Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

The Utility of 68Ga-DOTATATE and 18F-FDG PET/CT in Predicting the Response to Tyrosine Kinase Inhibitors in Patients with Advanced Medullary Thyroid Cancer. (#197)

Eline Jager 1 2 3 , James McNeil 1 , Alex Papachristos 4 5 , Mark Sywak 4 5 , Stanley Sidhu 4 5 , Rhonda Siddall 1 , Jeremy Hoang 6 , Geoffrey Schembri 6 , Venessa Tsang 1 4 , Ayanthi Wijewardene 1 7 , Lyndal Tacon 1 4 , Bruce Robinson 1 4 7 , Rodrick Clifton-Bligh 1 4 7 , Martyn Bullock 4 7 , Adrienne H Brouwers 8 , Thera Links 2 , Schelto Kruijff 3 , Anthony Glover 4 , Matti Gild 1 4 7
  1. Department of Endocrinology and Diabetes, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Department of Internal Medicine, Division of Endocrinology, University Medical Centre Groningen, Groningen, The Netherlands
  3. Department of Surgery, Division of Surgical Oncology, University Medical Centre Groningen, Groningen, The Netherlands
  4. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  5. Department of Endocrine Surgery, Royal North Shore Hospital, Sydney, NSW, Australia
  6. Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
  7. Cancer Genetics Laboratory , Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia
  8. Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen, The Netherlands

The introduction of tyrosine kinase inhibitors has significantly improved the prognosis of advanced medullary thyroid cancer (MTC). However, challenges remain in pinpointing timing of treatment and prediction of individual response. The aim was to evaluate the predictive value of 68Ga-DOTATATE and 18F-FDG PET/CT in TKI treatment response.

In this retrospective study, all patients treated with TKIs for metastatic MTC with 68Ga-DOTATATE or 18F-FDG PET/CTs <18 months prior to TKI were included. Patient and treatment data were collected and pathological uptake on PET/CTs was quantified (Standardized Uptake Value [SUVmax], SUVmean, Total Lesion Activity [TLA] and Metabolic Tumor Volume [MTV] were correlated with outcomes.

Of the 25 patients, mean age 48 (±15) years; 11 (44%) female and 21 had RET-mutated cancers (3/25 [12%] MEN2). At final follow-up, patients had distant metastases in mediastinum (17 [68%]), bone (17 [68%]), lungs (14 [56%]), liver (14 [56%]), and brain (3 [12%]). Ten patients (40%) had died. A total of 36 TKI treatments (11 patients [44%] received two TKIs sequentially). In 32 patients, the RECIST response was available. Response rates were; stable disease (SD) 8/32 (25%), partial response (PR) 23/32 (72%) and complete response 1/32 (3%). A total of 30 baseline PET/CTs (24 68Ga-DOTATATE PET/CTs, 6 18F-FDG PET/CTs) prior to TKI. In 4 patients 68Ga-DOTATATE PET/CT pre- and post-selpercatinib, avidity measures decreased. Overall pre-TKI 68Ga-DOTATATE PET/CTs did not correlate with structural response to TKI treatment. However, in the 18F-FDG cohort, high MTV and TLA correlated strongly with better structural response (both p<0.001).

MTV and TLA on the 18F-FDG PET/CT prior to TKI treatment have potential for predicting structural response and may guide initiation/continuation of TKI treatment, after validation in a larger cohort. On the contrary, TKI response is independent of uptake on 68Ga-DOTATATE PET/CT. 68Ga-DOTATATE PET/CT may have more value in disease mapping and response evaluation.

  1. Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167. doi:10.1038/nrclinonc.2017.175
  2. Papachristos AJ, Nicholls LE, Mechera R, et al. Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery. Oncologist. 2023;28(12):1064-1071. doi:10.1093/oncolo/oyad232
  3. Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery (United States). 2017;161(1):137-146. doi:10.1016/J.SURG.2016.04.053
  4. Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: Demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107(9):2134-2142. doi:10.1002/cncr.22244
  5. Gilliland FD, Hunt WC, Morris DM, Key CR. Prognostic factors for thyroid carcinoma. Cancer. 1997;79(3):564-573. doi:10.1002/(SICI)1097-0142(19970201)79:33.0.CO;2-0
  6. Machens A, Dralle H. Prognostic impact of N staging in 715 medullary thyroid cancer patients: Proposal for a revised staging system. Ann Surg. 2013;257(2):323-329. doi:10.1097/SLA.0b013e318268301d
  7. Giraudet AL, Vanel D, Leboulleux S, et al. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. Journal of Clinical Endocrinology and Metabolism. 2007;92(11):4185-4190. doi:10.1210/jc.2007-1211
  8. Kushchayev S V., Kushchayeva YS, Tella SH, Glushko T, Pacak K, Teytelboym OM. Medullary Thyroid Carcinoma: An Update on Imaging. J Thyroid Res. 2019;2019. doi:10.1155/2019/1893047
  9. Ong SC, Schöder H, Patel SG, et al. Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels. Journal of Nuclear Medicine. 2007;48(4):501-507. doi:10.2967/jnumed.106.036681
  10. Verbeek HHG, Plukker JTM, Koopmans KP, et al. Clinical relevance of18F-FDG PET and18F-DOPA PET in recurrent medullary thyroid carcinoma. Journal of Nuclear Medicine. 2012;53(12):1863-1871. doi:10.2967/jnumed.112.105940