Abstract 5099
Background
Biliary tract cancer (BTC) shows increasing incidence and is associated with a high mortality. Diagnosis is difficult due to the frequently occurring inaccessibility of the tumor for biopsy. Noninvasive approaches for assessing and monitoring the tumor-specific molecular setup are desirable to improve diagnosis and tailor treatment.
Methods
Blood and tumor tissue samples from patients with locally advanced or metastatic BTC were collected prior to and during palliative treatment. Tumor tissue and corresponding ctDNA samples were subjected to targeted resequencing of 15 genes frequently mutated in BTC (TP53, KRAS, ARID1A, BAP1, PBRM1, PIK3CA, SMAD4, FBXW7, IDH1, BCL2, BRAF, CDKN2A, ERBB2, IDH2, NRAS). Findings were correlated with clinical and imaging data.
Results
24 therapy naive patients with histologically confirmed BTC were included into the analyses. The mutational concordance (blood/tissue) was 74% overall and 92% for intrahepatic tumors only. Mean variant allele frequency (VAF) detected in tumor tissue was significantly higher compared to ctDNA (p = 0.0291). In turn, the sequencing depth for ctDNA was about double of that for tissue samples (1010x vs. 465x), enabling the detection of variants in ctDNA. ctDNA VAF at baseline significantly correlated with tumor load (Spearman, r = 0.4073, p = 0.0433). Interestingly, for intrahepatic BTC baseline ctDNA VAF also significantly correlated with progression-free survival (Spearman, r=-0.5878, p = 0.0288). 36% of therapy naive patients had a change in their mutational profile during chemotherapy.
Conclusions
The molecular landscape of BTC is represented in ctDNA and most tumor specific variants are detectable in ctDNA, especially in intrahepatic BTC. In this subgroup the baseline VAF in ctDNA was also of prognostic significance. Additionally, we detected hints for tumor evolution in a relevant portion of the analyzed BTC patients during chemotherapy, which have to be further investigated. Altogether, ctDNA analysis in BTC may support diagnosis, prognosis and the adaption of therapeutic strategies according to the specific molecular setup of the tumor detected at any time point during chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Ulm University.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4679 - Correlative analyses of serum biomarkers and efficacy outcomes in the randomized phase 2 trial of lenvatinib (LEN), everolimus (EVE), or LEN+EVE in patients with metastatic renal cell carcinoma
Presenter: Chung-Han Lee
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5379 - End-to-end learning to predict survival in patients with gastric cancer using convolutional neural networks
Presenter: Armin Meier
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5394 - Detection of Targetable Kinase Fusions in 7260 patients in an integrated Cancer System
Presenter: Ankur Parikh
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5884 - Clinical and analytical validation of an FDA approved comprehensive genomic profiling (CGP) assay incorporating multiple companion diagnostics for targeted and immunotherapies
Presenter: Yali Li
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5912 - SET overexpression promotes colorectal cancer progression and determines poor outcome in patients with localized disease.
Presenter: Blanca Torrejón
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1168 - The functional MDM4 genetic variant in advanced lung adenocarcinoma patients treated with EGFR-TKIs
Presenter: Nasha Zhang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3071 - PD-L1 expression on pre-treatment circulating tumour cells, but not serum VEGF, is predictive of response to pembrolizumab in melanoma
Presenter: Muhammad Khattak
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4062 - Olaparib plus paclitaxel sensitivity in biomarker subgroups of gastric cancer
Presenter: Yu-Zhen Liu
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4801 - A diagnostic model for hepatitis B virus-related hepatocellular carcinoma in China: a large-scale, multi-center study
Presenter: Tian Yang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4874 - Dissecting Gastric Cancer biology and how and when to use immunotherapy
Presenter: Meghna Das Thakur
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract