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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

2042 - Developing the liquid biopsy in gastroesophageal adenocarcinoma: Disease monitoring and detection of minimal residual disease

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

Mark Openshaw

Citation

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

Authors

M.R. Openshaw, B. Ottolini, C.J. Richards, D. Guttery, J.A. Shaw, A. Thomas

Author affiliations

  • Leicester Cancer Research Centre, University Hospitals of Leicester NHS Trust Leicester Royal Infirmary, LE1 5WW - Leicester/GB
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Resources

Abstract 2042

Background

Gastroesophageal adenocarcinoma (GOA) is a molecularly defined group of cancers with shared genetic alterations, poor overall survival and no routine blood based biomarker. The liquid biopsy, including circulating tumour DNA (ctDNA) is a promising technology that may improve our ability to monitor disease and enhance survival. This study aimed to determine the utility of ctDNA in GOA.

Methods

A pilot study of 37 patients with GOA were recruited. These comprised 24 patients treated with curative intent and 13 palliative patients. Tumour DNA was sequenced using a custom ampliseq six gene targeted next generation sequencing (NGS) panel. Tumours from patients treated with curative intent with no detectable somatic mutation were also analysed for gene amplification via Nanostring™ nCounter. Plasma from blood samples taken at multiple time points were analysed by NGS and digital droplet PCR to detect ctDNA.

Results

Somatic mutations at > 5% allele frequency were identified in 30 of 37 (81%) tumours, most commonly in TP53. Gene amplification was detected in a further three. In 11 of 13 (85%) palliative patients that had a detectable somatic mutation ctDNA was detected in 9 (82%). These ctDNA levels were dynamic, falling with treatment response and rising with disease progression, often prior to clinical relapse. 22 of 24 (92%) patients treated with curative intent had a detectable somatic mutation or gene amplification. 9 of these 22 (41%) relapsed during follow-up. CtDNA was detected prior to relapse in 7 of 22 (31%) patients and predicted poor survival (median PFS 298 vs > 1000 days, HR = 11.8, p < 0.001). In 4 patients, ctDNA was detected in the postsurgical blood test, of these 3 have relapsed and one remains disease free at 5 months (median PFS 203 vs > 1000 days, HR = 9.6, p = 0.004). This patient will be followed up for evidence of relapse as these ctDNA positive post surgical bloods suggest detection of minimal residual disease.

Conclusions

Tracking of ctDNA in patients with GOA provides valuable clinical information regarding disease progression and response, and presence of ctDNA is generally a poor prognostic sign. In addition, ctDNA may define patients with minimal residual disease who are at high risk of relapse after surgery.

Clinical trial identification

Not an inteventional clinical trial

Legal entity responsible for the study

University of Leicester.

Funding

HOPE against Cancer Experimental Cancer Medicine Centres Network.

Editorial Acknowledgement

Nil

Disclosure

B. Ottolini: Previous employee: DiaDx; Holding patents: DiaDx. C.J. Richards: Honoraria: MSD. J.A. Shaw: Travel, accommodation, expenses reimbursements: Thermofisher. A. Thomas: Honoraria: Amgen, Servier, BMS. All other authors have declared no conflicts of interest.

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