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Diagnosis

  • Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non–Small Cell Lung Cancer

    Aritoshi Hattori MD, Takeshi Matsunaga MD, Takuo Hayashi MD, Kazuya Takamochi MD, Shiaki Oh MD, Kenji Suzuki MD

    Journal of Thoracic Oncology, Volume 12, Issue 6, June 2017, Pages 954 - 962

    Category:
    Topic: Diagnosis

    Commentary by Nir Peled

    Moving towards screening for lung cancer by low dose CT scans for high risk cohort is expected to affect the stage split within the lung cancer epidemic. With a growing percentage of early disease, it is highly important to profile appropriately those subcentimeter lesions. This may affect therapeutic plans toward bigger surgeries for more aggressive appearance. The current retrospective study confirms the importance discrimination between GGO and solid pulmonary nodules.

  • Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non–Small Cell Lung Cancer

    Emily Castellanos MD, Emily Feld MD, Leora Horn MD, MSc

    Journal of Thoracic Oncology, Volume 12, Issue 4, April 2017, Pages 612 - 623

    Category:
    Topic: Diagnosis

    Commentary by Nir Peled

    Precision cancer care has been implemented in oncology and lung cancer has leaded this approach during the recent years with a great success. The specific mutation seems to play a significant role in the carcinogenesis process and therefore, a detailed report and a careful reading of the gene analysis are required. This review summarizes the current existing data about the prognostic and predictive power of common and uncommon mutations within the EGFR gene in lung cancer and emphasizes the importance of using high resolution technology to allow a better fit of our therapies.

  • Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs

    Chengjuan Zhang, Bing Wei, Peng Li et al.

    PLoS ONE, Volume 12, Issue 3, March 2017, Article number e0173524
    Category:
    Topic: Diagnosis

    Commentary by Nir Peled

    Seeing for T790M is highly important in EGFR+ treated patients as we may duplicate the success of the 1st line therapy by the approved osimertinib for progressed patients who are T790M positive. The most common approach for T790M detection is liquid biopsy and this study shows excellent sensitivity of ddPCR and ARMS PCR technologies which might be easily adopted into the clinical practice. Here we see that isolating T790M mutations is a poor prognostic marker; however, this study raises a un-answer question if we shell switch therapy upon the existence of T790M rather than waiting for clinical/imagine progression. It might be that early intervention may change disease history and prognostic will be shifted to predictive. Future studies will hopefully solve this question soon.

  • Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service

    Hamblin A, Wordsworth S, Fermont JM et al.

    PLoS Med. 2017 Feb 14;14(2):e1002230. doi: 10.1371/journal.pmed.1002230. eCollection 2017.
    Category:
    Topic: Diagnosis

    Commentary by Stefan Zimmermann

    Do you really perform gene panel testing to inform treatment decisions (usually conventional chemotherapy versus targeted therapy)? This audit of the UK NHS suggests otherwise! In fact, treatment data revealed that only about 40% of patients received any pharmacological therapy, targeted or otherwise: in contravention of operational policy, many samples were NOT from metastatic or otherwise advanced cancers. This highlights the 2 viewpoints of current genomic diagnostics: oncologists do not need more convincing to use gene panel testing on our tumor samples and could not work without their guidance, but health authorities and stakeholders do need to document value and utility. This audit establishes the cost-effectiveness of panel-testing rather than sequential gene testing in the NHS, with the additional benefits of speed, rationalization of processes and quality. With regards to the clinical utility, the study is limited by the restricted access to some targeted therapies within the NHS, but is expected to grow with the expanding number of validated targets and drugs. 

  • Clinical Impact of Hybrid Capture–Based Next-Generation Sequencing on Changes in Treatment Decisions in Lung Cancer

    Anna Belilovski Rozenblum MD, Maya Ilouze PhD, Elizabeth Dudnik MD, Addie Dvir MSc, Lior Soussan-Gutman PhD, Smadar Geva MSc, Nir Peled MD, PhD

    Journal of Thoracic Oncology, Volume 12, Issue 2, February 2017, Pages 258 - 268

    Category:
    Topic: Diagnosis

    Commentary by Nir Peled

    Precision care in lung cancer has shifted survival and quality of life for many of our patients. With appropriate diagnosis, more than half of our NSCLC may be treated first without chemotherapy (combining targeted therapies and pembrolizumab for eligible patients). This study shows the strong impact of multiplex hybrid capturing NGS above the routine approved PCR-based or ALK IHC/FISH methods. Using hybrid capturing NGS had huge impact on treatment decision which was later translated to 66% response rate and oversall survival benefit. Mis-diagnosis of a driver mutation hits the patients twice. First, patients are treated by chemo- and not by targeted drugs, and later, by immunotherapies where its benefit in patients with a valid driver mutation is very low. In conclusion, the use of sensitive technology is highly important in lung cancer therapy (tissue or ctDNA) and we shell do any possible effort to bring the best technology to our patients. 

  • PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project

    Fred R. Hirsch MD, PhD, Abigail McElhinny PhD, Dave Stanforth MBA, James Ranger-Moore PhD, Malinka Jansson MA, Karina Kulangara PhD, William Richardson BA, Penny Towne BS, MBA, Debra Hanks MD, Bharathi Vennapusa MD, Amita Mistry MD, Rasika Kalamegham PhD, Steve Averbuch MD, James Novotny PhD, Eric Rubin MD, Kenneth Emancipator MD, Ian McCaffery PhD, J. Andrew Williams PhD, Jill Walker PhD, John Longshore PhD, Ming Sound Tsao MD, Keith M. Kerr MB, FRCPath

    Journal of Thoracic Oncology, Volume 12, Issue 2, February 2017, Pages 208 - 222

    Category:
    Topic: Diagnosis

    Commentary by Nir Peled

    Pembrolizumab as first line therapy has become standard of care in NSCLC who express PDL1≥50%. In 2nd line, the survival benefit from all PD1/PDL1 agents is also correlated to PDL1 expression. However, each study used its own PDL1 biomarker. Therefore, tissue is required for primary diagnosis, molecular analysis and PDL1 staining.

    The Bluepring study aims to harmonize between the four PDL1 staining methods which were used for the different compounds. This effort is highly important as to avoid tissue exhaustion, if possible. The study shows a good correlation between three of the methods, while the SP142 assay (atezolizumab) stained less cells in comparison to the others which was later compensated by its immune-cell counts. Still, it is too early to jump into conclusions and the current recommendation is to use each biomarker for its related drug. To note, only pembrolizumab has been labeled upon PDL1 staining.

  • 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 2351-2358
    Category:
    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

    Category:
    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
    Category:
    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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A few pearls from ELCC 2017

5-8 May 2017, Geneva

by Stefan Zimmermann

A high-level forum where critical issues we face as thoracic oncologists are discussed, and cutting-edge new research is presented. 

Perspectives in Lung Cancer 2017

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


Now available: Webcast on demand


 

ECCO 2017

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


Did you miss the Satellite Symposium?

Now available: Webcast on demand


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

Interactive Case Reports

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