Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT).
Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA.
Results: 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations.
Conclusions: ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.
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http://dx.doi.org/10.1158/1078-0432.CCR-24-0924 | DOI Listing |
J Gastrointest Cancer
December 2024
Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, 518100, China.
Background And Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis.
View Article and Find Full Text PDFClin J Gastroenterol
December 2024
Faculty of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Special Capital Region of Jakarta, Pluit Raya Street No. 2, North Jakarta, 14440, Indonesia.
Background: Metastatic colorectal cancer (mCRC) remains a significant cause of mortality despite advancements in treatments. Fruquintinib, a potent VEGFR inhibitor, has shown promise as an advanced therapy for mCRC. This review evaluates the efficacy and safety of fruquintinib compared to placebo in patients with refractory mCRC, focusing on Phase II and III trials.
View Article and Find Full Text PDFClin Oncol (R Coll Radiol)
November 2024
State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. Electronic address:
Aims: Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have shown limited effectiveness in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Combining anti-angiogenesis inhibitors with PD-1 inhibitors has the potential to reverse the immunosuppressive tumour microenvironment, synergistically enhancing the anti-tumour immune response in MSS mCRC. The goal is to present real-world data that prove the clinical efficacy and safety of fruquintinib combined with PD-1 inhibitors in MSS mCRC.
View Article and Find Full Text PDFCancer Imaging
December 2024
Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Background: To verify overall survival predictions made with residual convolutional neural network-determined morphological response (ResNet-MR) in patients with unresectable synchronous liver-only metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy (BBC).
Methods: A retrospective review of liver-only mCRC patients treated with BBC from December 2011 to Apr 2021 was performed. Patients who had metachronous liver metastases or received locoregional treatment before the initiation of BBC were excluded.
Cell Death Discov
December 2024
Department of Immunology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
The emerging role of ubiquitin-specific peptidase 21 (USP21) in stabilizing Fra-1 (FOSL1) highlights its involvement in promoting colorectal cancer (CRC) metastasis. Additionally, a reciprocal link between EGFR signaling and Fra-1 activation has been identified, mediated through matrix metalloproteinases (MMPs). However, the functional implications of the USP21-EGFR signaling axis in metastatic CRC (mCRC) are not fully understood.
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