Recurrent Poorly Differentiated Thyroid Cancer Successfully Treated With Radiation and Immunotherapy

Abstract

A 65-year-old patient presented with recurrent, locally advanced poorly differentiated thyroid cancer despite 2 neck surgeries, and with newly diagnosed brain and skull base metastases. He was treated with palliative stereotactic radiosurgery to the brain and skull base lesions. Thereafter, as no targetable genetic alteration was identified and antiangiogenic multikinase inhibitors were deemed at high risk of hemorrhagic complications, off-label systemic therapies were considered. The mechanistic target of rapamycin (mTOR) inhibitor everolimus could not be obtained due to lack of insurance coverage, so the patient was treated with single-agent pembrolizumab. He showed an initial remarkable response, but unfortunately had disease progression in the neck and upper mediastinum after 1 year of therapy. At that time, he was treated with external beam radiotherapy, with concomitant pembrolizumab. He was then found to have an CTSB::ALK fusion, which has previously been described in 2 cases of thyroid cancer. However, as he showed a positive response to radiation with pembrolizumab, he continued single-agent immune checkpoint inhibition and had a persistent marked response almost a year after completing radiation. The patient was then followed at an outside institution and was transitioned to hospice at time of progression per his preference. He died 4 years after his initial diagnosis.

Keywords: ALK fusion; immunotherapy; pembrolizumab; poorly differentiated thyroid cancer; radiation therapy; synergy.

Figure 1.

Contrast-enhanced A and C, axial and B, coronal computed tomography images of the neck at initial presentation to our institution (July 2021) demonstrating a lobular 3.4 × 6 cm mass in the left thyroid bed, extending inferiorly into the anterior mediastinum (A and B, *). There is focal invasion of the right internal jugular vein (A, arrow). Conglomerate left level 2 nodal metastases also seen measuring up to 5.5 cm in craniocaudal dimension (B, dotted circle), as well as a 2.3 cm left retropharyngeal lymphadenopathy causing mass effect on the left lateral aspect of the pharynx (C, arrow). Contrast-enhanced axial magnetic resonance images of D, the brain and E, skull base demonstrating a 1.8 × 1.6 cm enhancing cerebral metastasis of the left parietal lobe (D, dotted circle) with regional edema and mild mass effect. An enhancing osseus metastasis to the skull base centered on the left petrous temporal bone with involvement of the jugular tubercle and likely soft tissue extension to the jugular foramen (E, arrows) was also present.

Figure 2.

Maximum intensity projection (MIP) ¹⁸FDG-PET/CT images A, at baseline (July 2021); B, after 10 cycles of pembrolizumab monotherapy demonstrating significant tumor reduction (April 2022); C, after 12 cycles of pembrolizumab showing disease progression in the left neck and upper mediastinum (July 2022); and D, 10 months after radiation therapy completion demonstrating a marked response to pembrolizumab + radiation (June 2023).

Figure 3.

Radiation fields to the left neck (2700 cGy in 3 fractions, upper series) and upper mediastinum (5250 cGy in 14 fractions, lower series).