Cancers (Oct 2021)

A Real-World Application of Liquid Biopsy in Metastatic Colorectal Cancer: The Poseidon Study

  • Letizia Procaccio,
  • Francesca Bergamo,
  • Francesca Daniel,
  • Cosimo Rasola,
  • Giada Munari,
  • Paola Biason,
  • Stefania Crucitta,
  • Giulia Barsotti,
  • Giulia Zanella,
  • Valentina Angerilli,
  • Cristina Magro,
  • Silvia Paccagnella,
  • Veronica Di Antonio,
  • Fotios Loupakis,
  • Romano Danesi,
  • Vittorina Zagonel,
  • Marzia Del Re,
  • Sara Lonardi,
  • Matteo Fassan

DOI
https://doi.org/10.3390/cancers13205128
Journal volume & issue
Vol. 13, no. 20
p. 5128

Abstract

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Background: First-line decision making is the key to the successful care of mCRC patients and RAS/BRAF status is crucial to select the best targeted agent. In hub centers, a relevant proportion of patients referred from small volume centers may not have standard tissue-based (STB) molecular results available at the time of the first visit (T0). Liquid biopsy (LB) may help circumvent these hurdles. Methods: A monoinstitutional prospective head-to-head comparison of LB versus (vs.) STB testing was performed in a real-world setting. Selection criteria included: mCRC diagnosis with unknown RAS/BRAF status at T0, tumoral tissue archived in external centers, no previous treatment with anti-EGFR. At T0, patients underwent plasma sampling for LB testing and procedure for tissue recovery. RAS/BRAF genotyping was carried out by droplet digital PCR on circulating-tumoral (ct) DNA. The primary endpoint was the comparison of time to LB (T1) vs. STB (T2) results using the Mann–Whitney U test. Secondary endpoints were the concordance between LB and STB defined as overall percent agreement and the accuracy of LB in terms of specificity, sensitivity, positive and negative predictive value. We also performed an exploratory analysis on urinary (u) ctDNA. Results: A total of 33 mCRC patients were included. Mean T1 and T2 was 7 and 22 days (d), respectively (p RAS mutation was found in 45% and 42% of patients, respectively; BRAF mutation in 15%. LB results included one false positive and four false negative. False negative cases showed a significantly lower tumor burden at basal CT scan. Concordance between STB and uctDNA testing was 89%. Conclusions: Faster turnaround time, high concordance and accuracy are three key points supporting the adoption of LB in routinary mCRC care, in particular when decision on first-line therapy is urgent and tissue recovery from external centers may require a long time. Results should be interpreted with caution in LB wild-type cases with low tumor burden.

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