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Nonoperative management of low-risk differentiated thyroid carcinoma.

ABSTRACT: PURPOSE OF REVIEW: The global incidence of small papillary thyroid carcinoma (PTC) is increasing remarkably, mostly due to the increased use of imaging studies worldwide. The issue of how to manage low-risk small PTC has become urgent. In this review, we focus on how to treat low-risk papillary thyroid microcarcinomas (PMCs; i.e., PTCs measuring ?10?mm). RECENT FINDINGS: Studies of large numbers of patients with low-risk PMC clarified that most of the PMCs did not grow or grew very slowly and were harmless. Active observations of these patients discriminated rare progressive cases from the majority. Surgery performed after the detection of progression signs was not too late, and surgery immediately after the detection and diagnosis of low-risk PMC may be overtreatment for most patients. Interestingly, low-risk PMCs in elderly patients were most unlikely to progress, in sharp contrast to clinical PTC. The reason for this phenomenon remains unknown. SUMMARY: Active observation without immediate surgery can be a leading alternative to the classical surgical treatment in the majority of the patients with low-risk PMC. It is not too late to perform surgery after the detection of progression signs for these patients. VIDEO ABSTRACT: http://links.lww.com/COON/A10

SUBMITTER: Ito Y

PROVIDER: S-EPMC4255758 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Nonoperative management of low-risk differentiated thyroid carcinoma.

Ito Yasuhiro Y Miyauchi Akira A

Current opinion in oncology 20150101 1

<h4>Purpose of review</h4>The global incidence of small papillary thyroid carcinoma (PTC) is increasing remarkably, mostly due to the increased use of imaging studies worldwide. The issue of how to manage low-risk small PTC has become urgent. In this review, we focus on how to treat low-risk papillary thyroid microcarcinomas (PMCs; i.e., PTCs measuring ≤10 mm).<h4>Recent findings</h4>Studies of large numbers of patients with low-risk PMC clarified that most of the PMCs did not grow or grew very ...[more]

PMID: 25340592

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Project description:Background: Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Methods: Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Results: Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%, p = 0.470), 4.1-6 cm cancers (98.8% vs. 100%, p = 0.599), or >6 cm cancers (97.3% vs. 100%, p = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%, p < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Conclusions: Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.

Project description:Thyroid carcinoma (TC) accounts for ~2.1% of newly diagnosed cancer cases. Mutations in KRAS, HRAS, NRAS and BRAF are primary participants in the development and progression of various types of malignancy, including differentiated TC (DTC). Therefore, the present prospective cohort study aimed to screen patients with DTC for variations in RAS gene family and BRAF gene. Exon 1 and 2 of KRAS, HRAS, NRAS and exon 15 of BRAF gene were screened for hotspot mutations in 72 thyroid tumor and adjacent normal tissue samples using di-deoxy Sanger sequencing. HRAS T81C mutation was found in 21% (15 of 72) of DTC tissue samples, therefore this mutation was investigated in blood samples from patients with DTC and controls as a genetic polymorphism. In addition, HRAS T81C genotypes were determined in 180 patients with DTC and 220 healthy controls by performing restriction fragment length polymorphism. BRAF V600E mutation was confined to classical variant of papillary thyoid cancer (CPTC; 44.4%) and was significantly associated with multifocality and lymph node (LN) metastasis. No mutation was found in exons 1 and 2 of KRAS and NRAS and exon 2 of HRAS genes, however, mutation was detected in exon 1 of HRAS gene (codon 27) at nucleotide position 81 in 21% (15 of 72) of DTC tumor tissue samples. Furthermore, HRAS T81C single nucleotide polymorphism was significantly associated with the risk of DTC with variant genotypes more frequently detected in cases compared with controls (P≤0.05). Moreover, frequency of variant genotypes (TC+CC) was significantly higher among DTC cases with no history of smoking, males, greater age, multifocality and LN metatasis compared with healthy controls (P<0.05). BRAF V600E mutation was primarily present in CPTC and associated with an aggressive tumor phenotype but mutations in RAS gene family were not present in patients with DTC. HRAS T81C polymorphism may be involved in the etiopathogenesis of DTC in a Pakistani cohort. Furthermore, testing for the BRAF V600E mutation may be useful for selecting initial therapy and follow-up monitoring.

Project description:BackgroundSurgical extent in the management of well-differentiated thyroid cancer (DTC) remains a recurrent subject of debate. This is especially relevant in low-risk DTC of 1-4 cm, which represent the majority of new thyroid cancer diagnoses. With trends towards treatment de-escalation and recent guidelines from the American Thyroid Association and British Thyroid Association endorsing hemithyroidectomy (HT) alone for low-risk DTC of 1-4 cm, we sought to systematically appraise the literature to examine recurrence rate outcomes after HT in this low-risk group.SummarySearching PubMed, Cochrane Library, and Ovid MEDLINE, we conducted a systematic review to assess the survival and recurrence rate data presented in all published studies that had a cohort of patients treated with HT for the treatment of DTC. Pooled 10-year survival and recurrence rates, odds ratios, and 95% confidence intervals were calculated for meta-analysis. We identified 31 studies (with a total of 228,746 patients (HT: 36,129, total thyroidectomy, TT: 192,617), which had published recurrence and/or survival data for patients having had HT for DTC. We discovered a pooled recurrence rate of 9.0% for HT, which is significantly higher than in previously published reports. Further, this rate is maintained when examining patients within low-risk cohorts established with recognised risk classifications. We also discovered that of those patients who develop recurrent disease, 48% recur outside the central neck.Key messagesOur study provides a comprehensive systematic review of evidence aimed primarily at defining the recurrence rate in DTC after HT, and more specifically within the low-risk subgroup. We describe pooled recurrence and 10-year survival rates from a larger, broader, and more contemporary patient population than has been previously reported. Our findings indicate that there is a small but significantly higher recurrence rate after HT than TT, but the evidence base is heterogenous and subject to confounding factors and would ultimately benefit from prospective randomised trials to overcome these deficiencies.

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Nonoperative management of low-risk differentiated thyroid carcinoma.

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Nonoperative management of low-risk differentiated thyroid carcinoma.

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