Friday, November 4, 2016

liquid biopsies have a mutation detection potential EGFR NSCLC predict cancer recurrence

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liquid biopsies have a mutation detection potential EGFR NSCLC predict cancer recurrence

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Three manuscripts published in the recent issue of Journal of Thoracic Oncology , the official journal of the international Association for the study of lung cancer (IASLC), explored the versatility of liquid biopsies by identifying EGFR mutations using circulating tumor DNA (ctDNA) in urine and plasma and review of circulating tumor cells (CTC) in plasma to predict the risk of recurrence of lung cancer after surgical resection. Collectively, these results illustrate the potential and scope of liquid biopsies both the identification of appropriate patients for targeted therapy and predict cancer recurrence.

Lung cancer is the most common type of cancer mortality related to the higher cancer worldwide. Non-small lung cancer small cell (NSCLC) accounts for approximately 85% of lung cancers and most patients have advanced disease at diagnosis. Surgical resection is the preferred treatment option for patients with medically inoperable tumors. However, recurrence of the disease occurs in about 50% of cases. Patients with advanced disease are often not candidates for surgical resection and commonly harbor driver mutations that can be targeted by drugs. A major challenge for the assessment of driver mutations, such as the receptor for epidermal growth factor receptor (EGFR) mutations in advanced disease is the scarcity of biopsy tissue suitable for molecular testing. A minimally invasive alternative to invasive tissue biopsy is the use of a liquid biopsy, which analyzes ctDNA CTC or in a sample of biological fluid (e.g. urine, blood or serum).

The first manuscript entitled Circulating free DNA derived tumor (ctDNA) Determination of EGFR mutation status in European Real-World and Japanese Patients with Advanced NSCLC: ASSESS study used samples of the great EVALUATE study to assess the status of EGFR mutation by analyzing ctDNA blood plasma. The results of the study demonstrated that the analysis ctDNA plasma is possible to identify mutations of the EGFR mutation with matching status in 1162 matched samples of 89% (sensitivity 46%, specificity 97%, the positive predictive value [PPV] 78% PV 0% negative). The authors comment that "mutation tests ctDNA accurate and accessible to address unmet needs in patients without tumor sample available / evaluable will be important to allow more patients to receive personalized treatments mutation status of their tumor."

The second manuscript entitled, a platform very sensitive and quantitative test for the detection of EGFR mutations in NSCLC urine and plasma, analyzed samples from patients enrolled in TIGER-X, a study clinical 1/2 rociletinib stage for previously treated patients with EGFR mutant positive advanced NSCLC for EGFR activating mutations query and analysis ctDNA T70M resistance mutation of urine or blood plasma. The results of the study show that NSCLC tumors derived ctDNA can be detected with high sensitivity in the urine and plasma, the 93% sensitivity for T70M, 80% L858R and exon 19 deletions 83% and the sensitivity of T70M 93%, 100% L858R and exon 19 deletions 87%, respectively. The authors note that, "In conclusion, our data demonstrate that urine testing using the method NGS mutation enrichment successfully identifies the EGFR mutations in patients with metastatic NSCLC and has a great consistency with the tumor and plasma, suggesting that the mutation detection of EGFR from urine or plasma should be considered a viable approach for the assessment of EGFR mutation status. "

Finally, third manuscript liquid entitled tumor cells biopsies circulating detected in the pulmonary vein draining tumor are associated with disease recurrence after surgical resection of non-lung small cell cancer, blood used and draining tumor tumor microemboli samples of the pulmonary vein in the surgical pre-resection and intra-operative patients to analyze CTC and outstanding (MLC, clusters). The researchers reported that the combination of CTC / CTM census in tumor draining the pulmonary veins and peripheral blood at the time of surgical resection with curative intent NSCLC better identify patients at high risk of lung cancer recurrence that numbers peripherals CTC / CTM only. "In addition to the potential role of CTCs as prognostic / predictive biomarker, isolation and genetic analysis individual CTCs from liquid biopsies can shed light on the biology of the tumor and the metastatic process," said Phil AJ Crosbie, MD, Ph.D., first author of the article.


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