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.