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Andreas Limbeck



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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • 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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      P2.06-21 - Low Intratumoral Platinum Concentration is Associated with Unfavorable Clinical Outcome in Malignant Pleural Mesothelioma (ID 12883)

      16:45 - 18:00  |  Author(s): Andreas Limbeck

      • Abstract
      • Slides

      Background

      Malignant pleural mesothelioma (MPM) is a rare but devastating malignancy characterized by poor prognosis. Systemic anti-MPM therapy is based on platinum compounds. Unfortunately, however, chemoresistance is a major obstacle in the treatment of MPM. Although inadequate intracellular drug uptake is one of the most frequent causes of platinum resistance, the impact of tumor tissue and circulating platinum concentrations on clinical outcome in MPM patients remains unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Spatial distribution and average tumor concentration of platinum was assessed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in tumor samples of MPM patients (n=26) receiving platinum-based induction chemotherapy followed by surgical resection. Circulating platinum concentration was also analyzed by ICP-MS in serum samples (n=29) taken prior to surgery. Tumor and serum drug levels were correlated with various clinicopathological parameters.

      4c3880bb027f159e801041b1021e88e8 Result

      Patients with low average tissue platinum concentrations had significantly shorter overall survival. Interestingly, the spatial distribution of platinum was very heterogenous in the tissue samples. The drug accumulated in collagen-rich, post-necrotic scar tissue compartments, while its level was relatively low in the viable tumor areas. Circulating cisplatin levels negatively correlated with the time between the last chemotherapy cycle and blood sampling.

      8eea62084ca7e541d918e823422bd82e Conclusion

      By using an innovative technique for lateral trace element distribution analysis, we demonstrate here for the first time that low tissue platinum uptake is associated with significantly worse clinical outcome in MPM and, furthermore, that relatively higher platinum levels are confined to areas of intratumoral scar tissue. Our results suggest that insufficient drug uptake might be an important factor of cisplatin resistance in the clinics. Further studies are needed to clarify the significance of heterogeneous intratumoral platinum distribution.

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