263 Background: Cell free DNA (cfDNA) has made it possible to actively monitor alterations of genes during the course of therapy. Herein we evaluate cfDNA pathologic mutations in TP53 after treatment resistance to AR targeted therapy and taxanes in mCRPC. In addition to the presence or absence of pathologic mutations, the quantity of the mutations was characterized as present/absent, quantitatively as > or < 1%, or >or <10%. Methods: A retrospective study was done for 111 patients, with 226 separate cfDNA testing dates. Each cfDNA test was treated as an individual sample; of the 226 tests, 112 were positive for pathologic TP53 mutations, and 114 were negative. Treatment histories were collected and TP53 data analyzed in relation to resistance for abiraterone (abi), enzalutamide (enza), abi + enza, or abi + enza and a taxane. Treatment resistance was categorized as being present for those patients completing therapy with an agent. Results: Patients with pathologic TP53 mutations were more likely to have had progression after a novel hormone and a taxane (P = 0.005). Higher concentrations of TP53 mutational loads as measured by cfDNA concentration of >1% and >10% were more likely to be present in patients progressing after a taxane, abi, and enza. Common alterations associated with TP53 included AR amplifications and mutations, MYC amplifications, and BRCA2 mutations. Conclusions: TP53 mutations in cfDNA of mCRPC are progressively more likely to be present in patients, especially after patients receiving both taxanes and a novel hormonal agent. The predictive and prognostic significance of these changes are being further evaluated.[Table: see text]
Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study
