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C.P. O'Brien



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    MA 04 - Advocacy: Listen to the Patients (ID 655)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Patient Advocacy
    • Presentations: 1
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      MA 04.10 - An Assessment of the Willingness to Provide Serial Bio-Specimens: Experience from an Irish Tertiary Cancer Centre (ID 10076)

      11:00 - 12:30  |  Author(s): C.P. O'Brien

      • Abstract
      • Presentation
      • Slides

      Background:
      The rising imperative to improve our understanding of cancer heterogeneity and individualised drug response has led to a high demand for biopsy material. With improvements in technologies, there is now a move away from more traditional tissue based sampling to liquid based biopsies. ‘Liquid biopsies’ provide a non-invasive means for molecularly profiling patients with cancer, thus benefiting patients and clinicians in terms of treatment choice and shared decision-making. We assessed the willingness of patients to undergo repeated tissue and/or ‘liquid’ based sampling.

      Method:
      Detailed questionnaires, assessing patients’ perceptions of, and willingness to undergo serial biopsies were distributed to ambulatory patients at a tertiary cancer referral centre (St. James’s Hospital, Dublin). Multivariate analysis was performed using ordinal logistic regression analysis.

      Result:
      The questionnaire response rate was 97% (247/255). Respondents were primarily female (73%), aged between 51-70 yrs (51%), with breast (39%), colorectal (16%), oesophagogastric (13%), and lung cancer (12%). Of those that responded, repeat biopsy of an easily accessible lesion was acceptable to 203 (82%) patients if recommended by an oncologist. However this reduced to 102 (41%) patients, if the purpose was solely for clinical trial. Acceptability decreased to 168 (68%) and 81 (33%) patients respectively for more invasive biopsies. Additionally, 79 (32%) patients were willing to undergo additional biopsy for research purposes only, with 54 (21%) patients uncertain of its utility in research. Lower performance status (OR=0.44, p=0.04) and the belief that biopsy was unimportant for research (OR=0.74, p=0.04) negatively impacted on willingness to undergo biopsy, while a prior invasive biopsy increased acceptance (OR=1.02, p=0.02). In terms of blood sampling, 82% of patients would consent to repeated blood sampling over the course of their treatment, with >5 samples considered acceptable by 51.5% of patients. Patients with lung cancer had 3.38 greater odds (OR=3.38, p=0.047) of consenting to a repeated blood sample for purely research purposes (compared to any other type of cancer); however their willingness to undergo repeat biopsy was similar to that of other patients (OR=1.99, p=0.129). Data analysis is currently on-going.

      Conclusion:
      Patients with cancer are willing to participate in serial sampling of blood and urine but are less likely to consent to repeated tissue biopsies. Patients with lung cancer were particularly amenable to repeated blood sampling compared to patients with other cancer types. This is significant given the recent data supporting the use of ‘liquid’ biopsy for real-time monitoring of resistance mutations and treatment response dynamics in patients with lung cancer.

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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-053 - Optimization and Characterization of Assays to Identify Met Exon 14 Skipping in FFPE Embedded NSCLC Samples (ID 9881)

      09:30 - 16:00  |  Author(s): C.P. O'Brien

      • Abstract

      Background:
      The hepatocyte growth factor (HGF)receptor (MET), is frequently altered in NSCLC. Despite having a significant number of diverse mutations/alterations, randomized trials with MET inhibitors have proved disappointing, with no clinical benefit (1). More recently MET exon 14 skipping alterations have emerged as potential therapeutic targets as MET exon as they inhibit the degradation of Met, prolonging its oncogenic activity (2). Patients with Met exon 14 skipping have been found to sensitive to MET inhibitors such as crizotinib, and clinical trials of MET TKIs in METex14 mutated NSCLC are ongoing (1).

      Method:
      A one-step RT-PCR end-point PCR assay to examine for the detection of Met exon14 skipped mRNAs in FFPE was designed, optimized and tested on a cohort of NSCLC patients. Positive samples were confirmed by targeted next-generation sequencing of these samples. Finally RNA in situ hybridization (RISH) was optimised on a cMET exon 14 skipped cell line (NCI-H596) and subsequently performed on full-face sections using a specific BaseScope™ Assay (Techne).

      Result:
      Initial studies found that standard end-point PCR resulted in significant false-positives. However, a one-step RT-PCR methodology resolved this issue. Met exon 14 skipped samples were then examined in a cohort of pulmonary sarcomatoid carcinomas (PSCs). In agreement with another study of Caucasian patients (3), we identified Met Exon 14 skipped mutations in 2/20 (10%) of patients. Expression of Met exon 14 skipped was confirmed using targeted resequencing by NGS. RISH was also examined in the same samples.

      Conclusion:
      These results demonstrate the optimization of a methodology to robustly detect Met exon 14 mutated patients in FFPE material by a PCR based assay, with results comparable to those obtained in similar studies. This methodology can be utilised by any standard hospital diagnostic laboratory without the need for any specialized technology such NGS, RISH or FISH. A qPCR based version of this assay is currently being optimized and the results will be presented at the meeting. References Reungwetwattana, T. et al., (2017). Lung Cancer 103: 27–37 Pilotto, S. et al. (2017). Ann Transl Med 5(1):2 Saffroy, R. et al (2017). Oncotarget. 2017 Mar 21. doi: 10.18632/oncotarget.16403. [Epub ahead of print]