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Christel Reuterswärd



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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.07 - A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer (ID 13145)

      15:55 - 16:00  |  Author(s): Christel Reuterswärd

      • Abstract
      • Presentation
      • Slides

      Background

      Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients’ medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].

      4c3880bb027f159e801041b1021e88e8 Result

      In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.

      References

      1. http://www.cancercentrum.se/vast/cancerdiagnoser/lunga-och-lungsack/kvalitetsregister

      2. Staaf J, Jönsson G, Jönsson M, Karlsson A, Isaksson S, Salomonsson A,Pettersson HM, Soller M, Ewers SB, Johansson L, Jönsson P, Planck M. Relation between smoking history and gene expression profiles in lung adenocarcinomas. BMC Med Genomics. 2012 Jun 7;5:22.

      3. Karlsson A, Ringnér M, Lauss M, Botling J, Micke P, Planck M, Staaf J. Genomic and transcriptional alterations in lung adenocarcinoma in relation to smoking history. Clin Cancer Res. 2014 Sep 15;20(18):4912-24.

      4. Lindquist KE, Karlsson A, Levéen P, Brunnström H, Reuterswärd C, Holm K, Jönsson M, Annersten K, Rosengren F, Jirström K, Kosieradzki J, Ek L, Borg Å, Planck M, Jönsson G, Staaf J. Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer. Oncotarget. 2017 May 23;8(21):34796-34810.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-48 - Predictive Factors in NSCLC Patients with Stage IIIB/IV Treated with First Line Platinum-Doublet Chemotherapy (ID 13695)

      16:45 - 18:00  |  Author(s): Christel Reuterswärd

      • Abstract
      • Slides

      Background

      Predictive factors for response to chemotherapy in non-small cell lung cancer (NSCLC) are deficient. We investigate the associations between mutation status and treatment outcome of first line platinum-doublet chemotherapy in a 1.5 years population-based cohort of stage IIIB/IV patients. Furthermore, we will investigate the usefulness of gene expression signatures in predicting chemotherapy response in patients with advanced NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the region of Skåne, Sweden, n= 600 (preliminary) patients with NSCLC stage I-IV (TNM 7th edition) had conclusive results from reflex NGS testing with Illumina TruSightTumor 26-gene panel between January 2015 – June 2016. From this cohort, we include all patients with stage IIIB/IV with first line platinum-doublet treatment not interrupted by other cause than progressive disease (PD) and evaluate their extra-cranial response to treatment by using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with slight modifications. Patients who received radiotherapy against the primary tumor and/or mediastinum before or concomitant with chemotherapy are excluded.

      4c3880bb027f159e801041b1021e88e8 Result

      So far, 91 patients have been included, 10 (11%) with stage IIIB and 81 (89%) with stage IV. First-line chemotherapy included carboplatin/cisplatin in combination with gemcitabine/pemetrexed/vinorelbine. Bevacizumab were given in addition to chemotherapy in 3 patients. 25 (28%) responded with progressive disease (PD), 27 (30%) with stable disease (SD) and 39 (43%) with partial response (PR). TP53+/KRAS+ tumors were detected in 22 (24%) patients, TP53+/KRAS- in 34 (37%), TP53-/KRAS+ in 21 (23%) and TP53-/KRAS- in 14 (15%). No difference in response to treatment (p=0.6, Fisher’s exact test) or progression-free survival (PFS) (log rank test, p=0.6) according to mutation status was seen, although we observed a weak tendency of worse PFS in TP53+ patients with or without KRAS mutation compared to TP53-/KRAS- patients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this population-based Swedish cohort, mutations in KRAS and/or TP53 are not significantly associated with first line chemotherapy response. However, also subtypes of these mutations should probably be considered. Additional analyses of potential predictors of treatment response, in association with other clinicopathological variables, will be presented.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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