Interim PET Evaluation in Diffuse Large B-Cell Lymphoma Using Published Recommendations: Comparison of the Deauville 5-Point Scale and the ΔSUV_max Method

Abstract

The value of interim 18F-fluorodeoxyglucose positron emission tomography (iPET) guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the deltaSUVmax (ΔSUV max) approachtwo methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL) trial, iPET scans of 596 patients originally evaluated using the ΔSUV max method were available for post-hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUV max approach is characterized as a relative reduction of the maximum standardized uptake value between baseline and iPET staging of less than or equal to 66%. We investigated the two methods' correlation and concordance by Spearman's rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the pre-specified cutoffs. Timedependent receiver operating curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and ΔSUV max approach differed in their iPET-based prognosis. The ΔSUV max approach outperformed the Deauville score in terms of discrimination performance-most likely due to a high number of false-positive decisions by the Deauville score. Cut-offindependent discrimination performance remained low for both methods, but cutoff related analyses showed promising results. Both favored the ΔSUV max approach, e.g. for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval (CI): 2.22-4.46) for ΔSUV max and 1.70 (95% CI: 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUV max criterion of a relative

Interim PET in Diffuse Large B-Cell Lymphoma

“…The results obtained with both quantitative methods imply that the currently recommended threshold to identify high-risk patients by virtue of the visual Deauville scale (score 1-3 versus 4-5) is of limited value. This conclusion complements our previous finding that SUVmax is superior to Deauville for interim PET-based outcome prediction when recommended thresholds are employed (17). A cut-off between scores 4 and 5 of the visual scale may be more appropriate, in particular when interim PET is used to select patients for more aggressive therapies.…”

Interobserver Agreement on Automated Metabolic Tumor Volume Measurements of Deauville Score 4 and 5 Lesions at Interim 18F-FDG PET in Diffuse Large B-Cell Lymphoma

“…However, MTV cut-offs were different, and it is unclear whether and/or to which extent this relates to the use of different semi-automated delineation algorithms; Oñate-Ocaña used a 40%SUVmax threshold, Zhang a 41%, Wu a 42% and Malek a 37%SUVmax threshold and a gradient-based segmentation method (Gradient), while Islam applied a SUV4.0 threshold and Yang and Mikhaeel a SUV2.5 threshold (7)(8)(9)(15)(16)(17)34). This precludes any meaningful meta-analysis to build the case of evidence for MTV as a predictor for clinical outcome additional to (delta)SUVmax and the five-point DS (10,11). The latter particularly for I-PET DLBCL studies, since correlation between MTVs obtained by different segmentation methods is generally low for lesions with SUVmax<10 (Supplemental Figure 3) frequently prevailing at I-PET in contrary to baseline PET.…”

“…Discrimination between true non-responders and responders might improve by quantification (e.g. the relative change of standardized tracer uptake) (5)(6)(7)(8)(9)(10)(11). Quantification will reduce observer variability, and this is essential for successful clinical implementation.…”

Progression Free Survival and Predictor of Recurrence in DLBCL patients with Negative Interim 18FDG PET/CT Using Standardized Imaging and Reporting Protocols

“…This high recurrence with negative iPET indeed questions the diagnostic accuracy of Deauville scores 1-3 (no uptake or ≤ mediastinal or ≤ liver uptake) to interpret an iPET as CMR. Recently published results from Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL Trial) found better diagnostic accuracy of delta SUVmax (∆SUVmax ≤66%) than Deauville scoring >3 on iPET for dose intensification to avoid over-treatment (Rekowski et al, 2020). However, DS ≤3 and ∆SUVmax ≤66% were found to have comparable event free survival (EFS) in PETAL trial (Rekowski et al, 2020).…”

“…Recently published results from Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL Trial) found better diagnostic accuracy of delta SUVmax (∆SUVmax ≤66%) than Deauville scoring >3 on iPET for dose intensification to avoid over-treatment (Rekowski et al, 2020). However, DS ≤3 and ∆SUVmax ≤66% were found to have comparable event free survival (EFS) in PETAL trial (Rekowski et al, 2020). Kwonet al, (2016) used DS-1 for negative iPET in homogenous population but the relapse rate is similar to our study with DS ≤ 3 as negative iPET in homogenous population with standardized imaging and reporting protocols.…”