10600 Background: Blood or saliva DNA generally considered to be representative of germline genome in genetic cancer risk assessment. However white blood cells from these samples may also include somatic origin DNA due to postzygotic variation or, most commonly, clonal hematopoiesis (CH). Low variant allele fraction (VAF) found in germline genetic testing suggest the possibility of somatic variant and may lead to misinterpretation of genetic risk. TP53, of which germline pathogenic variants are associated with Li-Fraumeni syndrome (LFS), is frequently mutated in CH. This analysis investigated characteristics of TP53 pathogenic variants with low VAF. Methods: We reviewed the prevalence and distribution of TP53 pathogenic variants(PVs) detected in 11,277 advanced cancer patients who underwent clinical testing with a clinical NGS pan-cancer panel. Potential somatic PVs were defined as variants with low VAF from 10% to 35%. The VAF were evaluated in matched tumor tissue samples if available. Results: TP53 pathogenic variants were detected in 36 (0.32%) patients from blood or saliva samples, VAF between 10% and 35% were identified in 8(22.22%) patients and 7 of them were performed NGS sequencing in matched tumor tissue samples. The average VAF of tissue samples were 9.31times lower than blood or saliva samples(21.69% vs 3.88%). Conclusions: TP53 pathogenic variants with low allele fraction in blood or saliva samples indicate the possibility of somatic variant, a reduced VAF in matched tumor tissue samples may contribute to confirmation for suspicion of somatic origin.
493 Background: To compare the efficacy and safety of sorafenib plus transarterial chemoembolization (SOR-TACE) versus sorafenib alone as postoperative adjuvant therapy for hepatocellular carcinoma (HCC) patients with portal vein thrombus (PVTT). Methods: This was a phase III, multicenter, randomized, control clinical trial. Eligible HCC patients with PVTT were included and randomly assigned (1:1) to receive SOR-TACE or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400mg twice a day. In the SOR-TACE group, TACE was performed one day after the administration of sorafenib. The primary endpoint was recurrence-free survival (RFS). Results: From October 2019 to March 2022, a total of 158 HCC patients with PVTT from China were enrolled and randomized. After a median follow-up duration of 28.4 months, the median RFS was significantly longer in the SOR-TACE group (16.8 vs. 12.6 months; hazard ratio, 0.57; P = 0.002). The median overall survival (OS) was also significantly longer with SOR-TACE than with sorafenib (30.4 vs. 22.5 months; hazard ratio, 0.57; P = 0.017). Multivariable analysis indicated SOR-TACE treatment was an independent risk factor for both RFS and OS. The SOR-TACE group did not show additional toxicity compared with the sorafenib alone group. Conclusions: The combination of sorafenib and TACE as postoperative adjuvant therapy in HCC patients with PVTT resulted in longer RFS and OS compared to sorafenib alone and was well tolerated. Clinical trial information: NCT04143191 .
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