Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non–Small Cell Lung Cancer

Page, Ray D.; Drusbosky, Leylah; Dada, Hiba I.; Raymond, Victoria M.; Daniel, Davey B.; Divers, Stephen G.; Reckamp, Karen L.; Villalona‐Calero, Miguel A.; Dix, Daniel; Odegaard, Justin I.; Lanman, Richard B.; Papadimitrakopoulou, Vassiliki A.; Leighl, Natasha B.

doi:10.1016/j.cllc.2021.10.001

Cited by 26 publications

(18 citation statements)

References 33 publications

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“…Previous studies have shown similar shorter turnaround times with liquid compared to tissue-based biopsy in NSCLC and shorter time to treatment. These studies include the Canadian VALUE study where the mean turnaround time ( ± SD) was 7.7 ± 1.6 vs. 20.8 ± 9.8 days for liquid vs. tissue-based biopsy, as well as the North American NILE study involving 282 patients with advanced lung adenocarcinoma where the time to treatment was significantly shorter with liquid biopsy compared to tumor tissue molecular profiling (median 18 vs. 31 days, respectively, p = 0.0008) ( 18 , 19 ). Our study is also consistent with the VALUE study with respect to the high concordance rate between the liquid and solid biopsy results ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Liquid First Is “Solid” in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing

et al. 2022

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PurposeMolecular profiling is crucial in naïve non-small cell lung cancer (NSCLC). While tissue-based analysis is challenged by turnaround time and scarcity of tissue, there is increasing demand for liquid biopsy. We aimed to analyze the use of upfront liquid biopsy as a molecular profiling approach.MethodsThis retrospective multicenter, non-interventional study compared findings and turnaround times of liquid vs. standard-of-care (SOC) tissue-biopsy molecular profiling. The study included naïve advanced NSCLC patients with available liquid biopsy (Guardant360 CDx).ResultsA total of 42 consecutive patients (60% men; median age, 69.5 [39–87] years; 86% stage IV NSCLC) were identified between September 2017 and December 2020. Liquid-biopsy analysis provided results for all 42 patients, whereas the tissue-based analysis failed in 5 (12%) patients due to insufficient tumor samples. In 17 patients, 18 actionable driver mutations were identified. Eleven mutations were detected by both approaches (i.e., concordance of 61%), 4 only by liquid biopsy and 3 only by tissue biopsy. The median time from the molecular request to receiving the molecular solid report on the last biomarker was 21 (range: 5–66) days, whereas the median time from blood draw to the liquid-biopsy results was 10.5 (7–19) days. The median time between the availability of liquid-biopsy findings and that of the last biomarker was 5 days. Treatment changes following the liquid-biopsy results were observed in 3 (7%) patients.ConclusionPerforming liquid-biopsy upfront is feasible and accurate and allows a shorter time for treatment in NSCLC, especially when tumor tissue is scarce.

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Section: Discussionmentioning

confidence: 99%

Liquid First Is “Solid” in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing

et al. 2022

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“…The Guardant 360 TM platform is a US FDA-approved, 73-gene next-generation sequencing (NGS) test that detects plasma ctDNA fragments along with germline and other somatic cell-free DNA (cfDNA). 18 A limitation of the Guardant 360 TM platform is its decreased sensitivity to detect ctDNA in mucinous tumors. 19 ctDNA analysis was performed on blood samples collected either pretreatment (chemotherapy, radiation, or surgery) or early treatment (within 1 month of the initiation of treatment).…”

Section: Methodsmentioning

confidence: 99%

Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis

Sullivan

et al. 2022

Ann Surg Oncol

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Introduction Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier. Methods We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360TM). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites. Results Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n = 61; visceral metastases: n = 138; other metastases: n = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p < 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%; p < 0.01). In a subset of patients (n = 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue. Conclusions PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.

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“…Limited but significant studies on ctDNA analysis have shown some important results regarding the detection of ROS1 rearrangements in plasma as a tissue surrogate. Most of the studies included NGS panels for the most important therapeutically targetable mutations for the appropriate TKI therapy in NSCLC patients or treatment monitoring [ 215 , 216 , 217 ] and also proved the clinical utility of cfDNA testing at diagnosis and the potential it offers for faster, minimally invasive therapeutic decisions [ 218 ]…”

Section: Liquid Biopsy Testing In Nsclcmentioning

confidence: 99%

Liquid Biopsy Analysis as a Tool for TKI-Based Treatment in Non-Small Cell Lung Cancer

Buszka

Ntzifa

Owecka

et al. 2022

Cells

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The treatment of non-small cell lung cancer (NSCLC) has recently evolved with the introduction of targeted therapy based on the use of tyrosine kinase inhibitors (TKIs) in patients with certain gene alterations, including EGFR, ALK, ROS1, BRAF, and MET genes. Molecular targeted therapy based on TKIs has improved clinical outcomes in a large number of NSCLC patients with advanced disease, enabling significantly longer progression-free survival (PFS). Liquid biopsy is an increasingly popular diagnostic tool for treating TKI-based NSCLC. The studies presented in this article show that detection and analysis based on liquid biopsy elements such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, and/or tumor-educated platelets (TEPs) can contribute to the appropriate selection and monitoring of targeted therapy in NSCLC patients as complementary to invasive tissue biopsy. The detection of these elements, combined with their molecular analysis (using, e.g., digital PCR (dPCR), next generation sequencing (NGS), shallow whole genome sequencing (sWGS)), enables the detection of mutations, which are required for the TKI treatment. Despite such promising results obtained by many research teams, it is still necessary to carry out prospective studies on a larger group of patients in order to validate these methods before their application in clinical practice.

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Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non–Small Cell Lung Cancer

Cited by 26 publications

References 33 publications

Liquid First Is “Solid” in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing

Liquid First Is “Solid” in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing

Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis

Liquid Biopsy Analysis as a Tool for TKI-Based Treatment in Non-Small Cell Lung Cancer

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