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E-Poster Display

420P - Minimal residual disease detection and tracking tumour evolution using ctDNA in stage I-III colorectal cancer patients

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Tenna Henriksen

Citation

Annals of Oncology (2020) 31 (suppl_4): S409-S461. 10.1016/annonc/annonc270

Authors

T.V. Henriksen1, N. Tarazona2, T. Reinert1, J.A. Carbonell-Asins2, D. Roda2, M. Huerta2, S. Roselló2, A.H. Madsen3, L.H. Iversen4, K.A. Gotschalck5, S. Sharma6, H. Wu6, S. Shchegrova6, A. Tin6, H. Sethi6, B. Zimmermann6, A. Aleshin6, C.L. Andersen1, A. Cervantes2

Author affiliations

  • 1 Department Of Molecular Medicine, Aarhus University Hospital, 8000 - Aarhus/DK
  • 2 Medical Oncology, INCLIVA Biomedical Research Institute. University of Valencia. Instituto de Salud Carlos III, CIBERONC., 46010 - Valencia/ES
  • 3 Department Of Surgery, Regional Hospital Herning, 7400 - Herning/DK
  • 4 Department Of Surgery, Aarhus University Hospital, 8200 - Aarhus N/DK
  • 5 Department Of Surgery, Regional Hospital Randers, 8930 - Randers NØ/DK
  • 6 Rnd, Natera Inc., 94070 - San Carlos/US
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Resources

Abstract 420P

Background

At diagnosis, ∼25% of colorectal cancer (CRC) patients have synchronous metastases and ∼30% develop metachronous metastases. Little is known about the heterogeneity of these tumours, which warrants better identification tools to detect recurrence. In this study, we sought to evaluate the clinical utility of circulating tumour DNA (ctDNA) in identifying minimal residual disease (MRD) and monitoring of recurrence.

Methods

The prospective, multicenter cohort study recruited patients (n=196) diagnosed with stage I-III CRC. Median follow-up time was 21.9 (1.4-41.9) months. For each patient, a personalized and tumour-informed multiplex PCR (mPCR) NGS assay was used to track ctDNA in plasma samples. The relationship between ctDNA status and clinical outcomes was evaluated. The analysis of spatial heterogeneity was performed between primary and metastatic tumours, as well as between synchronous primary tumours to track clonal and subclonal mutations.

Results

Phylogenetic comparison of paired primary and metastatic mutation profiles revealed 50% overlap in mPCR targeted variants, suggesting success in targeting clonal mutations. The mutational profiles of synchronous primary tumours were non-overlapping. This led to design of unique assays for each synchronous primary tumour to reliably detect recurrence. Postoperatively and prior to ACT, 9% (14/155) of patients showed MRD-positivity, and 78.5% (11/14) relapsed (HR: 14; 95% CI: 6.1-30; P<0.001). A shift to ctDNA-positivity during longitudinal monitoring (n=120) was associated with poor clinical outcome (HR: 58, 95% CI: 17-196; P<0.001). Multivariate analysis showed longitudinal ctDNA status to be the only significant prognostic factor associated with inferior RFS (HR: 57.7, 95% CI: 16.8-196; P<0.001). Serial ctDNA analysis detected MRD up to a median of 8.08 months (0.6 - 16.6 months) ahead of radiologic relapse (sensitivity: 87.5%, specificity: 99.1%).

Conclusions

Synchronous CRC tumours are genetically unrelated and require individual assays for ctDNA detection. Post-operative MRD status and longitudinal monitoring using ctDNA can detect patients with a high risk of recurrence and guide treatment decisions.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr. Andrés Cervantes and Prof. Claus L. Andersen.

Funding

Danish Council for Independent Research; Danish Council for Strategic Research; Novo Nordisk Foundation; Danish Cancer Society; Instituto de Salud Carlos III.

Disclosure

S. Sharma, H-T. Wu, S. Shchegrova, A. Tin, H. Sethi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera Inc. B. Zimmermann: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera Inc. A. Aleshin: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera Inc. A. Cervantes: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck Serono; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Beigene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Servier; Advisory/Consultancy, Research grant/Funding (self): Lilly; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): Astelas; Research grant/Funding (self): Genentech; Research grant/Funding (self): Pierre Fabre; Research grant/Funding (self): Fibrogen; Research grant/Funding (self): Amcure; Research grant/Funding (self): Sierra Oncology; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Medimmune; Research grant/Funding (self): BMS; Research grant/Funding (self): MSD; Speaker Bureau/Expert testimony: Angem; Speaker Bureau/Expert testimony: Foundation Medicine; Research grant/Funding (self): Serono; Officer/Board of Directors: ESMO; Leadership role, Officer/Board of Directors: INCLIVA. All other authors have declared no conflicts of interest.

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