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  • Detection of cancer specific mutations in early-stage non-small cell lung cancer using cell-free DNA by targeted sequencing

    He Y, Zhang X, Wang L, Tian Z, Liu Q, Yao J, Liu Y, Li C, Min L, Shan B

    International Journal of Oncology, Volume 49, Issue 6, December 2016, Pages 2351-
    Topic: Diagnosis

    Commentary by Nir Peled

    Screening for lung cancer is now recommended for high risk individuals. However, low dose CT programs do detect numerous nodules, where most of them are benign. Non-invasive biomarkers to support nodule' management are needed to direct clinicians toward a more or less aggressive approach to patients. This study shows the feasibility of cfDNA to detect cancer related gene mutations as another potential and highly specific tool. Next, its incorporation into a clinical setting should be presented. 

  • A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma

    Karen L. Reckamp MD, Vladislava O. Melnikova MD, PhD, Chris Karlovich PhD, Lecia V. Sequist MD, MPH, D. Ross Camidge MD, PhD, Heather Wakelee MD, Maurice Perol MD, Geoffrey R. Oxnard MD, Karena Kosco PhD, Peter Croucher PhD, Errin Samuelsz BS, Cecile Rose Vibat PhD, Shiloh Guerrero BS, Jennifer Geis PhD, David Berz MD, Elaina Mann MS, Shannon Matheny PhD, Lindsey Rolfe MB, ChB, Mitch Raponi PhD, Mark G. Erlander PhD, Shirish Gadgeel MD

    Journal of Thoracic Oncology, Volume 11, Issue 10, October 2016, Pages 1690 - 1700

    Topic: Diagnosis

    Commentary by Tom Stinchcombe

    Approximately 60% of patients treated with an EGFR TKI develop a T790M acquired resistance mutation, and these patients are candidates for treatment with a third generation EGFR TKI (e.g. osimertinib). Historically patients have undergone a repeat tumor biopsy to detect the T790M. This study investigated the use of plasma and urine testing. In this phase I/II study plasma, urine, and tumor samples were collected, and 60 patients had evaluable tumor specimens. When the tumor sample was used as a reference the sensitivity for plasma for T790M was 93%, for exon 21 L858R 100% and for exon 19 deletions was 87% When tumor samples were used as a reference the sensitivity of urine for T790M was 72%, for exon 21 L858R was 75%, and for exon 19 deletions was 67%. The urine and plasma together identified an additional 12 patients with a T790M mutation that were undetectable on tumor testing or the sample inadequate tumor tissue. This is a small study and the number of patients in each mutation subset is limited. The potential use of urine will facilitate the detection of additional patients with a T790M resistance mutation, and may assistance in the serial measurement of T790M levels.  Importantly if the original EGFR mutation, exon 19 deletion or exon 21 L858R, is not detected on these test this tests cannot be accurately interpreted. 

  • Prospective analysis of oncogenic driver mutations and environmental factors: Japan molecular epidemiology for lung cancer study

    Kawaguchi, T., Koh, Y., Ando, M., (...), Saka, H., Matsumura, A.

    Journal of Clinical Oncology 34, no. 19 (July 2016) 2247-2257
    Topic: Diagnosis

    Commentary by Tom Stinchcombe

    With the identification of oncogenic drivers of NSCLC there has been increase interest in identifying the potential causative factors, the prevalence and the association of environmental factors and oncogenic events. Many studies are retrospective and the patients tested may not be representative of the lung cancer patient population. This study prospectively collected exposure to active and passive smoke, occupational exposures, reproductive and hormonal risk factors, weight loss, family history of cancer, medication use, and diet and exercise. 72 cancer associated genes, copy number of 5 cancer associated genes, and IHC staining and scoring estrogen receptor and anaplastic lymphoma kinase (ALK) rearrangements were performed. Data on 876 samples (441 ever and 435 never smokers) was analyzed. P53 and KRAS increased proportionally with smoking status, and TP53 and NFE2L2 mutations were observed more frequently in advanced stage. In never smokers no environmental factors were associated with mutational changes. On multivariate analysis KRAS and SMAD4 mutations were associated with high body mass index. Only 3 patients (0.3%) were HPV positive suggesting little contribution of HPV to lung cancer. The prospective collection of prior exposure is a strength of this study, and the limitations are the environmental exposures were patient reported and the use of targeted rather than whole exome or genome sequencing. The study was performed in Japan and the prevalence and associations may vary depending on the patient population studied. Further epidemiological studies are warranted to identify the additional causative agents or environmental exposures associated with NSCLC.

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Perspectives in Lung Cancer 2017

How I optimize treatment for my NSCLC patients with advanced and aggressive disease

Hotel Meliã Avenida América,
Madrid, Spain

Friday, March 3rd, 2017
11:40 - 13:10

ECCO 2017

Debating the optimal management in advanced and metastatic lung cancer: The right treatment for the right patient at the right time

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This educational activity is provided by Elsevier. Independent sponsorship for this educational activity was provided by Lilly Oncology.

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