Clinical Utility of Liquid Comprehensive Genomic Profiling in Advanced Lung Adenocarcinoma Complicated by Disseminated Intravascular Coagulation: A Case Report.

Comprehensive genomic profiling (CGP) is increasingly important for identifying actionable driver mutations and selecting targeted therapies in advanced lung adenocarcinoma, particularly when tissue re-biopsy is precluded by severe complications. A 74-year-old woman with no history of smoking presented with hemoptysis and abnormal findings on chest imaging. She was diagnosed with lung adenocarcinoma, cT2bN2M1c, Stage IVB, with bone and brain metastases. Initial molecular testing using AmoyDx® (AmoyDx Essential NGS Panel, Amoy Diagnostics, Xiamen, China) did not reveal any actionable driver mutations. Despite multiple lines of systemic therapy and whole-brain irradiation, the disease progressed with multiple liver metastases and cancer-associated disseminated intravascular coagulation (DIC). Given the patient's never-smoking status and the lack of residual tissue for repeat testing, comprehensive liquid biopsy-based genomic profiling was performed using FoundationOne® Liquid CDx (Foundation Medicine, Boston, MA, US). This analysis identified a human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutation (p.G776delinsAVGC). Treatment with trastuzumab deruxtecan (T-DXd) resulted in marked tumor shrinkage and prompt resolution of DIC. During the sixth cycle of T-DXd, the patient developed Grade 3 drug-induced interstitial lung disease (ILD)/pneumonitis, necessitating permanent discontinuation of T-DXd and high-dose corticosteroid therapy. Subsequently, the patient developed carcinomatous meningitis and was transitioned to palliative care. This case demonstrates that liquid biopsy-based CGP can identify actionable alterations and enable life-saving targeted therapy in patients with advanced lung adenocarcinoma complicated by severe DIC; however, severe drug-induced toxicities, such as ILD, remain a critical bottleneck that requires careful monitoring to balance treatment efficacy and safety.