Dubbink 2016.

Study characteristics
Patient Sampling	Inclusion/exclusion criteria Inclusion criteria for EORTC 26951: quote: "Patients were eligible for this study if they had been diagnosed by the local pathologist with an anaplastic oligodendroglioma or anaplastic mixed oligoastrocytoma with at least 25% oligodendroglial elements; had at least three of five anaplastic characteristics (high cellularity, mitosis, nuclear abnormalities, endothelial proliferation, and necrosis); were between 16 and 70 years old; had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2; had provided written informed consent; had not undergone prior chemotherapy or RT to the skull; had no diseases interfering with follow‐up; and had adequate hematologic, renal, and hepatic function (WBC [white blood cell] count ≥ 3.0 × 109/L, platelets ≥ 100 × 109/L, serum creatinine < 120 μmol/L, and serum bilirubin < 25 μmol/L)". How participants were selected for this study was NR. Prior testing Histopathological diagnosis. For participants with sufficient tissue to assess 1p and 19q status, this was performed by FISH in EORTC 26951. FISH results for the participants included in this study were NR.
Patient characteristics and setting	Number of participants/tumours with results for 1p/19q status by ≥ 2 DNA‐based tests: 49 Country: Austria, Belgium, Finland, France, Germany, Hungary, Italy, the Netherlands, Sweden, UK Population source and setting: quote "Forty‐nine glioma tissues were collected between 1997 and 2003 during the European Organization of Research and Treatment of Cancer study 26951 on adjuvant procarbazine, lomustine, and vincristine chemotherapy of anaplastic oligodendrogliomas and anaplastic oligoastrocytomas". Agea*: median: 48.6 years in the RT plus PCV arm; 49.8 years in the RT arm, interquartile range: NR; range: 18.6–68.7 years in the RT plus PCV arm; 19.2–68.7 years in the RT only arm. Gendera: 57.6% male Karnofsky performance status: NR First diagnosis/recurrent disease: unclear. Patients with "newly diagnosed" anaplastic oligodendrogliomas or anaplastic oligoastrocytomas recruited into the trial. However, some had had previous resections for lower‐grade tumours. aFor whole population: results are for the 368 patients included in EORTC 26951, only 49 samples included in this study.
Index tests	2 tests: NGS and PCR‐based LOH NGS Tumour sample type: FFPE Region(s) analysed: chromosome 1p: SNP rs7663, position 16112795; SNP rs169957, position 19683301; SNP rs169885, position 21628545; SNP rs742358, position 22459170; SNP rs309481, position 23210600; SNP rs189882, position 24868045; SNP rs9259, position 25168124; SNP rs7491, position 25895238; SNP rs159525, position 26213991; SNP rs7504, position 27238150; SNP rs6564, position 28212975; SNP rs157208, position 29245406; SNP rs6425953, position 36168038; SNP rs7686, position 38268918; SNP rs7315, position 40306898; SNP rs7903, position 45976472; SNP rs504816, position 53307957; SNP rs7374, position 55316322; SNP rs87061, position 60594980; SNP rs11811946, position 65952428; SNP rs5680, position 71477315; SNP rs191142, position 76990862; SNP rs12754569, position 85462971; SNP rs54396, position 88776278; SNP rs106075, position 91604522, SNP rs1132, position 95394352; SNP rs8888, position 101338324; SNP rs6604120, position 109289487; SNP rs8128, position 115110683; Chromosome 19q: SNP rs7283, position 30106659, SNP rs2542297, position 31883906; SNP rs33841, position 34011248; SNP rs12852, position 35615179; SNP rs1291, position 38229378; SNP rs17628, position 39926509; SNP rs166539, position 40931717; SNP rs3817, position 44090195; SNP rs10113, position 47112648; SNP rs8355, position 48833800; SNP rs6521, position 49519873; SNP rs11573, position 51359497; SNP rs193040, position 53073605; SNP rs3814, position 53611187; SNP rs10217, position 56030428; SNP rs10448, position 59093239 Cut‐off: quote: "A SNP was considered to be imbalanced or relatively lost when the variant B‐allele frequency of a heterozygous SNP was either higher than 55% or lower than 45%. All variant frequencies between 45% and 55% were considered not to be aberrant. Similarly, cut‐off lines were indicated at 5% and 95%, if not otherwise stated … Typical oligodendroglial co‐deletion of 1p and 19q was defined as equivalent of all informative SNP on both chromosomal arms". Additional details: quote: "A custom primer panel was designed that includes SNPs on chromosomes 1p and 19q using the Ion AmpliSeq Designer 2.0 (ThermoFisher Scientific Inc.).23 Highly polymorphic SNPs on both chromosomes were selected via the NCBI SNP database (http://www.ncbi.nlm.nih.gov/SNP, last accessed September 17, 2013) with a global minor allele frequency of at least 45% to obtain a high number of informative SNPs in each assay. The mean SNP density for chromosomes 1p and 19q was set arbitrarily to approximately 1SNP per 3.5Mb and 1 SNP per 2 Mb, respectively, yielding a total of 29 SNPs on chromosome 1p and 16 SNPs on chromosome 19q that covered the entire chromosomal arms (Figure 1A). Selected SNPs and their chromosomal localization (SNP database 138) are shown in Table 2. Next‐generation targeted sequencing was performed by semiconductor sequencing with the Ion Torrent Personal Genome Machine". PCR Tumour sample type: FFPE Region(s) analysed: D1S199 (locus: 1p36.13), D1S513 (1p35.2), D1S197 (1p32.3), D1S2806 (1p31.3), D1S495 (1p21.1), D19S875 (19q12), D19S198 (19q13.2), D19S412 (19q13.32), D19S606 (19q13.32), D19S572 (19q13.42) Cut‐off: quote: "Allelic losses were assessed based on the analysis of multiple informative markers, as described elsewhere.10 Typical oligodendroglial co‐deletion of 1p and 19q was defined as equivalent imbalance of all informative SNPs on both chromosomal arms. If not all informative markers were lost, a chromosome was considered partially lost". Additional details: PCR without the need for comparison to normal DNA: reference Hatanpaa 2003a, and state no normal tissue available.
Target condition and reference standard(s)	Target condition was absolute 1p/19q deletion. PCR‐based LOH used as reference standard in some of 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?	Unclear
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)
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?	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 (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)
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?	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 (NGS or aCGH (or both))
DOMAIN 2: Index Test (Methylation array)
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)
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?	Yes
Could the patient flow have introduced bias?		Low risk