10
Diagnosis
Section 6: Additional Topics
➤ Testing circulating free DNA (cfDNA): Genomic testing on cfDNA is
most helpful when genomic testing is indicated, archival tissue is
unavailable, and new tumor biopsies are not feasible.
➤ Testing for minimal residual disease: ctDNA testing has the potential
to identify patients at higher risk of distant recurrence.
➤ Pharmacogenomic biomarkers: Germline polymorphisms in specific
genes may affect the patient's ability to metabolize anticancer
therapies, leading to drug efficacy or toxicity consequences.
➤ Testing in cancers of unknown primary (CUP): CUP (primarily
adenocarcinoma CUP) may harbor therapeutically actionable
alterations identified through genomic profiling.
➤ Mutational signatures: Mutational signatures can be imputed using
large-panel sequencing assays. Mutational signatures may identify
processes, such as dMMR or HRD, that may be missed by other
assays and can guide therapeutic strategies targeting these pathway
alterations. Additionally, they may help identify tumor origin or
classification in CUP.
➤ HRD assays: Studies have not established the utility of these
assays to predict the benefit of poly-ADP ribose polymerase (PARP)
inhibitors or other DNA-damaging agents in diseases beyond ovarian
cancer, and the degree of equivalency between available assays has
not been assessed.
➤ The diagnostic and prognostic value of NGS: Genomic testing can
also assist in diagnosis, prognosis, and identifying alterations that
predispose to other diseases or that can affect drug metabolism and/
or risk of adverse events.
➤ Intertumoral and intratumoral heterogeneity: A cancer may contain
different molecular alterations, both within a single primary tumor
(intratumoral) and among multiple metastases (intertumoral). These
may represent different mechanisms of therapeutic resistance and
therefore account for treatment failure or recurrence.
➤ Assessing genomic coalterations: Coalterations may impact the
efficacy of the therapy or patient prognosis thereby modifying the
predictive value of the genomic alteration being tested.
➤ Repeat genomic testing: Repeat genomic testing may be justified for
patients initially sequenced with limited NGS panels, for patients
with acquired resistance on targeted therapies, and for identifying
new targets in tumors after progression or after prolonged stable
disease on targeted therapies.
