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Poster Discussion session - Gastrointestinal tumours, colorectal 2

5433 - Serial circulating tumor DNA analysis for detection of residual disease, assessment of adjuvant therapy efficacy and for early recurrence detection in colorectal cancer

Date

21 Oct 2018

Session

Poster Discussion session - Gastrointestinal tumours, colorectal 2

Topics

Translational Research

Tumour Site

Colon and Rectal Cancer

Presenters

Thomas Reinert

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

T. Reinert1, T.V. Henriksen2, M.H. Rasmussen2, H. Sethi3, R. Salari3, S. Shchegrova4, R. Swenerton3, H. Wu3, S. Sharma3, E. Christensen1, P. Natarajan4, S. Dashner4, T. Tin4, A. Olson4, H. Pawar4, B. Zimmermann4, L.H. Iversen5, M.R. Madsen6, J. Lin4, C.L. Andersen1

Author affiliations

  • 1 Department Of Molecular Medicine, Aarhus University Hospital, 8200 - Aarhus/DK
  • 2 Department Of Molecular Medicine, Aarhus University Hospital, Aarhus/DK
  • 3 Rnd, Natera Inc., 94070 - San Carlos/US
  • 4 Rnd, Natera, 94070 - San Carlos/US
  • 5 Department Of Surgery, Aarhus University Hospital, Aarhus/DK
  • 6 Department Of Surgery, Herning Regional Hospital, Herning/DK
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Resources

Abstract 5433

Background

Early detection of disease recurrence has been shown to improve survival in patients with colorectal cancer (CRC). Previous studies have analyzed circulating tumor DNA (ctDNA) to monitor tumor burden in CRC using small gene panels and ddPCR. Here, we use a personalized multiplex-PCR and NGS platform (SignateraTM RUO) to detect ctDNA in serially collected plasma samples to assess if ctDNA detection defines the subset of patients with high risk of recurrence both before and after adjuvant chemotherapy (ACT).

Methods

A cohort of 130 patients with stage I–IV CRC, treated according to standard of care was analyzed. For each patient, tumor-specific panels of 16 mutations were designed using somatic mutation signatures obtained from WES. Plasma samples (n = 829) collected pre- and post-surgery, and during ACT were analyzed. Recurrence-free survival was calculated for patients stratified by ctDNA status post-surgery (n = 91) and post-ACT (n = 58).

Results

ctDNA status after surgery, but prior to ACT, was assessed in 91 patients. Relapse was observed for 75% (6/8) of the ctDNA+, and only for 13% (11/83) of the ctDNA- patients. Effective ACT treatment was observed for 30% (3/10) of the post-operative ctDNA+ patients. These were consistently ctDNA- in post-ACT serially collected blood samples, and concordantly relapse free at end of follow-up. ctDNA status post-ACT was assessed in 58 patients. Radiologically confirmed relapse was observed for 77% (10/13) of the ctDNA+ and for 4% (2/45) of ctDNA- patients. On average ctDNA detected relapse 9.13 months earlier than standard-of-care CT-imaging.

Conclusions

Serial post-operative ctDNA analysis enables stratification of patients into high or low recurrence risk subgroups, assessment of ACT treatment efficacy, and early detection of recurrence. Importantly, it also indicates that ACT can eliminate residual disease in up to 30% of the post-operative ctDNA+ patients and therefore can be a treatment option for ctDNA+ patients. In summary, ctDNA analysis has great potential to guide treatment decisions, both in the adjuvant and post-adjuvant settings.

Clinical trial identification

Legal entity responsible for the study

Claus Lindbjerg Andersen.

Funding

Natera Inc, San Carlos, California.

Editorial Acknowledgement

Disclosure

H. Sethi, R. Salari, S. Shchegrova, R. Swenerton, H-T. Wu, S. Sharma, P. Natarajan, S. Dashner, T. Tin, A. Olson, H. Pawar, B. Zimmermann, J. Lin: Employees: Natera, Inc., and own stock, or options to stock in the company. All other authors have declared no conflicts of interest.

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