<sup>18</sup>F-FDG PET Improves Baseline Clinical Predictors of Response in Diffuse Large B-Cell Lymphoma: The HOVON-84 Study
Coreline N. Burggraaff, Jakoba J. Eertink, Pieternella J. Lugtenburg, Otto S. Hoekstra, Anne I.J. Arens, Bart de Keizer, Martijn W. Heymans, Bronno van der Holt, Sanne E. Wiegers, Simone Pieplenbosch, Ronald Boellaard, Henrica C. W. de Vet, Josée M. Zijlstra, on behalf of the HOVON Imaging Working Group and the HOVON Lymphoma Working Group
Abstract
We aimed to determine the added value of baseline metabolic tumor volume (MTV) and interim positron emission tomography (I-PET) to age-adjusted international prognostic index (aaIPI) to predict 2-year progression-free survival (PFS) in diffuse large B-cell lymphoma (DLBCL). Secondary objectives were to investigate optimal I-PET response criteria (using Deauville score (DS) - or quantitative change in maximum Standardized Uptake Value (ΔSUV<sub>max</sub>) between baseline and I-PET). <b>Methods:</b> Observational I-PET scans were performed after four cycles R(R)-CHOP14 (I-PET4) in the HOVON-84 randomized clinical trial (EudraCT 2006-005174-42), and centrally reviewed using DS (cut-off 4-5). Additionally, ΔSUV<sub>max</sub> (prespecified cut-off 70%) and baseline MTV were measured. Multivariable hazard ratios (HR), positive (PPV), and negative predictive values (NPV) were obtained for 2-year PFS. <b>Results:</b> 513 I-PET4 scans were reviewed according to DS, and ΔSUV<sub>max</sub> and baseline MTV were available for 367 and 296 patients. NPV of I-PET ranged between 82% and 86% for all PET response criteria. Univariate HR and PPV were optimal for ΔSUV<sub>max</sub> (4·8 and 53%, respectively) compared to DS (3·1 and 38%, respectively). AaIPI and ΔSUV<sub>max</sub> independently predicted 2-year PFS (HRs 3·2 and 5·0, respectively); adding MTV slightly improved this. Low/low-intermediate aaIPI combined with ΔSUV<sub>max</sub>>70% (37% of patients) yielded a NPV of 93%, and the combination of high-intermediate/high aaIPI and ΔSUV<sub>max</sub>≤70% a PPV of 65%. <b>Conclusion:</b> In this DLBCL study, I-PET after four cycles R(R)-CHOP14 added predictive value to aaIPI for 2-year PFS, and both were independent response biomarkers in a multivariable Cox model. We externally validated that ΔSUV<sub>max</sub> outperformed Deauville score in 2-year PFS prediction.