Characterization of Metastatic Urothelial Carcinoma via Comprehensive Genomic Profiling of Circulating Tumor DNA

被引：81

作者：

Agarwal, Neeraj ^{[1
]}

Pal, Sumanta K. ^{[2
]}

Hahn, Andrew W. ^{[1
]}

Nussenzveig, Roberto H. ^{[1
]}

Pond, Gregory R. ^{[3
]}

Gupta, Sumati V. ^{[1
]}

Wang, Jue ^{[4
]}

Bilen, Mehmet A. ^{[5
]}

Naik, Gurudatta ^{[6
]}

Ghatalia, Pooja ^{[7
]}

Hoimes, Christopher J. ^{[8
]}

Gopalakrishnan, Dharmesh ^{[9
]}

Barata, Pedro C. ^{[10
]}

Drakaki, Alexandra ^{[11
]}

Faltas, Bishoy M. ^{[12
]}

Kiedrowski, Lesli A. ^{[13
]}

Lanman, Richard B. ^{[13
]}

Nagy, Rebecca J. ^{[13
]}

Vogelzang, Nicholas J. ^{[14
]}

Boucher, Kenneth M. ^{[15
]}

Vaishampayan, Ulka N. ^{[16
]}

Sonpavde, Guru ^{[17
]}

Grivas, Petros ^{[10
]}

机构：

[1] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Div Oncol, Salt Lake City, UT 84112 USA

[2] City Hope Comprehens Canc Ctr, Dept Med Oncol, Duarte, CA USA

[3] McMaster Univ, Dept Oncol, Hamilton, ON, Canada

[4] Univ Arizona, St Josephs Hosp & Med Ctr, Genitourinary Oncol Sect, Ctr Canc,Dign Hlth, Phoenix, AZ USA

[5] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA

[6] Univ Alabama Birmingham, Dept Oncol, Birmingham, AL USA

[7] Fox Chase Canc Ctr, Dept Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[8] Case Western Reserve Univ, Seidman Canc Ctr, Div Hematol Oncol, Cleveland, OH 44106 USA

[9] Cleveland Clin, Dept Hosp Med, Cleveland, OH 44106 USA

[10] Univ Washington, Dept Med, Div Oncol, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[11] Univ Calif Los Angeles, Med Ctr, Dept Hematol Oncol, Los Angeles, CA 90024 USA

[12] Weill Cornell Med Coll, Dept Med Oncol, New York, NY USA

[13] Guardant Hlth Inc, Redwood City, CA USA

[14] Comprehens Canc Ctr Nevada, Dept Oncol, Las Vegas, NV USA

[15] Univ Utah, Div Biostat, Huntsman Canc Inst, Salt Lake City, UT USA

[16] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA

[17] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

来源：

CANCER | 2018年 / 124卷 / 10期

关键词：

bladder cancer; circulating tumor DNA; metastatic urothelial carcinoma; next-generation sequencing; upper tract urothelial carcinoma; GENERATION SEQUENCING NGS; OPEN-LABEL; TARGETED THERAPY; CANCER; MULTICENTER; TRASTUZUMAB; GEMCITABINE; REVEALS; METHOTREXATE; DOXORUBICIN;

D O I：

10.1002/cncr.31314

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

BACKGROUND: Biomarker-guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available are not eligible. Technological advancements in sequencing have made cell-free circulating DNA (cfDNA) next-generation sequencing (NGS) readily available in the clinic. The objective of the current study was to determine whether the genomic profile of mUC detected by NGS of cfDNA is similar to historical tumor tissue NGS studies. A secondary objective was to determine whether the frequency of genomic alterations (GAs) differed between lower tract mUC (mLTUC) and upper tract mUC (mUTUC). METHODS: Patients from 13 academic medical centers in the United States who had a diagnosis of mUC between 2014 and 2017 and for whom cfDNA NGS results were available were included. cfDNA profiling was performed using a commercially available platform (Guardant360) targeting 73 genes. RESULTS: Of 369 patients with mUC, 294 were diagnosed with mLTUC and 75 with mUTUC. A total of 2130 GAs were identified in the overall mUC cohort: 1610 and 520, respectively, in the mLTUC and mUTUC cohorts. In the mLTUC cohort, frequently observed GAs were similar between cfDNA NGS and historical tumor tissue studies, including tumor protein p53 (TP53) (P = 1.000 and .115, respectively), AT-rich interaction domain 1A (ARID1A) (P = .058 and .058, respectively), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (P = .058 and .067, respectively), erb-b2 receptor tyrosine kinase 2 (ERBB2) (P = .565 and .074, respectively), and fibroblast growth factor receptor 3 (FGFR3) (P = .164 and .014, respectively). No significant difference was observed with regard to the frequency of GAs between patients with mLTUC and mUTUC. CONCLUSIONS: Among patients with mUC for whom no tumor tissue was available, cfDNA NGS was able to identify a similar profile of GAs for biomarker-driven clinical trials compared with tumor tissue. Despite the more aggressive clinical course, cases of mUTUC demonstrated a circulating tumor DNA genomic landscape that was similar to that of mLTUC. (C) 2018 American Cancer Society.

引用

页码：2115 / 2124

页数：10

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