Dataset Information

Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA.

ABSTRACT:

Purpose

Cell-free DNA (cfDNA) next-generation sequencing is a noninvasive approach for genomic testing. We report the frequency of identifying alterations and their clinical actionability in patients with advanced/metastatic cancer.

Patients and methods

Prospectively consented patients had cfDNA testing performed. Alterations were assessed for therapeutic implications.

Results

We enrolled 575 patients with 37 tumor types. Of these patients, 438 (76.2%) had at least one alteration detected, and 205 (35.7%) had one or more alterations of high potential for clinical action. In diseases with 10 or more patients enrolled, 50% or more had at least one alteration deemed of high potential for clinical action. Trials were identified in 80% of patients (286 of 357) with any alteration and in 92% of patients (188 of 205) with one or more alterations of high potential for clinical action of whom 57.6% (118 of 205) had 6 or more months of follow-up available. Of these patients, 10% (12 of 118) had received genomically matched therapy through enrollment in clinical trials (n = 8), off-label drug use (n = 3), or standard of care (n = 1). Although 88.6% of all patients had a performance status of 0 or 1 upon enrollment, the primary reason for not acting on alterations was poor performance status at next treatment change (28.1%; 27 of 96).

Conclusion

cfDNA testing represents a readily accessible method for genomic testing and allows for detection of genomic alterations in most patients with advanced disease. Utility may be higher in patients interested in investigational therapeutics with adequate performance status. Additional study is needed to determine whether utility is enhanced by testing earlier in the treatment course.

SUBMITTER: Sanchez NS

PROVIDER: S-EPMC7448805 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA.

Sánchez Nora S NS Kahle Michael P MP Bailey Ann Marie AM Wathoo Chetna C Balaji Kavitha K Demirhan Mehmet Esat ME Yang Dong D Javle Milind M Kaseb Ahmed A Eng Cathy C Subbiah Vivek V Janku Filip F Raymond Victoria M VM Lanman Richard B RB Mills Shaw Kenna R KR Meric-Bernstam Funda F

JCO precision oncology 20190924

<h4>Purpose</h4>Cell-free DNA (cfDNA) next-generation sequencing is a noninvasive approach for genomic testing. We report the frequency of identifying alterations and their clinical actionability in patients with advanced/metastatic cancer.<h4>Patients and methods</h4>Prospectively consented patients had cfDNA testing performed. Alterations were assessed for therapeutic implications.<h4>Results</h4>We enrolled 575 patients with 37 tumor types. Of these patients, 438 (76.2%) had at least one alte ...[more]

PMID: 32923868

Similar Datasets

Project description:PurposeWe report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC).Experimental designA query of our institutional clinical sequencing database (MSK-IMPACT) was performed that included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge database (OncoKB) and the available clinical data stratified by level of evidence. Alterations associated with response to immune-checkpoint blockade (ICB) were analyzed separately; these included DNA mismatch repair (MMR) gene alterations, tumor mutational burden (TMB), and microsatellite instability (MSI). Data from The Cancer Genome Atlas (TCGA) consortium as well as public data from several clinical trials in metastatic RCC were used for validation purposes. Multiregional sequencing data from the TRAcking Cancer Evolution through Therapy (TRACERx) RENAL cohort were used to assess the clonality of somatic mutations.ResultsOf the 753 individuals with RCC identified in the MSK-IMPACT cohort, 115 showed evidence of targetable alterations, which represented a prevalence of 15.3% [95% confidence interval (CI), 12.7%-17.8%). When stratified by levels of evidence, the alterations identified corresponded to levels 2 (11.3%), 3A (5.2%), and 3B (83.5%). A low prevalence was recapitulated in the TCGA cohort at 9.1% (95% CI, 6.9%-11.2%). Copy-number variations predominated in papillary RCC tumors, largely due to amplifications in the MET gene. Notably, higher rates of actionability were found in individuals with metastatic disease (stage IV) compared with those with localized disease (OR, 2.50; 95% CI, 1.16-6.16; Fisher's P = 0.01). On the other hand, the prevalence of alterations associated with response to ICB therapy was found to be approximately 5% in both the MSK-IMPACT and TCGA cohorts and no associations with disease stage were identified (OR, 1.35; 95% CI, 0.46-5.40; P = 0.8). Finally, multiregional sequencing revealed that the vast majority of actionable mutations occurred later during tumor evolution and were only present subclonally in RCC tumors.ConclusionsRCC harbors a low prevalence of clinically actionable alterations compared with other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.

Dataset Information

Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA.

Purpose

Patients and methods

Results

Conclusion

Publications

Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA.

Similar Datasets

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