Introduction: Metabolic tumor volume (MTV) is a promising biomarker of pretreatment risk in diffuse large B-cell lymphoma (DLBCL). Different segmentation methods can be used which predict prognosis equally well but give different optimal cut-offs for risk stratification. Segmentation can be cumbersome meaning a fast, easy and robust method is needed. Aims were to i) evaluate the best automated MTV workflow in DLBCL ii) determine if uptake time, (non)compliance with standardized recommendations for FDG scanning and subsequent disease progression influenced the success of segmentation iii) assess differences in MTV values and discriminatory power of segmentation methods. Methods: 140 baseline FDG-PET/CT scans were selected from UK and Dutch studies in DLBCL to provide a balance between scans at 60-or 90-minutes uptake, parameters compliant or non-compliant with standardized recommendations for scanning and patients with or without progression. An automated tool was used for segmentation using i) standardized uptake value (SUV) 2.5 ii) SUV 4.0 iii) adaptive thresholding [A50P] iv) 41% of maximum SUV [41%] v) majority vote including voxels detected by ≥2 methods [MV2] and vi) detected by ≥3 methods [MV3]. Two independent observers rated the success of the tool to delineate MTV. Scans that required minimal interaction were rated "success"; scans where > 50% of tumor was missed or required more than 2 editing steps were rated as "failure". Results: 138 scans were evaluable, with significant differences in success and failure ratings between methods. The best performing was SUV4.0, with higher success and lower failure rates than all other methods except MV2 which also performed well. SUV4.0 gave a good approximation of MTV in 105 (76%) scans, with simple editing for a satisfactory result in additionally 20% of cases. MTV was significantly different for all methods between patients with and without progression. SUV41% performed slightly worse with longer uptake times, otherwise scanning conditions and patient outcome did not influence the tool's performance. The discriminative power of methods was similar, but MTV values were significantly greater using SUV4.0 and MV2 than other thresholds except for SUV2.5. Conclusion:SUV4.0 and MV2 are recommended for further evaluation. Automated estimation of MTV is feasible.

Purpose: Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods: Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumorto-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results: We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions: Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data.

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.