Relying solely on Next-Generation Sequencing (NGS) is insufficient for HER2 testing in biliary tract cancers. Data shows NGS misses up to 15% of patients with HER2 overexpression detected by immunohistochemistry (IHC). Performing both tests is essential to avoid denying patients effective targeted therapies.

To reduce treatment delays, pathologists should initiate biomarker testing reflexively. Waiting for a medical oncologist to order tests at a first visit is a system failure, wasting critical time and risking the need to retrieve archived samples.

Dr. Deb Schrag suggests the main challenge for new molecular cancer screening technologies is not invention, but implementation. The critical task will be deploying these tools at a population scale and effectively managing the logistical challenge of distinguishing true positives from false alarms.

Beyond clinical validation, the adoption of novel biomarkers like microRNA is hindered by practical lab issues. Disagreements over sample type (serum vs. plasma), establishing universal cutoffs, and achieving high concordance between different testing centers are critical, non-clinical hurdles that must be overcome for widespread clinical use.

Establishing a multi-disciplinary molecular tumour board helps operationalize biomarker strategies. This collaborative body, including oncologists and surgeons, not only interprets complex molecular data for trial matching but also collectively advocates for health insurance reimbursement for necessary tests, addressing a key practical barrier.

Clinicians ordering "NGS for lung" often misunderstand that Next-Generation Sequencing alone does not cover all actionable biomarkers, such as PD-L1 or HER2. This requires pathologists to interpret the clinician's intent and order a more comprehensive and appropriate test panel.

Despite acknowledging that a one-size-fits-all treatment duration is suboptimal, the expert consensus is to follow the study protocol. This conservative, evidence-based approach prevails due to the absence of validated biomarkers, like ctDNA, to safely guide treatment de-escalation for individual patients.

While re-biopsying at disease progression is the "by-the-book" standard to confirm biomarkers like HER2, clinicians acknowledge it is often skipped. The difficulty of obtaining tissue and the desire to provide patients with potential treatment options create a gap between guidelines and clinical reality.

Despite mutation testing being a critical first step for effective treatment planning in gastrointestinal stromal tumors (GIST), a significant number of patients in the United States still do not receive this essential diagnostic. This highlights a major gap between established best practices and real-world clinical application.