Multimodal Impact of Number of Metastases and Genetic Alterations on Survival in Metastatic Non-Small Cell Lung Cancer.

PURPOSE: Oligometastatic disease (OMD) is an intermediate state of metastatic disease in which metastasis-directed therapy (MDT) may improve outcomes. The classification of OMD is inconsistent, typically defined by number of metastases without considering tumor biologic characteristics. To help optimize patient selection for MDT, we analyzed integrated genomic sequencing results from patients with metastatic non-small cell lung cancer (NSCLC).

MATERIALS AND

METHODS

Patients with metastatic NSCLC who had molecular sequencing through a validated institutional assay (MSK-IMPACT) were included. The number and location of metastases were manually annotated (assigned 1-10 and >10). Individual gene variant scores were analyzed by gene length and patient mutation burden. Analysis was completed in R and included maximally selected rank statistics, agglomerative hierarchical clustering, and the chi-square test for independence.

RESULTS

In total, 844 patients had clinical data, tissue sequencing, and annotated imaging for analysis. Of these, 635 had >10 metastases (75.2%), and 209 had 1-10 metastases (24.8%). The cutpoint that maximized overall survival (OS) was four metastases, and six mutation signatures were identified. For patients with 1-4 metastases, TERT and KMT2D had inferior OS, while for those with ≥5 metastases, EGFR, ALK, and TBX3 had superior OS.

CONCLUSION

The cutpoint that maximized difference in OS was four metastases, but incorporating genetic alteration information modified this criterion. These findings were proof of principle that integrating multimodal data beyond number of lesions can better identify patients with metastatic NSCLC who may be candidates for MDT.