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E-Poster Display

1491P - Bespoke circulating tumor DNA assay for the detection of minimal residual disease in esophageal adenocarcinoma patients

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Emma Ococks

Citation

Annals of Oncology (2020) 31 (suppl_4): S841-S873. 10.1016/annonc/annonc284

Authors

E. Ococks1, A. Ng2, G. Devonshire2, S. Dashner3, W. Chan3, S. Sharma3, H. Wu3, A. Redmond1, A. Northrop1, N. Grehan4, H. Sethi3, B. Zimmermann3, E.C. Smyth5, A. Aleshin6, R.C. Fitzgerald1, T. Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium1

Author affiliations

  • 1 Mrc Cancer Unit, Hutchison/mrc Research Centre, University of Cambridge, CB2 0XZ - Cambridge/GB
  • 2 Cancer Research Uk Cambridge Institute, University of Cambridge, CB2 0RE - Cambridge/GB
  • 3 Research And Development Department, Natera, 94070 - San Carlos/US
  • 4 Upper Gi, Cambridge University Hospitals, NHS Foundation Trust, Addenbrooke's Hospital., CB2 0QQ - Cambridge/GB
  • 5 Medical Oncology, Cambridge University Hospitals, NHS Foundation Trust, Addenbrooke's Hospital., CB2 0QQ - Cambridge/GB
  • 6 Medical Affairs, Oncology, Natera, Inc., 94070 - San Carlos/US
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Resources

Abstract 1491P

Background

Over half of Esophageal Adenocarcinoma (EAC) patients treated with curative intent relapse. In clinical practice risk stratification is limited to TNM staging, which highlights the need for additional methods. Circulating tumor DNA (ctDNA) following surgical resection is prognostic across different tumor types. However, the sensitivity and specificity of tumor-naive ctDNA panels are limited in the minimal residual disease (MRD) setting. Additionally, EAC is known to be a low shedding tumor type, thus, a personalized, tumor-informed approach for ctDNA analysis is ideal for MRD detection after treatment and for providing prognostic value in EAC patients.

Methods

Using the prospectively collected multi-centre UK OCCAMS dataset we identified patients (n=12) with pre- and post-surgical plasma samples (n=26). Mutational profiles derived from tumor tissue were used to design assays targeting patient-specific somatic variants (Signatera™ bespoke multiplex-PCR NGS assay). The personalized assays were used to determine the presence of ctDNA in the plasma samples of EAC patients. Additional patients are currently being processed and will be presented during the meeting.

Results

The cohort consisted of 12 patients with a median age of 62.8 (48.9 – 75.8) years, of which 83% were male and were T3 at diagnosis. All patients were treated with neoadjuvant chemotherapy, of which 2 also received radiotherapy. Minimal residual disease post-surgery was detected down to a mean variant allele frequency of 0.001%. Post-operative ctDNA analysis detected clinical relapse in 4 patients with a median lead time of 196 days giving a sensitivity and specificity of 100%.

Conclusions

In this pilot study, we showed that bespoke multiplex-PCR assays for esophageal samples achieve with high sensitivity and specificity to detect recurrence in this low shedding cancer type. This result is a vast improvement over other ctDNA assays, which show <40% EAC sensitivity. Further prospective studies are warranted to investigate the clinical utility of the bespoke ctDNA assay as a modern risk stratification tool in this cancer type.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Natera.

Disclosure

E. Ococks: Travel/Accommodation/Expenses: Roche. S. Dashner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. W-C. Chan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. S. Sharma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. H-T. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. H. Sethi: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. B. Zimmermann: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. E.C. Smyth: Honoraria (self), and personal fees: Astellas; Honoraria (self), and personal fees: Astra Zeneca; Honoraria (self), and personal fees: Merck; Honoraria (self), and personal fees: Celgene; Honoraria (self), and personal fees: Five Prime; Honoraria (self), and personal fees: Gritstone Oncology ; Honoraria (self), and personal fees: Servier. A. Aleshin: Advisory/Consultancy, Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera. R.C. Fitzgerald: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cyted Ltd; Licensing/Royalties, Named on patent: Cytosponge; Research grant/Funding (self): Astra Zeneca; Research grant/Funding (self): Roche. T. Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium: Research grant/Funding (self): CRUK. All other authors have declared no conflicts of interest.

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