Lori Wirth, MD: This is a patient who was referred to me in July of 2021 by his endocrinologist, but let's go back to when he was first diagnosed at an outside hospital. That was in 2018. He had a chest x-ray that showed an incidental left lower lung mass that led to a PET-CT [positron emission tomography-computed tomography] scan. The PET-CT showed an FDG [fluorodeoxyglucose]-avid left thyroid nodule and a 4-cm FDG-avid left lower lobe lung mass. This patient, who happens to be in his early seventies now, had 2 lung biopsies—CT-guided fine-needle aspirations [FNAs] that were nondiagnostic. He then went on to have a left lower lobectomy in July of 2018, and the pathology showed an acute organizing pneumonia with granulomatous inflammation and foreign body reaction. And then there was also an incidental 4-ml carcinoid microcarcinoma. Then the patient had a thyroid FNA that showed atypia of undetermined significance or AUS. The patient went on and had a total thyroidectomy and central neck dissection in September of 2018. The pathology was fairly worrisome. It showed poorly differentiated thyroid carcinomas arising in the background of papillary thyroid carcinoma. It was widely invasive. There were mixed oncocytic and solid features. The blue-inked margins were positive. There was extensive lymphovascular invasion involving large vessels and perineural invasion. Interestingly, 5 nodes were all negative. This patient had post-op radioiodine treatment with 100 millicuries. The whole-body scan following that showed uptake in the thyroid bed only, consistent with a little bit of thyroid remnant tissue. The patient was followed up by his endocrinologist. They were keeping an eye on several small cervical nodes on ultrasound. His TSH [thyroid stimulating hormone] was maintained, suppressed, and thyroglobulins were being followed, and the thyroglobulin levels were slowly but surely creeping up. In November of 2019 the thyroglobulin was 0.3. In September of 2020, the thyroglobulin was 1.4. In between that time, he had another thyrogen-stimulated I-123 [radioisotope of iodine-123] whole-body scan because of the rising thyroglobulin level, and that was negative. Then in January of 2021, the thyroglobulin was 2.6. That prompted an FNA of 1 of the small lymph nodes in the neck that had been followed, and that cytology was negative. They also did a thyroglobulin washout of the needle; that was negative. Then in May of 2021, his thyroglobulin was 5.6, prompting a PET-CT. That was done in June of 2021. You can see here in these images that there were a couple of subcentimeter lymph nodes in the chest, up to 9 ml in the left upper lobe of the lung. And you can see here that small nodule on the chest CT and on the PET part of the study you can see it's FDG-avid.

Lori Wirth, MD: In July of 2021, the patient was referred to me at Mass. General [Massachusetts General Hospital, Boston, Massachusetts]. My concern initially in the case was that we didn't have a tissue diagnosis for what was going on in the lungs. He had FDG-avid progressive lung lesions. He did have a carcinoid microcarcinoma seen in the pathology of the lung resection. I thought we needed a tissue diagnosis, and eventually the patient agreed to undergo another CT-guided lung biopsy. The core biopsy did show metastatic carcinoma consistent with the thyroid primary based on the histology and immunochemistry including PAX8 that was positive. However, thyroglobulin was negative—kind of concerning for the more poorly differentiated version of his thyroid cancer. We also did an NGS [next-generation sequencing] testing for mutations with our in-house snapshot that includes an Archer fusion assay looking for rearranged targets, and I saw these results. His cancer harbored an NF1 mutation and TP53 mutation which, again, goes along with a poorly differentiated thyroid cancer and more aggressive disease, and then a CDKN2A mutation. I should say also that the fusion assay was negative for actionable fusions such as NTRK or RET fusions, unfortunately. My impression overall is that the patient did have iodine refractory, totally differentiated thyroid cancer. He is a fit elderly man. At the time I thought he had low-volume disease, certainly asymptomatic, and I wasn't too impressed with the rate of progression of the disease. I felt that active surveillance was appropriate for this patient with ongoing TSH suppression, except that now we can’t call it active surveillance because the ATA [American Thyroid Association] guidelines are stealing that for surveilling small thyroid cancers that are not resected, so we have to call it disease monitoring now. I suggested that we need to establish the pace of the disease; let's not do anything other than have you come back in 4 months and repeat the neck and chest CT scans and see what's happening with the thyroid globulin level—and I was tempted to consider SBRT [stereotactic body radiosurgery] to the small FDG-avid lung nodule in the chest if this does indeed bear itself out as oligometastatic disease, and I was hoping to send him to my radiation oncology colleagues after that follow-up CT scan. In November of 2021 he still felt fine. His CT scans however unfortunately showed an increase in the size and number of the lung nodules, including a progressive right lobe lesion that had the appearance of a tubular branching lesion—concerning for tumor embolus. Oligometastatic disease is not on the table. I didn't think that SBRT was appropriate after all. However, he still had very low volume disease. I didn't think that we needed to start any systemic therapy right away. At that point his thyroglobulin was 17, so again we did restaging scans in March of 2022. At that time, he still feels perfectly fine. His thyroglobulin had gone from 17 in November to 36 in March, and you can see on his CT scans that there is a fair amount of progression in those nodules in the chest. At the clinic visit he was normotensive. We had other labs showing that his counts were all fine. He has normal liver and renal function. We did an EKG [electrocardiogram] that showed no QTC [corrected for heart rate] prolongation, and we had the talk. I thought that it was time to pull the trigger and initiate systemic therapy, and I recommended starting lenvatinib [Lenvima] 24 mg a day, and he got the drug delivered to him. Three days later he started dosing. The next day he called and was hypertensive, and we had him check his blood pressure that day again and the next day, and he was persistently hypertensive, so we added an ACE [angiotensin-converting enzyme] inhibitor on day 3 of therapy. And that was just 10 days ago.

Transcript edited for clarity.