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
5964 - Longitudinal Assessment of Multiplex Patient-Specific ctDNA Biomarkers in Bladder Cancer for Diagnosis, Surveillance, and Recurrence
Presenter: Karin Birkenkamp-Demtröder
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
2197 - Distinct functional consequences of HER2 gene amplification in colorectal and lung adenocarcinomas
Presenter: Evgeny Imyanitov
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
2422 - Role of AR-V7 and AR-FL in resistance to hormonal therapy in mCRPC: independent actors or reciprocal drivers? A translational study by Meet-Uro group
Presenter: Marzia Del Re
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
2750 - Validation of a 90-gene assay for tissue origin diagnosis of brain metastases
Presenter: Yulong Zheng
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
2960 - Development of a Pan-Cancer Biomarker Panel for Improved Detection of MSI Across all Cancer Types
Presenter: Jeff Bacher
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
3791 - bMSI better predicts the responses to immune checkpoint inhibitors (ICI) than MMR/MSI from historical tissue specimens in metastatic gastrointestinal cancer patients
Presenter: Zhenghang Wang
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
5189 - Vall d’Hebron Institute of Oncology (VHIO) Immuno-Oncology prognostic index (VIO): a new tool for improved patient (pt) selection in Phase 1 (Ph1) trials with Immune Checkpoint Inhibitors (ICI).
Presenter: Cinta Hierro
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
5372 - Augmenting TNM Staging with Machine Learning-based Immune Profiling for Improved Prognosis Prediction in Muscle-Invasive Bladder Cancer Patients
Presenter: Nicolas Brieu
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
2249 - HPV circulating tumor DNA as predictive biomarker of sustained response to chemotherapy in advanced anal carcinoma
Presenter: Alice Bernard-Tessier
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
2287 - Predicting toxicity and response to pembrolizumab (P) through germline genomic HLA class I analysis
Presenter: Marco Iafolla
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