There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.
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A key conceptual shift is viewing ctDNA not as a statistical risk marker, but as direct detection of molecular residual disease (MRD). This framing, similar to how a CT scan identifies metastases, explains its high positive predictive value and justifies its use in making critical treatment decisions.
ctDNA testing (liquid biopsy) is more effective than tissue biopsy for identifying ESR1 mutations. It samples DNA from all metastatic sites, capturing the disease's genetic heterogeneity and reflecting the most active resistance mechanisms, unlike a single-site needle biopsy which can miss them.
The traditional "germinal center" (GC) classification for DLBCL is overly simplistic. Molecular analysis reveals distinct subtypes within GC, such as "dark zone" and "light zone" signatures, which have different prognoses and responses to targeted therapies like polatuzumab.
ESR1 mutations in breast cancer are acquired alterations, meaning they can be missed by a single test. The speaker advocates for serial testing, especially after disease progression, using blood-based ctDNA analysis. This dynamic monitoring approach is essential for identifying patients who become eligible for targeted therapies over time.
An individual tumor can have hundreds of unique mutations, making it impossible to predict treatment response from a single genetic marker. This molecular chaos necessitates functional tests that measure a drug's actual effect on the patient's cells to determine the best therapy.
Experts believe molecular tests like Decipher and PTEN status are superior to simply counting bone lesions for guiding treatment. While not yet standard practice for all decisions, this represents a significant shift towards using underlying tumor biology to determine therapy, like adding docetaxel.
The InVigor11 study was the first to show that detecting recurrence via a ctDNA test before it's visible on scans is not just a prognostic sign, but an actionable clinical state. Intervening with therapy at this early stage was proven to improve patient outcomes, establishing a new paradigm for cancer surveillance.
The success of perioperative osimertinib means oncologists cannot choose the optimal strategy (targeted therapy vs. chemoimmunotherapy) for resectable lung cancer without first knowing the patient's EGFR, ALK, and PD-L1 status. This elevates biomarker profiling from a metastatic-setting tool to a critical first step in early-stage disease.
In mixed histology bladder cancers treated with standard urothelial therapy, the variant component (e.g., squamous) is hypothesized to be the source of the resistant clone that emerges after treatment. This suggests post-progression biopsies are key to understanding resistance.
Testing for PI3K/AKT alterations at the initial diagnosis of metastatic disease, rather than waiting for progression, provides a crucial window of time. This allows clinicians to implement proactive dietary and medical strategies to mitigate future side effects like hyperglycemia before the targeted therapy is even started.
