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R. Damhuis



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    OA09 - Locally Advanced NSCLC: Innovative Treatment Strategies (ID 384)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      OA09.06 - Metformin Use during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (Abstract under Embargo until December 6, 7:00 CET) (ID 3753)

      11:00 - 12:30  |  Author(s): R. Damhuis

      • Abstract
      • Presentation
      • Slides

      Background:
      An increasing body of (pre)clinical evidence has suggested that metformin has an anticancer effect. The aim of this study was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.

      Methods:
      A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS)

      Results:
      No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p = 0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p = 0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p = 0.02 and 0.03).

      Conclusion:
      Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial.

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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-006 - Interlaboratory Variation in Molecular Testing (EGFR, KRAS and ALK) in Stage IV Non-Squamous Non-Small Cell Lung Cancer in the Netherlands in 2013 (ID 4112)

      14:30 - 15:45  |  Author(s): R. Damhuis

      • Abstract
      • Slides

      Background:
      Adequate testing for molecular changes in non-small cell lung cancer (NSCLC) is necessary to ensure the best possible treatment. However, it is unknown how well molecular testing is performed in daily practice. Therefore we aimed to assess the performance of testing for EGFR, KRAS mutation and ALK translocation in metastatic NSCLC on a nationwide basis.

      Methods:
      Using the Netherlands Cancer Registry, all stage IV non-squamous NSCLC from 2013 were identified and matched to the Dutch Pathology Registry (PALGA). Data on molecular testing for EGFR, KRAS and ALK were extracted from excerpts of pathology reports. Proportions of tested and positive cases were determined and interlaboratory variation was assessed. Finally, degree of concordance between ALK immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) results was evaluated.

      Results:
      In total, 3393 stage IV non-squamous NSCLCs were identified, and 3183 (93.8%) were matched to PALGA. Fifty-two tumors were excluded as pathology reports described a lung tumor other than non-squamous NSCLC or a tumor with another origin, leaving 3131 tumors. All 48 laboratories had access to molecular testing, either in house or via outsourcing. The table shows the nationwide proportions of cases tested and positive for EGFR, KRAS and ALK, as well as the interlaboratory variation. EGFR and KRAS mutations occurred together in 8 patients, ALK translocation occurred together with EGFR mutation in 3 patients and with KRAS mutation in 2 patients. In 272 cases, ALK had been tested using both IHC and FISH, and the methods were conclusive in 253 cases. IHC and FISH were concordant in 239 cases (94.5%; Kappa 0.728, p=0.069), 5 discordant cases were IHC+/FISH- and 9 were IHC-/FISH+.

      Nationwide proportions of tested and positive cases and interlaboratory variation.
      Total Tested cases; n (%) Range in tested cases between Laboratories Positive cases; n (%) Range in positive cases between laboratories
      EGFR 3131 2237 (71.4) 33.7% to 93.5% 243 (10.9) 6.1% to 21.6%
      KRAS 3131 2292 (73.2) 20.9% to 93.6% 845 (36.9)´╗┐ 27.0% to 48.1%
      ALK 3131 905 (28.9) 7.0% to 72.6% 51 (5.6) 0% to 13.6%
      ALK (in case of EGFR and KRAS wildtype) 1227 685 (55.8) 19.4% to 100%


      Conclusion:
      These results suggest that in 2013 molecular testing was suboptimal in the Netherlands, especially for ALK. To determine whether molecular testing has improved, 2015 data will be analyzed in the near future as well.

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