• Wragg, Christopher
• Jefferies, Sarah
• Dawson, Sarah
• Palmer, Abigail
• Kurian, Kathreena
• Vale, Luke
• Brandner, Sebastian
• Jones, Hayley E.
• Faulkner, Claire L.
• Kernohan, Ashleigh
• Higgins, Julian
• Mcaleenan, Alexandra

Abstract

Background<br/>Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in gliomas. It occurs in a type of glioma known as oligodendroglioma and its higher grade counterpart known as anaplastic oligodendroglioma. Detection of 1p/19q codeletion in gliomas is important because, together with another mutation in an enzyme known as isocitrate dehydrogenase, it is needed to make the diagnosis of an oligodendroglioma. Presence of 1p/19q codeletion also informs patient prognosis and prediction of the best drug treatment. The main two tests in use are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)‐based loss of heterozygosity (LOH) assays (also known as PCR‐based short tandem repeat or microsatellite analysis). Many other tests are available. None of the tests is perfect, although PCR‐based LOH is expected to have very high sensitivity.<br/><br/>Objectives<br/>To estimate the sensitivity and specificity and cost‐effectiveness of different deoxyribonucleic acid (DNA)‐based techniques for determining 1p/19q codeletion status in glioma.<br/><br/>Search methods<br/>We searched MEDLINE, Embase and BIOSIS up to July 2019. There were no restrictions based on language or date of publication. We sought economic evaluation studies from the results of this search and using the National Health Service Economic Evaluation Database.<br/><br/>Selection criteria<br/>We included cross‐sectional studies in adults with glioma or any subtype of glioma, presenting raw data or cross‐tabulations of two or more DNA‐based tests for 1p/19q codeletion. We also sought economic evaluations of these tests.<br/><br/>Data collection and analysis<br/>We followed procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened titles/abstracts/full texts, performed data extraction, and undertook applicability and risk of bias assessments using QUADAS‐2. Meta‐analyses used the hierarchical summary ROC model to estimate and compare test accuracy. We used FISH and PCR‐based LOH as alternate reference standards to examine how tests compared with those in common use, and conducted a latent class analysis comparing FISH and PCR‐based LOH. We constructed an economic model to evaluate cost‐effectiveness.<br/><br/>Main results<br/>We included 53 studies examining: PCR‐based LOH, FISH, single nucleotide polymorphism (SNP) array, next‐generation sequencing (NGS), comparative genomic hybridisation (CGH), array comparative genomic hybridisation (aCGH), multiplex‐ligation‐dependent probe amplification (MLPA), real‐time PCR, chromogenic in situ hybridisation (CISH), mass spectrometry (MS), restriction fragment length polymorphism (RFLP) analysis, G‐banding, methylation array and NanoString. Risk of bias was low for only one study; most gave us concerns about how patients were selected or about missing data. We had applicability concerns about many of the studies because only patients with specific subtypes of glioma were included. 1520 participants contributed to analyses using FISH as the reference, 1304 participants to analyses involving PCR‐based LOH as the reference and 262 participants to analyses of comparisons between methods from studies not including FISH or PCR‐based LOH.<br/><br/>Most evidence was available for comparison of FISH with PCR‐based LOH (15 studies, 915 participants): PCR‐based LOH detected 94% of FISH‐determined codeletions (95% credible interval (CrI) 83% to 98%) and FISH detected 91% of codeletions determined by PCR‐based LOH (CrI 78% to 97%). Of tumours determined not to have a deletion by FISH, 94% (CrI 87% to 98%) had a deletion detected by PCR‐based LOH, and of those determined not to have a deletion by PCR‐based LOH, 96% (CrI 90% to 99%) had a deletion detected by FISH. The latent class analysis suggested that PCR‐based LOH may be slightly more accurate than FISH. Most other techniques appeared to have high sensitivity (i.e. produced few false‐negative results) for detection of 1p/19q codeletion when either FISH or PCR‐based LOH was considered as the reference standard, although there was limited evidence. There was some indication of differences in specificity (false‐positive rate) with some techniques. Both NGS and SNP array had high specificity when considered against FISH as the reference standard (NGS: 6 studies, 243 participants; SNP: 6 studies, 111 participants), although we rated certainty in the evidence as low or very low. NGS and SNP array also had high specificity when PCR‐based LOH was considered the reference standard, although with much more uncertainty as these results were based on fewer studies (just one study with 49 participants for NGS and two studies with 33 participants for SNP array).<br/><br/>G‐banding had low sensitivity and specificity when PCR‐based LOH was the reference standard. Although MS had very high sensiti...

Topics

• impedance spectroscopy
• extraction
• mass spectrometry
• spectrometry