OCT 16, 2013 11:00 AM PDT

Molecular Prognosis in the Management of Early Stage Lung Cancer

  • Associate Professor of Surgery, Division of Adult Cardiothoracic Surgery, Chief of General Thoracic Surgery, University of California, San Francisco, VA Medical Center
      Michael J. Mann, M.D. is a leader in the development of genetic and molecular therapies and diagnostics for thoracic and cardiovascular disease. Dr. Mann joined the UCSF Thoracic Oncology Program in 2003 as a cardiothoracic surgeon. He had received an A.B. in synthetic chemistry from Princeton University and an M.D. from Stanford University, and was awarded a Ruth L. Kirschstein National Research Service Award (NRSA) Research Training Fellowship through the NIH. Dr. Mann completed his General Surgery residency at Brigham and Women's Hospital/Harvard Medical School, where he also served on the Faculty of Cardiovascular Medicine, and completed his Cardiothoracic Surgery fellowship at UCSF. Dr. Mann is widely admired for his teaching skills and is Associate Director of the Thoracic Surgery Training Program at UCSF. He holds memberships in numerous professional organizations, including the Society of Thoracic Surgeons, American College of Surgeons, American Heart Association, and the Massachusetts Medical Society. Highly respected by his peers, Dr. Mann was named to the list of U.S. News "Top Doctors;" his areas of clinical expertise include lung cancer, management of metastatic disease in the chest, sarcoma, mesothelioma, and minimally invasive (video-assisted) thoracoscopic surgery. He has received numerous awards including the Cardiovascular Medicine Award for Excellence in Research and the William Randolph Hearst Endowment for Young Investigators. Dr. Mann also serves as a scientific reviewer for numerous professional journals.
      While on the faculty at Harvard Medical School, Dr. Mann founded the Cardiovascular Gene Therapy Group. He also invented several novel drug and delivery technologies and helped pioneer the application of gene regulation and vascular biology principles to the problem of coronary bypass graft failure. This led to one of the first large scale programs to evaluate the surgical integration of an advanced molecular therapy. More recently, Dr. Mann's focus on oncogenic signaling pathways and molecular profiles of lung cancer and sarcoma has led to the development and international validation of a molecular diagnostic assay that has enabled personalization of the management of early stage lung cancer. Dr. Mann's research in genetic and molecular therapies has been widely recognized, and he is a founder of the first international co-operative study group designed to harness immense untapped clinical research resources in mainland China. He is currently an Associate Investigator in the UCSF Cardiovascular Research Institute, has served as a scientific advisor to the American Heart Association, to the NIH Recombinant-DNA Advisory Committee and to numerous device and pharmaceutical companies, and his Cardiothoracic Translational Research Laboratory has enjoyed continuous NIH R01 funding since its founding in 2006.


    Survival rates for early stage non-small cell lung cancer (NSCLC) remain unacceptably low compared to other common solid tumors. This mortality reflects a weakness in conventional staging, as 30-45% even of stage I patients harbor undetected metastasis. The need for better discrimination of high-risk patients in both stages I and II NSCLC is underscored by the documentation that adjuvant chemotherapy offers the possibility of cure for occult metastasis of NSCLC. Despite this possibility to improve survival through early intervention, however, many stage II and nearly all stage I patients with occult metastasis still forgo adjuvant chemotherapy because there has been no well-validated means of identifying those patients at highest risk. Gene expression profiles have become the gold standard for delineating risk and improving clinical decisions in early stage breast cancer. Previous efforts to develop a similarly practical and effective means of improving decision-making in the management of early stage NSCLC, however, have lacked both a clinically relevant approach and adequate large-scale validation. A PCR-based, 14-gene expression assay that uses paraffin-embedded tissue was recently reported to discriminate high- and low-risk patients with non-squamous NSCLC, and has been validated in ~1,500 patients in two large scale, international, independent, blinded studies (Lancet 2012;379:823, JAMA 2012;308:1629). The molecular profile outperforms all conventional risk criteria and staging methods at identifying patients at the highest risk of mortality after an attempt at curative surgery, even within individual staging groups. Published guidelines already recommend adjuvant chemotherapy for high-risk stage I and stage II patients; this molecular assay therefore represents a more effective means of implementing the current standard of care and of improving clinical decision-making in patients with early stage non-squamous, NSCLC.

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