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BT 15.000 718.042 Td /F2 21.0 Tf  [(DecisionDx-GBM Gene Expression Assay for Prognostic )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Testing in Glioblastoma Multiform)] TJ ET
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BT 15.000 675.088 Td /F3 9.8 Tf  [(October 14, 2010)] TJ ET
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BT 26.250 663.247 Td /F1 9.8 Tf  [(Diane Allingham-Hawkins)] TJ ET
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BT 142.733 663.247 Td /F1 9.8 Tf  [(Andrew Lea)] TJ ET
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BT 200.180 663.247 Td /F1 9.8 Tf  [(Susan Levine)] TJ ET
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BT 26.250 651.342 Td /F1 9.8 Tf  [(Allingham-Hawkins D, Lea A, Levine S. DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Multiform. PLOS Currents Evidence on Genomic Tests. 2010 Oct 14 . Edition 1. doi: 10.1371/currents.RRN1186.)] TJ ET
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BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(It is estimated that approximately 22,000 Americans will be diagnosed with tumor of the brain or nervous system in 2010. )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(Among primary brain tumors, approximately 60% are gliomas, the most common and most malignant of which is glioblastoma )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(multiforme \(GBM\).The DecisionDx-GBM test is a multigene expression assay that is designed to predict which patients are )] TJ ET
BT 26.250 554.667 Td /F1 9.8 Tf  [(likely to experience long-term \(> 2 years\) progression-free survival.)] TJ ET
BT 26.250 518.064 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 498.110 Td /F1 9.8 Tf  [(In 2010, approximately 22,000 Americans will be diagnosed with a tumor of the brain or nervous system )] TJ ET
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BT 476.027 498.110 Td /F1 9.8 Tf  [([1])] TJ ET
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BT 486.869 498.110 Td /F1 9.8 Tf  [(. Glioblastoma )] TJ ET
BT 26.250 486.205 Td /F1 9.8 Tf  [(multiforme \(GBM\) are the most common primary brain tumors. GBMs are aggressive tumors and despite improvements in )] TJ ET
BT 26.250 474.300 Td /F1 9.8 Tf  [(treatment regimens, which include surgical resection, radiation, and chemotherapy, prognosis is poor with a median survival of )] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(14.6 months )] TJ ET
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BT 82.615 462.396 Td /F1 9.8 Tf  [([2])] TJ ET
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BT 93.457 462.396 Td /F1 9.8 Tf  [( Research has indicated that the genomes of GBMs have multiple changes including deletion of tumor )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(suppressor genes and amplification or over-expression of tyrosine kinase receptors leading to both survival advantage and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(apoptosis resistance in tumor cells. Consequently, it has been suggested that any successful targeted therapy must take into )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(account multiple genomic changes simultaneously )] TJ ET
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BT 245.713 426.681 Td /F1 9.8 Tf  [([2])] TJ ET
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BT 256.555 426.681 Td /F1 9.8 Tf  [( . The DecisionDx-GBM test is a multigene expression assay that is )] TJ ET
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BT 481.146 414.777 Td /F1 9.8 Tf  [([3])] TJ ET
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BT 491.988 414.777 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 378.174 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 358.220 Td /F1 9.8 Tf  [(The DecisionDx-GBM test uses formalin-fixed, paraffin-embedded \(FFPE\) tumor tissue. RNA is extracted from this specimen )] TJ ET
BT 26.250 346.315 Td /F1 9.8 Tf  [(and used to measure the expression of 9 genes reported to be associated with survival including 7 genes correlated with )] TJ ET
BT 26.250 334.410 Td /F1 9.8 Tf  [(decreased survival \(aquaporin 1 [ )] TJ ET
BT 173.105 334.410 Td /F5 9.8 Tf  [(AQP1)] TJ ET
BT 199.118 334.410 Td /F1 9.8 Tf  [( ], chitinase 3-like 1 [ )] TJ ET
BT 290.699 334.410 Td /F5 9.8 Tf  [(CHI3L1)] TJ ET
BT 323.752 334.410 Td /F1 9.8 Tf  [( ], epithelial membrane protein 3 [ )] TJ ET
BT 471.152 334.410 Td /F5 9.8 Tf  [(EMP-3)] TJ ET
BT 500.948 334.410 Td /F1 9.8 Tf  [( ], glycoprotein )] TJ ET
BT 26.250 322.506 Td /F1 9.8 Tf  [(NMB [GPNMB], insulin-like growth factor-binding protein 2 [ )] TJ ET
BT 285.249 322.506 Td /F5 9.8 Tf  [(IGFBP2)] TJ ET
BT 319.930 322.506 Td /F1 9.8 Tf  [( ], galectin 3 [ )] TJ ET
BT 380.633 322.506 Td /F5 9.8 Tf  [(LGALS3)] TJ ET
BT 417.488 322.506 Td /F1 9.8 Tf  [( ] and podoplanin [ )] TJ ET
BT 500.422 322.506 Td /F5 9.8 Tf  [(PDPN)] TJ ET
BT 527.507 322.506 Td /F1 9.8 Tf  [( ]\) and 2 )] TJ ET
BT 26.250 310.601 Td /F1 9.8 Tf  [(genes associated with improved survival \(oligodendrocyte lineage transcription factor 2 [ )] TJ ET
BT 408.820 310.601 Td /F5 9.8 Tf  [(OLIG2)] TJ ET
BT 437.544 310.601 Td /F1 9.8 Tf  [( ] and reticulon 1 [ )] TJ ET
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BT 543.215 310.601 Td /F1 9.8 Tf  [( ]\) as )] TJ ET
BT 26.250 298.696 Td /F1 9.8 Tf  [(well as 3 control genes \(eukaryotic translation elongation factor 1, alpha-1 [ )] TJ ET
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BT 388.794 298.696 Td /F1 9.8 Tf  [( ]; beta-glucoronidase [ )] TJ ET
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BT 26.250 286.791 Td /F1 9.8 Tf  [(ribosomal protein S27 [ )] TJ ET
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BT 182.318 286.791 Td /F1 9.8 Tf  [( . A proprietary algorithm is used to convert expression levels to a DecisionDx-GBM score, )] TJ ET
BT 26.250 274.887 Td /F1 9.8 Tf  [(which is then compared to an underlying clinical database. Results are reported as both a DecisionDx-GBM score and a quintile )] TJ ET
BT 26.250 262.982 Td /F1 9.8 Tf  [(rank compared to other patients in the database. The likelihood of 2-year survival is provided, along with the expected median )] TJ ET
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BT 263.048 251.077 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 214.475 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 194.520 Td /F1 9.8 Tf  [(Although standard histo-pathological methods can accurately diagnosis GBM, no information on patient prognosis is provided. )] TJ ET
BT 26.250 182.616 Td /F1 9.8 Tf  [(Having prognostic information may lead to a change in patient management such that more aggressive treatments are used )] TJ ET
BT 26.250 170.711 Td /F1 9.8 Tf  [(earlier in patients with a poorer predicted prognosis. However, it is important to note that there have been no demonstrations )] TJ ET
BT 26.250 158.806 Td /F1 9.8 Tf  [(that the use of a gene expression assay such as DecisionDx-GBM to guide management of patients with GBM results in )] TJ ET
BT 26.250 146.901 Td /F1 9.8 Tf  [(improved patient outcomes.)] TJ ET
BT 26.250 110.299 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 90.345 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 70.940 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 51.535 Td /F4 9.8 Tf  [(Recommendations by independent group)] TJ ET
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BT 15.000 693.094 Td /F2 21.0 Tf  [(Testing in Glioblastoma Multiform)] TJ ET
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BT 15.000 675.088 Td /F3 9.8 Tf  [(October 14, 2010)] TJ ET
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BT 26.250 663.247 Td /F1 9.8 Tf  [(Diane Allingham-Hawkins)] TJ ET
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BT 142.733 663.247 Td /F1 9.8 Tf  [(Andrew Lea)] TJ ET
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BT 194.759 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 200.180 663.247 Td /F1 9.8 Tf  [(Susan Levine)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Allingham-Hawkins D, Lea A, Levine S. DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Multiform. PLOS Currents Evidence on Genomic Tests. 2010 Oct 14 . Edition 1. doi: 10.1371/currents.RRN1186.)] TJ ET
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BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(It is estimated that approximately 22,000 Americans will be diagnosed with tumor of the brain or nervous system in 2010. )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(Among primary brain tumors, approximately 60% are gliomas, the most common and most malignant of which is glioblastoma )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(multiforme \(GBM\).The DecisionDx-GBM test is a multigene expression assay that is designed to predict which patients are )] TJ ET
BT 26.250 554.667 Td /F1 9.8 Tf  [(likely to experience long-term \(> 2 years\) progression-free survival.)] TJ ET
BT 26.250 518.064 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
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BT 476.027 498.110 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 486.869 498.110 Td /F1 9.8 Tf  [(. Glioblastoma )] TJ ET
BT 26.250 486.205 Td /F1 9.8 Tf  [(multiforme \(GBM\) are the most common primary brain tumors. GBMs are aggressive tumors and despite improvements in )] TJ ET
BT 26.250 474.300 Td /F1 9.8 Tf  [(treatment regimens, which include surgical resection, radiation, and chemotherapy, prognosis is poor with a median survival of )] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(14.6 months )] TJ ET
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BT 82.615 462.396 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 93.457 462.396 Td /F1 9.8 Tf  [( Research has indicated that the genomes of GBMs have multiple changes including deletion of tumor )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(suppressor genes and amplification or over-expression of tyrosine kinase receptors leading to both survival advantage and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(apoptosis resistance in tumor cells. Consequently, it has been suggested that any successful targeted therapy must take into )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(account multiple genomic changes simultaneously )] TJ ET
0.267 0.267 0.267 rg
BT 245.713 426.681 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 256.555 426.681 Td /F1 9.8 Tf  [( . The DecisionDx-GBM test is a multigene expression assay that is )] TJ ET
BT 26.250 414.777 Td /F1 9.8 Tf  [(designed to predict which patients are likely to experience long-term \(> 2 years\) progression-free survival )] TJ ET
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BT 481.146 414.777 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 491.988 414.777 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 378.174 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 358.220 Td /F1 9.8 Tf  [(The DecisionDx-GBM test uses formalin-fixed, paraffin-embedded \(FFPE\) tumor tissue. RNA is extracted from this specimen )] TJ ET
BT 26.250 346.315 Td /F1 9.8 Tf  [(and used to measure the expression of 9 genes reported to be associated with survival including 7 genes correlated with )] TJ ET
BT 26.250 334.410 Td /F1 9.8 Tf  [(decreased survival \(aquaporin 1 [ )] TJ ET
BT 173.105 334.410 Td /F5 9.8 Tf  [(AQP1)] TJ ET
BT 199.118 334.410 Td /F1 9.8 Tf  [( ], chitinase 3-like 1 [ )] TJ ET
BT 290.699 334.410 Td /F5 9.8 Tf  [(CHI3L1)] TJ ET
BT 323.752 334.410 Td /F1 9.8 Tf  [( ], epithelial membrane protein 3 [ )] TJ ET
BT 471.152 334.410 Td /F5 9.8 Tf  [(EMP-3)] TJ ET
BT 500.948 334.410 Td /F1 9.8 Tf  [( ], glycoprotein )] TJ ET
BT 26.250 322.506 Td /F1 9.8 Tf  [(NMB [GPNMB], insulin-like growth factor-binding protein 2 [ )] TJ ET
BT 285.249 322.506 Td /F5 9.8 Tf  [(IGFBP2)] TJ ET
BT 319.930 322.506 Td /F1 9.8 Tf  [( ], galectin 3 [ )] TJ ET
BT 380.633 322.506 Td /F5 9.8 Tf  [(LGALS3)] TJ ET
BT 417.488 322.506 Td /F1 9.8 Tf  [( ] and podoplanin [ )] TJ ET
BT 500.422 322.506 Td /F5 9.8 Tf  [(PDPN)] TJ ET
BT 527.507 322.506 Td /F1 9.8 Tf  [( ]\) and 2 )] TJ ET
BT 26.250 310.601 Td /F1 9.8 Tf  [(genes associated with improved survival \(oligodendrocyte lineage transcription factor 2 [ )] TJ ET
BT 408.820 310.601 Td /F5 9.8 Tf  [(OLIG2)] TJ ET
BT 437.544 310.601 Td /F1 9.8 Tf  [( ] and reticulon 1 [ )] TJ ET
BT 517.757 310.601 Td /F5 9.8 Tf  [(RTN1)] TJ ET
BT 543.215 310.601 Td /F1 9.8 Tf  [( ]\) as )] TJ ET
BT 26.250 298.696 Td /F1 9.8 Tf  [(well as 3 control genes \(eukaryotic translation elongation factor 1, alpha-1 [ )] TJ ET
BT 352.485 298.696 Td /F5 9.8 Tf  [(EEF1A1)] TJ ET
BT 388.794 298.696 Td /F1 9.8 Tf  [( ]; beta-glucoronidase [ )] TJ ET
BT 490.681 298.696 Td /F5 9.8 Tf  [(GUSB)] TJ ET
BT 518.313 298.696 Td /F1 9.8 Tf  [( ]; and )] TJ ET
BT 26.250 286.791 Td /F1 9.8 Tf  [(ribosomal protein S27 [ )] TJ ET
BT 129.210 286.791 Td /F5 9.8 Tf  [(RPS27)] TJ ET
BT 160.098 286.791 Td /F1 9.8 Tf  [( ]\) )] TJ ET
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BT 171.476 286.791 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 182.318 286.791 Td /F1 9.8 Tf  [( . A proprietary algorithm is used to convert expression levels to a DecisionDx-GBM score, )] TJ ET
BT 26.250 274.887 Td /F1 9.8 Tf  [(which is then compared to an underlying clinical database. Results are reported as both a DecisionDx-GBM score and a quintile )] TJ ET
BT 26.250 262.982 Td /F1 9.8 Tf  [(rank compared to other patients in the database. The likelihood of 2-year survival is provided, along with the expected median )] TJ ET
BT 26.250 251.077 Td /F1 9.8 Tf  [(survival and median progression-free survival )] TJ ET
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BT 225.101 251.077 Td /F1 9.8 Tf  [([3] [4] [5])] TJ ET
0.271 0.267 0.267 rg
BT 263.048 251.077 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 214.475 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 194.520 Td /F1 9.8 Tf  [(Although standard histo-pathological methods can accurately diagnosis GBM, no information on patient prognosis is provided. )] TJ ET
BT 26.250 182.616 Td /F1 9.8 Tf  [(Having prognostic information may lead to a change in patient management such that more aggressive treatments are used )] TJ ET
BT 26.250 170.711 Td /F1 9.8 Tf  [(earlier in patients with a poorer predicted prognosis. However, it is important to note that there have been no demonstrations )] TJ ET
BT 26.250 158.806 Td /F1 9.8 Tf  [(that the use of a gene expression assay such as DecisionDx-GBM to guide management of patients with GBM results in )] TJ ET
BT 26.250 146.901 Td /F1 9.8 Tf  [(improved patient outcomes.)] TJ ET
BT 26.250 110.299 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 90.345 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 70.940 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 51.535 Td /F4 9.8 Tf  [(Recommendations by independent group)] TJ ET
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BT 15.000 693.094 Td /F2 21.0 Tf  [(Testing in Glioblastoma Multiform)] TJ ET
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BT 15.000 675.088 Td /F3 9.8 Tf  [(October 14, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 663.247 Td /F1 9.8 Tf  [(Diane Allingham-Hawkins)] TJ ET
0.271 0.267 0.267 rg
BT 137.312 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 142.733 663.247 Td /F1 9.8 Tf  [(Andrew Lea)] TJ ET
0.271 0.267 0.267 rg
BT 194.759 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 200.180 663.247 Td /F1 9.8 Tf  [(Susan Levine)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Allingham-Hawkins D, Lea A, Levine S. DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Multiform. PLOS Currents Evidence on Genomic Tests. 2010 Oct 14 . Edition 1. doi: 10.1371/currents.RRN1186.)] TJ ET
q
15.000 41.654 577.500 595.403 re W n
0.271 0.267 0.267 rg
BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(It is estimated that approximately 22,000 Americans will be diagnosed with tumor of the brain or nervous system in 2010. )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(Among primary brain tumors, approximately 60% are gliomas, the most common and most malignant of which is glioblastoma )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(multiforme \(GBM\).The DecisionDx-GBM test is a multigene expression assay that is designed to predict which patients are )] TJ ET
BT 26.250 554.667 Td /F1 9.8 Tf  [(likely to experience long-term \(> 2 years\) progression-free survival.)] TJ ET
BT 26.250 518.064 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 498.110 Td /F1 9.8 Tf  [(In 2010, approximately 22,000 Americans will be diagnosed with a tumor of the brain or nervous system )] TJ ET
0.267 0.267 0.267 rg
BT 476.027 498.110 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 486.869 498.110 Td /F1 9.8 Tf  [(. Glioblastoma )] TJ ET
BT 26.250 486.205 Td /F1 9.8 Tf  [(multiforme \(GBM\) are the most common primary brain tumors. GBMs are aggressive tumors and despite improvements in )] TJ ET
BT 26.250 474.300 Td /F1 9.8 Tf  [(treatment regimens, which include surgical resection, radiation, and chemotherapy, prognosis is poor with a median survival of )] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(14.6 months )] TJ ET
0.267 0.267 0.267 rg
BT 82.615 462.396 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 93.457 462.396 Td /F1 9.8 Tf  [( Research has indicated that the genomes of GBMs have multiple changes including deletion of tumor )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(suppressor genes and amplification or over-expression of tyrosine kinase receptors leading to both survival advantage and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(apoptosis resistance in tumor cells. Consequently, it has been suggested that any successful targeted therapy must take into )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(account multiple genomic changes simultaneously )] TJ ET
0.267 0.267 0.267 rg
BT 245.713 426.681 Td /F1 9.8 Tf  [([2])] TJ ET
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BT 45.750 403.232 Td /F1 9.8 Tf  [(Gene expression data derived from expression microarray studies on frozen tumors specimens from a total of 110 patients )] TJ ET
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BT 45.750 600.681 Td /F1 9.8 Tf  [(growth factor binding protein 2 OR LGALS3 OR galectin 3 OR OLIG2 OR oligodendrocyte lineage transcription factor 2 OR )] TJ ET
BT 45.750 588.777 Td /F1 9.8 Tf  [(PDPN OR podoplanin OR RTN1 OR reticulon 1\); and Colman H \(au\). Limits used were human, English language, and )] TJ ET
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38.185 565.891 37.741 565.707 37.425 565.391 c
37.109 565.075 36.925 564.631 36.925 564.185 c
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37.741 562.662 38.185 562.478 38.631 562.478 c
39.078 562.478 39.522 562.662 39.838 562.978 c
40.154 563.294 40.337 563.738 40.337 564.185 c f
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38.185 462.370 37.741 462.186 37.425 461.870 c
37.109 461.554 36.925 461.110 36.925 460.664 c
36.925 460.217 37.109 459.773 37.425 459.457 c
37.741 459.141 38.185 458.957 38.631 458.957 c
39.078 458.957 39.522 459.141 39.838 459.457 c
40.154 459.773 40.337 460.217 40.337 460.664 c f
BT 45.750 457.696 Td /F1 9.8 Tf  [(No information regarding the analytical validity of the DecisionDx-GBM assay was identified in either the primary publication )] TJ ET
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39.522 407.722 39.078 407.906 38.631 407.906 c
38.185 407.906 37.741 407.722 37.425 407.406 c
37.109 407.090 36.925 406.646 36.925 406.200 c
36.925 405.753 37.109 405.309 37.425 404.993 c
37.741 404.677 38.185 404.493 38.631 404.493 c
39.078 404.493 39.522 404.677 39.838 404.993 c
40.154 405.309 40.337 405.753 40.337 406.200 c f
BT 45.750 403.232 Td /F1 9.8 Tf  [(Gene expression data derived from expression microarray studies on frozen tumors specimens from a total of 110 patients )] TJ ET
BT 45.750 391.327 Td /F1 9.8 Tf  [(from 4 institutions \(Massachusetts General Hospital, M.D. Anderson Cancer Center, University of California Los Angeles )] TJ ET
BT 45.750 379.422 Td /F1 9.8 Tf  [(and University of California San Francisco\) were used to identify 38 genes whose expression was significantly associated )] TJ ET
BT 45.750 367.518 Td /F1 9.8 Tf  [(with survival)] TJ ET
0.267 0.267 0.267 rg
BT 98.839 367.518 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 109.681 367.518 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 347.331 m 
40.337 347.777 40.154 348.221 39.838 348.537 c
39.522 348.853 39.078 349.037 38.631 349.037 c
38.185 349.037 37.741 348.853 37.425 348.537 c
37.109 348.221 36.925 347.777 36.925 347.331 c
36.925 346.884 37.109 346.440 37.425 346.124 c
37.741 345.808 38.185 345.624 38.631 345.624 c
39.078 345.624 39.522 345.808 39.838 346.124 c
40.154 346.440 40.337 346.884 40.337 347.331 c f
BT 45.750 344.363 Td /F1 9.8 Tf  [(A reverse-transcription polymerase chain reaction \(RT-PCR\) assay for the 38 genes was developed and validated on a )] TJ ET
BT 45.750 332.458 Td /F1 9.8 Tf  [(separate set of 68 FFPE GBM tumor specimens. From this validation, the 9 genes with the highest survival associations )] TJ ET
BT 45.750 320.553 Td /F1 9.8 Tf  [(were selected)] TJ ET
0.267 0.267 0.267 rg
BT 105.898 320.553 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 116.740 320.553 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 307.866 m 
40.337 308.313 40.154 308.757 39.838 309.073 c
39.522 309.389 39.078 309.573 38.631 309.573 c
38.185 309.573 37.741 309.389 37.425 309.073 c
37.109 308.757 36.925 308.313 36.925 307.866 c
36.925 307.420 37.109 306.976 37.425 306.660 c
37.741 306.344 38.185 306.160 38.631 306.160 c
39.078 306.160 39.522 306.344 39.838 306.660 c
40.154 306.976 40.337 307.420 40.337 307.866 c f
BT 45.750 304.899 Td /F1 9.8 Tf  [(The 9-gene assay was validated on a final set of 101 FFPE GBM tumor specimens. Expression of these 9 genes was found )] TJ ET
BT 45.750 292.994 Td /F1 9.8 Tf  [(through multivariate analysis to be an independent predictor of progression-free survival \(Cox proportional hazard ratio [HR] )] TJ ET
BT 45.750 281.089 Td /F1 9.8 Tf  [(= 2.7; P=0.0003\) and overall survival \(Cox HR = 2.7; P=0.0003\) compared to age, performance score, and methylation )] TJ ET
BT 45.750 269.184 Td /F1 9.8 Tf  [(status of the methylguanine methyltransferase gene \(MGMT\). MGMT methylation has previously been reported to be an )] TJ ET
BT 45.750 257.280 Td /F1 9.8 Tf  [(independent predictor of response of GBM to radiation and chemotherapy)] TJ ET
0.267 0.267 0.267 rg
BT 363.873 257.280 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 374.715 257.280 Td /F1 9.8 Tf  [(. Interestingly, MGMT methylation was not )] TJ ET
BT 45.750 245.375 Td /F1 9.8 Tf  [(found to be an independent predictor of survival in the DecisionDx-GBM validation studies)] TJ ET
0.267 0.267 0.267 rg
BT 433.215 245.375 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 444.057 245.375 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 222.220 Td /F6 9.8 Tf  [(Clinical Utility)] TJ ET
BT 90.727 222.220 Td /F4 9.8 Tf  [( : )] TJ ET
BT 99.394 222.220 Td /F1 9.8 Tf  [( Net benefit of test in improving health outcomes)] TJ ET
40.337 205.783 m 
40.337 206.230 40.154 206.674 39.838 206.990 c
39.522 207.305 39.078 207.489 38.631 207.489 c
38.185 207.489 37.741 207.305 37.425 206.990 c
37.109 206.674 36.925 206.230 36.925 205.783 c
36.925 205.336 37.109 204.892 37.425 204.576 c
37.741 204.261 38.185 204.077 38.631 204.077 c
39.078 204.077 39.522 204.261 39.838 204.576 c
40.154 204.892 40.337 205.336 40.337 205.783 c f
BT 45.750 202.815 Td /F1 9.8 Tf  [(No published studies demonstrating improved health outcomes were identified.)] TJ ET
40.337 182.628 m 
40.337 183.075 40.154 183.519 39.838 183.835 c
39.522 184.151 39.078 184.335 38.631 184.335 c
38.185 184.335 37.741 184.151 37.425 183.835 c
37.109 183.519 36.925 183.075 36.925 182.628 c
36.925 182.182 37.109 181.738 37.425 181.422 c
37.741 181.106 38.185 180.922 38.631 180.922 c
39.078 180.922 39.522 181.106 39.838 181.422 c
40.154 181.738 40.337 182.182 40.337 182.628 c f
BT 45.750 179.661 Td /F1 9.8 Tf  [(Two clinical trials have the DecisionDx-GBM test as part of the study as either a risk stratification method or as a )] TJ ET
BT 532.343 179.661 Td /F1 9.8 Tf  [(secondary )] TJ ET
BT 45.750 167.756 Td /F1 9.8 Tf  [(endpoint. These studies are: )] TJ ET
0.39 w 1 J 1 j
59.837 155.069 m 
59.837 155.515 59.654 155.959 59.338 156.275 c
59.022 156.591 58.578 156.775 58.131 156.775 c
57.685 156.775 57.241 156.591 56.925 156.275 c
56.609 155.959 56.425 155.515 56.425 155.069 c
56.425 154.622 56.609 154.178 56.925 153.862 c
57.241 153.546 57.685 153.363 58.131 153.363 c
58.578 153.363 59.022 153.546 59.338 153.862 c
59.654 154.178 59.837 154.622 59.837 155.069 c s
BT 65.250 152.101 Td /F1 9.8 Tf  [(Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed )] TJ ET
BT 65.250 140.196 Td /F1 9.8 Tf  [(Glioblastoma \(NCT00884741\))] TJ ET
0.39 w 1 J 1 j
59.837 127.509 m 
59.837 127.956 59.654 128.400 59.338 128.716 c
59.022 129.032 58.578 129.216 58.131 129.216 c
57.685 129.216 57.241 129.032 56.925 128.716 c
56.609 128.400 56.425 127.956 56.425 127.509 c
56.425 127.063 56.609 126.619 56.925 126.303 c
57.241 125.987 57.685 125.803 58.131 125.803 c
58.578 125.803 59.022 125.987 59.338 126.303 c
59.654 126.619 59.837 127.063 59.837 127.509 c s
BT 65.250 124.542 Td /F1 9.8 Tf  [(Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma )] TJ ET
BT 65.250 112.637 Td /F1 9.8 Tf  [(\(NCT00304031\))] TJ ET
BT 26.250 68.534 Td /F4 12.0 Tf  [(Limitations)] TJ ET
40.337 51.548 m 
40.337 51.994 40.154 52.438 39.838 52.754 c
39.522 53.070 39.078 53.254 38.631 53.254 c
38.185 53.254 37.741 53.070 37.425 52.754 c
37.109 52.438 36.925 51.994 36.925 51.548 c
36.925 51.101 37.109 50.657 37.425 50.341 c
37.741 50.025 38.185 49.841 38.631 49.841 c
39.078 49.841 39.522 50.025 39.838 50.341 c
40.154 50.657 40.337 51.101 40.337 51.548 c f
BT 45.750 48.580 Td /F1 9.8 Tf  [(Specimen numbers � to date the current version of the DecisionDx-GBM assay has only been validated on 101 specimens. )] TJ ET
Q
q
15.000 34.294 577.500 742.706 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 748.071 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 692.064 Td /F4 12.0 Tf  [(Search Strategy)] TJ ET
0.271 0.267 0.267 RG
40.337 675.077 m 
40.337 675.524 40.154 675.968 39.838 676.284 c
39.522 676.600 39.078 676.784 38.631 676.784 c
38.185 676.784 37.741 676.600 37.425 676.284 c
37.109 675.968 36.925 675.524 36.925 675.077 c
36.925 674.631 37.109 674.187 37.425 673.871 c
37.741 673.555 38.185 673.371 38.631 673.371 c
39.078 673.371 39.522 673.555 39.838 673.871 c
40.154 674.187 40.337 674.631 40.337 675.077 c f
BT 45.750 672.110 Td /F1 9.8 Tf  [(Searches of MEDLINE and EMBASE were conducted on September 16, 2010, using the search terms \(glioblastoma OR )] TJ ET
BT 45.750 660.205 Td /F1 9.8 Tf  [(GBM\) AND \(AQP1 OR aquaporin 1\) AND \(CHI3L1 OR chitinase 3-like 1 OR YKL-40\) AND \(EMP-3 OR epithelial )] TJ ET
BT 45.750 648.300 Td /F1 9.8 Tf  [(membrane protein 3\) AND \(GPNMB OR glycoprotein NMB\) AND \(IGFBP2 OR insulin-like growth factor binding protein 2\) )] TJ ET
BT 45.750 636.396 Td /F1 9.8 Tf  [(AND \(LGALS3 OR galectin 3\) AND \(OLIG2 OR oligodendrocyte lineage transcription factor 2\) AND \(PDPN OR podoplanin\) )] TJ ET
BT 45.750 624.491 Td /F1 9.8 Tf  [(AND \(RTN1 OR reticulon 1\); \(glioblastoma OR GBM\) AND \(AQP1 OR aquaporin 1 OR CHI3L1 OR chitinase 3-like 1 OR )] TJ ET
BT 45.750 612.586 Td /F1 9.8 Tf  [(YKL-40 OR EMP-3 OR epithelial membrane protein 3 OR GPNMB OR glycoprotein NMB OR IGFBP2 OR insulin-like )] TJ ET
BT 45.750 600.681 Td /F1 9.8 Tf  [(growth factor binding protein 2 OR LGALS3 OR galectin 3 OR OLIG2 OR oligodendrocyte lineage transcription factor 2 OR )] TJ ET
BT 45.750 588.777 Td /F1 9.8 Tf  [(PDPN OR podoplanin OR RTN1 OR reticulon 1\); and Colman H \(au\). Limits used were human, English language, and )] TJ ET
BT 45.750 576.872 Td /F1 9.8 Tf  [(published since January 1, 1996.)] TJ ET
40.337 564.185 m 
40.337 564.631 40.154 565.075 39.838 565.391 c
39.522 565.707 39.078 565.891 38.631 565.891 c
38.185 565.891 37.741 565.707 37.425 565.391 c
37.109 565.075 36.925 564.631 36.925 564.185 c
36.925 563.738 37.109 563.294 37.425 562.978 c
37.741 562.662 38.185 562.478 38.631 562.478 c
39.078 562.478 39.522 562.662 39.838 562.978 c
40.154 563.294 40.337 563.738 40.337 564.185 c f
BT 45.750 561.217 Td /F1 9.8 Tf  [(The above search strategies yielded 0, 126, and 53 citations, respectively. Only a single study directly related to the )] TJ ET
BT 45.750 549.312 Td /F1 9.8 Tf  [(DecisionDx-GBM test was identified.)] TJ ET
BT 26.250 508.960 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 489.006 Td /F6 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 489.006 Td /F4 9.8 Tf  [( : )] TJ ET
BT 110.236 489.006 Td /F1 9.8 Tf  [( Test accuracy and reliability in measuring expression of 9 survival and 3 control genes \(analytic sensitivity )] TJ ET
BT 26.250 477.101 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
40.337 460.664 m 
40.337 461.110 40.154 461.554 39.838 461.870 c
39.522 462.186 39.078 462.370 38.631 462.370 c
38.185 462.370 37.741 462.186 37.425 461.870 c
37.109 461.554 36.925 461.110 36.925 460.664 c
36.925 460.217 37.109 459.773 37.425 459.457 c
37.741 459.141 38.185 458.957 38.631 458.957 c
39.078 458.957 39.522 459.141 39.838 459.457 c
40.154 459.773 40.337 460.217 40.337 460.664 c f
BT 45.750 457.696 Td /F1 9.8 Tf  [(No information regarding the analytical validity of the DecisionDx-GBM assay was identified in either the primary publication )] TJ ET
BT 45.750 445.791 Td /F1 9.8 Tf  [(or on the Castle Biosciences website )] TJ ET
0.267 0.267 0.267 rg
BT 207.775 445.791 Td /F1 9.8 Tf  [([3][5])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 422.637 Td /F6 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 422.637 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 422.637 Td /F1 9.8 Tf  [( Test accuracy and reliability in accurately predicting patient prognosis \(predictive value\).)] TJ ET
40.337 406.200 m 
40.337 406.646 40.154 407.090 39.838 407.406 c
39.522 407.722 39.078 407.906 38.631 407.906 c
38.185 407.906 37.741 407.722 37.425 407.406 c
37.109 407.090 36.925 406.646 36.925 406.200 c
36.925 405.753 37.109 405.309 37.425 404.993 c
37.741 404.677 38.185 404.493 38.631 404.493 c
39.078 404.493 39.522 404.677 39.838 404.993 c
40.154 405.309 40.337 405.753 40.337 406.200 c f
BT 45.750 403.232 Td /F1 9.8 Tf  [(Gene expression data derived from expression microarray studies on frozen tumors specimens from a total of 110 patients )] TJ ET
BT 45.750 391.327 Td /F1 9.8 Tf  [(from 4 institutions \(Massachusetts General Hospital, M.D. Anderson Cancer Center, University of California Los Angeles )] TJ ET
BT 45.750 379.422 Td /F1 9.8 Tf  [(and University of California San Francisco\) were used to identify 38 genes whose expression was significantly associated )] TJ ET
BT 45.750 367.518 Td /F1 9.8 Tf  [(with survival)] TJ ET
0.267 0.267 0.267 rg
BT 98.839 367.518 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 109.681 367.518 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 347.331 m 
40.337 347.777 40.154 348.221 39.838 348.537 c
39.522 348.853 39.078 349.037 38.631 349.037 c
38.185 349.037 37.741 348.853 37.425 348.537 c
37.109 348.221 36.925 347.777 36.925 347.331 c
36.925 346.884 37.109 346.440 37.425 346.124 c
37.741 345.808 38.185 345.624 38.631 345.624 c
39.078 345.624 39.522 345.808 39.838 346.124 c
40.154 346.440 40.337 346.884 40.337 347.331 c f
BT 45.750 344.363 Td /F1 9.8 Tf  [(A reverse-transcription polymerase chain reaction \(RT-PCR\) assay for the 38 genes was developed and validated on a )] TJ ET
BT 45.750 332.458 Td /F1 9.8 Tf  [(separate set of 68 FFPE GBM tumor specimens. From this validation, the 9 genes with the highest survival associations )] TJ ET
BT 45.750 320.553 Td /F1 9.8 Tf  [(were selected)] TJ ET
0.267 0.267 0.267 rg
BT 105.898 320.553 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 116.740 320.553 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 307.866 m 
40.337 308.313 40.154 308.757 39.838 309.073 c
39.522 309.389 39.078 309.573 38.631 309.573 c
38.185 309.573 37.741 309.389 37.425 309.073 c
37.109 308.757 36.925 308.313 36.925 307.866 c
36.925 307.420 37.109 306.976 37.425 306.660 c
37.741 306.344 38.185 306.160 38.631 306.160 c
39.078 306.160 39.522 306.344 39.838 306.660 c
40.154 306.976 40.337 307.420 40.337 307.866 c f
BT 45.750 304.899 Td /F1 9.8 Tf  [(The 9-gene assay was validated on a final set of 101 FFPE GBM tumor specimens. Expression of these 9 genes was found )] TJ ET
BT 45.750 292.994 Td /F1 9.8 Tf  [(through multivariate analysis to be an independent predictor of progression-free survival \(Cox proportional hazard ratio [HR] )] TJ ET
BT 45.750 281.089 Td /F1 9.8 Tf  [(= 2.7; P=0.0003\) and overall survival \(Cox HR = 2.7; P=0.0003\) compared to age, performance score, and methylation )] TJ ET
BT 45.750 269.184 Td /F1 9.8 Tf  [(status of the methylguanine methyltransferase gene \(MGMT\). MGMT methylation has previously been reported to be an )] TJ ET
BT 45.750 257.280 Td /F1 9.8 Tf  [(independent predictor of response of GBM to radiation and chemotherapy)] TJ ET
0.267 0.267 0.267 rg
BT 363.873 257.280 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 374.715 257.280 Td /F1 9.8 Tf  [(. Interestingly, MGMT methylation was not )] TJ ET
BT 45.750 245.375 Td /F1 9.8 Tf  [(found to be an independent predictor of survival in the DecisionDx-GBM validation studies)] TJ ET
0.267 0.267 0.267 rg
BT 433.215 245.375 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 444.057 245.375 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 222.220 Td /F6 9.8 Tf  [(Clinical Utility)] TJ ET
BT 90.727 222.220 Td /F4 9.8 Tf  [( : )] TJ ET
BT 99.394 222.220 Td /F1 9.8 Tf  [( Net benefit of test in improving health outcomes)] TJ ET
40.337 205.783 m 
40.337 206.230 40.154 206.674 39.838 206.990 c
39.522 207.305 39.078 207.489 38.631 207.489 c
38.185 207.489 37.741 207.305 37.425 206.990 c
37.109 206.674 36.925 206.230 36.925 205.783 c
36.925 205.336 37.109 204.892 37.425 204.576 c
37.741 204.261 38.185 204.077 38.631 204.077 c
39.078 204.077 39.522 204.261 39.838 204.576 c
40.154 204.892 40.337 205.336 40.337 205.783 c f
BT 45.750 202.815 Td /F1 9.8 Tf  [(No published studies demonstrating improved health outcomes were identified.)] TJ ET
40.337 182.628 m 
40.337 183.075 40.154 183.519 39.838 183.835 c
39.522 184.151 39.078 184.335 38.631 184.335 c
38.185 184.335 37.741 184.151 37.425 183.835 c
37.109 183.519 36.925 183.075 36.925 182.628 c
36.925 182.182 37.109 181.738 37.425 181.422 c
37.741 181.106 38.185 180.922 38.631 180.922 c
39.078 180.922 39.522 181.106 39.838 181.422 c
40.154 181.738 40.337 182.182 40.337 182.628 c f
BT 45.750 179.661 Td /F1 9.8 Tf  [(Two clinical trials have the DecisionDx-GBM test as part of the study as either a risk stratification method or as a )] TJ ET
BT 532.343 179.661 Td /F1 9.8 Tf  [(secondary )] TJ ET
BT 45.750 167.756 Td /F1 9.8 Tf  [(endpoint. These studies are: )] TJ ET
0.39 w 1 J 1 j
59.837 155.069 m 
59.837 155.515 59.654 155.959 59.338 156.275 c
59.022 156.591 58.578 156.775 58.131 156.775 c
57.685 156.775 57.241 156.591 56.925 156.275 c
56.609 155.959 56.425 155.515 56.425 155.069 c
56.425 154.622 56.609 154.178 56.925 153.862 c
57.241 153.546 57.685 153.363 58.131 153.363 c
58.578 153.363 59.022 153.546 59.338 153.862 c
59.654 154.178 59.837 154.622 59.837 155.069 c s
BT 65.250 152.101 Td /F1 9.8 Tf  [(Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed )] TJ ET
BT 65.250 140.196 Td /F1 9.8 Tf  [(Glioblastoma \(NCT00884741\))] TJ ET
0.39 w 1 J 1 j
59.837 127.509 m 
59.837 127.956 59.654 128.400 59.338 128.716 c
59.022 129.032 58.578 129.216 58.131 129.216 c
57.685 129.216 57.241 129.032 56.925 128.716 c
56.609 128.400 56.425 127.956 56.425 127.509 c
56.425 127.063 56.609 126.619 56.925 126.303 c
57.241 125.987 57.685 125.803 58.131 125.803 c
58.578 125.803 59.022 125.987 59.338 126.303 c
59.654 126.619 59.837 127.063 59.837 127.509 c s
BT 65.250 124.542 Td /F1 9.8 Tf  [(Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma )] TJ ET
BT 65.250 112.637 Td /F1 9.8 Tf  [(\(NCT00304031\))] TJ ET
BT 26.250 68.534 Td /F4 12.0 Tf  [(Limitations)] TJ ET
40.337 51.548 m 
40.337 51.994 40.154 52.438 39.838 52.754 c
39.522 53.070 39.078 53.254 38.631 53.254 c
38.185 53.254 37.741 53.070 37.425 52.754 c
37.109 52.438 36.925 51.994 36.925 51.548 c
36.925 51.101 37.109 50.657 37.425 50.341 c
37.741 50.025 38.185 49.841 38.631 49.841 c
39.078 49.841 39.522 50.025 39.838 50.341 c
40.154 50.657 40.337 51.101 40.337 51.548 c f
BT 45.750 48.580 Td /F1 9.8 Tf  [(Specimen numbers � to date the current version of the DecisionDx-GBM assay has only been validated on 101 specimens. )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(2)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET
0.39 w 1 J 1 j
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BT 45.750 767.476 Td /F1 9.8 Tf  [(Validation with a larger data set is needed to ensure that preliminary findings are consistent.)] TJ ET
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BT 45.750 751.821 Td /F1 9.8 Tf  [(Lack of transparency � the proprietary algorithm used to generate the risk score has not been independently validated.)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Conclusion)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(There is currently only a single peer-reviewed publication on the derivation and validation of this assay. No information is )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(provided on the analytical validity of the assay. No studies on the clinical utility of this test in the care of patients with GBM have )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(been published. Therefore, there is currently insufficient evidence to recommend adoption of this test for routine use in the care )] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(of patients with GBM.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(Links)] TJ ET
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BT 45.750 599.244 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 576.089 Td /F1 9.8 Tf  [(Last updated:October 8, 2010 )] TJ ET
BT 26.250 546.986 Td /F4 12.0 Tf  [(Acknowledgments)] TJ ET
BT 26.250 527.032 Td /F1 9.8 Tf  [(The authors would like to acknowledge the contributions of the members of the Hayes Genetic Test Evaluation team, )] TJ ET
BT 26.250 515.127 Td /F1 9.8 Tf  [(particularly Lisa Spock, Linnie Wieselquist and Charlotte Kuo-Benitez.)] TJ ET
BT 26.250 478.525 Td /F4 12.0 Tf  [(Funding information)] TJ ET
BT 26.250 458.571 Td /F1 9.8 Tf  [(Funding for the Health Technology Assessment that informed this work was provided by Hayes, Incorporated. Funding to create )] TJ ET
BT 26.250 446.666 Td /F1 9.8 Tf  [(this Knol was provided by the Centers for Disease Control and Prevention under Contract No. 200-2009-F-32675.This funding )] TJ ET
BT 26.250 434.761 Td /F1 9.8 Tf  [(was provided through the Genetic Alliance.)] TJ ET
BT 26.250 398.159 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 378.204 Td /F1 9.8 Tf  [(The authors are employees at Hayes, Inc., an independent health technology research and consulting company. None of the )] TJ ET
BT 26.250 366.300 Td /F1 9.8 Tf  [(employees at this company has any financial or personal interest in any of the technologies reviewed by Hayes, Inc.. No input )] TJ ET
BT 26.250 354.395 Td /F1 9.8 Tf  [(on report content or conclusions is permitted by manufacturers. Although the CDC funded the work to produce this article, the )] TJ ET
BT 26.250 342.490 Td /F1 9.8 Tf  [(content is based entirely on Hayes, Inc.�s own analysis and there was no input from the CDC.)] TJ ET
BT 26.250 305.888 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 278.433 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 278.433 Td /F1 9.8 Tf  [(Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto )] TJ ET
BT 26.250 266.529 Td /F1 9.8 Tf  [(A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK \(eds\). SEER Cancer Statistics Review, )] TJ ET
BT 26.250 254.624 Td /F1 9.8 Tf  [(1975-2007, National Cancer Institute. Bethesda, MD, based on November 2009 SEER data submission, posted to the SEER )] TJ ET
BT 26.250 242.719 Td /F1 9.8 Tf  [(web site, 2010.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 234.233 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 215.683 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 215.683 Td /F1 9.8 Tf  [(Krakstad C, Chekenya M. Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted )] TJ ET
BT 26.250 203.778 Td /F1 9.8 Tf  [(therapeutics. Mol Cancer. 2010 Jun 1;9:135. Review. PubMed PMID: 20515495; PubMed Central PMCID: PMC2893101.)] TJ ET
BT 26.250 184.374 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 184.374 Td /F1 9.8 Tf  [(DecisionDx-GBM. Castle Biosciences. Accessed September 17, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 175.888 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 157.338 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 157.338 Td /F1 9.8 Tf  [(Decision-Dx-GBM. Castle Biosciences. Sample report Accessed October 5, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 148.852 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 130.302 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 130.302 Td /F1 9.8 Tf  [(Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, )] TJ ET
BT 26.250 118.397 Td /F1 9.8 Tf  [(Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB, Aldape K. A multigene )] TJ ET
BT 26.250 106.492 Td /F1 9.8 Tf  [(predictor of outcome in glioblastoma. Neuro Oncol. 2010 Jan;12\(1\):49-57. Epub 2009 Oct 20. PubMed PMID: 20150367.)] TJ ET
BT 26.250 87.087 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 87.087 Td /F1 9.8 Tf  [(Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, )] TJ ET
BT 26.250 75.183 Td /F1 9.8 Tf  [(Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from )] TJ ET
BT 26.250 63.278 Td /F1 9.8 Tf  [(temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352\(10\):997-1003. PubMed PMID: 15758010.)] TJ ET
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39.078 753.083 39.522 753.267 39.838 753.582 c
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BT 45.750 751.821 Td /F1 9.8 Tf  [(Lack of transparency � the proprietary algorithm used to generate the risk score has not been independently validated.)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Conclusion)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(There is currently only a single peer-reviewed publication on the derivation and validation of this assay. No information is )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(provided on the analytical validity of the assay. No studies on the clinical utility of this test in the care of patients with GBM have )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(been published. Therefore, there is currently insufficient evidence to recommend adoption of this test for routine use in the care )] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(of patients with GBM.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(Links)] TJ ET
40.337 602.211 m 
40.337 602.658 40.154 603.102 39.838 603.418 c
39.522 603.734 39.078 603.917 38.631 603.917 c
38.185 603.917 37.741 603.734 37.425 603.418 c
37.109 603.102 36.925 602.658 36.925 602.211 c
36.925 601.765 37.109 601.321 37.425 601.005 c
37.741 600.689 38.185 600.505 38.631 600.505 c
39.078 600.505 39.522 600.689 39.838 601.005 c
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BT 45.750 599.244 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 576.089 Td /F1 9.8 Tf  [(Last updated:October 8, 2010 )] TJ ET
BT 26.250 546.986 Td /F4 12.0 Tf  [(Acknowledgments)] TJ ET
BT 26.250 527.032 Td /F1 9.8 Tf  [(The authors would like to acknowledge the contributions of the members of the Hayes Genetic Test Evaluation team, )] TJ ET
BT 26.250 515.127 Td /F1 9.8 Tf  [(particularly Lisa Spock, Linnie Wieselquist and Charlotte Kuo-Benitez.)] TJ ET
BT 26.250 478.525 Td /F4 12.0 Tf  [(Funding information)] TJ ET
BT 26.250 458.571 Td /F1 9.8 Tf  [(Funding for the Health Technology Assessment that informed this work was provided by Hayes, Incorporated. Funding to create )] TJ ET
BT 26.250 446.666 Td /F1 9.8 Tf  [(this Knol was provided by the Centers for Disease Control and Prevention under Contract No. 200-2009-F-32675.This funding )] TJ ET
BT 26.250 434.761 Td /F1 9.8 Tf  [(was provided through the Genetic Alliance.)] TJ ET
BT 26.250 398.159 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 378.204 Td /F1 9.8 Tf  [(The authors are employees at Hayes, Inc., an independent health technology research and consulting company. None of the )] TJ ET
BT 26.250 366.300 Td /F1 9.8 Tf  [(employees at this company has any financial or personal interest in any of the technologies reviewed by Hayes, Inc.. No input )] TJ ET
BT 26.250 354.395 Td /F1 9.8 Tf  [(on report content or conclusions is permitted by manufacturers. Although the CDC funded the work to produce this article, the )] TJ ET
BT 26.250 342.490 Td /F1 9.8 Tf  [(content is based entirely on Hayes, Inc.�s own analysis and there was no input from the CDC.)] TJ ET
BT 26.250 305.888 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 278.433 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 278.433 Td /F1 9.8 Tf  [(Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto )] TJ ET
BT 26.250 266.529 Td /F1 9.8 Tf  [(A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK \(eds\). SEER Cancer Statistics Review, )] TJ ET
BT 26.250 254.624 Td /F1 9.8 Tf  [(1975-2007, National Cancer Institute. Bethesda, MD, based on November 2009 SEER data submission, posted to the SEER )] TJ ET
BT 26.250 242.719 Td /F1 9.8 Tf  [(web site, 2010.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 234.233 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 215.683 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 215.683 Td /F1 9.8 Tf  [(Krakstad C, Chekenya M. Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted )] TJ ET
BT 26.250 203.778 Td /F1 9.8 Tf  [(therapeutics. Mol Cancer. 2010 Jun 1;9:135. Review. PubMed PMID: 20515495; PubMed Central PMCID: PMC2893101.)] TJ ET
BT 26.250 184.374 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 184.374 Td /F1 9.8 Tf  [(DecisionDx-GBM. Castle Biosciences. Accessed September 17, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 175.888 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 157.338 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 157.338 Td /F1 9.8 Tf  [(Decision-Dx-GBM. Castle Biosciences. Sample report Accessed October 5, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 148.852 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 130.302 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 130.302 Td /F1 9.8 Tf  [(Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, )] TJ ET
BT 26.250 118.397 Td /F1 9.8 Tf  [(Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB, Aldape K. A multigene )] TJ ET
BT 26.250 106.492 Td /F1 9.8 Tf  [(predictor of outcome in glioblastoma. Neuro Oncol. 2010 Jan;12\(1\):49-57. Epub 2009 Oct 20. PubMed PMID: 20150367.)] TJ ET
BT 26.250 87.087 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 87.087 Td /F1 9.8 Tf  [(Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, )] TJ ET
BT 26.250 75.183 Td /F1 9.8 Tf  [(Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from )] TJ ET
BT 26.250 63.278 Td /F1 9.8 Tf  [(temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352\(10\):997-1003. PubMed PMID: 15758010.)] TJ ET
Q
q
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0.271 0.267 0.267 rg
BT 45.750 767.476 Td /F1 9.8 Tf  [(Validation with a larger data set is needed to ensure that preliminary findings are consistent.)] TJ ET
0.271 0.267 0.267 RG
40.337 754.789 m 
40.337 755.236 40.154 755.680 39.838 755.996 c
39.522 756.311 39.078 756.495 38.631 756.495 c
38.185 756.495 37.741 756.311 37.425 755.996 c
37.109 755.680 36.925 755.236 36.925 754.789 c
36.925 754.342 37.109 753.898 37.425 753.582 c
37.741 753.267 38.185 753.083 38.631 753.083 c
39.078 753.083 39.522 753.267 39.838 753.582 c
40.154 753.898 40.337 754.342 40.337 754.789 c f
BT 45.750 751.821 Td /F1 9.8 Tf  [(Lack of transparency � the proprietary algorithm used to generate the risk score has not been independently validated.)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Conclusion)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(There is currently only a single peer-reviewed publication on the derivation and validation of this assay. No information is )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(provided on the analytical validity of the assay. No studies on the clinical utility of this test in the care of patients with GBM have )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(been published. Therefore, there is currently insufficient evidence to recommend adoption of this test for routine use in the care )] TJ ET
BT 26.250 655.800 Td /F1 9.8 Tf  [(of patients with GBM.)] TJ ET
BT 26.250 619.198 Td /F4 12.0 Tf  [(Links)] TJ ET
40.337 602.211 m 
40.337 602.658 40.154 603.102 39.838 603.418 c
39.522 603.734 39.078 603.917 38.631 603.917 c
38.185 603.917 37.741 603.734 37.425 603.418 c
37.109 603.102 36.925 602.658 36.925 602.211 c
36.925 601.765 37.109 601.321 37.425 601.005 c
37.741 600.689 38.185 600.505 38.631 600.505 c
39.078 600.505 39.522 600.689 39.838 601.005 c
40.154 601.321 40.337 601.765 40.337 602.211 c f
BT 45.750 599.244 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 576.089 Td /F1 9.8 Tf  [(Last updated:October 8, 2010 )] TJ ET
BT 26.250 546.986 Td /F4 12.0 Tf  [(Acknowledgments)] TJ ET
BT 26.250 527.032 Td /F1 9.8 Tf  [(The authors would like to acknowledge the contributions of the members of the Hayes Genetic Test Evaluation team, )] TJ ET
BT 26.250 515.127 Td /F1 9.8 Tf  [(particularly Lisa Spock, Linnie Wieselquist and Charlotte Kuo-Benitez.)] TJ ET
BT 26.250 478.525 Td /F4 12.0 Tf  [(Funding information)] TJ ET
BT 26.250 458.571 Td /F1 9.8 Tf  [(Funding for the Health Technology Assessment that informed this work was provided by Hayes, Incorporated. Funding to create )] TJ ET
BT 26.250 446.666 Td /F1 9.8 Tf  [(this Knol was provided by the Centers for Disease Control and Prevention under Contract No. 200-2009-F-32675.This funding )] TJ ET
BT 26.250 434.761 Td /F1 9.8 Tf  [(was provided through the Genetic Alliance.)] TJ ET
BT 26.250 398.159 Td /F4 12.0 Tf  [(Competing interests)] TJ ET
BT 26.250 378.204 Td /F1 9.8 Tf  [(The authors are employees at Hayes, Inc., an independent health technology research and consulting company. None of the )] TJ ET
BT 26.250 366.300 Td /F1 9.8 Tf  [(employees at this company has any financial or personal interest in any of the technologies reviewed by Hayes, Inc.. No input )] TJ ET
BT 26.250 354.395 Td /F1 9.8 Tf  [(on report content or conclusions is permitted by manufacturers. Although the CDC funded the work to produce this article, the )] TJ ET
BT 26.250 342.490 Td /F1 9.8 Tf  [(content is based entirely on Hayes, Inc.�s own analysis and there was no input from the CDC.)] TJ ET
BT 26.250 305.888 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 278.433 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 278.433 Td /F1 9.8 Tf  [(Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto )] TJ ET
BT 26.250 266.529 Td /F1 9.8 Tf  [(A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK \(eds\). SEER Cancer Statistics Review, )] TJ ET
BT 26.250 254.624 Td /F1 9.8 Tf  [(1975-2007, National Cancer Institute. Bethesda, MD, based on November 2009 SEER data submission, posted to the SEER )] TJ ET
BT 26.250 242.719 Td /F1 9.8 Tf  [(web site, 2010.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 234.233 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 215.683 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 215.683 Td /F1 9.8 Tf  [(Krakstad C, Chekenya M. Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted )] TJ ET
BT 26.250 203.778 Td /F1 9.8 Tf  [(therapeutics. Mol Cancer. 2010 Jun 1;9:135. Review. PubMed PMID: 20515495; PubMed Central PMCID: PMC2893101.)] TJ ET
BT 26.250 184.374 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 184.374 Td /F1 9.8 Tf  [(DecisionDx-GBM. Castle Biosciences. Accessed September 17, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 175.888 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 157.338 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 157.338 Td /F1 9.8 Tf  [(Decision-Dx-GBM. Castle Biosciences. Sample report Accessed October 5, 2010)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 148.852 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 130.302 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 130.302 Td /F1 9.8 Tf  [(Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, )] TJ ET
BT 26.250 118.397 Td /F1 9.8 Tf  [(Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB, Aldape K. A multigene )] TJ ET
BT 26.250 106.492 Td /F1 9.8 Tf  [(predictor of outcome in glioblastoma. Neuro Oncol. 2010 Jan;12\(1\):49-57. Epub 2009 Oct 20. PubMed PMID: 20150367.)] TJ ET
BT 26.250 87.087 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 87.087 Td /F1 9.8 Tf  [(Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, )] TJ ET
BT 26.250 75.183 Td /F1 9.8 Tf  [(Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from )] TJ ET
BT 26.250 63.278 Td /F1 9.8 Tf  [(temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352\(10\):997-1003. PubMed PMID: 15758010.)] TJ ET
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BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET
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