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      The Prognostic Value of Tumor Multifocality in Clinical Outcomes of Papillary Thyroid Cancer

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          Abstract

          Context:

          Multifocality is often treated as a risk factor for papillary thyroid cancer (PTC), prompting aggressive treatments, but its prognostic value remains unestablished.

          Objective:

          To investigate the role of tumor multifocality in clinical outcomes of PTC.

          Methods:

          Multicenter study of the relationship between multifocality and clinical outcomes of PTC in 2638 patients (623 men and 2015 women) with median [interquartile range (IQR)] age of 46 (35 to 58) years and median (IQR) follow-up time of 58 (26 to 107) months at 11 medical centers in six countries. Surveillance, Epidemiology and End Results (SEER) data were used for validation.

          Results:

          Disease recurrence in multifocal and unifocal PTC was 198 of 1000 (19.8%) and 221 of 1624 (13.6%) ( P < 0.001), with a hazard ratio of 1.55 [95% confidence interval (CI), 1.28 to 1.88], which became insignificant at 1.13 (95% CI, 0.93 to 1.37) on multivariate adjustment. Similar results were obtained in PTC variants: conventional PTC, follicular-variant PTC, tall-cell PTC, and papillary thyroid microcarcinoma. There was no association between multifocality and mortality in any of these PTC settings, whereas there was a strong association between classic risk factors and cancer recurrence or mortality, which remained significant after multivariate adjustment. In 1423 patients with intrathyroidal PTC, disease recurrence was 20 of 455 (4.4%) and 41 of 967 (4.2%) ( P = 0.892) and mortality was 0 of 455 (0.0%) and 3 of 967 (0.3%) ( P = 0.556) in multifocal and unifocal PTC, respectively. The results were reproduced in 89,680 patients with PTC in the SEER database.

          Conclusions:

          Tumor multifocality has no independent risk prognostic value in clinical outcomes of PTC; its indiscriminate use as an independent risk factor, prompting overtreatments of patients, should be avoided.

          Abstract

          Despite common belief, this study shows no independent role of multifocality in clinical outcomes of PTC; its indiscriminate use as a risk factor, prompting overtreatment, should be avoided.

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          Author and article information

          Journal
          J Clin Endocrinol Metab
          J. Clin. Endocrinol. Metab
          jcem
          jcem
          The Journal of Clinical Endocrinology and Metabolism
          Endocrine Society (Washington, DC )
          0021-972X
          1945-7197
          01 September 2017
          05 June 2017
          : 102
          : 9
          : 3241-3250
          Affiliations
          [1 ]Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
          [2 ]Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
          [3 ]Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, 56124 Pisa, Italy
          [4 ]Department of Internal Medicine, University of Perugia, 06100 Perugia, Italy
          [5 ]Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano and Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
          [6 ]Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 44-101 Gliwice, Poland
          [7 ]Cancer Molecular Pathology of School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia
          [8 ]Department of Medicine, Endocrinology Unit, University of Padua, Padua 35128, Italy
          [9 ]Veneto Institute of Oncology, Instituto di Ricovero e Cura a Carattere Scientifico, Padua 35128, Italy
          [10 ]Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213
          [11 ]Department of Endocrinology and Nutrition, Hospital La Paz, Health Research Institute, and Hospital Universitario de Móstoles, Department of Endocrinology, Hospital Universitario de Móstoles, 28029 Madrid, Spain
          [12 ]Biomedical Research Institute, “Alberto Sols,” Spanish Council of Research Consejo Superior de Investigaciones Científicas and Autonomous University of Madrid, 28029 Madrid, Spain
          [13 ]Endocrine Surgical Unit, The University of Sydney, Sydney 2052, Australia
          [14 ]Department of Molecular Endocrinology, Institute of Endocrinology, Prague 11694, Czech Republic
          [15 ]Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
          [16 ]Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Jinan 250021, China
          Author notes
          [*]

          These investigators are co-first authors.

          Address all correspondence and requests for reprints to: Mingzhao Xing, MD, PhD, The Johns Hopkins Thyroid Tumor Center, Division of Endocrinology, Diabetes and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: mxing1@ 123456jhmi.edu ; or Shihua Zhao, MD, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Email: zshqdfy@ 123456163.com .
          Article
          PMC5587077 PMC5587077 5587077 jcem_201700277
          10.1210/jc.2017-00277
          5587077
          28582521
          d5075766-30ba-41d3-accc-2d4ac4cab223
          Copyright © 2017 Endocrine Society
          History
          : 29 January 2017
          : 31 May 2017
          Page count
          Figures: 2, Tables: 3, Equations: 0, References: 27, Pages: 10
          Categories
          Clinical Research Articles
          Thyroid

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