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Alka Saxena



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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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      MA12.05 - Genomic Analysis of Long Term Malignant Pleura Mesothelioma Patients Treated with Palliative Chemotherapy (Now Available) (ID 2750)

      14:00 - 15:30  |  Author(s): Alka Saxena

      • Abstract
      • Presentation
      • Slides

      Background

      Malignant Pleural Mesothelioma (MPM) is an aggressive tumor related to asbestos exposure with a median survival of 9 months from diagnosis. The aim of this study was to evaluate correlation between genetic mutations and survival in patients who received only palliative chemotherapy.

      Method

      From 2005 to 2015, 720 patients underwent a surgical pleural biopsy and were diagnosed with malignant pleural mesothelioma. Among these, 27 patients survived longer than 30 months (long survival) from diagnosis and 113 survived less than 30 months. The pleural biopsy of the long term survival patients were reviewed and 12 FFPE samples were considered suitable and matched with 12 FFPE biopsy samples from patients who survived less than 12 months.

      Result

      The DNA of 24 patients was sequenced. One sample did not reach quality to be further considered and was excluded. The mean age of total population was 71.6±8.8 and 15 patients were males (table 1). Eleven patients had a mean overall survival of 5.5 months while 12 patients lived more than 30 months. The mutational analysis identified a total of 428 alterations of which 148, classified as somatic and functional, were further considered. Among these, 85% were missense variants, 8% were variants causing a stop gain, 6% were splice variants. UQCRC1 was significantly associated with a reduced survival of MPM patients (p=0.027); figure 1. Positive trend of correlation was observed between mutations in ACTR1 and CUL1 and short MPM survival. By contrast, no significant correlation was observed between gene mutations and long survival.

      Figure 1.

      figure 1 updated.jpg

      Table 1. patient characteristics.

      Variable

      Long survival

      n=12 (%)

      Short Survival

      n=11 (%)

      P value
      Age (median) 67 72 0.216
      Sex 0.193
      Female 6 (50) 2 (18.2)
      Male 6 (50) 9 (81.8)
      Side 0.684
      Right 7 (58.3) 5 (45.5)
      Left 5 (41.7) 6 (54.5)

      Conclusion

      This is the first study that focusing on MPM patients not suitable for multimodality treatment investigated differences in mutational profile between short and long survivors. Our results suggest a possible role of mitochondria metabolism in mesothelioma aggressiveness.

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