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Chapter 4
Our primary objective was to assess the interobserver agreement of I-PET and EoT-PET using DS in a large randomized clinical trial in DLBCL patients. Secondary objectives were to identify potential sources of observer variation (timing of PET— that is, I-PET vs. EoT-PET; baseline imaging modality— CT vs. PET or PET/CT, and the site of residual tracer uptake). The results are reported in accordance with Guidelines for Reporting Reliability and Agreement studies [17].
Materials and methods
Study Population
I-PET and EoT-PET scans were collected from the HOVON84 study, an international multicenter phase 3 trial in DLBCL (EudraCT 2006-005174- 42). Patients were enrolled from 69 hospitals in The Netherlands, Belgium, and Denmark between November 2007 and April 2012. The main inclusion criteria were newly diagnosed, histologically proven, CD-20–positive DLBCL patients with Ann Arbor stage II–IV, age 18–80 y, and World Health Organization performance status 0–2. Exclusion criteria were primary central nervous system, testicular, transformed indolent, and primary mediastinal B-cell lymphoma, as well as posttransplant lymphoproliferative disease. Patients were randomized between standard R-CHOP14 or R-CHOP14 with intensification of rituximab in the first 4 cycles (R2- CHOP14). Administration of granulocyte colony-stimulating factor was mandatory and served to oppose the neutropenic side effects of the R-CHOP14 scheme. Six milligrams of pegfilgrastim were injected subcutaneously on day 2 of each R-CHOP cycle. I-PET and EoT-PET were performed after 4 cycles of therapy for observational purposes only, and after 6 (patients aged >65 y) or 8 cycles (patients ≤60 y), respectively. Baseline PET was recommended but not mandatory. HOVON84 has been approved by the institutional review board, and all subjects signed an informed consent form for use of their data for scientific purposes.
Image Analysis
DS was used for central image review [2]. Between 2013 and 2016, each I-PET and EoT-PET scan was read independently by 2 reviewers from a pool of 10, who randomly drew scans from the image warehouse. All PET and CT scans
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