As flagged by Friends of Cancer Research, the RECIST working group has published a consensus paper on the promise and current status of minimal residual disease detection (MDR) in cancer therapy management.
See the Linked In article from FOCR here. (They note, look for more at their annual meeting in November).
See the original paper by Wyatt et al. here:
The paper looks like it is subscription only. Below I clip the abstract, and further below (in "AI Corner") some takeaways.
They suggest that response accuracy may vary by cancer type and therapy class, exactly the approach that Medicare's MolDx program has been taking on coverage of MRD tests.
Authors' Abstract
Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The Response Evaluation Criteria in Solid Tumors (RECIST) based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals.
However, these criteria do not provide insight before 6 – 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggests that measuring on-treatment changes in the amount or proportion of circulating tumor DNA (ctDNA) in peripheral blood plasma may accurately identify responding and non-responding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials, to identify areas of focus for future research and validation.
Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically-meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class, and must be assessed before ctDNA can be considered as a potential pan-cancer response evaluation biomarker.
Despite the need for additional data, minimally-invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST, and offer opportunities for developing novel early endpoints for modern clinical trials.
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AI CORNER
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Here are ten key takeaways for expert oncology readers regarding the potential of MRD (ctDNA) as a treatment response biomarker:
Early Detection of Treatment Response: Plasma ctDNA kinetics can identify responding and non-responding cancers at earlier time points compared to imaging-based RECIST criteria, which typically require 6-12 weeks for assessment.
Minimally Invasive Monitoring: ctDNA measurement offers a minimally invasive alternative to traditional imaging, potentially reducing patient burden and allowing for more frequent monitoring.
Enhanced Sensitivity: ctDNA levels are associated with tumor burden and can provide a more sensitive measure of treatment response, even in cases where traditional imaging may not detect changes.
Applicability Across Tumor Types: While ctDNA kinetics can vary by cancer type, the approach has shown promise in multiple solid tumors, suggesting potential for broad applicability in oncology.
Improved Decision-Making: Early ctDNA response can guide treatment decisions more quickly, enabling earlier discontinuation of ineffective therapies and a potential shift to alternative treatments.
Complementary to RECIST: ctDNA offers an opportunity to complement existing RECIST-based assessments, providing additional data points to enhance the evaluation of therapeutic efficacy.
Assay Standardization: There is a need for large, standardized trial datasets to define optimal ctDNA collection time points, assay thresholds, and establish ctDNA as a pan-cancer response biomarker.
Technical and Biological Challenges: Current challenges include understanding ctDNA shedding and clearance, defining clinically meaningful ctDNA changes, and standardizing assay methods to ensure consistent and accurate results.
Regulatory and Clinical Integration: Efforts are underway to integrate ctDNA into clinical practice, with discussions around its use as a surrogate endpoint for drug approvals and in early-phase clinical trials.
Patient-Centric Advantages: ctDNA monitoring is less onerous than imaging and may improve cancer care accessibility, especially in remote areas or for patients contraindicated for certain scans.
These points highlight the potential advantages of MRD (ctDNA) over traditional imaging, particularly in terms of sensitivity, early detection, and the ability to guide treatment decisions more effectively.