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• W3139043362 abstract "Recent studies have reported that the more molecular matches, the better prognosis of clinical treatments is. “Matching score” based on a targeted panel is such an index to evaluate the prognosis of previously treated cancer patients receiving targeted- and immune-therapy, while no similar scoring system has been established for treatment-naïve patients. This research aims to construct a new therapeutic index (T-Index) to predict clinical prognosis for both treatment-naïve and treated NSCLC patients receiving targeted- and immune-therapy. Whole exome sequencing (WES, ∼39Mb CDS of over 18,000 genes) and targeted sequencing (TS, ∼1.1Mb CDS of 457 genes) were conducted on tumor samples from 102 stage IV NSCLC patients (treated N=32, treatment-naïve N=70) before targeted- (N=84) and immune-therapy (N=18) from 2018 to 2019. Molecular feature shared by WES and TS (SNV/Indel, CNV and tumor mutation burden (TMB)), and WES-specific molecular features (HLA genotyping, tumor neoantigen burden (TNB), loss of heterozygosity (LOH) and intra-tumoral heterogeneity (ITH)) were analyzed to identify prognostic predictors, and T-Index of WES and TS was each calculated. The association of both T-Indexes with objective response rate (ORR) and progression-free survival (PFS) were analyzed and compared. The cutoff of 0.5 was chosen according to the minimum P value approach. ORR and PFS were significantly higher and longer in patients with T-Index>0.5 than those with T-Index<=0.5 in previously treated patients (N=39) using WES (p=7e-0.4 for ORR, p=0.005 for PFS), but not using TS (p=0.388 for ORR, p=0.119 for PFS) (Figure 1A and 1C). In the treatment-naïve patients (N=70, targeted N=62, immunotherapy N=8), ORR in patients with T-Index>0.5 was significantly higher than those with T-Index<=0.5 using both WES (73.5% vs. 31.8%, p=0.002, Figure 1B) and TS (73.9% vs. 36.4% p=0.004, Figure 1D). A higher T-Index was also an independent predictor of longer PFS in WES (8.4mo vs. 5.5mo, p=0.012) and TS (9.5mo vs. 7.4mo, p=0.035) for treatment-naïve patients (Figure 1B and 1D). Our results showed that T-Index by WES including non-canonical biomarkers, TNB, HLA genotyping, LOH and ITH, is significantly associated with clinical outcome whether in treatment-naïve or previously treated patients. Since TS are more practical for companion diagnostics in clinical, a new version of sequencing panel which covers non-canonical biomarkers related to immunotherapy listed above is needed to be developed and tested with the study going forward." @default.
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• W3139043362 date "2021-03-01" @default.
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• W3139043362 title "FP12.13 Therapeutic Index Predicts Clinical Outcome of both Treated and Treatment-Naïve NSCLC Patients Receiving Targeted- and Immune-Therapy" @default.
• W3139043362 doi "https://doi.org/10.1016/j.jtho.2021.01.139" @default.
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