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Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial.

ABSTRACT: As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.

SUBMITTER: Schoder H

PROVIDER: S-EPMC7316220 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.

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:BackgroundDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive lymphoma. Rituximab-based conventional chemotherapy still leads to drug resistance or relapse in 30-40% of patients. Therefore, early identification of high-risk patients and accurate assessment of prognosis are very important for clinical decision-making. The aim of this study is to investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of tumor metabolic, clinical and biological parameters in the prognostic risk stratification of DLBCL before treatment.MethodsWe retrospectively collected clinical data on 63 patients with newly diagnosed DLBCL admitted to Shanxi Bethune Hospital during the period from November 2016 to April 2020 who underwent 18F-FDG PET/CT prior to treatment in a cohort study. Metabolic, clinical, and biological parameters were analyzed by Cox regression. Kaplan-Meier curves of patient survival were compared by the log-rank test.ResultsThe median follow-up was 21 months. The 2-year progression-free survival (PFS) was 47.62%, and the overall survival (OS) was 53.97%. The subtype, double expression, Ann Abor stage, NCCN-IPI score, Ki-67, maximum standardized uptake value (SUVmax), bulk volume glycolysis (BVG), total lesion glycolysis (TLG), total metabolic tumor volume (TMTV) were the influencing factors for PFS and OS (P<0.050) in univariate analysis. BVG (PFS: HR =6.62, P<0.001; OS: HR =3.53, P=0.029), TLG (PFS: HR =8.56, P<0.001; OS: HR =5.20, P=0.004), TMTV (PFS: HR =12.02, P=0.001; OS: HR =5.05, P=0.033) and Ki-67 were found to be independent prognostic risk stratification parameters affecting PFS and OS by multivariate regression analysis. The 2-year PFS and OS rates for patients with high BVG (≥288.00 cm3), TLG (≥1,854.00 cm3), TMTV (≥103.00 cm3), and Ki-67 (≥85%) were 20% and 28.57%, 9.68% and 22.58%, 20.51%, and 30.77%, and 25% and 33.33%, respectively; and the 2-year PFS and OS rates for patients with low BVG (<288.00 cm3), TLG (<1,854.00 cm3), TMTV (<103.00 cm3), and Ki-67 (<85%) patients were 82.14% and 85.71%, 84.37% and 84.37%, 91.67% and 91.67%, and 61.54% and 66.67%, respectively. Patients with high BVG, TLG, TMTV, and Ki-67 had a worse 2-year PFS as well as OS rate (Ki-67: P=0.0018/P=0.0025; P<0.0001 for the rest of the groups).ConclusionsOur findings suggest that BVG, TLG, TMTV, and Ki-67 are independent prognostic indicators for survival in patients with pre-treatment DLBCL, especially BVG, which is a novel prognostic indicator that has to be validated in future research.

Project description:The present study aimed to investigate the prognostic value of baseline 18F-FDG PET/CT quantitative parameters and interim treatment response, and to assess whether the combination of these could improve the predictive efficacy in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. PET/CT images and clinical data of 64 patients with DLBCL who had undergone 18F-FDG PET/CT scan before and after 3 or 4 cycles of R-CHOP chemotherapy were retrospectively reviewed. The quantitative parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter of the maximum lesion (Dmax) were measured on baseline PET/CT images. Cox proportional hazards model was used to evaluate the influence of baseline PET/CT parameters, clinical indicators and interim treatment response on prognosis. Survival analysis was performed using Kaplan-Meier method. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive efficacy of the combination of baseline PET/CT parameters and interim treatment response. Ann Arbor stage, International Prognostic Index (IPI), lactate dehydrogenase (LDH), necrosis, MTVmax, TLGmax, Dmax and interim treatment response showed association with 2-year progression-free survival (PFS, P<0.05). LDH, necrosis, MTVmax, MTVsum, TLGmax, TLGsum, Dmax and interim treatment response showed association with 2-year overall survival (OS, P<0.05). Ann Arbor stage, Dmax and interim treatment response were found to be independent predictors of 2-year PFS (P<0.05), while Dmax and interim treatment response were found to be independent predictors of 2-year OS (P<0.05). The PFS and OS curves of Dmax <5.7 cm group and Dmax ≥5.7 cm group, complete response (CR) group and non-CR group were significantly different, respectively (P<0.05). The baseline 18F-FDG PET/CT parameters and interim treatment response have important prognostic values in DLBCL patients who received R-CHOP chemotherapy. Combined application of Dmax and interim treatment response improved the predictive efficacy of 2-year PFS. It may be helpful to identify patients who are at high-risk of relapse and to guide early clinical intervention of these patients.

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Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial.

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