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.