SUN-484 Complex Thyroid Cancer with Several Recurrences and Metastases

56-year-old male with metastatic papillary thyroid cancer who underwent total thyroidectomy in 8/2014, and I-131 ablation in 9/2014, with post-operative pathology revealing multifocal, bilateral papillary thyroid cancer with extrathyroidal extension with surgical resection margins uninvolved. There were positive lymphovascular spread and multiple central compartments and bilateral neck nodes metastases with extranodal extension. Subsequent thyrogen stimulated whole-body scan in 2/2016 showed no areas of uptake.However, in 12/2016 he was found to have right supraclavicular lymph nodes positive for recurrence which was resected and given another 168 mCi I-131 and 33 treatments of XRT to R shoulder.A repeat PET in 7/2019 showed persistent hyper metabolic lesion in C7, multiple hyper metabolic nodules throughout the R lung, and a new 1.1 cm left Hilar lymph node suggesting disease progression. Biopsy of the C7 lesion confirmed dedifferentiated papillary thyroid cancer and demonstrated the presence of an NTRK mutation.This time he was given lenvatinib 24 mg daily for 4 weeks, followed by 200 mCi I-131. Post-treatment whole body scan showed good uptake in all lesions, except the C7 lesion which was treated with external radiation. DiscussionWhile cure is achieved in most cases of differentiated thyroid cancer, a minority of cases demonstrate disease progression. Loss of response to I-131, very low serum thyroglobulin levels despite known disease, and high PET avidity provide clinical evidence of dedifferentiation, confirmed with tissue sampling.If feasible targeted systemic therapy remains the best tolerated treatment option.While several studies demonstrate an increase in iodine avidity in approximately 50-60% of patients with dedifferentiated thyroid cancer that were treated with tyrosine kinase inhibitors (TKI), (cite alan Ho’s 2013 NEJM article, and the 2015 debrafenib study Rothenberg SM et al, clin cancer res 2015), selumetanib remains unavailable for clinical use and dabrafenib may only be beneficial in cases with known BRAF V600E mutations. Moreover, it is unknown whether a planned short course of TKI therapy would potentially induce resistance to future TKI therapy.Therefore, lenvatinib, which inhibits activity of at least 6[VM1] different tyrosine kinase enzymes important in thyroid cancer was chosen rather than entrectanib, which was reserved for use if the need arises. This patient demonstrated excellent response to I-131 therapy with lenvatinib pretreatment.A number of formal studies of various TKIs for thyroid cancer re-differentiation are currently underway. (cite Brown SR, Hall A, et al BMC cancer 2019; and also cite the CIII trial with cabozatanib)Conclusion This case represents the emerging paradigm for the ability of TKI therapy to redifferentiate advanced thyroid cancer and allow for re-treatment with I-131 targeted therapy.