Page 198 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 7
Supplemental materials
Study protocol
Complete protocol is available as supplemental file and on line at the HOVON website: http://www.hovon.nl/studies/studies-per-ziektebeeld/nhl.html?action= showstudie&studie_id=107&categorie_id=1
National screening program to support implementation of FISH screening in pathology practice
To support timely diagnosis of MYC+ LBCL and optimal enrolment in the present clinical trial, a nationwide diagnostic support program for MYC rearrangement assessment by fluorescence in situ hybridization (FISH) was implemented [1].
In brief, at registration of de novo aggressive B-cell lymphoma in the program, limited financial support was provided for FISH diagnostics. With this support, pathology labs, who did not have these assays available in-house were invited to submit cases to dedicated regional reference laboratories to guarantee access to standard FISH testing for MYC, BCL2 and BCL6. An initiating quality control validation was performed prior to acceptance as reference or “in-house” lab (August 2013, coordinators D. de Jong, P.M. Kluin). Both technical quality and scoring reproducibility were monitored. Validation was repeated as more labs implemented FISH diagnostics over time during trial accrual. At initial quality control validation, labs performed FISH according to routine procedures with standard commercial probes: MYC Break-apart provided by Vysis/Abbott (n=7) DAKO (n=7) and Kreatech (n=1); BCL2 Break-apart provided by Vysis/Abbott (n=6), DAKO (n=9); BCL6 break-apart provided by Vysis/Abbott (n=4), DAKO (n=6) and Kreatech (n=1). Initially, 10/15 labs were accepted as reference or “in-house” lab based on optimal performance and 5 labs were rejected based on insufficient quality (high false negative and/or false positive rate). During trial accrual, 7 additional labs passed quality assessment criteria and were accepted. It should be noted, that over time MYC Break-apart from DAKO was replaced for Vysis/Abbot by most labs based on the results of the validation round.
Central pathology review
Central pathology review included classification according to the criteria of the WHO classification 2008 and 2017, including appropriate immunohistochemistry (IHC) for at least CD20, CD10, BCL6 and BCL2 and confirmation of MYC
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