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Federica Torricelli
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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
- Moderators:Prasad S Adusumilli, Francisco Perez Ochoa
- Coordinates: 9/09/2019, 14:00 - 15:30, Melbourne (1991)
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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): Federica Torricelli
- Abstract
- Presentation
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.
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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P1.06 - Mesothelioma (ID 169)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.06-16 - Molecular Signature in Malignant Pleural Mesothelioma (MPM). Preliminary Data of Rames Study (ID 254)
09:45 - 18:00 | Author(s): Federica Torricelli
- Abstract
Background
MPM is an uncommon cancer with limited therapeutic options and poor clinical outcomes. The relative rarity of these tumor has limited the identification of MPM-driver molecular as well as the development of specific drugs
Method
RAMES study evaluated the second-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo.
From December 2016 to July 2018 (end of enrolment), 164 patients (pts) were admitted to this study.
We evaluated by NGS the mutational profile of a panel of 34 genes (ACTB, ACTG1, ACTG2, ACTR1A, BAP1,CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6,-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53,TXNRD1, UQCRC1, XRCC6).
We reported the results of the first 87 pts (54%): hystotype was epithelioid in 70 pts (80%), biphasic in 14 pts (16%) and sarcomatoid in 3 pts (4%). Median age was 63 years (range 45-81). 70 pts were male (80%) and 17 pts were female (20%). In the present analysis, we included 55 pts in stage III (63%), 26 pts in stage IV (30%) and 6 pts whose stage was unknown. Median first-line PFS platinum/pemetrexed therapy was for 5.75 months (I.C. 95% 4.75-6.76). PFS was ≤6 months for 40 pts (49%), and 6 months for 41 pts (51%).
Result
187 functional somatic mutations were identified. Genomic alterations/patient were 1 gene in 29 pts (33%), 3 genes in 18 pts (21%) and ≥5 genes in 2 pts (2%). The most frequent somatic mutations were RDX in 35 pts (40%), MXRA5 in 20 pts (23%), BAP1 in 13 pts (15%) and ACTG 1 in 9 pts (11%). When patients were collated by stage, the most frequent mutations were: MXRA5 in 16 pts in stage III (29%), BAP1 in 5 pts in stage IV (19%) and RDX in 16 pts in stage IV (62%). The percentage of somatic mutations in patients with PFS as first-line chemotherapy for ≤6 and >6 months was 2.2 and 1.6 (p=0.032), respectively. The most frequent mutations/patient for ≤6 and >6 months PFS were: RDX in 14 pts (35%) with PFS < 6, RDX in 19 pts (46%) with PFS >6 and MXRA5 in 11 pts (27%) with PFS >6.
Conclusion
This preliminary data suggests a possible role that a genetic signature may play in distinguishing MPM with different clinical-pathological features. The results are expected to be clarified further in the second step of the study, which is ongoing.
