Research:TheNationalLungScreeningTrial(NLST)demonstrateda20%reductioninmortalitywiththeuse ofannualCTscreeningbutwithsignificantmorbidityduetoproceduresperformedforevaluationofthe94%of nodulesthatwerenotcancerous.Thegoalofthisproposalistoimprovethespecificityfordistinguishingwhich of these ?indeterminate? nodules is lung cancer by using quantitative features associated with emphysema availablefromasingleCTscan.Ourpreliminarydataindicatethatmoderatecentrilobularemphysema(MCE), anditsassociatedvascularfeatures,provideanicheforthegrowthofnascentlung.Aninnovativeapproachof this proposal is to use features of MCE in the sphere of lung around a nodule to improve specificity for detecting cancer. However, increasing specificity results in decreasing sensitivity. In the case of lung cancer screening more ?missed? cancers may increase lung cancer deaths. To understand the effect of decreasing sensitivity on mortality we will use the novel UVM Lung Cancer Model, which accurately recapitulates lung cancerdeathandCTscreeningrates,toidentifyanoptimalsetofbiomarkersforidentifyingcanceramongthe manyscreendetectednodules. Candidate: Dr. Kinsey?s clinical practice is in Interventional Pulmonary, a specialty that focuses on dealing with the problem of indeterminate nodules. He has applied his MPH epidemiology and biostatistical training, coupledwithexperienceinquantitativeCTimaging,tobegintoaddresstheproblemofindeterminatenodules intheCOPDGenedatasetandasthePrincipalInvestigatoroftheUVMMolecular,Epigenetic,andRadiologic Biomarkers for Thoracic Cancers (MEROPTIC) study. However, he needs further training in the process of developingCTfeaturesasimagingbiomarkersandincomputermodeling,whichwillallowhimtounderstand the effect of deployment of these biomarkers on lung cancer mortality. To address these critical gaps in knowledge his primary mentor, Dr. Jason Bates, has designed a program of didactic training and supervised researchthatwillpropelDr.Kinseytoanindependentinvestigatorinthefieldoflungcancerdiagnosis. Environment:Dr.Kinsey?sprimarymentor,Dr.Bates,isinternationallyrecognizedforhisworkinpulmonary physiology and computer modeling and has a proven track record of training investigators and physician scientists. The co-mentor, Dr. George Washko, is an expert in quantitative imaging analysis and has an established mentoring relationship with Dr. Kinsey. A scientific advisory committee with established expertise in radiology, biostatistics, lung cancer, and biomarker development complements this outstanding mentoring team. Dr. Kinsey is further supported by a network of individuals and resources, under the auspices of the VermontLungCenterandUniversityofVermontCancerCenter,thatiscommittedtothedevelopmentofjunior investigators.
CT screening for lung cancer results in decreased lung cancer deaths but at the cost of identifying approximately 19 non-cancerous nodules for every cancer, resulting in the performance of many potentially avoidable invasive procedures in an attempt to diagnose these nodules. The first goal of this proposal is to gaincriticalskillsinCTbiomarkerdevelopmentbyusingfeaturesofthelungaroundanoduletopredictlung cancer using data from two studies: COPDGene and the actively enrolling UVM MEROPTIC study. The second career development goal is to develop abilities in computer modeling in order to estimate the large- scale effect of implementing CT and other biomarkers into a lung cancer screening program using the UVM LungCancerModel.
| Carr, Laurie L; Jacobson, Sean; Lynch, David A et al. (2018) Features of COPD as Predictors of Lung Cancer. Chest 153:1326-1335 |
| Ramsey, Jon; Butnor, Kelly; Peng, Zhihua et al. (2018) Loss of RUNX1 is associated with aggressive lung adenocarcinomas. J Cell Physiol 233:3487-3497 |
| Kinsey, C Matthew; San José Estépar, Raul; van der Velden, Jos et al. (2017) Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer. Cancer Epidemiol Biomarkers Prev 26:38-43 |
| Kinsey, C Matthew; Hamlington, Katharine L; O'Toole, Jacqueline et al. (2016) Predicting the Mortality Benefit of CT Screening for Second Lung Cancer in a High-Risk Population. PLoS One 11:e0165471 |
