Stage IIIB RET-fusion lung adenocarcinoma: disease-free after pralsetinib, surgery and maintenance therapy

What happened, in summary

A 34-year-old man with a 15-year smoking history developed persistent right-sided chest pain. CT showed a right middle-lobe mass measuring 34 x 24 x 44 mm, with enlarged mediastinal and left supraclavicular lymph nodes. Brain MRI and abdominal, adrenal, and urinary-system imaging showed no distant metastasis. Biopsy of a left supraclavicular lymph node confirmed poorly differentiated carcinoma consistent with pulmonary adenocarcinoma: CK7, thyroid transcription factor-1, and Napsin A were positive, while CK20 and CDX2 were negative. Molecular testing identified a RET exon 12 fusion. The lung cancer was staged as T2N3M0, Stage IIIB. He was initially considered inoperable and declined chemotherapy, so pralsetinib 400 mg once daily was started on December 16, 2022. Treatment was briefly interrupted during COVID-19 infection and later adjusted to 300 mg once daily because of symptoms such as headache and abdominal pain. After 3 months, CT showed a partial response, with the lung lesion reduced to about 8 x 5 mm and nodal shrinkage. On April 13, 2023, he underwent VATS right middle lung resection. Pathology showed pathological complete response, with 0% viable tumor cells and no metastatic cancer in sampled lymph nodes. He resumed pralsetinib as adjuvant therapy. Elective supraclavicular radiotherapy was started but stopped after 9 sessions because of grade 3 acute esophagitis. As of April 16, 2025, he remained disease-free on pralsetinib maintenance. Postoperative plasma circulating tumor DNA testing was negative 2 weeks after surgery. The radiotherapy complication resolved after 1 week of corticosteroid therapy, and later surveillance included chest CT, abdominal and brain MRI, and neck ultrasonography.