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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

5099 - Genotyping of circulating tumor DNA in biliary tract cancer reveals diagnostic and prognostic information

Date

20 Oct 2018

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

Presenters

Thomas Ettrich

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

T.J. Ettrich1, D. Schwerdel1, A. Dolnik2, F. Beuter1, T. Blätte2, S.A. Schmidt3, N. Stanescu-Siegmund3, J. Steinacker3, R. Marienfeld4, A. Kleger1, L. Bullinger2, T. Seufferlein5, A.W. Berger1

Author affiliations

  • 1 Internal Medicine I, Ulm Medical University, 89081 - Ulm/DE
  • 2 Internal Medicine Iii, Ulm Medical University, 89081 - Ulm/DE
  • 3 Diagnostic And Interventional Radiology, Ulm Medical University, 89081 - Ulm/DE
  • 4 Pathology, Ulm Medical University, 89081 - Ulm/DE
  • 5 Department Of Internal Medicine I  , Ulm Medical University, 89081 - Ulm/DE
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Resources

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.

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