Ignacio I. Wistuba, MD

Dr. Wistuba emphasizes the critical need for reinforcing RNA testing alongside DNA testing for comprehensive NGS in lung cancer.

Dr. Leal outlines her approach to frontline treatment selection for newly diagnosed patients with ROS1-positive lung cancer.

Dr. Rodriguez outlines patient education strategies emphasizing partnership from treatment initiation, as clinical trials demonstrate over half of patients require dose adjustments.

Dr. Rodriguez reviews historical toxicity profiles from earlier ROS1 inhibitors, noting that crizotinib and entrectinib presented novel side effects including visual field changes preventing night driving due to floaters, along with liver function test (LFT) abnormalities requiring monitoring.

Dr. Wistuba explains that acquired resistance to ROS1-targeted therapies frequently involves on-target mutations, with G2032R representing the most frequently observed resistance mutation among 10 to 12 described mutations that affect the ATP binding site and reduce drug binding efficiency.

Dr. Wistuba addresses the complexity of NGS reports that may include multiple abnormalities beyond ROS1 fusions.

Dr. Wistuba confirms that fusion variant identification does not impact treatment selection, emphasizing that ROS1-positive versus ROS1-negative status represents the key clinical decision point.

Dr. Wistuba provides detailed information about ROS1 gene fusions, discovered in the 1980s with over 30 to 40 fusion partners identified that constitutively activate ROS1 in cells, leading to malignant properties.

Dr. Leal emphasizes that although actionable genomic alterations like ROS1 are rare, their clinical implications are enormous. Following National Comprehensive Cancer Network (NCCN) guidelines, these targets should be acted upon in the first-line setting as the initial targeted therapy treatment.

Panelists discuss the role of ctDNA (liquid biopsy) in clinical practice, highlighting its benefits and limitations in detecting actionable mutations, interpreting results, and guiding treatment decisions when tissue testing is insufficient.

This final segment broadens the discussion beyond TROP2 to explore the broader implications of QCS and computational pathology for biomarker development and clinical practice. Dr. Wistuba explains that QCS represents a platform capable of objectively quantifying protein expression across multiple cellular compartments, including membrane, cytoplasmic, nuclear, and immune cell populations, using digital image analysis. This flexibility creates opportunities to apply the approach to a wide range of biomarkers, including additional ADC targets, immune markers, and even routine diagnostic proteins.

Panelists discuss strategies for identifying and managing ROS1-positive NSCLC, focusing on comprehensive testing approaches, emerging clinical data, and factors that guide treatment decisions.

Phase 3 trials test AI-scored Trop-2 NMR to guide first-line NSCLC ADC therapy, reshaping biomarker-driven treatment and lab adoption.

How Trop-2 NMR scoring may predict response to Trop-2 ADCs in NSCLC, why lower ratios matter, and what validation comes next.

Real-world studies show high concordance for AI TRK2‑NMR scoring in lung cancer; next, phase III trials test clinical validation.

Trop-2 levels alone fail to predict ADC response in lung cancer; an AI pathology biomarker (Trop-2 NMR) links cytoplasmic ratio to outcomes.

Trop-2 ADC trials in lung cancer show H-score fails to predict benefit, spotlighting drug internalization and target engagement as key efficacy drivers.

This segment examines the operational aspects of biomarker testing in non-small cell lung cancer, emphasizing the importance of multidisciplinary collaboration and efficient institutional workflows to ensure timely molecular testing, while highlighting the limitations of conventional TROP2 immunohistochemistry in predicting response to antibody-drug conjugate therapies and the need for more precise approaches such as computational pathology.

This segment introduces the program by emphasizing the critical role of comprehensive biomarker testing, including tissue-based next-generation sequencing, liquid biopsy, and immunohistochemistry, in guiding personalized treatment decisions for patients with non-small cell lung cancer.

The panel shares the data that excited them the most from ESMO 2022, and what to look forward to in the future.

Recommendations for community hospitals and physicians on the critically necessary molecular tests needed for patients with NSCLC.

Drs Spicer and Sabari explain if and when they test patients with NSCLC for EGFR mutations after surgical resection.

Key opinion leaders share their thoughts on data updates from the ADUARA trial on the use of osimertinib as an adjuvant therapy for NSCLC.

Drs Bill W. Loo and Joshua Sabari discusses whether there is a role for any adjuvant therapies in NSCLC treatment, and which patients might benefit.

Joshua Sabari, MD, describes which stage groups of patients with NSCLC should receive neoadjuvant therapies, and which therapies are typically used.

Drs Wakelee, Sabari, and Wistuba review updated data on neoadjuvant treatment in NSCLC from key studies including CheckMate-816 and NADIM-2.

The panel reviews updates in the treatment of stage I-IIIA NSCLC and discusses its impact in clinical practice.

Ignacio Wistuba, MD, leads the discussion on the role of liquid biopsies for molecular testing in early NSCLC.

Jonathan Spicer, MD, explains the role of molecular testing in patients with stage I-IIIA NSCLC, and how it informs treatment decision-making.

A panel of lung cancer experts provides an overview of molecular testing in early-stage non-small cell lung cancer (NSCLC) and recommendations for biomarkers to test for and at what treatment stages to perform testing.