3136 Kinetic monitoring of EGFR and KRAS mutations in urinary circulating tumor DNA predicts radiographic progression and response in patients with metastatic lung adenocarcinoma

Husain, Hatim; Melnikova, Vladislava O.; Kosco, Karena; Hancock, Saege; Samuëlsz, Errin; Woodward, Brian; Guerrero, Shiloh; Vibat, Cecile Rose T.; Erlander, M. G.; Cohen, Esti; Lippman, Scott M.; Kurzrock, Razelle

doi:10.1016/s0959-8049(16)31777-4

Cited by 2 publications

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“…Of the 15 patients positive for T790M by urine, 10 patients had T790M mutation in the tissue biopsy using the Clinical Laboratory Improvement Amendments test [32].…”

Section: Identification Of T790m In Tki-resistant and -Naïve Patientsmentioning

confidence: 99%

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Levy

Cordova

et al. 2016

The Oncologist

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A firmer understanding of the genomic landscape of lung cancer has recently led to targeted, therapeutic advances in non-small cell lung cancer. Historically, the reference standard for the diagnosis and genetic interrogation for advanced-stage patients has been tissue acquisition via computed tomography-guided core or fine needle aspiration biopsy. However, this process can frequently put the patient at risk and remains complicated by sample availability and tumor heterogeneity. In addition, the time required to complete the diagnostic assays can negatively affect clinical care. Technological advances in recent years have led to the development of blood-based diagnostics or “liquid biopsies” with great potential to quickly diagnose and genotype lung cancer using a minimally invasive technique. Recent studies have suggested that molecular alterations identified in cell-free DNA (cfDNA) or circulating tumor DNA can serve as an accurate molecular proxy of tumor biology and reliably predict the response to tyrosine kinase therapy. In addition, several trials have demonstrated the high accuracy of microRNA (miRNA) platforms in discerning cancerous versus benign nodules in high-risk, screened patients. Despite the promise of these platforms, issues remain, including varying sensitivities and specificities between competing platforms and a lack of standardization of techniques and downstream processing. In the present report, the clinical applications of liquid biopsy technologies, including circulating tumor cells, proteomics, miRNA, and cfDNA for NSCLC, are reviewed and insight is provided into the diagnostic and therapeutic implications and challenges of these platforms.

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“…Of the 15 patients positive for T790M by urine, 10 patients had T790M mutation in the tissue biopsy using the Clinical Laboratory Improvement Amendments test [32].…”

Section: Identification Of T790m In Tki-resistant and -Naïve Patientsmentioning

confidence: 99%

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Levy

Cordova

et al. 2016

The Oncologist

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“…Potential application scenarios include using ctDNA to supplement or substitute for tissue biopsies, especially in cases where tissue biopsies are risky or the quantity/quality of the tissue biopsied does not allow testing, and to use repeat sampling and genomic profiling to detect tumor evolution, response, and resistance (6,(19)(20)(21). Of interest, fluids such as urine can also be used to detect ctDNA (22,23). Finally, the use of ctDNA tests would increase chances to interrogate shed DNA from multiple metastases, perhaps better reflecting heterogeneity of the cancer burden in its entirety.…”

Section: Introductionmentioning

confidence: 99%

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

Schwaederlé¹,

Husain²,

Fanta³

et al. 2016

Clinical Cancer Research

126

124

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Purpose: There is a growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer. Experimental Design: A total of 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined. Results: Fifty-eight percent of patients (98/168) had ≥1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had ≥ 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with ≥ 1 alteration in common compared with 14.4 months (P = 0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with ≥ 1 alteration with ctDNA ≥ 5% and shorter survival (median = 4.03 months vs. not reached at median follow-up of 6.1 months; P < 0.001). Finally, 5 of the 12 evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease ≥ 6 months/partial remission compared with 2 of 28 patients (7.1%) for the unmatched patients, P = 0.02. Conclusions: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497–505. ©2016 AACR.

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3136 Kinetic monitoring of EGFR and KRAS mutations in urinary circulating tumor DNA predicts radiographic progression and response in patients with metastatic lung adenocarcinoma

Cited by 2 publications

References 0 publications

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Clinical Utility of Liquid Diagnostic Platforms in Non-Small Cell Lung Cancer

Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients

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