When does a plasma mutation count toward the tumor or host denominator?
A large tumor-type-resolved analysis reports distinct prognostic information from ctDNA and clonal hematopoiesis mutations, including independent contributions in lung adenocarcinoma. The dual-compartment interpretation depends on how each plasma variant entered its denominator. Were variants attributed through paired leukocyte sequencing, matched tumor evidence, longitudinal clone behavior, or another prespecified rule? Collection time relative to therapy also belongs beside that attribution. Without both conditions, an apparent host signal could include tumor-derived variants, while an absent ctDNA signal could reflect low shedding or an inadequately timed sample rather than biology.
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