How would you approach a locally advanced, radioiodine naive papillary thyroid carcinoma not amenable to a non-morbid surgery?

In certain cases there may a be a potential benefit.  We have an 87 year old male with significant co-morbidities that prevented him from being a surgical candidate.  Stage 4 papillary thyroid cancer with 1.7 cm right thyroid primary, 2.5 cm RML lung mass and 5 cm right cervical neck mass that was very symptomatic.  Initial plan was to treat with a small thyroid ablating dose followed up by higher standard RAI dose.  Given 40 millicuries I-131. Four months later he was hypothyroid by TSH.  Interestingly, the RML lesion and right neck mass have continued to decrease in size without have to give the higher RAI dose.  This was a collaborative decision with our Tumor Board, Nuc Med radiology and their conversations with Duke University Nuc Med radiologists

RAI prior to total thyroidectomy is of no benefit and may be toxic. Pre-op TKI should not be considered outside of clinical trial. There are some successful case reports of this approach in literature but I am not aware of any trials looking into this. I am unclear as to why this tumor is unresectable. Is it patient- related or tumor related? I am not a radiation oncologist but EBRT is generally considered for palliation and for differentiated thyroid cancer, benefit is minimal. If there are no impending airway issues and tumor is truly unresectable, would treat as metastatic disease with lenvatinib or sorafenib. 

There is no proven role for preoperative RAI in patients with unresectable iodine-avid well-differentiated thyroid cancer. The penetration of the isotope is minimal and the high likelihood of glandular edema resulting from the treatment would be morbid.  I have no experience with neoadjuvant systemic therapies and in this situation, I'd ponder whether the patient would benefit from a second surgical opinion. As a surgical disease, I believe the radiation oncologist should always try to get the "ultimate" surgical opinion before declaring the patient unresectable.  If unresectable is the final word, I'd offer the patient XRT to as high a dose as 70 Gy.  I would not expect any great cytoreduction which may render the patient resectable. Fortunately these scenarios are rare as most patients and providers would generally pick up a huge thyroid malignancy/goiter much earlier on.