104. Oncogenic Pathway Alterations Were Correlated with Tumor Progression and Survival Benefits from Immunotherapy in Lung Adenocarcinoma
UCSF Medical Center
San Francisco, CA
United States - Contact Me
Dr. David Jablons is a renowned lung cancer expert and is the Chief of General Thoracic Surgery at UCSF Medical Center. As the leader of the Thoracic Oncology Program at the UCSF Helen Diller Family Comprehensive Cancer Center, he is also the Director of the UCSF Thoracic Oncology Laboratory where he investigates molecular biology and genomics and drug discovery for cancer. Dr. Jablons is an ADA Distinguished Professor of Thoracic Oncology and is also the Nan T. McEvoy Distinguished Professor of Thoracic Surgical Oncology.
Jablons earned an undergraduate degree from Yale University and a medical degree from Albany Medical College of Union University. He completed a surgical residency at Tufts Medical Center. Subsequently he completed a surgical oncology research fellowship under Dr. Steven Rosenberg, a world-renowned surgical oncologist and tumor immunologist, at the National Cancer Institute, NIH. He then completed Cardiothoracic Surgical Fellowship at Memorial Sloan Kettering Cancer Center training with Dr. Robert Ginsberg and at Cornell Medical Center in New York under Dr. Wayne Isom. Dr. Jablons co-founded the UCSF Thoracic Oncology Conference and was the co-chair of the 13th World Conference on Lung Cancer in 2009.
Dr. Jablons is a dedicated teacher and outstanding mentor for both clinical fellows and surgical residents. He is a member of many distinguished associations such as the American Association of Thoracic Surgeons (AATS), American Surgical Association (ASA), American Association for Cancer Research, International Association for the Study of Lung Cancer, Society of Thoracic Surgeons (STS), American Medical Association, American Association of Immunologists, Society of University Surgeons, San Francisco Surgical Society, and the American Association for the Advancement of Science among many others.
Fudan Shanghai Cancer Center
Shanghai, Shanghai
China - Contact Me
Dr. Fu earned a medical doctor degree from Fudan University in Shanghai, China. He completed a surgical residency at Fudan University Shanghai Cancer Center. He is having his Thoracic Surgical Felllowshio at Fudan University Shanghai Cancer Center under Dr. Haiquan Chen.
Dr. Fu's research focuses on ground-glass opacities and genomics of lung cancer. He has published over 15 papers, including two at Journal of Thoracic Oncology.
Abstract
Methods: We calculated NPA for each patient with lung adenocarcinoma from our two prospective cohorts with available DNA sequencing data (250 patients receiving 520-gene target sequencing and 99 patients receiving whole-exome sequencing). Two public cohorts from MSKCC and POPLAR/OAK were utilized to explore the predictive value of NPA in the efficacy of immunotherapy. A pathway was considered to be "altered" if at least one nonsynonymous mutation from this pathway was discovered.
Results: Among patients having panel sequencing, the most prevalent pathway alteration was RTK/RAS, appearing in 98.4% of the whole cohort (Figure 1A). Increased NPA was associated with larger TMB (P < 0.001) and tumor size (P < 0.001). High-grade adenocarcinoma (P < 0.001), visceral pleural invasion (P = 0.063), advanced TNM stage (P < 0.001), and high expression of PD-L1 (P = 0.033) were more common in patients with higher NPA. Survival analyses of patients receiving whole-exome sequencing demonstrated patients with larger NPA had significantly worse recurrence-free survival (P = 0.007) and overall survival (P < 0.001). Furthermore, high NPA was associated improved survival in the MSKCC cohort receiving immunotherapy (Figure 1B). Combination of NPA and tumor mutation burden provided better performance in identifying patients benefitting from immunotherapy in the POPLAR&OAK cohort (Figure 1C).
Conclusions: Increased NPA was associated with advanced TNM stage and poor survival in lung adenocarcinoma. NPA was a novel predictor of efficacy to immunotherapy.