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Yangsi Li
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-81 - A New Prognostic Index Combines the Metabolic Response and RECIST 1.1 to Evaluate the Therapeutic Response in Patients with Lung Cancer (ID 752)
09:45 - 18:00 | Author(s): Yangsi Li
- Abstract
Background
Response Evaluation Criteria in Solid Tumors (RECIST) is occasionally insufficient for evaluation. We propose a new prognostic index (NPI) that combines the standardized uptake value (SUV), metabolic tumor volume (MTV) and RECIST.
Method
In total, 163 patients with lung cancer who underwent positron emission tomography-computed tomography prior to and after treatment were included. We formulated the NPI by estimating the hazard ratios of overall survival for ∆MTV, ∆SUVmax and ∆D (tumor size based on RECIST). Then the regression coefficients were used, which gave rise to the HRs, as weights to formulate the new prognostic index (NPI). Progression-free survival (PFS) and overall survival (OS) were compared between RECIST and the NPI.
Result
ROC curve analysis identified two cutoff values based on the NPI (≤-44.0% and >40.4%) to discriminate partial remission (NPR), stable disease (NSD) and progressive disease (NPD). The concordance rate between RECIST and NPI was 74.2% (κ = 0.572, P<0.001). Based on RECIST, survival analysis did not discriminate significantly on either PFS or OS between the PR, SD and PD groups. However, according to the NPI, PFS and OS differed significantly between the NPR, NSD, and NPD groups (training set: PFS, P = 0.007; OS, P = 0.027; validation set: PFS, P = 0.003; OS, P = 0.044). In total, 83 patients with SD were reclassified based on the NPI (20 with NPR, 57 with NSD, 6 with NPD), and the patients reclassified as NPR showed prolonged PFS (P = 0.004) and OS (P = 0.026) compared with those in the NSD+NPD group.
Conclusion
The NPI shows superiority for evaluation of the therapeutic response and survival for patients with lung cancer, especially in the assessment of SD patients based on RECIST.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-88 - Molecular Alterations in Cerebrospinal Fluid Predict Clinical Outcomes of Central Nervous System Metastases in Lung Cancer (ID 1511)
10:15 - 18:15 | Author(s): Yangsi Li
- Abstract
Background
Cerebrospinal fluid (CSF) has been proven as good media for genetic profiling of central nervous system (CNS) metastases. However, the association of genetic alterations in CSF and clinical outcomes remains elusive.
Method
A total of 94 lung cancer patients with CNS metastases underwent lumbar puncture. Circulating tumor DNA were extracted from CSF and profiled by next-generation sequencing. The effect of genetic alterations in CSF on survival and treatment outcomes were evaluated.
Result
The most common genes seen in CSF were EGFR, TP53, MET, CDKN2A, MYC, NTRK1 and CDK6. Kaplan-Meier survival analysis indicated that CDK4, CDK6, FGFR1, MET and MYC alterations, which were also characterized by more copy number changes, were associated with poor survival. Multivariate analysis found only MET (HR, 2.01; 95% CI, 1.15 to 3.52) and MYC alterations (HR, 2.31; 95% CI, 1.27 to 4.21) were correlated to poor OS. Forty-two patients harbored high n-CNVs (defined as the number of genes with copy number variations >2) while 50 patients carried low n-CNVs (defined as the number of genes with copy number variations <=2). Median overall survival (OS) of patients with high n-CNVs in CSF was 14.9 months (95% CI, 9.2 to 25.8 months), significantly shorter than those with low n-CNVs (21.6 months, 95% CI, 17.9 months to not reached (NR); HR, 1.9; 95% CI, 1.11 to 3.24; P=0.016). Patients with high n-CNVs and MET and MYC CNVs (copy number variations) were associated with the poorest OS. Osimertinib significantly prolonged OS only among patients with high n-CNVs (with vs. without osimertinib, 25.8 vs. 9.2 months; P=0.004). Among T790M negative patients, high n-CNVs seemed to positively associate with better response to osimertinib (OS with vs. without osimertinib, 23 vs. 7.8 months; P=0.058). Further analysis indicated that EGFR and FGFR1 CNV were the most significant factors associated with OS benefit from osimertinib among the high n-CNVs group (P=0.014; P=0.02). TP53_LOH and Wnt pathway alterations were significantly more prevalent in the high n-CNVs group than in the low n-CNVs group (P=0.016, P=0.006). With regard to clinical characteristics, higher performance status score (HR, 2.06; 95% CI, 1.38 to 3.07; P=0.0004) and occurrence of extracranial metastases (HR, 3.21; 95% CI, 1.25 to 8.24; P=0.015) suggested poor OS.
Conclusion
While genetic profiles in CSF, like high n-CNVs as well as MET and MYC CNV were related to poor prognosis, patients with high n-CNVs, especially those with EGFR or FGFR1 CNV might benefit more from osimertinib, further supporting CSF as liquid biopsy of CNS metastases in lung cancer.
