Wiestler 2014.
| Study characteristics | |||
| Patient Sampling |
Inclusion/exclusion criteria Inclusion criteria for NOA‐04: adults with centrally confirmed diagnosis of a WHO grade III anaplastic glioma, Karnofsky performance score ≥ 70, no prior systemic chemotherapy or RT to the brain, and adequate bone marrow reserve, liver and renal functions, and stable or decreasing corticosteroid dose within 14 days before random assignment. Prior testing Histopathological diagnosis according to WHO 1993 and WHO 2000 classifications. |
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| Patient characteristics and setting |
Number of participants/tumours with results for 1p/19q status by ≥ 2 DNA‐based tests: 99 Country: Germany Population source and setting: people enrolled in the NOA‐04 trial from 39 sites in Germany. Time period NR Agea: median: 42 years in the RT arm and 41.5 years in the procarbazine, lomustine and vincristine/temozolomide arm, interquartile range: NR; range: 23–74 years Genderb: 57.7% male Karnofsky performance status**: median 90, range 70–100 First diagnosis/recurrent disease: NR, although presumably first diagnosis. aFor whole population: these data were for the biomarker cohort (the 115 participants with sufficient amount and quantity of tumour DNA). Methylation array and MLPA data was only available for 99 participants. bFor whole population: these data were for the modified intention‐to‐treat population of NOA‐04. This included 274 participants, we had data on both tests for 99 participants. |
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| Index tests |
2 tests: methylation array and MLPA Methylation array Tumour sample type: FFPE Region(s) analysed: genome wide Cut‐off: quote: "Copy number aberrations were detected from the HM450 data as described.20,22 Copy number plots were manually analysed for 1p/19q codeletion". Additional details: HM450 BeadChip (Illumina, San Diego, California, USA) MLPA Tumour sample type: FFPE Region(s) analysed: used Salsa MLPA P088, MRC Holland, Amsterdam, the Netherlands Cut‐off: quote: "Chromosomal regions were scored as under‐ or overrepresented if two or more loci on 1p or 19q adjacent to each other exhibited a gene dosage ratio less than 70% or more than 130% relative to the reference value". Additional details: Salsa MLPA, P088 lots 0305 and 0706, MRC Holland, Amsterdam, the Netherlands |
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| Target condition and reference standard(s) | Target condition was absolute 1p/19q deletion. No tests used as reference standard in our analyses. | ||
| Flow and timing | We presumed that all tests were performed on biopsied tumour material collected on 1 occasion. | ||
| Comparative | |||
| Notes | |||
| Methodological quality | |||
| Item | Authors' judgement | Risk of bias | Applicability concerns |
| DOMAIN 1: Patient Selection | |||
| Was a consecutive or random sample of patients enrolled? | Unclear | ||
| Was a case‐control design avoided? | Yes | ||
| Did the study avoid inappropriate exclusions? | Unclear | ||
| Could the selection of patients have introduced bias? | Unclear risk | ||
| Are there concerns that the included patients and setting do not match the review question? | High | ||
| DOMAIN 2: Index Test (NanoString) | |||
| DOMAIN 2: Index Test (aCGH) | |||
| DOMAIN 2: Index Test (NGS) | |||
| DOMAIN 2: Index Test (G‐banding) | |||
| DOMAIN 2: Index Test (FISH (variant 4)) | |||
| DOMAIN 2: Index Test (SNP array) | |||
| DOMAIN 2: Index Test (PCR (with comparison to normal DNA)) | |||
| DOMAIN 2: Index Test (PCR (without comparison to normal DNA)) | |||
| DOMAIN 2: Index Test (CISH) | |||
| DOMAIN 2: Index Test (MS) | |||
| DOMAIN 2: Index Test (RFLP) | |||
| DOMAIN 2: Index Test (PCR‐based LOH) | |||
| DOMAIN 2: Index Test (NGS or aCGH (or both)) | |||
| DOMAIN 2: Index Test (Methylation array) | |||
| If a threshold was used, was it pre‐specified? | Unclear | ||
| Were the index test results interpreted without knowledge of the results of the other tests being compared? | Unclear | ||
| Could the conduct or interpretation of the index test have introduced bias? | Unclear risk | ||
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? | Low concern | ||
| DOMAIN 2: Index Test (FISH) | |||
| DOMAIN 2: Index Test (FISH (variant 1)) | |||
| DOMAIN 2: Index Test (FISH (variant 2)) | |||
| DOMAIN 2: Index Test (FISH (variant 3)) | |||
| DOMAIN 2: Index Test (Real‐time PCR) | |||
| DOMAIN 2: Index Test (MLPA) | |||
| If a threshold was used, was it pre‐specified? | Yes | ||
| Were the index test results interpreted without knowledge of the results of the other tests being compared? | Yes | ||
| Could the conduct or interpretation of the index test have introduced bias? | Low risk | ||
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? | Low concern | ||
| DOMAIN 2: Index Test (CGH) | |||
| DOMAIN 3: Reference Standard | |||
| Is the reference standards likely to correctly classify the target condition? | No | ||
| Could the reference standard, its conduct, or its interpretation have introduced bias? | High risk | ||
| Are there concerns that the target condition as defined by the reference standard does not match the question? | Low concern | ||
| DOMAIN 4: Flow and Timing | |||
| Was there an appropriate interval between index test and reference standard? | Yes | ||
| Were all patients included in the analysis? | No | ||
| Could the patient flow have introduced bias? | High risk | ||
aCGH: array comparative genomic hybridisation; CGH: comparative genomic hybridisation; CI: confidence interval; CISH: chromogenic in situ hybridisation; DNA: deoxyribonucleic acid; EORTC: European Organisation for Research and Treatment of Cancer; FFPE: formalin‐fixed, paraffin‐embedded; FISH: fluorescent in situ hybridisation; IDH: isocitrate dehydrogenase; LOH: loss of heterozygosity; MLPA: multiplex‐ligation‐dependent probe amplification; MS: mass spectrometry; NGS: next‐generation sequencing; NR: not reported; PCR: polymerase chain reaction; RFLP: restriction fragment length polymorphism; RT: radiotherapy; SNP: single nucleotide polymorphism; WHO: World Health Organization.