Clinical Research Papers:
Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma
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Monika Joshi1, Monali Vasekar1, Petros Grivas2, Hamid Emamekhoo2, JoAnn Hsu3, Vincent A. Miller4, Philip J. Stephens4, Siraj M. Ali4, Jeffrey S. Ross5, Junjia Zhu1, Joshua Warrick6, Joseph J. Drabick1, Sheldon L. Holder1, Matthew Kaag7, Min Li8, Sumanta Kumar Pal3
1Department of Medicine, Division of Hematology/Medical Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA
2Department of Hematology/Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
3Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
4Foundation Medicine, Cambridge, MA, USA
5Department of Pathology, Albany Medical College, Albany, NY, USA
6Department of Pathology, Penn State Hershey Cancer Institute, Hershey, PA, USA
7Department of Surgery, Division of Urology, Penn State Hershey Cancer Institute, Hershey, PA, USA
8Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
Sumanta Kumar Pal, email: [email protected]
Keywords: advanced, chemotherapy, metastatic, genomic profiling, smoking
Received: March 17, 2016 Accepted: April 16, 2016 Published: May 18, 2016
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.
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