Dataset Information

¹⁸F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

ABSTRACT:

Purpose

To determine whether interim 3'-deoxy-3'-[¹⁸F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim ¹⁸F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH).

Methods

Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18-24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS.

Results

iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1-3) in 53 (58%) and positive (DS = 4-5) in 39 (42%) patients. Of the 67 iFLT-PET/CT-negative patients, 7 (10.4%) progressed at a median of 14.1 months whereas 14/25 (56.0%) iFLT-PET/CT-positive patients progressed at a median of 7.8 months (P < .0001). Of the 53 Deauville-negative patients, 9 (17.0%) progressed at a median of 14.1 months whereas 12/39 (30.8%) Deauville-positive patients progressed at a median of 5.6 months (P = .11). In multivariate analysis, including iFLT-PET/CT, PERCIST, interim TLG, and interim SUV_max, only iFLT-PET/CT was an independent predictor for 3- and 5-year PFS (P < .0001 and P = .001, respectively).

Conclusions

In patients with DLBCL given R-CHOP/R-EPOCH, iFLT-PET/CT is a superior independent predictor of outcome compared with iFDG-PET/CT.

SUBMITTER: Minamimoto R

PROVIDER: S-EPMC8263539 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

<sup>18</sup>F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

Minamimoto Ryogo R Fayad Luis L Vose Julie J Meza Jane J Advani Ranjana R Hankins Jordan J Mottaghy Felix F Macapinlac Homer H Heinzel Alexander A Juweid Malik E ME Quon Andrew A

European journal of nuclear medicine and molecular imaging 20210428 9

<h4>Purpose</h4>To determine whether interim 3'-deoxy-3'-[<sup>18</sup>F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim <sup>18</sup>F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH).<h4>Methods</h4>Ninety-two ...[more]

PMID: 33909086

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Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL.ResultsA total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell's concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403).ConclusionsRadiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Project description:We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline 18F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Methods: From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and 18F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmaxpatient), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan-Meier survival analyses were performed. Results: With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmaxpatient were 375 cm3 and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmaxpatient were adverse factors for PFS (P = 0.027 and P = 0.0003, respectively) and for OS (P = 0.0007 and P = 0.0095, respectively). In multivariate analysis, only Dmaxpatient was significantly associated with PFS (P = 0.0014) whereas both factors remained significant for OS (P = 0.037 and P = 0.0029, respectively). Combining MTV (>384 cm3) and Dmaxpatient (>58 cm) yielded 3 risk groups for PFS (P = 0.0003) and OS (P = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, n = 18), low with no adverse factor (94% and 97%, n = 36), and an intermediate category with 1 adverse factor (73% and 88%, n = 41). Conclusion: Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.

Project description:PurposeThis study aimed to develop a novel analytic approach based on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) radiomic signature (RS) and International Prognostic Index (IPI) to predict the progression-free survival (PFS) and overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL).MethodsWe retrospectively enrolled 152 DLBCL patients and divided them into a training cohort (n = 100) and a validation cohort (n = 52). A total of 1245 radiomic features were extracted from the total metabolic tumor volume (TMTV) and the metabolic bulk volume (MBV) of pre-treatment PET/CT images. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to develop the RS. Cox regression analysis was used to construct hybrid nomograms based on different RS and clinical variables. The performances of hybrid nomograms were evaluated using the time-dependent receiver operator characteristic (ROC) curve and the Hosmer-Lemeshow test. The clinical utilities of prediction nomograms were determined via decision curve analysis. The predictive efficiency of different RS, clinical variables, and hybrid nomograms was compared.ResultsThe RS and IPI were identified as independent predictors of PFS and OS, and were selected to construct hybrid nomograms. Both TMTV- and MBV-based hybrid nomograms had significantly higher values of area under the curve (AUC) than IPI in training and validation cohorts (all P < 0.05), while no significant difference was found between TMTV- and MBV-based hybrid nomograms (P > 0.05). The Hosmer-Lemeshow test showed that both TMTV- and MBV-based hybrid nomograms calibrated well in the training and validation cohorts (all P > 0.05). Decision curve analysis indicated that hybrid nomograms had higher net benefits than IPI.ConclusionThe hybrid nomograms combining RS with IPI could significantly improve survival prediction in DLBCL. Radiomic analysis on MBV may serve as a potential approach for prognosis assessment in DLBCL.Trial registrationNCT04317313. Registered March 16, 2020. Public site: https://clinicaltrials.gov/ct2/show/NCT04317313.

Project description:The current standard front-line therapy for patients with diffuse large-B cell lymphoma (DLBCL)-rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-is found to be ineffective in up to one-third of them. Thus, their early identification is an important step towards testing alternative treatment options. In this retrospective study, we assessed the ability of 18F-FDG PET/CT imaging features (radiomic + PET conventional parameters) plus clinical data, alone or in combination with genomic parameters to predict complete response to first-line treatment. Imaging features were extracted from images prior treatment. Lesions were segmented as a whole to reflect tumor burden. Multivariate logistic regression predictive models for response to first-line treatment trained with clinical and imaging features, or with clinical, imaging, and genomic features were developed. For imaging feature selection, a manual selection approach or a linear discriminant analysis (LDA) for dimensionality reduction were applied. Confusion matrices and performance metrics were obtained to assess model performance. Thirty-three patients (median [range] age, 58 [49-69] years) were included, of whom 23 (69.69%) achieved long-term complete response. Overall, the inclusion of genomic features improved prediction ability. The best performance metrics were obtained with the combined model including genomic data and built applying the LDA method (AUC of 0.904, and 90% of balanced accuracy). The amplification of BCL6 was found to significantly contribute to explain response to first-line treatment in both manual and LDA models. Among imaging features, radiomic features reflecting lesion distribution heterogeneity (GLSZM_GrayLevelVariance, Sphericity and GLCM_Correlation) were predictors of response in manual models. Interestingly, when the dimensionality reduction was applied, the whole set of imaging features-mostly composed of radiomic features-significantly contributed to explain response to front-line therapy. A nomogram predictive for response to first-line treatment was constructed. In summary, a combination of imaging features, clinical variables and genomic data was able to successfully predict complete response to first-line treatment in DLBCL patients, with the amplification of BCL6 as the genetic marker retaining the highest predictive value. Additionally, a panel of imaging features may provide important information when predicting treatment response, with lesion dissemination-related radiomic features deserving especial attention.

Project description: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.

Dataset Information

¹⁸F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

Purpose

Methods

Results

Conclusions

Publications

<sup>18</sup>F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

18F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

Purpose

Methods

Results

Conclusions

Publications

<sup>18</sup>F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

¹⁸F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.