Liquid Pulse — October 2026

The theme this October is consolidation: liquid biopsy moved from a collection of promising single-trial signals toward codified practice. ASCO issued its first formal ctDNA guideline, a new FDA companion-diagnostic approval widened the clinical reach of plasma genotyping, and multiple syntheses sharpened the evidence for minimal residual disease (MRD) testing in solid tumors.

ASCO publishes its first formal ctDNA guideline ASCO released its inaugural guideline on circulating tumor DNA testing in solid tumors and lymphoma [1]. The central recommendation is restraint: ctDNA testing outside a clinical trial should be offered only when the result can change a clinical decision. The guideline gives clinicians a shared framework for distinguishing validated applications, such as genotyping to select targeted therapy, from uses where evidence remains preliminary. For a field where assay availability has often outpaced evidence, a professional-society standard sets a reference point for appropriate use and reimbursement conversations [1].

FDA approves Guardant360 CDx as companion diagnostic for zongertinib The FDA approved Guardant360 CDx as a companion diagnostic to identify patients with HER2-altered solid tumors eligible for Boehringer Ingelheim's HERNEXEOS (zongertinib) [2]. The approval adds a HER2-targeted indication to the assay's label and extends blood-based testing as a route to match patients with a targeted therapy without requiring tissue biopsy. The practical significance is access: patients whose tumors are difficult to biopsy, or whose tissue is exhausted, gain a plasma-based path to eligibility assessment [2].

Foundational validation underpinning Guardant360 CDx The current approval rests on earlier analytic and clinical validation of the plasma-based cfDNA sequencing assay [3]. That primary study reported greater than 99.6% technical success and 85.9% clinical sensitivity across 10,593 advanced solid tumor samples, using orthogonal tissue- and plasma-based methods for confirmation [3]. The validation data explain why the assay has been the backbone for successive companion-diagnostic approvals rather than requiring de novo analytic work for each new indication.

Meta-analysis quantifies ctDNA MRD accuracy in breast cancer A meta-analysis in Frontiers in Oncology pooled studies on ctDNA-based MRD detection after breast cancer surgery [4]. The analysis found that post-surgical ctDNA positivity is a significant predictor of recurrence, strengthening the case for folding MRD testing into surveillance protocols. The finding matters because it moves breast cancer MRD from anecdote toward quantified performance, giving clinicians pooled estimates to weigh rather than single-study results [4]. The evidence remains investigational, it supports prognostic stratification, not yet a mandate to change treatment based on an MRD result alone.

Review confirms ctDNA MRD utility across solid tumors A complete review in Cancer synthesized recent trial data on ctDNA MRD as a prognostic and predictive biomarker across gastrointestinal, lung, breast, and other solid tumors [5]. The authors frame MRD as relevant to treatment escalation and de-escalation decisions, intensifying therapy for MRD-positive patients, or sparing MRD-negative patients unnecessary treatment. The review consolidates the tumor-type-specific literature into one reference point, clarifying where the evidence is maturing and where it is still forming [5]. These applications remain investigational pending prospective trials that test whether acting on MRD improves outcomes.

City of Hope launches prospective ctDNA MRD trial in triple-negative breast cancer City of Hope opened a clinical trial (NCT07136493) evaluating ctDNA-based MRD detection for surveillance in early-stage and metastatic triple-negative breast cancer [6]. The study pairs biospecimen collection with EHR integration to assess clinical utility beyond current standard of care. Prospective design is the key feature: much existing MRD evidence is retrospective, and trials like this one are needed to establish whether MRD-guided surveillance changes management and outcomes rather than only predicting risk [6].

Looking ahead

The next question for liquid biopsy is interventional, whether acting on an MRD result, not measuring it, improves patient outcomes, and prospective trials now underway will begin to answer it.

References

[1] Lockwood CM et al. (ASCO Guideline Panel). Circulating Tumor DNA Testing in Solid Tumors and Lymphoma: ASCO Guideline. American Society of Clinical Oncology (ASCO) / Guideline Central, 2026. https://www.guidelinecentral.com/guideline/5225889

[2] Guardant Health, Inc. Guardant Health Announces FDA Approval of Guardant360 CDx as Companion Diagnostic for Boehringer Ingelheim's HERNEXEOS®. Guardant Health Investor Relations Press Release, 2026. https://investors.guardanthealth.com/press-releases/press-releases/2026/Guardant-Health-Announces-FDA-Approval-of-Guardant360-CDx-as-Companion-Diagnostic-for-Boehringer-Ingelheims-HERNEXEOS/default.aspx

[3] Odegaard JI, Vincent JJ, Mortimer S, et al. Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies. Clinical Cancer Research, 24(15):3539-3549, 2018. https://doi.org/10.1158/1078-0432.CCR-17-3831

[4] Authors listed in Frontiers in Oncology article. Accuracy of ctDNA-based minimal residual disease detection in predicting postoperative recurrence of breast cancer: a meta-analysis. Frontiers in Oncology, Volume 16, 2026. https://doi.org/10.3389/fonc.2026.1735752

[5] Abdo T et al. Minimal residual disease in solid tumors: Clinical applications. Cancer (American Cancer Society / Wiley), doi: 10.1002/cncr.70286, 2026. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.70286

[6] City of Hope Medical Center. Circulating Tumor DNA Based Minimal Residual Disease Detection for Patients With Early-Stage Breast Cancer (NCT07136493). ClinicalTrials.gov / CenterWatch, 2026. https://www.centerwatch.com/clinical-trials/listings/NCT07136493/circulating-tumor-dna-based-minimal-residual-disease-detection-for-patients-with-early-stage-breast-cancer