Coreline N Burggraaff1, Jakoba J Eertink1, Pieternella J Lugtenburg2, Otto S Hoekstra3, Anne I J Arens4, Bart de Keizer5, Martijn W Heymans6, Bronno van der Holt7, Sanne E Wiegers1, Simone Pieplenbosch1, Ronald Boellaard3, Henrica C W de Vet6, Josée M Zijlstra8. 1. Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 2. Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 4. Department of Radiology, Nuclear Medicine, and Anatomy, Radboud University Medical Center, Nijmegen, The Netherlands. 5. Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. 6. Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; and. 7. Department of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 8. Department of Hematology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; j.zijlstra@amsterdamumc.nl.
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 [ΔSUVmax] 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, ΔSUVmax (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 ΔSUVmax 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 ΔSUVmax (4.8% and 53%, respectively) than for DS (3.1% and 38%, respectively). aaIPI and ΔSUVmax 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 ΔSUVmax of more than 70% (37% of patients) yielded an NPV of 93%, and the combination of high-intermediate or high aaIPI and a ΔSUVmax 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 ΔSUVmax outperformed DS in 2-y PFS prediction.
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 [ΔSUVmax] 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, ΔSUVmax (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 ΔSUVmax 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 ΔSUVmax (4.8% and 53%, respectively) than for DS (3.1% and 38%, respectively). aaIPI and ΔSUVmax 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 ΔSUVmax of more than 70% (37% of patients) yielded an NPV of 93%, and the combination of high-intermediate or high aaIPI and a ΔSUVmax 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 ΔSUVmax outperformed DS in 2-y PFS prediction.
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