Corrigendum: 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.

[This corrects the article DOI: 10.3389/fonc.2018.00652.].

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.

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 < 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 naïve 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-naïve 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.

Head and neck squamous cell carcinoma: Ambiguous human papillomavirus status, elevated p16, and deleted retinoblastoma 1.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is potentially curable, but treatment planning remains a challenge. Oncogenic human papillomavirus (HPV)-positive disease is often associated with a good prognosis compared with HPV-negative disease. However, some HPV-positive HNSCC recurs, often with distant metastases and significant treatment resistance. METHODS AND RESULTS: We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high-risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5-17) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1). Genomic and transcriptomic data available through FoundationOne and The Cancer Genome Atlas (TCGA) were reviewed for additional HNSCC cases with RB1 alterations. CONCLUSION: RB1 alterations may have important prognostic implications, particularly in the context of high p16 expression, in both HPV-positive and HPV-negative HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: E34-E39, 2017.

Plasma from chronic liver disease subjects exhibit differential ability to generate thrombin.

Liver fibrosis in chronic liver disease (CLD) results in complex alterations in procoagulant and anticoagulant proteins. Although an elevated international normalized ratio (INR) is a prominent feature of progressive fibrosis, the utility of the INR to accurately reflect the net effect of these changes on the coagulation system is uncertain. In subjects with CLD, elevated INRs have been observed in both bleeding and thrombotic complications, suggesting limitations of the INR in characterizing the coagulation status. Unlike the INR, which is preferentially sensitive to the extrinsic pathway, the direct measurement of thrombin generation better captures the global coagulation cascade. We conducted a pilot study measuring the INR, chromogenic factor X and thrombin generation in CLD subjects and compared them with control subjects and subjects on warfarin anticoagulation. We observed a large interquartile range in thrombin generation among compensated CLD subjects across a narrow INR range, suggesting that the INR is a suboptimal surrogate measure of thrombin generation in CLD subjects.