Genomic features and its potential implication in bone oligometastatic NSCLC

Liao, Rongxin; Ge, Yi; Shen, Lu; Zhang, Xiaoyue; Xu, Zaicheng; Yuan, Peng; Yang, Zhenzhou

doi:10.1186/s12890-023-02354-2

Cited by 4 publications

(1 citation statement)

References 59 publications

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“…Metastatic lung cancer is a highly heterogeneous disease with a vast histological, genetic and immunological diversity that requires a personalized treatment approach [ 17 , 18 ]. In this study, we performed a genotyping of oligometastatic NSCLC with matched primary tumours and BM using NGS on FFPE tissue specimens.…”

Section: Discussionmentioning

confidence: 99%

Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases

Werner,

Rechsteiner,

Moch

et al. 2024

European Journal of Cardio-Thoracic Surgery

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Objectives In patients with oligometastatic non-small cell lung cancer, systemic therapy in combination with local ablative treatment of the primary tumor and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary non-small cell lung cancer and corresponding brain metastases. Methods We retrospectively identified patients with oligometastatic non-small cell lung cancer and synchronous (<3 months) or metachronous (>3 months) brain metastases who underwent surgical resection of both primary tumor and brain metastases. Mutation profiling of formalin-fixed paraffin-embedded tumor cell blocks was performed by targeted next generation sequencing using the oncomine focus assay panel. Results Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumors (67.4%) and 40 brain metastases (86.9%). The alteration of the primary tumors was preserved in the corresponding brain metastases in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumors and brain metastases was a KRAS mutation (n = 21). In 16 patients (34.8%), the brain metastasis harbored additional oncogenic alterations. The presence of a private genetic alteration in the brain metastasis was an independent predictor of shorter overall survival. Conclusions In oligometastatic non-small cell lung cancer, brain metastases retain the main genetic alterations of the primary tumors. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the brain metastases are dismal.

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Section: Discussionmentioning

confidence: 99%

Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases

Werner,

Rechsteiner,

Moch

et al. 2024

European Journal of Cardio-Thoracic Surgery

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Molecular features of NSCLC patients with liver metastasis

Zhao,

Zhong,

Chen

et al. 2024

Ther Adv Med Oncol

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Background: Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear. Objectives: This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients. Design: We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022. Methods: Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome. Results: More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells. Conclusion: Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.

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