Non-invasive follicular thyroid neoplasm with papillary-like nuclei: reducing overtreatment by reclassifying an indolent variant of papillary thyroid cancer
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Worldwide the rising incidence of cancer is attributed to ageing populations, environmental and lifestyle factors, and increased cancer surveillance. Cancer surveillance leads to increased early detection of indolent cancers, and in some cases to cancer ‘overdiagnosis’.1 In the thyroid, the increased incidence of thyroid cancer and cancer detection is primarily due to widespread use of thyroid ultrasound.2 This excess of newly diagnosed thyroid cancers occurs almost entirely because of greater detection of papillary thyroid cancers, a tumour which under the microscope shows a characteristic papillary growth pattern together with typical nuclear features. Follicular variant of papillary thyroid carcinoma (FVPTC) is one of two major subtypes of papillary thyroid cancer. The encapsulated type of FVPTC (eFVPTC), a tumour that under the microscope shows no invasion of surrounding thyroid, blood vessels or lymphatics, has increased in incidence 2–3 times over the last 20–30 years. eFVPTC is now estimated …Keywords:
Overdiagnosis
Thyroid neoplasm
Follicular thyroid cancer
Worldwide the rising incidence of cancer is attributed to ageing populations, environmental and lifestyle factors, and increased cancer surveillance. Cancer surveillance leads to increased early detection of indolent cancers, and in some cases to cancer ‘overdiagnosis’.1 In the thyroid, the increased incidence of thyroid cancer and cancer detection is primarily due to widespread use of thyroid ultrasound.2 This excess of newly diagnosed thyroid cancers occurs almost entirely because of greater detection of papillary thyroid cancers, a tumour which under the microscope shows a characteristic papillary growth pattern together with typical nuclear features. Follicular variant of papillary thyroid carcinoma (FVPTC) is one of two major subtypes of papillary thyroid cancer. The encapsulated type of FVPTC (eFVPTC), a tumour that under the microscope shows no invasion of surrounding thyroid, blood vessels or lymphatics, has increased in incidence 2–3 times over the last 20–30 years. eFVPTC is now estimated …
Overdiagnosis
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Follicular thyroid cancer
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Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981-2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20-49 and 50+ and 41.1 and 60.1% in women ages 20-49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early-stage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.
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Abstract Objectives To analyze the variant‐specific survival benefits and usage patterns of standardized treatment combinations of surgery (S), radioactive iodine ablation (RAI), and thyroid‐stimulating hormone suppression therapy (THST) for high‐risk differentiated thyroid cancer. Study Design Retrospective cohort study. Setting National Cancer Database. Methods The 2004‐2017 National Cancer Database was queried for patients receiving definitive surgery for high‐risk papillary, follicular, or Hurthle cell thyroid cancer. Cox proportional hazards and Kaplan‐Meier analyses assessed for treatment‐associated survival. Results Of 21,076 cases, 18,214 underwent survival analysis with a mean ± SD age of 50.6 ± 17.1 years (71.3% female). When compared with surgery alone, S + RAI was associated with reduced mortality in papillary (hazard ratio [HR], 0.574; P < .001) and follicular (HR, 0.489; P = .004) thyroid cancer. S + RAI + THST was associated with reduced mortality in papillary (HR, 0.514; P < .001), follicular (HR, 0.602; P = .016), and Hurthle cell (HR, 0.504; P = .021) thyroid cancer. In papillary thyroid cancer, S + RAI (91.3%), S + THST (89.2%), and S + RAI + THST (92.7%) were associated with higher 5‐year overall survival rates than surgery (85.4%, all P < .001). Papillary thyroid cancer treatments involving THST were associated with higher 5‐year overall survival rates than corresponding regimens without THST (all P < .001). In follicular thyroid cancer, S + RAI (73.9%) and S + RAI + THST (78.7%) were associated with higher 5‐year overall survival rates than surgery (65.6%, all P < .05). In Hurthle cell thyroid cancer, S + RAI (66.5%) and S + RAI + THST (73.4%) were associated with higher 5‐year overall survival rates than surgery (53.7%, all P < .05). On linear regression, THST usage increased by 77.5% ( R 2 = 0.944, P < .001), while RAI usage declined by 11.3% ( R 2 = 0.320, P = .035). Conclusions High‐risk differentiated thyroid cancer exhibited varying susceptibilities to different treatment combinations depending on histology, with greatest responses to regimens that included RAI. Physician practices have trended toward decreased RAI and increased THST usage.
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Papillary thyroid carcinoma (PTC) in children has a distinctive set of clinicopathologic features and molecular signature compared to their adult counterparts. The recent recommendation to reclassify encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) without invasion as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is based on evidence derived almost exclusively from studies in adults. Clinicopathologic studies restricted to pediatric NIFTP are limited.We retrospectively analyzed all pediatric PTC and NIFTP diagnosed and treated in our institution from 1999 to 2016 (n = 31).Using recently published consensus diagnostic criteria, we identified 3 NIFTP and 2 infiltrative follicular variants of papillary thyroid carcinoma (FVPTC) among 31 cases. Two of the NIFTP cases were initially diagnosed as EFVPTC. All 3 patients with NIFTP had unifocal tumors of lower American Joint Committee on Cancer (AJCC) classification (T2 or lower) and were free of lymph node or distant metastasis. Total (n = 1) or completion (n = 2) thyroidectomy was performed in all cases, and only 1 NIFTP patient received subsequent radioablative therapy. No residual or recurrent disease has been observed during follow-up (15-138 months) in patients with NIFTP.Our experience with NIFTP in children is similar to outcomes reported in adult studies, suggesting that pediatric NIFTP behave indolently as evidenced by the absence of local recurrence in our cohort.
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The incidence of follicular variant of papillary thyroid carcinoma (FVPTC) has increased to 20% to 30% of all papillary thyroid carcinomas (PTC) over the last three decades in the USA. Non-invasive encapsulated FVPTC comprises of half to two-thirds of all FVPTCs, and is now reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Asian populations were found to have a lower incidence of NIFTP than the Western populations. In our institution, the incidence of NIFTP for the time period of 2008-2011 was 0.3% (95% confidence interval: 0.1% - 0.5%) of all PTCs, whereas it showed a much higher rate of 3.4% during the period of 2012 to 2014 (95% confidence interval: 2.7% - 4.1%) ( P < 0.0001). The rising incidence of NIFTP in recent years is mainly attributed to the lowering diagnostic threshold for PTC-type nuclear features in encapsulated follicular tumors. However, despite the increased incidence of NIFTP in our institution, the rate was still 3-6 times less than the 15-25% prevalence reported in the Western series. We discuss implications of this paradigm shift on the prevalence, diagnosis and treatment of thyroid cancers in Korea.
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Abstract Thyroid cancer is the most common endocrine malignancy, and incidence has been steadily increasing, suggesting occurrence will exceed that of colon cancer by 2030. Papillary and follicular thyroid cancer subtypes are most common, which are activated by BRAF and HRAS mutations, respectively. Interestingly, papillary and follicular thyroid cancers are associated with different pathologies and metastases. Currently, both papillary and follicular thyroid cancers are treated by surgical removal of the thyroid, followed by radioactive iodine treatment to eliminate any remaining tumor cells. Unfortunately, for individuals with progressive thyroid cancer, these treatment options are not effective, highlighting a need for increased investigation into mechanisms of drug sensitivity. In this study, we sought to evaluate mechanisms of differential drug sensitivity through RNA-seq analysis of cell lines derived from mouse models of papillary and follicular thyroid cancer. Additionally, we evaluated the effects of MAPK, AKT, and mTOR inhibitors on murine papillary and follicular thyroid cancer cell proliferation. To accurately assess drug efficacy, we calculated GR50 concentrations for each inhibitor in six papillary and follicular thyroid cancer cell lines. We discovered that papillary and follicular thyroid cancer cell lines responded differently to MAPK and AKT inhibitors, suggesting that treatment approaches should be tailored to subtype despite having mutations in the same signaling pathway. Citation Format: Brianna LeBoeuf, Braxton Anderson, Margaret Young, Aime Franco, Laura MacDonald. Evaluating the effectiveness of MAPK, AKT, and mTOR inhibitors in reducing proliferation in cellular models of papillary and follicular thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2887.
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Background: There is worldwide consensus on an alarming increase in overdiagnosis and overtreatment of papillary thyroid cancer in recent decades, mostly attributable to increased screening with more advanced diagnostic technology (eg, ultrasound, computed tomography and magnetic resonance imaging) detecting small papillary nodules. In 2009, evidence-based guidelines by the American Thyroid Association recommended against routine fine needle aspiration for unsuspicious papillary nodules of < 1 cm. The purpose of this study is to compare the change in the ratio of patients with thyroid cancer to all patients with thyroid nodules before and after the issuance of the 2009 guidelines as well as to provide national health care cost estimates.
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