Recurrent lung cancer with multi-organ metastases showing remarkable regression after two weeks of targeted therapy:...

Recurrent pulmonary malignancy with multi-organ metastasis remains one of the most refractory scenarios in thoracic oncology. Despite advances in systemic therapy, the prognosis for such cases remains poor. We report a case of disease recurrence with multiple metastatic lesions detected 34 months following initial surgical resection. After repeat surgical intervention, targeted therapy was initiated, resulting in complete resolution of brain and pericardial metastatic foci within two weeks-a response rarely observed in clinical practice. This case underscores the critical role of surgical intervention combined with precision targeted therapy in managing advanced lung cancer. It also highlights the potential of individualized treatment strategies to achieve favorable outcomes in refractory cases; it underscores the imperative for dynamic molecular monitoring and reaffirms the transformative potential of precision therapy in managing refractory metastatic non-small-cell lung cancer (NSCLC).

A 53-year-old woman was referred to our institution after a computed tomography (CT) scan identified a 1.2 cm × 0.9 cm solid nodule in the anterior segment of the left upper lobe. Preoperative assessments-including complete blood count, liver and renal function, coagulation profile, pulmonary function, electrocardiography, echocardiography, and tumor markers (alpha-fetoprotein and carcinoembryonic antigen)-were within normal limits. The patient underwent uncomplicated resection of the anterior segment. Histopathology confirmed a moderately differentiated invasive lung adenocarcinoma, and next-generation sequencing (NGS) detected an epidermal growth factor receptor (EGFR) exon 21 p.L858R mutation with a variant allele frequency (VAF) of 23.59%. Thirty-four months later, she developed intermittent chest tightness and exertional dyspnea. Chest CT showed a 9 mm × 8 mm part-solid nodule adjacent to the left mediastinal pleura and significant pericardial effusion. Brain imaging revealed metastatic lesions in the brainstem and left cerebellum, confirmed by magnetic resonance imaging (MRI). Thoracoscopic wedge resection confirmed recurrent lung adenocarcinoma. Repeat NGS identified the same EGFR p.L858R mutation with a markedly elevated VAF of 85.15%. Oral almonertinib was initiated, leading to complete resolution of brain metastases and near-complete resolution of pericardial effusion within two weeks. At eight-month follow-up, the patient remained asymptomatic with no evidence of disease progression.

This case illustrates key aspects of recurrent lung adenocarcinoma management. Initial resection of a small nodule achieved local control, but recurrence with brain metastases and pericardial effusion later occurred, emphasizing the need for vigilant follow-up and multimodal imaging. Critical to the outcome was genotype-guided therapy: post-biopsy genetic testing guided almonertinib administration, leading to complete resolution of brain metastases and improved pericardial effusion within 2 weeks, which was defined according to response evaluation criteria in solid tumors (RECIST) 1.1 criteria. In NSCLC, activating mutations in the EGFR gene are detected, and these mutations render tumor cells highly sensitive to tyrosine kinase inhibitors (TKIs). The rapid response of the central nervous system (CNS) to targeted drugs highlights the value of personalized therapy in advanced-stage diseases.

This case demonstrates the efficacy of genotype-guided targeted therapy in the management of recurrent lung adenocarcinoma presenting with brain metastases and pericardial effusion. The rapid and complete resolution of brain metastases and marked improvement in pericardial effusion within two weeks of initiating almonertinib therapy underscore the pivotal role of molecular profiling in guiding personalized treatment for advanced EGFR-mutated NSCLC. It also emphasizes the importance of rigorous postoperative surveillance for early detection of recurrence, thereby facilitating timely intervention and optimizing clinical outcomes in patients with advanced NSCLC.