Background: A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.
Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification.
Results: In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy.
Conclusion: ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.
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http://dx.doi.org/10.3389/fonc.2024.1407003 | DOI Listing |
Cancer Lett
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China. Electronic address:
This study, conducted as part of a multicenter phase III clinical trial, aimed to assess the utility of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) in comparing the efficacy of short-course and long-course chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). A total of 244 plasma samples from 79 LARC patients undergoing neoadjuvant therapy (NAT) before surgery were collected at various time points. Targeted deep sequencing using a novel MRD panel was performed.
View Article and Find Full Text PDFBMJ Open
January 2025
Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Introduction: The standard of care for stage III colon cancer is 3 or 6 months of double-drug regimen chemotherapy following radical surgery. However, patients with positive circulating tumour DNA (ctDNA) exhibit a high risk of recurrence risk even if they receive standard adjuvant chemotherapy. The potential benefit of intensified adjuvant chemotherapy, oxaliplatin, irinotecan, leucovorin and fluoropyrimidine (FOLFOXIRI), for ctDNA-positive patients remains to be elucidated.
View Article and Find Full Text PDFClin Chem
January 2025
Broad Institute of MIT and Harvard, Cambridge, MA, United States.
Background: Minimally invasive molecular profiling using cell-free DNA (cfDNA) is increasingly important to the management of cancer patients; however, low sensitivity remains a major limitation, particularly for brain tumor patients. Transiently attenuating cfDNA clearance from the body-thereby, allowing more cfDNA to be sampled-has been proposed to improve the performance of liquid biopsy diagnostics. However, there is a paucity of clinical data on the effect of higher cfDNA recovery.
View Article and Find Full Text PDFJ Thorac Oncol
December 2024
Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Introduction: Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB-IIIA non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).
Methods: This is a single center, pilot study of patients with clinical stage IA-IIIA NSCLC (AJCC 8th edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838).
Trends Cell Biol
December 2024
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase.
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