Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic
Authors: Arthur Winer
Vineela Kasireddy
Pooja Ghatalia
Patricia D Saltzberg
Nicole Bubes
Fern M Anari
Chad H Smith
Eric A Ross
Yang Liu
Jiangtao Gou
Lesli A Kiedrowski
Asya Varshavsky
Michael Slifker
Wafik S El-Deiry
Journal: Frontiers in Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: cfDNA; drug resistance; liquid biopsy; molecular target; precision oncology
Affiliations: Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States., Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, United States., Guardant Health, Redwood City, CA, United States.

Abstract:  Background: Liquid biopsy (LB) captures dynamic genomic alterations (alts) across metastatic colorectal cancer (mCRC) therapy and may complement tissue biopsy (TB). We sought to describe the utility of LB and better understand mCRC biology during therapy. Methods: Thirty-three patients (pts) with mCRC underwent LB. We used permutation-based t-tests to assess associations between alts, and clinical variables and used Kendall's tau to measure correlations. Results: Of 33 pts, 15 were women; 22 had colon, and the rest rectal cancer. Pts received a median of two lines of therapy before LB. Nineteen pts had limited testing on TB (RAS/RAF/TP53/APC), 11 extended NGS, and 3 no TB. Maxpct and alts correlated with CEA (p &lt; 0.001, respectively). In 3/5 pts with serial LB, CEA correlated with maxpct trend, and CT tumor burden. In 6 pts, mutant RAS was seen in LB and not TB; 5/6 had received anti-EGFR therapy prior to LB, suggesting RAS alts developed post-therapy. In two pts RAS-mutated by TB, no RAS alts were detected on LB; these pts had low disease burden on CT at time of LB that also did not reveal APC or TP53 alts. In six patients who were KRAS wt based on TB, post anti-EGFR LB revealed subclonal KRAS mutations, likely a treatment effect. The median number of alts was higher post anti-EGFR LB (n = 12) vs. anti-EGFR na√Øve LB (n = 22) (9.5 vs. 5.5, p = 0.059) but not statistically significant. More alts were also noted in post anti-EGFR therapy LB vs. KRAS wt anti-EGFR-na√Øve LB (n = 6) (9.5 vs. 5) among patients with KRAS wild-type tumors, although the difference was not significant (p = 0.182). Conclusions: LB across mCRC therapy detects driver mutations, monitors disease burden, and identifies sub-clonal alts that reflect drug resistance, tumor evolution, and heterogeneity. Interpretation of LB results is impacted by clinical context. 

Retracted: No

PubPeer comments:
 Two sets of images in the upper section of figure 3 appear to be repeated. Note: For reasons that are unclear to me the paper provided a personal email address for the corresponding (and last) author; I used the institutional email address for this PubPeer thread. ***  *** Full figure  , 
 #1 Thank you for bringing this to our attention. There is indeed an error in the CT scan images for patient 2 that appear identical to those of patient 1. This error was missed by all the authors and reviewers of the paper. The correct images for patient 2 have been located and a revised version  is uploaded. Upon query by the journal, we have communicated this information to them along with the correct figure. , 
 #2 I have located a copy of our ASCO meeting poster from 2018, and the poster has the correct images for the CT scans from patient 2. Thus the error occurred sometime between poster presentation in 2018 and getting the data organized for the published paper. , 
 #3 Thank you for responding and announcing your plans to make a correction. Another paper with shared authors that I commented on has yet to be addressed: https: pubpeer.com publications 84AD1F914C45BC6E40763348D77435 , 
 #4 We have responded to the comments on the other paper. Sincerely, W. El-Deiry , 
 This paper was corrected May 7, 2021. https: www.ncbi.nlm.nih.gov pmc articles PMC8139244 pdf fonc-11-674782.pdf ,