Page 128 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 6a
Abstract
We aimed to determine the added value of baseline metabolic tumor volume (MTV) and interim PET (I-PET) to the age-adjusted international prognostic index (aaIPI) to predict 2-y progression-free survival (PFS) in diffuse large B-cell lymphoma. Secondary objectives were to investigate optimal I-PET response criteria (using Deauville score [DS] or quantitative change in SUVmax [∆SUVmax] between baseline and I-PET4 [observational I-PET scans after 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone administered in 2-wk intervals with intensified rituximab in the first 4 cycles [R(R)-CHOP14]).
Methods:
I-PET4 scans in the HOVON-84 (Hemato-Oncologie voor Volwassenen Nederland [Haemato Oncology Foundation for Adults in the Netherlands]) randomized clinical trial (EudraCT 2006-005174-42) were centrally reviewed using DS (cutoff 4-5). Additionally, ∆SUVmax (prespecified cutoff, 70%) and baseline MTV were measured. Multivariable hazard ratio (HR), positive predictive value (PPV ), and negative predictive value (NPV ) were obtained for 2-y PFS.
Results:
In total, 513 I-PET4 scans were reviewed according to DS, and ∆SUVmax and baseline MTV were available for 367 and 296 patients.The NPV of I-PET ranged between 82% and 86% for all PET response criteria. Univariate HR and PPV were better for ∆SUVmax (4.8 and 53%, respectively) than for DS (3.1 and 38%, respectively). AaIPI and ∆SUVmax independently predicted 2-y PFS (HR, 3.2 and 5.0, respectively); adding MTV brought about a slight improvement. Low or low-intermediate aaIPI combined with a ∆SUVmax of more than 70% (37% of patients) yielded an NPV of 93%, and the combination of high-intermediate or high aaIPI and a ∆SUVmax of 70% or less yielded a PPV of 65%.
Conclusion:
In this study on diffuse large B-cell lymphoma, I-PET after 4 cycles of R(R)- CHOP14 added predictive value to aaIPI for 2-y PFS, and both were independent response biomarkers in a multivariable Cox model. We externally validated that ∆SUVmax outperformed DS in 2-y PFS prediction.
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