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.
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.
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%.
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.
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Editoral support was provided by Allyson Koyen Malashevich, Ph.D. from Natera, Inc.
The authors.
Natera Inc.
E. Ococks: Travel/Accommodation/Expenses: Roche. A. Ng: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. S. Dashner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. W-C. Chan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. S. Sharma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. H-T. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. H. Sethi: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. B. Zimmermann: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. E. Smyth: Honoraria (self): Astellas; Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Zymeworks; Honoraria (self): Celgene; Honoraria (self): Five Prime; Honoraria (self): Gritstone Oncology; Honoraria (self): Servier. A. Aleshin: Advisory/Consultancy: Notable Labs; Advisory/Consultancy: Mission Bio; Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. R. Fitzgerald: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cyted Ltd.; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche; Licensing/Royalties, named on patents related to Cytosponge and associated assays: Patent. All other authors have declared no conflicts of interest.