy. All patients had evidence of progressive disease (PD) before start of therapy, with a median PFS of only 4 months. Best response in target lesions was: partial response (PR) in three (20%), stable disease (SD) in nine (60%), and PD in three (20%). Clinical benefit (PR+SD) was 80%. The sunitinib patient previously refractory to sorafenib had a 38% reduction in tumor size. The most noticeable organ-specific response was observed in lung (median change, -22%) compared to lymph nodes (median change, 0%). Pleural disease and nonirradiated bone metastases demonstrated PD. All histological subtypes had similar responses. The median PFS was 19 months. The median overall survival has not yet been reached, but at 2 yr of follow-up, overall survival is 67%. Log Tg correlated with radiographic response (P = 0.0005). CONCLUSIONS: Sorafenib and sunitinib appear to be effective in patients with widely metastatic, progressive DTC, with most patients achieving SD or PR, despite having PD at baseline. The most noticeable responses occurred in the lungs in contrast with minimal changes in nodal metastases and PD in pleural and nonirradiated bone metastases, suggesting a tissue-specific response to therapy. Log Tg significantly correlated with response to treatment and therefore may have value as a surrogate marker of response.

The successful use of sorafenib to treat pediatric papillary thyroid carcinoma.

BACKGROUND: Pediatric papillary thyroid cancer (PTC) typically presents with more advanced disease as compared with adults, yet the prognosis, even in the presence of distant metastatic disease, is usually excellent. Systemic therapies other than radioactive iodine (RAI) are rarely required. Sorafenib is an orally administered multi-kinase inhibitor that has shown promise in the treatment of adults with advanced thyroid cancer, but it has not yet been studied in children with this disease. OBJECTIVE: Our objective is to present an adolescent with a progressive RAI-resistant PTC who was successfully treated with sorafenib. PATIENT AND INTERVENTION: A 14-year-old girl had progressive lung metastases from PTC despite previous therapies with almost 400 mCi (131)I. Sorafenib was initiated at a starting dose of 200 mg twice daily and decreased to a maintenance dose of 200 mg daily due to side effects that developed within 3 weeks of treatment. After 67 days on the lower dose, there was a dramatic improvement in the lung metastases. The patient was monitored while continuing thyrotropin-suppressive therapy only. Minimal regrowth of the pulmonary metastases was observed, and a second treatment course of sorafenib 200 mg every other day was equally successful in achieving a clinical response. Thyroglobulin autoantibodies declined over the course of therapy and observation. CONCLUSION: In the very rare case of the pediatric patient with progressive RAI-refractory PTC, for which no good systemic therapy exists, sorafenib may play an important role in the management of this disease.