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      Machine Learning Prediction of Radiofrequency Thermal Ablation Efficacy: A New Option to Optimize Thyroid Nodule Selection

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          Abstract

          Background: Radiofrequency (RF) is a therapeutic modality for reducing the volume of large benign thyroid nodules. If thermal therapies are interpreted as an alternative strategy to surgery, critical issues in their use are represented by the extent of nodule reduction and by the durability of nodule reduction over a long period of time. Objective: To assess the ability of machine learning to discriminate nodules with volume reduction rate (VRR) < or ≥50% at 12 months following RF treatment. Methods: A machine learning model was trained with a dataset of 402 cytologically benign thyroid nodules subjected to RF at six Italian Institutions. The model was trained with the following variables: baseline nodule volume, echostructure, macrocalcalcifications, vascularity, and 12-month VRR. Results: After training, the model could distinguish between nodules having VRR <50% from those having VRR ≥50% in 85% of cases (accuracy: 0.85; 95% confidence interval [CI]: 0.80–0.90; sensitivity: 0.70; 95% CI: 0.62–0.75; specificity: 0.99; 95% CI: 0.98–1.0; positive predictive value: 0.95; 95% CI: 0.92–0.98; negative predictive value: 0.95; 95% CI: 0.92–0.98). Conclusions: This study demonstrates that a machine learning model can reliably identify those nodules that will have VRR < or ≥50% at 12 months after one RF treatment session. Predicting which nodules will be poor or good responders represents valuable data that may help physicians and patients decide on the best treatment option between thermal ablation and surgery or in predicting if more than one session might be necessary to obtain a significant volume reduction.

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          Most cited references 21

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          Management of simple nodular goiter: current status and future perspectives.

          The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. Its management is still the cause of considerable controversy. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, we support the increasing use of fine-needle aspiration biopsy (cytology). Most patients need no treatment after malignancy is ruled out. In case of cosmetic or pressure symptoms, the choice in multinodular goiter stands between surgery, which is still the first choice, and radioiodine if uptake is adequate. In addition to surgery, the solitary nodule, whether hot or cold, can be treated with percutaneous ethanol injection therapy. If hot, radioiodine is the therapy of choice. Randomized studies are scarce, and the side effects of nonsurgical therapy are coming into focus. Therefore, the use of the optimum option in the individual patient cannot at present be based on evidence. However, we are of the view that levothyroxine, although widely used, should no longer be recommended routinely for this condition. Within a few years, the introduction of recombinant human TSH and laser therapy may profoundly alter the nonsurgical treatment of simple nodular goiter.
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            Gross and microscopic findings in clinically normal thyroid glands.

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              Percutaneous laser ablation of cold benign thyroid nodules: a 3-year follow-up study in 122 patients.

              Percutaneous laser ablation (PLA) is a proposed therapeutic procedure for the management of benign thyroid nodules. However, long-term results are unknown. The aim of this study was to evaluate retrospectively the safety and effects of PLA treatment in patients with benign nonfunctioning thyroid nodules in a 3-year follow-up. One hundred twenty-two patients (95 women and 27 men; age 52.2 ± 12.3 years) with benign cold thyroid solitary nodules or a dominant nodule within a normo-functioning multinodular goiter (volume range: 2.6-86.4 mL) underwent thermal Nd:YAG laser ablation of thyroid nodular tissue by 1-4 optical fibers positioned into the tissue by 21-gauge needles under ultrasound real-time assistance. The setting was an interventional suite and outpatient endocrine clinics in a community hospital in Italy. Nodule volume, ablation volume, side effects, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (fT4), thyroglobulin (Tg), anti-Tg, anti-thyroperoxidase antibodies, symptoms, and cosmetic signs were recorded. Data are mean ± standard deviation. Energy delivered was 8522  ± 5365 J with an output power of 3.1 ± 0.5 W. Three years after PLA, nodule volume decreased from 23.1 ± 21.3 to 12.5 ± 18.8 mL (-47.8%  ± 33.1% of initial volume, p ≤ 0.001). At day 1, TSH and fT4 values significantly changed (time 0 vs. day 1: TSH = 1.16  ± 1.06 vs. 0.62 ± 0.81 μU/mL, p ≤ 0.001; fT4 = 11.68 ± 1.88 vs. 13.20 ± 3.32 pg/mL, p ≤ 0.01) and normalized within 1 month. No change in free triiodothyronine, thyroperoxidase antibodies, and Tg antibodies values was observed. Symptoms improved in 89 patients (73.0%), were unchanged in 28 (22.9%), and worsened in 5 (4.1%). Cosmetic signs improved in 87 patients (71.3%), were unchanged in 29 (23.8%), and worsened in 6 (4.9%). In 11 patients (9%), nodules regrew above baseline. Two patients (1.6%) experienced delayed (12-24 hours) laryngeal dysfunction with vocal cord motility recovery after 6-10 weeks. Two patients (1.6%) became hypothyroid and two patients (1.6%) hyperthyroid after PLA. After 3 years, the PLA technique achieved shrinkage of about 50% of the initial volume in a wide size range of benign cold thyroid nodules, with an improvement in local symptoms and signs. Side effects and failures were few although not negligible. PLA may be a new option for the management of benign cold thyroid nodules. Long-term controlled studies are required to establish the eligibility of patients for routine PLA.
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                Author and article information

                Journal
                ETJ
                ETJ
                10.1159/issn.2235-0640
                European Thyroid Journal
                S. Karger AG
                2235-0640
                2235-0802
                2020
                July 2020
                19 December 2019
                : 9
                : 4
                : 205-212
                Affiliations
                aDivision of Endocrinology, V. Fazzi Hospital, Lecce, Italy
                bUnited Technology Research Center, Trento, Italy
                cDivision of Endocrinology and Metabolism, Mauriziano Hospital Umberto I, Turin, Italy
                dDivision of Endocrinology and Metabolism, Molinette Hospital, Turin, Italy
                eEndocrine Surgery, Ospedale del Mare, ASL NA1 Centro, Naples, Italy
                fEndocrinology Unit, Azienda Ospedaliera Universitaria Sant’Andrea, Rome, Italy
                gRadiology Department, Villa Salus Hospital, Venice, Italy
                hRadiology Department, Policlinico G.B. Rossi, Verona, Italy
                Author notes
                *Roberto Negro, Division of Endocrinology, V. Fazzi Hospital, Piazza Muratore, IT–73100 Lecce (Italy), E-Mail dr.negro@libero.it
                Article
                504882 Eur Thyroid J 2020;9:205–212
                10.1159/000504882
                7445654
                32903883
                © 2019 European Thyroid Association Published by S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, Tables: 3, Pages: 8
                Categories
                Clinical Thyroidology / Research Article

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