Abstract

BackgroundSemi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication.Materials and methodsQuantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV2.5 (SUV 2.5 cut-off) and MTV41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTVVAS) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers.ResultsIn the quantitative analysis, a ROC-determined MTV2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTVVAS and eMTV were not consistently correlated with the outcome.ConclusionPredictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Highlights

  • Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately

  • One hundred and eighteen patients with newly diagnosed DLBCL treated with R-CHOP/R-CHOP-like therapy and undergoing diagnostic work-up including baseline 18F-FDG PET/CT in the period 2007–2012 at Aalborg University Hospital were included in this retrospective study

  • Two patients turned out to be CD20 negative and had rituximab removed from their treatment regimens

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Summary

Introduction

Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. The majority of patients with DLBCL respond to standard immunochemotherapy with a combination of the drugs rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone (R-CHOP), but 30–40% of the patients are refractory or relapse following initial response [1]. These patients have dismal outcomes and only a minority can be cured by salvage high-dose therapy and autologous stem cell transplantation [2, 3]. Combinations of tumor volume measurements on baseline PET/CT and early treatment response have been proposed to identify high-risk DLBCL patients likely to fail standard therapy [14]. To test the superiority of quantitative PET/CT over simple and unsupervised assessment of prognosis by experienced nuclear medicine specialists, we compared the prognostic value of both methods in a consecutive cohort of 118 patients

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