Abstract 413P
Background
The use of circulating tumor DNA (ctDNA)-based comprehensive genomic profiling (CGP) has rapidly grown and it is now considered an important supplement or alternative to tissue-based CGP. In addition to the improved sensitivity in detecting somatic variants, incorporation of advanced features such fusion detection, tumor mutation burden (TMB) and microsatellite instability (MSI) are expected to increase the utility of ctDNA-based CGP tests. However, the validation of these features are often insufficient.
Methods
The results of hybrid-capture based ctDNA CGP tests performed in a single institute, from Dec. 2022 to Jul. 2023 using TruSight Oncology 500 ctDNA assay (Illumina, CA, USA) were retrospectively reviewed. For the cases with targetable fusions reported, medical records were reviewed to identify whether targeted therapy was delivered and whether there was a response. For the cases with existing tissue-derived TMB/MSI and/or deficient mismatch repair status, the results were compared to those from ctDNA CGP. To identify the effect of tumor fraction on TMB, correlation of tissue TMB (tTMB) and blood TMB (bTMB) was analyzed before and after the stratification by maximum somatic allele fraction (MSAF), which is a surrogate for the tumor fraction.
Results
Total number of tests performed during the study period was 634 and major cancer types included non-small cell lung cancer, colon cancer, gastric cancer, etc. Fusions involving actionable drivers such as RET, ALK, and FGFR2 were identified from 19 tests (3.0%) from 17 patients. Four patients started targeted therapy based solely on ctDNA result and as a result, three showed response and one was yet to be evaluated. For ctDNA-derived MSI, adjustment in the cutoff value provided by manufacturer, based on the results from matched tissue, deemed necessary. The correlation between bTMB and tTMB was not observed (ρ=0.063, P=0.641). Instead, bTMB was affected by tumor fraction, showing higher value in specimens with higher MSAF.
Conclusions
Fusions detected from ctDNA CGP showed promising clinical utility based on the observed response to the targeted agents. Adjustments in the cutoff and correction of the effect from tumor fraction is required for ctDNA-derived TMB/MSI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
153P - IMbrave150: Exploratory analyses for investigating associations between overall survival (OS) and depth of response (DpR) or duration of response (DoR) in patients (pts) with unresectable hepatocellular carcinoma (HCC)
Presenter: Masatoshi Kudo
Session: Poster Display
Resources:
Abstract
154P - Adverse events (AEs) as potential predictive factors of activity in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (AB)
Presenter: Mara Persano
Session: Poster Display
Resources:
Abstract
155P - Penpulimab combined with anlotinib and nab-paclitaxel plus gemcitabine (PAAG) as first-line treatment for advanced metastatic pancreatic cancer: A prospective, multicenter, single-arm, phase II study
Presenter: Juan Du
Session: Poster Display
Resources:
Abstract
156P - Phase II trial of second-line regorafenib in patients with unresectable hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab: REGONEXT trial
Presenter: Jaekyung Cheon
Session: Poster Display
Resources:
Abstract
157P - T/N ratio and radiation dose delivered do not correlate with the development of Radioembolization-Induced Liver Disease (REILD) in Hepatocellular Carcinoma (HCC) following Y90 selective internal radiation therapy (Y90-SIRT): A retrospective, single tertiary centre cohort study
Presenter: Daniel Yang Yao Peh
Session: Poster Display
Resources:
Abstract
158P - Single-cell RNA sequencing via Endoscopic Ultrasoundguided Fine-Needle Biopsy (EUS-FNB) Pancreatic Biopsies uncovered an aggressive subclone with a poor prognosis
Presenter: Yung-yeh Su
Session: Poster Display
Resources:
Abstract
159P - Classical computer vision and modern deep-learning of pancreatic stroma histology features to diagnose cancer
Presenter: Abdelhakim Khellaf
Session: Poster Display
Resources:
Abstract
160P - Interim analysis of the NAPOLEON-2 study: Safety evaluation of nano-liposomal irinotecan with fluorouracil and folinic acid for advanced pancreatic cancer
Presenter: Wataru Kusano
Session: Poster Display
Resources:
Abstract
161P - Screening and COnsensus based on Practices and Evidence (SCOPE): Real-world survey on Japanese and rest-of-world practice patterns in resectable pancreatic cancer
Presenter: Elizabeth Smyth
Session: Poster Display
Resources:
Abstract
162P - Recurrence pattern of hepatocellular carcinoma patients receiving curative surgery of RFA: An update
Presenter: Long Chan
Session: Poster Display
Resources:
Abstract