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Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma.

ABSTRACT: Although therapeutic options for patients with advanced renal cell carcinoma (RCC) have increased in the past decade, no biomarkers are yet available for patient stratification or evaluation of therapy resistance. Given the dynamic and heterogeneous nature of clear cell RCC (ccRCC), tumor biopsies provide limited clinical utility, but liquid biopsies could overcome these limitations. Prior liquid biopsy approaches have lacked clinically relevant detection rates for patients with ccRCC. This study employed ccRCC-specific markers, CAIX and CAXII, to identify circulating tumor cells (CTC) from patients with metastatic ccRCC. Distinct subtypes of ccRCC CTCs were evaluated for PD-L1 and HLA-I expression and correlated with patient response to therapy. CTC enumeration and expression of PD-L1 and HLA-I correlated with disease progression and treatment response, respectively. Longitudinal evaluation of a subset of patients demonstrated potential for CTC enumeration to serve as a pharmacodynamic biomarker. Further evaluation of phenotypic heterogeneity among CTCs is needed to better understand the clinical utility of this new biomarker.

SUBMITTER: Bade RM

PROVIDER: S-EPMC8410529 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma.

Bade Rory M RM Schehr Jennifer L JL Emamekhoo Hamid H Gibbs Benjamin K BK Rodems Tamara S TS Mannino Matthew C MC Desotelle Joshua A JA Heninger Erika E Stahlfeld Charlotte N CN Sperger Jamie M JM Singh Anupama A Wolfe Serena K SK Niles David J DJ Arafat Waddah W Steinharter John A JA Jason Abel E E Beebe David J DJ Wei Xiao X XX McKay Rana R RR Choueri Toni K TK Lang Joshua M JM

Molecular oncology 20210303 9

Although therapeutic options for patients with advanced renal cell carcinoma (RCC) have increased in the past decade, no biomarkers are yet available for patient stratification or evaluation of therapy resistance. Given the dynamic and heterogeneous nature of clear cell RCC (ccRCC), tumor biopsies provide limited clinical utility, but liquid biopsies could overcome these limitations. Prior liquid biopsy approaches have lacked clinically relevant detection rates for patients with ccRCC. This stud ...[more]

PMID: 33604999

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Project description:BackgroundRenal cell carcinoma (RCC) can exhibit a unique vascular tropism that enables tumor thrombus extension into the inferior vena cava (IVC). While most RCC subtypes that form tumor thrombi are of clear cell (cc) histology, non-clear cell (ncc) subtypes can also exhibit this unique growth pattern.ObjectiveTo characterize clinicopathologic differences and survival outcomes among patients with IVC tumor thrombus arising from ccRCC versus nccRCC.Design setting and participantsPatients diagnosed with IVC tumor thrombus secondary to RCC in our institutional experience from 2003 to 2021 were identified.Outcome measurements and statistical analysisClinicopathologic characteristics were compared by histology. Perioperative and oncologic outcomes including recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survival were assessed using multivariable Cox regression analyses.Results and limitationsThe analyzed cohort included 103 patients (82 ccRCC and 21 nccRCC). There were no significant differences in baseline demographic parameters. Patients with nccRCC were more likely to have regional lymph node involvement (42.9% vs 20.7%, p = 0.037). No differences in perioperative outcomes, IVC resection, or IVC reconstruction were observed between groups. The median follow-up time was 30 mo. The median RFS was 30 (nccRCC) versus 53 (ccRCC) mo (p = 0.1). There was no significant difference in OS or CSS. This study was limited by its small sample size.ConclusionsPatients with IVC tumor thrombus arising from ccRCC and nccRCC exhibit similar perioperative and oncologic outcomes. While surgical appropriateness was not impacted by histologic subtype, multimodal strategies are needed to improve outcomes for patients with tumor thrombus.Patient summaryRenal cell carcinoma (RCC) can uniquely invade vasculature and form a tumor thrombus. This study examined the difference in outcomes of patients with tumor thrombus based on RCC subtype (clear cell vs non-clear cell). We found that patients exhibited similar surgical and survival outcomes regardless of RCC type.

Dataset Information

Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma.

Publications

Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma.

Similar Datasets

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