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B. Vrugt



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    P1.09 - Mesothelioma (ID 695)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P1.09-009 - Evaluation of a Combined MicroRNA-Clinical Score as Prognostic Factor for Malignant Pleural Mesothelioma (ID 9245)

      09:30 - 09:30  |  Author(s): B. Vrugt

      • Abstract
      • Slides

      Background:
      In 2015, a 6-microRNA signature (miR-Score, Kirschner et al 2015) was demonstrated to show high prognostic accuracy in a series of surgical specimens (with and without induction chemotherapy) from patients with malignant pleural mesothelioma. In-depth analysis of matching pre- and post-chemotherapy tissue specimens has recently shown that a refined 2-miR-Score appears more suitable for use in diagnostic chemo-naïve specimens (Kirschner et al, WCLC 2016). Here, in addition to continued validation, we also aimed to further improve the prognostic accuracy by combining the 2-miR-Score with known clinical prognostic factors.

      Method:
      Binary logistic regression modelling was used to build a combined score consisting of the 2-miR-Score and the clinical prognostic factors age (<60 years vs >60 years at diagnosis), gender and histological subtype (epithelioid vs non-epithelioid). In addition, microRNA analysis (RT-qPCR) was performed in an additional 33 pairs of chemo-naïve (diagnostic biopsy) and chemo-treated (EPP) specimens. Accuracy of the investigated scores in predicting a good prognosis (>20 months survival post-surgery) was evaluated by ROC curve analysis.

      Result:
      Combining the refined 2-miR-Score with the clinical prognostic factors histological subtype and age at diagnosis, increased the overall accuracy of the 2-miR-Score in both chemo-naïve diagnostic (AUC=0.80; 95% CI: 0.65-0.95) and post-chemotherapy (AUC=0.86; 95% CI: 0.73-0.98) specimens. Addition of gender as clinical prognostic factor, did not result in further increases, hence this factor was not included in the combined score. Investigation of an additional set of 33 matched pairs of chemo-naïve and post-chemotherapy tissue samples, confirmed the improved prognostic accuracy of the combined score, with AUCs of 0.76 (95% CI: 0.59-0.92) and 0.79 (95% CI: 0.64-0.95) for chemo-naïve and post-Chemotherapy specimens, respectively. Furthermore, addition of the clinical factors resulted in an increase in specificity of the prognostic score from previously 55-65% to now 65-75%, while keeping sensitivities at the previous levels of 75-85%. Importantly, the combined microRNA-clinical Score did not only outperform the 2-miR-Score, but also the clinical factors alone.

      Conclusion:
      This validation has confirmed the prognostic potential of the novel 2-miR-Score. Furthermore, addition of known clinical prognostic factors was shown to result in a combined Score with increased prognostic accuracy. In addition to continued validation, in currently ongoing analyses we are also investigating combining the 2-miR-Score with our previously proposed multimodality prognostic score (MMPS; Opitz et al 2015).

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