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Assunta De Rienzo

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    MA12 - New Frontiers from Pathology to Genomics (ID 138)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA12.06 - Patient-Derived Organotypic Tumor Spheroids (PDOTS) Facilitate Therapeutic Screening for Malignant Pleural Mesothelioma (Now Available) (ID 2561)

      14:00 - 15:30  |  Author(s): Assunta De Rienzo

      • Abstract
      • Presentation
      • Slides


      While genotype directed therapies are an essential aspect of personalized medicine in non-small cell lung cancer (NSCLC), this modality is not currently an option in mesothelioma. Instead there is a need for improved functional testing via predictive platforms that can help identify the susceptibility of patient tumors to drug therapies. Here, we demonstrate the use of a novel ex vivo functional system utilizing 3D microfluidic culture and patient-derived organotypic tumor spheroids (PDOTS) as a platform to study the tumor microenvironment and predict tumor responses to treatment in mesothelioma.


      We evaluated 31 mesothelioma patient specimens under an IRB approved protocol. PDOTS of mesothelioma were generated as previously described (Larios et al. AACR. 2017; Jenkins et al. Cancer Discovery. 2017). Samples were treated with standard chemotherapy (pemetrexed and cisplatin combined) as well as immunotherapy (ipilimumab and pembrolizumab combined) and live/dead quantification was conducted using dual labeling de-convolution fluorescence microscopy. Positive responses ex vivo included samples with significant cell death to control while positive in vivo responses were based on radiologic lack of tumor recurrence using the response evaluation criteria in solid tumors (RECIST, version 1.1) to assess for disease progression.


      We found that in treatment naïve specimens prolonged ischemic times were associated with decreased tissue viability (ischemia >25 minutes resulted in decrease of live cells from an average of 81% to 56%), lower tumor yield (< 50% tumor content), and decreased generation of spheroids (< 20 spheroids/well). Specimens with prior treatment were consistently associated with low tissue viability irrespective of ischemic times. Of the 31 specimens studied, 10 samples met viability and tumor content standards to undergo further treatment with standard chemotherapy and immunotherapy, and 5 of those samples were tracked to available patient-treatment response data. Ultimately, comparison of ex vivo and in vivo treatment responses demonstrated that 4 of 5 samples treated with standard chemotherapy had concordant responses to those of patients who received the same or similar post-operative therapy. Notably, our discordant sample exhibited large variation in standard deviations due to technical variability.


      Here we demonstrate that analysis of ex vivo mesothelioma tissue correlates to in vivo responses. These results suggest that PDOTS can serve as a predictive platform for therapies. Further work streamlining human tissue collection and optimizing factors that affect formation of PDOTS prior to ex vivo treatment analysis should be further investigated.

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