Radioactive Iodine Resistant Papillary Thyroid Cancer “Redifferentiated” With Dabrafenib

Background: Differentiated thyroid cancers (DTC) make up 95% of all thyroid cancers. Radioactive iodine therapy (RAI Rx) is an integral part of DTC management. However, 5-15% of DTC and 50% of metastatic DTC become resistant to RAI Rx and carries a 10-year survival of only 10%. One of the newer therapeutic options target “redifferentiation” of the tumor using RAI sensitizers, notably with short-term use of tyrosine kinase inhibitors (TKI). Clinical Case: A 62-year-old women with a 3-year history of Papillary TC s/p surgery (Sx) and 175 mCi RAI presented to establish care and was found to have bulky palpable disease in her left lateral neck. Imaging showed bilateral enlarged lymph nodes in the neck and multiple bilateral pulmonary nodules. Her stimulated thyroglobulin (TG) level was 5341 (1.59 - 50.03 ng/dL) with negative TG antibodies. Bone scan showed no evidence of bone mets. She underwent repeat neck dissection (49 positive lymph nodes) and was BRAF V600E positive. Post-Sx her non-stimulated (NS) TG was 340 ng/dL (0.00 - 41.00 ng/mL) and she received 200mCi RAI Rx with post-Rx whole body scan (WBS) showed uptake only in the thyroid bed. Imaging 6 months later showed stable lung nodules but increase in lymphadenopathy in the neck and her NS-TG was 181 ng/dL. She received 250 mCi of RAI Rx, 10 months after the first dose. Post Rx WBS again showed uptake only in the neck. Her non-stim TG, 9 months later was still high at 130 ng/dL. Given the discordant imaging and TG findings, functional imaging was done which showed multiple avid lesions in bone and lymph nodes confirming the diagnosis of radioiodine-refractory (RAI-R) DTC. Given BRAF V600E positive status, she received Dabrafenib 150 mg PO BID for 6 weeks followed by RAI 300 mCi. Post-RAI WBS showed extensive uptake in base of skull, sternum, cervical spine and right supraclavicular area. Six months post Dabrafenib and RAI, her NS-TG had come down from 130 to 25.7 ng/dL and imaging showed stable structural disease. Her TG levels and imaging have remained stable over the last 18 months indicating both biochemical and structural response to Dabrafenib. Conclusion: The goal of TKIs in redifferentiation of RAI-R DTC is to target specific molecular mechanisms to render the tissue sensitive to RAI. There are several published trials using TKIs for redifferentiation based on the mutation present. Dabrafenib alone and in combination with other TKI’s (Vemurafenib, Trametinib) followed by RAI has shown some response in 60-70% of treated patients with RAI-R tumors. In a study with 10 RAI-R patients with BRAF V600E mutations, dabrafenib used as a radiosensitizer showed RAI uptake in 60%. Three months post Rx, 2 of 6 had a reduction in disease burden while the other 4 had stable disease. Redifferentiation Rx can be successful in slowing disease progression and could be an option in the treatment of RAI-R DTC before initiation of long term TKI Rx.