Background: A 71-year-old female never-smoker, with a remote history of secondhand smoke and a medical history including hyperlipidemia, hypertension, fatty liver, and chronic thrombocytopenia. Additionally, her family history is significant for multiple first-degree relatives with malignancy, including a father with lung cancer. Case Description: An initial abdominal ultrasound revealed multiple hepatic lesions concerning for metastatic disease. Further imaging revealed a right upper lobe lung mass with hepatic, osseous, and craniofacial metastases, including calvarial and right masticator space lesions with epidural extension. A biopsy confirmed adenocarcinoma with an EGFR exon 19 deletion (p.E746_P753delinsVS). The final clinical stage was assigned as stage IVB cT3N3M1c. Prior to systemic therapy, a total dose of 30 Gray using stereotactic body radiation therapy was delivered to the right maxilla and skull base for local control. The patient was then initiated on combination therapy with carboplatin (area under the curve 5), pemetrexed (500 mg/m2), and osimertinib (80 mg), completing six cycles. Maintenance therapy with pemetrexed and osimertinib was initiated thereafter and is ongoing. Follow-up imaging revealed interval reduction of the primary lung mass, pulmonary nodules, and hepatic metastases, along with increased sclerosis of osseous lesions, resolution of the epidural extension, and improvement in the right masticator lesion. Conclusions: The treatment has been well tolerated, with sustained clinical and radiographic responses. Although limited to a single case, our findings support the growing interest in combining systemic and local therapies in EGFR-mutant non-small cell lung cancer and offer a potential framework for adapting these strategies to molecularly analogous tumors. Longer-term follow-up and further studies are needed to refine patient selection and optimize treatment intensity.
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