High-risk Papillary Thyroid Cancer Research Articles

High-dose radioactive iodine therapy is associated with decreased risk of recurrence in high-risk papillary thyroid cancer

ObjectivesWe aimed to determine the effect of adjuvant radioactive iodine dose on recurrence rate in high-risk papillary thyroid cancer. MethodsMore than 1,500 patients treated for papillary thyroid cancer at high-volume centers in France and the United States from 2004–2014 were reviewed. Patients considered at high risk for recurrence per the 2015 American Thyroid Association guidelines were analyzed and grouped by initial radioactive iodine dose: intermediate (median 100 mCi) or high dose (median 150 mCi). Propensity score matching was performed to control for baseline characteristics. ResultsIn a propensity-matched cohort of 66 patient pairs, there were equivalent rates of gross extrathyroidal extension (71% vs 71%, P = 1.00), positive margins (55% vs 55%, P = 1.00), lymph node metastases ≥ 3 cm (9% vs 9%, P = 1.00), extranodal extension (32% vs 33%, P = .85), and distant metastases (2% vs 5%, P = .31). Over a median follow-up of 4.5 years (interquartile ratio 2.0–7.5 years), the intermediate-dose radioactive iodine group had a significantly higher rate of recurrence than patients in the high-dose radioactive iodine group: 24 out of 66 (36%) vs 13 out of 66 (20%), P = .03. ConclusionHigh-dose radioactive iodine is associated with lower recurrence rate compared with intermediate-dose radioactive iodine for patients with American Thyroid Association high-risk papillary thyroid cancer.

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study.

To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis. This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding. In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAFV600E-positive (P = 0.324) subgroups. Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAFV600E, lymph node metastases, or unfavorable thyroglobulin levels.

A comparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: a meta-analysis.

Papillary thyroid cancer (PTC) accounts for 80–90% of all thyroid malignancies. The tall cell variant (TCV) is a rare aggressive histotype of PTC. We performed a meta-analysis to compare the clinicopathological characteristics and prognostic factors of TCV with those of classical papillary thyroid carcinoma (cPTC). A literature search was performed using the PubMed and EMBASE databases using Medical Subject Headings and keywords. Twenty studies that included 1871 patients with TCV and 75323 patients with cPTC were included in our meta-analysis. Odds ratios and confidence intervals were calculated for each study. Patients with TCV were associated with multifocality, higher TNM stage, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, BRAF mutation, disease-specific survival, and overall survival. We found that TCV cases were associated with more aggressive clinicopathological characteristics and poorer prognoses than cPTC cases were. Our results suggest that TCV is a high-risk PTC that warrants aggressive treatment and follow-up strategies.

Cost-effectiveness analysis of papillary thyroid cancer surveillance.

The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured.

Application of molecular diagnostics to the evaluation of the surgical approach to thyroid cancer.

Recent important studies that include long-term follow-up have shown that BRAF and RAS mutations can have negative implications for disease recurrence and survival. BRAF positivity has been shown to be associated with decreased survival and is an independent predictor of poor prognosis. Reliable pre-operative identification of high-risk papillary thyroid cancer (PTC) patients may productively guide initial surgical management since reoperative neck surgery is associated with increased morbidity. However, it is probably too early to conclude that at present it is possible to tailor surgical therapy patient by patient only on the basis of their mutational status. Other important parameters, not including molecular testing, represented by some specific morphological aspects, still play an important role, probably still more significant than molecular diagnostics, such as neck ultrasonography. Pre-operative knowledge of BRAF-positive PTC could alter the initial surgical treatment for at least 20% of patients and can potentially prevent the increased morbidity associated with reoperative neck exploration. However, additional multi-institutional and randomized studies will be needed to further define the role of the pre-operative identification of BRAF positivity to guide not only the initial extent of total thyroidectomy (TT) but also the need for and extent of lymphadenectomy.

Low-risk papillary thyroid cancer: times are changing

The prevalence of papillary thyroid cancer (PTC), particularly of low-risk PTC (MACIS <6), is rising due to the increasingly use of neck imaging techniques, fine-needle aspiration and whole body PET scans. Observational cohort studies carried out in the last two decades suggest that low-risk PTC are being overtreated due to the current management paradigm being built on studies done in the 70s and 80s that still echo in some influential guidelines. With the progressive adoption of total thyroidectomy and central neck dissection as the mainstay of treatment for PTC, and suppressed basal thyroglobulin and neck ultrasound once a year as the essential tools for follow-up, the use of radioiodine ablation, body scans and stimulated thyroglobulin concentrations has become obsolete for the vast majority of patients with low-risk PTC. Future guidelines on the management of differentiated thyroid cancer should discuss separately three different diseases: low-risk PTC, high-risk PTC and follicular cancer.

Detection of Residual Lymph Node Metastases in High-Risk Papillary Thyroid Cancer Patients Receiving Adjuvant I-131 Therapy

The aims of this retrospective study were to evaluate the incidence of residual lymph node (LN) metastases in high-risk papillary thyroid cancer (PTC) patients receiving adjuvant I-131 therapy, especially in those without I-131 accumulation, and to evaluate the clinical usefulness of F-18 FDG PET/CT to detect those lesions. The 37 PTC patients receiving adjuvant I-131 therapy were retrospectively evaluated. We examined the incidence of residual LN metastasis and compared the accumulation of F-18 FDG and I-131 in those lesions, and compared the serum thyroglobulin (Tg) levels between patients with and without residual LN metastases. A total of 33 lesions were diagnosed as residual LN metastases in 9 patients. FDG accumulated in all of the lesions, but 19 lesions (57.6%) of them had no I-131 accumulation. The SUVmax was significantly higher in lesions without I-131 accumulation than in lesions with I-131 accumulation (6.6 +/- 2.8 vs. 4.2 +/- 1.8; P = 0.007). The serum Tg levels were significantly higher in patients with residual LN metastases than in patients without it (709.9 +/- 1470.8 vs. 25.6 +/- 37.1 ng/mL; P = 0.005). The incidence of residual LN metastasis was significantly higher in patients with a detectable serum Tg level than in patients without it (35.0% vs. 0%, P = 0.03). These results indicate that the residual LN metastasis was relatively common in high-risk PTC patients receiving adjuvant I-131 therapy whose serum Tg levels remained detectable, and those lesions often had no I-131 accumulation. FDG-PET/CT would be recommended for PTC patients with detectable serum Tg levels to detect residual LN metastases.

Clinicopathologic and molecular disease prognostication for papillary thyroid cancer

Despite its increasing incidence over the last 30 years, the mortality rate of papillary thyroid cancer (PTC) has decreased significantly. Nevertheless, a minority of patients still present with an aggressive form of PTC that can lead to death, even after a prolonged period of survival. Many classifications exist that allow one to stratify the clinical risk of recurrence and death in patients with PTC; however, the parameters upon which they are established are pathological and molecular and, therefore, are revealed only after surgery. The preoperative identification of these aggressive variants of PTC would allow one to schedule a more aggressive operation (e.g., total thyroidectomy together with central and/or mono- or bi-lateral node dissections) in patients with high-risk PTC. This article reviews the parameters used most commonly to differentiate low-risk PTCs from their more aggressive variants and describes some of the newest molecular therapies for this latter group of tumors.

Extent of Thyroidectomy Is Not a Major Determinant of Survival in Low- or High-Risk Papillary Thyroid Cancer

The optimal extent of thyroidectomy for papillary thyroid cancer (PTC) is controversial. Our objective was to evaluate the effect of total thyroidectomy or partial thyroidectomy on survival in low- and high-risk patients. The Surveillance, Epidemiology, and End Results database was used to identify PTC patients who underwent thyroidectomy. The independent effects of age, distant metastases, extrathyroidal extension, tumor size, sex, lymph node metastases, radioactive iodine use, and extent of thyroidectomy on survival were analyzed for low- and high-risk PTC. There were 4402 (81%) low-risk and 1030 (19%) high-risk patients; 84.9% underwent total thyroidectomy. The 5- and 10-year survival were 95% and 89% in the low-risk patients and 84% and 73% in the high-risk patients, respectively (P = .001). In the low-risk patients, 10-year survival after total thyroidectomy was 89%, compared with 91% after partial thyroidectomy (adjusted hazard ratio for death, 1.73; 95% confidence interval, 1.28-2.33; P < .001); older age, male sex, larger tumor, lymph node metastases, and lack of radioactive iodine were associated with higher mortality. In the high-risk patients, 10-year survival after total thyroidectomy was 72%, compared with 78% after partial thyroidectomy (adjusted hazard ratio for death, 1.46; 95% confidence interval, .89-2.40; P = .14); older age, distant metastases, larger tumors, and lack of radioactive iodine were associated with higher mortality. Survival of patients with PTC was not significantly influenced by the extent of thyroidectomy. The survival after partial thyroidectomy was similar to total thyroidectomy within both the low- and high-risk prognostic groups.