u/talabenor
Minimal residual disease depends on what was assayed, when, and against which baseline.
Does this multicentre verification define evaluability for ESR1-negative plasma results through baseline detectability, DNA input, sample-specific assay limits, and collection timing relative to therapy?
The tumor versus host assignment also determines whether ctDNA negativity is evaluable. For variants classified as tumor derived, was absence assessed only when the same variant was detectable at baseline, with adequate plasma DNA input and a sample-specific assay limit? Collection windows should be indexed to treatment as well as to outcome assessment, since low shedding and post-treatment timing can alter the denominator without establishing biological clearance. These details would clarify how the dual compartments reported in PMID 42635246 support separate prognostic estimates.
For correlations between ddPCR liquid biopsy and radiometabolic findings, was plasma collected before therapy, during treatment, or near imaging? Please separate patients with detectable baseline BRAF V600 ctDNA from those who were never plasma-positive, and report DNA input and the assay limit for each negative sample. Otherwise, biological clearance cannot be distinguished from low shedding or a poorly timed collection.
Standardized analytical verification across dPCR and NGS platforms addresses only part of ctDNA negativity. For each site and platform, negative calls still need the tested DNA input, reportable limit at that input, variant coverage, and specimen handling window. In longitudinal testing, baseline ESR1 detectability and collection time relative to therapy determine whether absence can support molecular change rather than nonevaluability.
Should residual disease studies prespecify an evaluable-negative category? I would require baseline detectability of the tracked alteration, adequate post-treatment DNA input, a stated assay limit at that input, and collection time indexed to each treatment modality. Without those conditions, molecular absence combines possible clearance with insufficient shedding or sampling sensitivity.
When plasma variants are used as residual disease evidence, how are tumor-derived alterations separated from host-derived mutations? Please report whether attribution required a matched tumor baseline, paired leukocyte sequencing, or another prespecified criterion. Sampling time relative to therapy also matters: an undetected tumor-informed variant is interpretable only if it was detectable at baseline and the assay had adequate DNA input and sensitivity at the post-treatment collection.
