Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers

被引：54

作者：

Hirshfield, Kim M. ^{[1
]}

Tolkunov, Denis ^{[2
]}

Zhong, Hua ^{[3
]}

Ali, Siraj M. ^{[8
]}

Stein, Mark N. ^{[1
]}

Murphy, Susan ^{[4
]}

Vig, Hetal ^{[1
]}

Vazquez, Alexei ^{[5
]}

Glod, John ^{[4
]}

Moss, Rebecca A. ^{[1
]}

Belyi, Vladimir ^{[2
]}

Chan, Chang S. ^{[1
]}

Chen, Suzie ^{[9
]}

Goodell, Lauri ^{[3
]}

Foran, David ^{[3
]}

Yelensky, Roman ^{[8
]}

Palma, Norma A. ^{[8
]}

Sun, James X. ^{[8
]}

Miller, Vincent A. ^{[8
]}

Stephens, Philip J. ^{[8
]}

Ross, Jeffrey S. ^{[8
,10
]}

Kaufman, Howard ^{[6
]}

Poplin, Elizabeth ^{[1
]}

Mehnert, Janice ^{[1
]}

Tan, Antoinette R. ^{[1
]}

Bertino, Joseph R. ^{[1
]}

Aisner, Joseph ^{[1
]}

DiPaola, Robert S. ^{[1
]}

Rodriguez-Rodriguez, Lorna ^{[6
,7
]}

Ganesan, Shridar ^{[1
]}

机构：

[1] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Div Med Oncol, Dept Med, 195 Little Albany St, New Brunswick, NJ 08901 USA

[2] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Dept Clin Informat, New Brunswick, NJ USA

[3] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Dept Pathol & Lab Med, New Brunswick, NJ USA

[4] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Dept Pediat, New Brunswick, NJ USA

[5] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ USA

[6] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Div Surg Oncol, Dept Surg, New Brunswick, NJ USA

[7] Rutgers Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Div Gynecol Oncol, Dept Obstet & Gynecol, 195 Little Albany St, New Brunswick, NJ 08901 USA

[8] Fdn Med, Cambridge, MA USA

[9] Rutgers State Univ, Dept Biol Chem, New Brunswick, NJ USA

[10] Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA

来源：

ONCOLOGIST | 2016年 / 21卷 / 11期

基金：

美国国家卫生研究院;

关键词：

Molecular sequencing; Cancer; Tumor genomics; Molecular targeted therapy; Mutation; COLORECTAL CANCERS; RESISTANCE; MUTATIONS; TUMOR; BRAF; CHEMOTHERAPY; INHIBITION; EVOLUTION; IDENTIFICATION; BRAF(V600E);

D O I：

10.1634/theoncologist.2016-0049

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88(96%) hadat least one genomic alteration(average3.6, range 0-10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK(rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability.

引用

页码：1315 / 1325

页数：11

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