Marloes Nies1,2, Rena Vassilopoulou-Sellin2, Roland L Bassett3, Sireesha Yedururi4, Mark E Zafereo5, Maria E Cabanillas2, Steven I Sherman2, Thera P Links1, Steven G Waguespack2,6. 1. Department of Endocrinology, Internal Medicine, University of Groningen, University Medical Center Groningen, GZ Groningen, the Netherlands. 2. Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 5. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 6. Department of Pediatrics-Patient Care, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abstract
CONTEXT: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. OBJECTIVE: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. METHODS: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. RESULTS: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). CONCLUSION: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.
CONTEXT: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. OBJECTIVE: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. METHODS: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. RESULTS: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). CONCLUSION: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.
Authors: Mariëlle S Klein Hesselink; Marloes Nies; Gianni Bocca; Adrienne H Brouwers; Johannes G M Burgerhof; Eveline W C M van Dam; Bas Havekes; Marry M van den Heuvel-Eibrink; Eleonora P M Corssmit; Leontien C M Kremer; Romana T Netea-Maier; Heleen J H van der Pal; Robin P Peeters; Kurt W Schmid; Johannes W A Smit; Graham R Williams; John T M Plukker; Cécile M Ronckers; Hanneke M van Santen; Wim J E Tissing; Thera P Links Journal: J Clin Endocrinol Metab Date: 2016-03-10 Impact factor: 5.958
Authors: Pierre Vanden Borre; Alexa B Schrock; Peter M Anderson; John C Morris; Andreas M Heilmann; Oliver Holmes; Kai Wang; Adrienne Johnson; Steven G Waguespack; Sai-Hong Ignatius Ou; Saad Khan; Kar-Ming Fung; Philip J Stephens; Rachel L Erlich; Vincent A Miller; Jeffrey S Ross; Siraj M Ali Journal: Oncologist Date: 2017-02-16
Authors: Steven G Waguespack; Steven I Sherman; Michelle D Williams; Gary L Clayman; Cynthia E Herzog Journal: Thyroid Date: 2009-04 Impact factor: 6.568
Authors: C Spinelli; S Strambi; L Rossi; S Bakkar; M Massimino; A Ferrari; P Collini; G Cecchetto; G Bisogno; A Inserra; F Bianco; P Miccoli Journal: J Endocrinol Invest Date: 2016-04-29 Impact factor: 4.256
Authors: Anthony R Hogan; Ying Zhuge; Eduardo A Perez; Leonidas G Koniaris; John I Lew; Juan E Sola Journal: J Surg Res Date: 2009-05-08 Impact factor: 2.192
Authors: Julio C Ricarte-Filho; Stephen Halada; Alison O'Neill; Victoria Casado-Medrano; Theodore W Laetsch; Aime T Franco; Andrew J Bauer Journal: Cancer Genet Date: 2022-01-19
Authors: Richard M Yeker; Amber D Shaffer; Pushpa Viswanathan; Selma F Witchel; Kevin Mollen; Linwah Yip; Sara E Monaco; Umamaheswar Duvvuri; Jeffrey P Simons Journal: Laryngoscope Date: 2021-10-23 Impact factor: 2.970
Authors: Sasha R Howard; Sarah Freeston; Barney Harrison; Louise Izatt; Sonali Natu; Kate Newbold; Sabine Pomplun; Helen A Spoudeas; Sophie Wilne; Tom R Kurzawinski; Mark N Gaze Journal: Endocr Relat Cancer Date: 2022-09-07 Impact factor: 5.900
Authors: Steven G Waguespack; Alexander Drilon; Jessica J Lin; Marcia S Brose; Ray McDermott; Mohammed Almubarak; Jessica Bauman; Michela Casanova; Anuradha Krishnamurthy; Shivaani Kummar; Serge Leyvraz; Do-Youn Oh; Keunchil Park; Davendra Sohal; Eric Sherman; Ricarda Norenberg; Josh D Silvertown; Nicoletta Brega; David S Hong; Maria E Cabanillas Journal: Eur J Endocrinol Date: 2022-04-29 Impact factor: 6.558