Combined Analysis Using Visual and SUV-Based Quantitative Assessments Improves Predictive Value of Interim Positron Emission Tomography Scan in Diffuse Large B-Cell Lymphoma Treated with R-CHOP
Authors: Yhim Ho-Young , Lee Na-Ri , Song Eun-Kee , Jeon So Yeon , Yim Chang-Yeol , Han Yeon-Hee , Sohn Myung-Hee , Lee Bohee , Kim Jeong-A , Park Young Ha , Choi Woo Hee , Kim Hee Sun , Kwak Jae-Yong 
Published: October 2019

Abstract
Abstract 3690

Introduction
Positron emission tomography (PET) has been identified as a useful tool for initial staging and end-of-therapy response assessment in patients with diffuse large B-cell lymphoma (DLBCL). However, the role of an interim PET to predict outcome is still controversial. This may be related that reliable criteria to interpret interim PET has not been established. Recently, Deauville five-point scale (5-PS) and standardized uptake value (SUV)-based analysis were proposed for the interpretation of interim PET. However, Deauville 5-PS might still be related to false positive results in some patients and SUV-based analysis not be suitable for patients with low baseline or high interim SUVmax. Therefore, the aim of this study was to investigate the prognostic implication of interim PET interpretation combining visual and SUV-based quantitative assessments in patients with DLBCL treated with R-CHOP chemotherapy.

Patients and methods
We consecutively enrolled newly diagnosed DLBCL patients, treated with R-CHOP chemotherapy and had the baseline PET data with 31 evaluable hypermetabolic lesion between 2006 and 2011 in two Korean institutions. Interim PET scan was performed after 3 or 4 cycles of R-CHOP, before 1 week of the next cycle. All PET assessment was performed by 2 nuclear medicine specialists at each institution, and the discrepancy of assessment was resolved by the agreement through discussion. Interim PET response was assessed by visual analysis using Deauville 5-PS and quantitative method based on SUVmax reduction rate. After using the receiver operating characteristics analysis, SUVmax reduction <78.6% was selected as optimal cut-off for positive PET.

Results
One hundred thirty-two patients were included in this study. The median age was 62 years (range, 15–88) and 85 (64%) were male. Sixty-four patients (49%) were presented as advanced stage disease and 30 (23%) had B symptoms. ECOG performance status was 0 or 1 in 100 (76%) and serum LDH level was elevated in 76 (58%). Thus, 44 (33%) were classified as high-intermediate to high risk of International Prognostic Index (IPI). One hundred twenty-three patients (93%) completed planned R-CHOP ± involved-field radiotherapy.
Using visual analysis based on Deauville 5-PS and quantitative analysis by SUVmax reduction, 28 (21%) and 26 patients (20%) were positive on interim PET scan, respectively. 18 patients (14%) showed positive PET in agreement between visual and quantitative assessments. However, 10 (8%) of the 28 PET positive patients on visual analysis showed negative PET based on quantitative assessment. Similarly, 8 (6%) among 26 positive patients on quantitative analysis were negative on visual assessment. Thus, 18 patients showed discordant interim PET results between visual and quantitative assessments.
With a median follow-up of 25.3 (range, 5.6–75.5) months, 2-year progression-free survival (PFS) was significantly worse in patients with positive interim PET according to visual (27.4% vs. 88.2%, P<0.001) and quantitative (25.4% vs. 86.6%, P<0.001) assessments than those with negative results, respectively. Combining both visual and quantitative assessments, 2-year PFS was significantly different according to the point of positive results in each assessment (0 point, 90.4% vs. 1 point, 57.3% vs. 2 point, 9.3%, respectively, P<0.001). In multivariate analysis for PFS, high-intermediate to high risk of IPI (HR, 4.67; 95% CI, 1.96–11.14) and 2 points in the combined visual and quantitative analysis of interim PET (HR, 7.20; 95% CI, 2.81–18.46) were independent prognostic factors for worse PFS

Conclusion
Interim PET appears to predict early outcomes of patients with DLBCL treated with R-CHOP. A positive interim PET in both analyses shows highly predictive of extremely poor outcome. Therefore, combined analysis of visual and SUV-based quantitative assessments makes it possible to more clearly differentiate the clinical outcomes in patients with DLBCL. Further studies are needed to validate our results.

Disclosures:
No relevant conflicts of interest to declare.