Background: Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). Methods: Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings. Results: A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/μl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004). Conclusions: The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies.

The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs

Del Re, Marzia
Primo
Writing – Original Draft Preparation
;
Crucitta, Stefania;Paolieri, Federico;Cucchiara, Federico;Bloise, Francesco;Ciampi, Raffaele;Mercinelli, Chiara;Danesi, Romano
Ultimo
Writing – Review & Editing
2022-01-01

Abstract

Background: Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). Methods: Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings. Results: A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/μl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004). Conclusions: The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies.
2022
Del Re, Marzia; Crucitta, Stefania; Paolieri, Federico; Cucchiara, Federico; Verzoni, Elena; Bloise, Francesco; Ciampi, Raffaele; Mercinelli, Chiara; ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1150524
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