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      The effect of surveillance for differentiated thyroid carcinoma in childhood cancer survivors on survival rates: a decision-tree-based analysis

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          Abstract

          Background

          Childhood cancer survivors (CCS) who received radiation therapy exposing the thyroid gland are at increased risk of developing differentiated thyroid cancer (DTC). Therefore, the International Guideline Harmonization Group (IGHG) on late effects of childhood cancer therefore recommends surveillance. It is unclear whether surveillance reduces mortality.

          Aim

          The aim of this study was to compare four strategies for DTC surveillance in CCS with the aim of reducing mortality: Strategy-1, no surveillance; Strategy-2, ultrasound alone; Strategy-3, ultrasound followed by fine-needle biopsy (FNB); Strategy-4, palpation followed by ultrasound and FNB.

          Materials and methods

          A decision tree was formulated with 10-year thyroid cancer-specific survival as the endpoint, based on data extracted from literature.

          Results

          It was calculated that 12.6% of CCS will develop DTC. Using Strategy-1, all CCS with DTC would erroneously not be operated upon, but no CCS would have unnecessary surgery. With Strategy-2, all CCS with and 55.6% of CCS without DTC would be operated. Using Strategy-3, 11.1% of CCS with DTC would be correctly operated upon, 11.2% without DTC would be operated upon and 1.5% with DTC would not be operated upon. With Strategy-4, these percentages would be 6.8, 3.9 and 5.8%, respectively. Median 10-year survival rates would be equal across strategies (0.997).

          Conclusion

          Different surveillance strategies for DTC in CCS all result in the same high DTC survival. Therefore, the indication for surveillance may lie in a reduction of surgery-related morbidity rather than DTC-related mortality. In accordance with the IGHG guidelines, the precise strategy should be decided upon in a process of shared decision-making.

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          Most cited references33

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          An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management.

          There is a high prevalence of thyroid nodules on ultrasonographic (US) examination. However, most of them are benign. US criteria may help to decide cost-effective management. Our objective was to develop a standardized US characterization and reporting data system of thyroid lesions for clinical management: the Thyroid Imaging Reporting and Data System (TIRADS). This was a prospective study using the TIRADS, which is based on the concepts of the Breast Imaging Reporting Data System of the American College of Radiology. A correlation of the US findings and fine needle aspiration biopsy (FNAB) results in 1959 lesions biopsied under US guidance and studied histologically during an 8-yr period was divided into three stages. In the first stage, 10 US patterns were defined. In the second stage, four TIRADS groups were defined according to risk. The percentages of malignancy defined in the Breast Imaging Reporting and Data System were followed: TIRADS 2 (0% malignancy), TIRADS 3 ( 80% malignancy). The TIRADS classification was evaluated at the third stage of the study in a sample of 1097 nodules (benign: 703; follicular lesions: 238; and carcinoma: 156). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88, 49, 49, 88, and 94%, respectively. The ratio of benign to malignant or follicular FNAB results currently is 1.8. The TIRADS has allowed us to improve patient management and cost-effectiveness, avoiding unnecessary FNAB. In addition, we have established standard codes to be used both for radiologists and endocrinologists.
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            Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany.

            Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266), intermediate-volume providers 27% (50-150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups, the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter. Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism, larger extent of resection [relative risk (RR) 1.5-2.1] and recurrent goiter (RR 1.8-3.4) consistently evolved as independent risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1-2.4), hospital operative volume (RR 0.8-1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN identification (RR 1.6) significantly (p = 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification, independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify patients at increased risk whom they might consider for specialist care.
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              Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study.

              Survivors of malignant disease in childhood who have had radiotherapy to the head, neck, or upper thorax have an increased risk of subsequent primary thyroid cancer, but the magnitude of risk over the therapeutic dose range has not been well established. We aimed to quantify the long-term risk of thyroid cancer after radiotherapy and chemotherapy. In a nested case-control study, 69 cases with pathologically confirmed thyroid cancer and 265 matched controls without thyroid cancer were identified from 14,054 5-year survivors of cancer during childhood from the Childhood Cancer Survivor Study cohort. Childhood cancers were diagnosed between 1970 and 1986 with cohort follow-up to 2000. Risk of thyroid cancer increased with radiation doses up to 20-29 Gy (odds ratio 9.8 [95% CI 3.2-34.8]). At doses greater than 30 Gy, a fall in the dose-response relation was seen. Both the increased and decreased risks were more pronounced in those diagnosed with a first primary malignant disease before age 10 years than in those older than 10 years. Furthermore, the fall in risk remained when those diagnosed with Hodgkin's lymphoma were excluded. Chemotherapy for the first cancer was not associated with thyroid-cancer risk, and it did not modify the effect of radiotherapy. 29 (42%) cases had a first diagnosis of Hodgkin's lymphoma compared with 49 (19%) controls. 11 (42%) of those who had Hodgkin's lymphoma had subsequent thyroid cancers smaller than 1 cm compared with six (17%) of those who had other types of childhood cancer (p=0.07). The reduction in radiation dose-response for risk of thyroid cancer after childhood exposure to thyroid doses higher than 30 Gy is consistent with a cell-killing effect. Standard long-term follow-up of patients who have had Hodgkin's lymphoma for detection of thyroid cancer should also be undertaken for survivors of any cancer during childhood who received radiotherapy to the thorax or head and neck region.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                14 October 2022
                01 December 2022
                : 11
                : 12
                : e220092
                Affiliations
                [1 ]RWTH University Hospital Aachen , Department of Nuclear Medicine, Aachen, Germany
                [2 ]Institute for Health Economics and Clinical Epidemiology , University of Cologne, Cologne, Germany
                [3 ]Wilhelmina Children’s Hospital , University Medical Center Utrecht, Department of Pediatric Endocrinology, Utrecht, The Netherlands
                [4 ]Princess Máxima Center for Pediatric Oncology , Utrecht, The Netherlands
                [5 ]Emma Children’s Hospital , Amsterdam UMC, Department of Pediatrics, Amsterdam, The Netherlands
                [6 ]University of Illinois at Chicago , Department of Medicine, Chicago, IL, USA
                [7 ]Erasmus MC Rotterdam , Department of Radiology & Nuclear Medicine, Rotterdam, The Netherlands
                [8 ]University Hospital Würzburg , Department of Nuclear Medicine, Würzburg, Germany
                Author notes
                Correspondence should be addressed to F A Verburg: f.verburg@ 123456erasmusmc.nl

                This paper forms part of a collection on the Late Effects of Cancer Treatment. The guest editors for this collection were Claire E Higham and Judith Gebauer.

                Author information
                http://orcid.org/0000-0002-6773-6931
                http://orcid.org/0000-0001-8805-1379
                http://orcid.org/0000-0003-1401-1993
                Article
                EC-22-0092
                10.1530/EC-22-0092
                9716375
                36240044
                ec8c7e74-9e42-43ac-86dd-bc1a4852a1b3
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 10 October 2022
                : 14 October 2022
                Categories
                Review

                childhood cancer survivors,differentiated thyroid cancer,screening strategies

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