Methods and Case Description
A 9-year-old former 33-week female triplet presented with exercise-induced dyspnea and intermittent oral cyanosis when chest x-ray revealed innumerable pulmonary nodules thought to be consistent with miliary tuberculosis or granulomatous disease. At age 11 she was evaluated for a right-sided neck mass; ultrasound showed a 2.7x1.7x2.9 cm hypervascular lesion at the carotid bifurcation. Magnetic resonance imaging was attempted, but due to hypoxemia, study was aborted and she was hospitalized for further evaluation and respiratory support. Chest computed tomography demonstrated diffuse sub-centimeter nodules with mediastinal and cervical lymphadenopathy. Rheumatologic and infectious work-ups were unrevealing. She underwent thoracoscopic lung biopsy where pathology confirmed metastatic PTC. Total thyroidectomy and lymph node dissection was performed showing classic subtype, with final tumor-node-metastasis staging of T1bN1bM1. Post-surgical thyroglobulin (Tg) level was 2850 ng/mL; antithyrogloblulin antibody was elevated at 46 IUnits/mL (normal <1.8 IUnits/mL).
The patient then started RAI treatment, receiving an initial dose of 20 mCi, which was initially complicated by radiation pneumonitis requiring hospitalization and steroid therapy. The next dose was reduced to 10mCi without recurrent symptoms of radiation pneumonitis. Subsequent doses were slowly increased and well-tolerated. She received a cumulative 280 millicuries from 7 treatments over 29 months. Post-treatment total body iodine scans performed 3-5 days after RAI administration continued to show stable, diffuse increased uptake throughout her lungs and thyroid stimulating hormone (TSH)-suppressed Tg level remained persistently elevated at 810 ng/mL, anti-Tg antibody was 8.1 IUnits/mL. She continued to require 3 liters of oxygen via nasal cannula and endorsed dyspnea with exertion. Somatic genetic testing was pursued using TEMPUS (Chicago, IL) and revealed a NCOA4-RET fusion.
The patient began oral selpercatinib 120 mg twice daily (BID) at the age of 13 years, following weight-based dosing guidelines (120 mg BID for weight <50 kg and 160 mg BID for weight \(\geq\)50 kg). Within 1 week, we noted an increase in oxygen saturation levels to ≥98% off supplementation while active in clinic. After two 28-day cycles imaging showed improving partially calcified mediastinal lymphadenopathy with marked improvement in innumerable pulmonary metastases (Fig.1). Tg level decreased to 143 ng/mL with anti-thyroglobulin antibody of 16 IUnits/mL (Fig. 2). Dosing was subsequently increased to 160 mg BID due to weight gain. The patient slowly trialed off of oxygen support, and after 4 cycles of therapy, she was off of supplemental oxygen and cleared by pulmonology for exercise.
Overall selpercatinib has been well tolerated; however, the patient continued to gain weight above her expected baseline and underwent a dose reduction to 120 mg BID after 9 cycles of therapy for possibly-related grade 3 weight gain. The patient noted a decrease in her appetite after the reduction but continued to endorse poor food choices and limited activity. Dose reduction again occurred after 18 cycles of therapy to 80 mg BID. She otherwise continued on levothyroxine for appropriate TSH suppression to <0.1 mcIUnit/mL.
The patient remains on selpercatinib at dose level -2 and was last evaluated after initiation of her twenty-eighth cycle. Imaging, thyroglobulin response, and resolution of anti-Tg antibodies (Figs. 1-2), as well as elimination of supplemental oxygen need, has continued despite dose adjustments. We plan to continue therapy indefinitely barring disease progression or intolerable toxicities.