التفاصيل البيبلوغرافية
| العنوان: |
Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers. |
| المؤلفون: |
Hirshfield, Kim M., Tolkunov, Denis, Zhong, Hua, Ali, Siraj M., Stein, Mark N., Murphy, Susan, Vig, Hetal, Vazquez, Alexei, Glod, John, Moss, Rebecca A., Belyi, Vladimir, Chan, Chang S., Chen, Suzie, Goodell, Lauri, Foran, David, Yelensky, Roman, Palma, Norma A., Sun, James X., Miller, Vincent A., Stephens, Philip J. |
| المصدر: |
Oncologist; Nov2016, Vol. 21 Issue 11, p1315-1325, 11p, 1 Color Photograph, 1 Diagram, 1 Chart, 2 Graphs |
| مصطلحات موضوعية: |
TUMOR classification, TUMOR prevention, RARE diseases, CANCER treatment, LONGITUDINAL method, GENETIC mutation, RESEARCH funding, GENOMICS, SPECIALTY hospitals, DATA analysis software, GENE expression profiling, DESCRIPTIVE statistics, PREVENTION |
| مصطلحات جغرافية: |
NEW Jersey |
| مستخلص: |
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%) had at least onegenomic alteration (average 3.6, 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 wereclinical 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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