title: Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma.
abstract: Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets. Fisher's exact test identified significant associations between GAs and smoking status. Amongst 83 patients, 23%, 55% and 22% were CS, ES, and NS, respectively, and 95% of patients had stage IV disease. With a median follow up of 14.4 months, the median overall survival (OS) was significantly higher in NS and ES (combined) as compared to CS (51.6 vs 15.6 months; P = 0.04). Of 315 cancer-related genes and 31 genes often related to rearrangement tested, heatmaps show some variations amongst the subsets. GAs in NSD1 were more frequent in CS as compared to other groups (P < 0.001). CS status negatively impacts OS in patients with mUC and is associated with genomic alterations that could have therapeutic implications.
authors.affiliation: Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
authors.affiliation: Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Monali
authors.initials: M
authors.lastname: Vasekar
authors.affiliation: Department of Hematology/Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Grivas
authors.affiliation: Department of Hematology/Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Emamekhoo
authors.affiliation: Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Department of Pathology, Albany Medical College, Albany, NY, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Warrick
authors.affiliation: Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Drabick
authors.affiliation: Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Holder
authors.affiliation: Department of Surgery, Division of Urology, Penn State Hershey Cancer Institute, Hershey, PA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kaag
authors.affiliation: Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
authors.forename: Sumanta Kumar
authors.initials: SK
authors.lastname: Pal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D023281:Genomics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
keywords: advanced; chemotherapy; genomic profiling; metastatic; smoking