Background Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma. Despite established clinical prognostic scoring such as that of the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Extranodal Lymphoma Study Group, outcome prediction needs to be improved. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in PCNSL. We sought to assess the association between hematological parameters and overall survival (OS) in patients with PCNSL. Methods Pretreatment blood tests were analyzed in patients with newly diagnosed PCNSL (n = 182), and we divided the analysis into two cohorts (A and B, both n = 91). OS was evaluated using the Cox proportional hazards models and log‐rank test. Furthermore, the accuracy of the different multivariate models was assessed by Harrell's concordance index (C‐index). Results Using prechemotherapy blood tests, anemia was found in 38 patients (41.8%) in cohort A and 34 patients (37.4%) in cohort B. In univariate analysis, anemia (<12 g/dL in women and <13 g/dL in men) was significantly associated with OS. None of the other blood tests parameters (neutrophils, lymphocyte, or platelets counts) or their ratios (neutrophil‐to‐lymphocyte ratio and neutrophil‐to‐platelets ratio) were associated with OS. In multivariate analysis, after adjusting by MSKCC score, anemia remained an independent prognostic factor. Interestingly, the prediction accuracy of OS using Harrell's C‐index was similar using anemia or MSKCC (mean C‐index, 0.6) and was increased to 0.67 when combining anemia and MSKCC. Conclusion The presence of anemia was associated with poor prognosis in both cohorts of PCNSL. Validation of these results and biologic role of hemoglobin levels in PCNSL requires further investigation. Implications for Practice The prediction of the outcome of primary central nervous system lymphoma (PCNSL) using the most frequently used scores (i.e., Memorial Sloan Kettering Cancer Center [MSKCC] or International Extranodal Lymphoma Study Group) needs to be improved. We analyzed a large cohort of PCNSL to dissect the potential prognostic value of blood tests in this rare entity. We found anemia as an independent predictor for overall survival in PCNSL. Interestingly, the accuracy to predict PCNSL outcome was improved using hemoglobin level. This improvement was additional to the currently used clinical score (i.e., MSKCC). Finally, none of the other blood tests parameters or their ratios had a prognostic impact in this study.
BACKGROUND CPG2 is an efficient rescue recombinant bacterial enzyme that cleaves MTX into inactive metabolites. As hdMTX is the key agent in PCNSL, delayed MTX excretion (DME), and/or MTX induced nephrotoxicity (MIN) may expose the patients to severe toxicities and prevent the further use of the drug. Little is known on the use of CPG2 and its impact on patient outcome.Objective: To describe the clinical characteristics, indications, risk factors, outcomes of PCNSL patients treated with CPG2. MATERIAL AND METHODS Retrospective analysis of patients from the LOC network database with histologically proven PCNSL, aged >18, who received CPG2 following hdMTX. RESULTS From 2011 to 2018, 41(3%) of 1236 patients treated with hdMTX used CPG2. Median age: 70 years [46–86], sex ratio M/F 3.6, median KPS 70. Indications of CPG2 were DME (12%), MIN (34%), both (49%). 37/41 (90%) of the patients had either a cardiovascular history (CVH) (76%) or a preexisting chronic kidney disease (CKD) (56%) and 59% had at least one additional risk factor: delayed MTX elimination or renal toxicity in prior cycles (20%), other grade III-IV toxicity (20%), concomitant drugs interfering with MTX excretion (29%), active infection (22%), hypoalbuminemia (59%). Median hdMTX dose was 3 g/m2 [1–3.5], median number of MTX injection received at the time of CPG2: 2[1–6]. At time of the CPG2 administration, median serum creatinine was 185 μmol/l [108–410] and median serum MTX: 25 μmol/l [1–240]. 24% of patients underwent hemodialysis, 76% return to baseline creatinine, in a median of 30 days; no MTX related deaths were reported. Extrarenal grade III-IV toxicities: lymphopenia (46%), neutropenia (22%), mucocutaneous toxicity (15%), thrombopenia (12%), hepatotoxicity (12%), sepsis (12%). Median time to chemotherapy resumption: 26 days (cytarabine-based or hdMTX rechallenge). HdMTX was reintroduced safely in 14 patients (34%) but one. The outcome (ORR, PFS OS) was similar with that expected of patients who would not have had toxicity to MTX. CONCLUSION In our study, a small number of patients have received CPG2 regarding the incidence of MIN and DME, probably due to treatment cost. The high frequency of risk factors points out the need of careful attention of this issue and for adapted hdMTX protocol for this vulnerable population. CPG2 treated patients do not have a worse prognosis than expected. A controlled study is warranted to compare the cost/benefit of the management of MIN /DME with or without CPG2.
BACKGROUND Lower-grade gliomas (LGG) are divided into three histo-molecular groups: i) IDH-wildtype, ii) IDH mutant and 1p19q intact and iii) IDH mutant and 1p19q co-deleted. The current classification has improved the clinical stratification and its reproducibility. However, LGGs are still associated with an important degree of clinical heterogeneity. We sought to analyze the cross-talk between the spatial distribution and the quantitative imaging features (radiomics) with the clinical evolution and their molecular background (radiogenomics). MATERIAL AND METHODS We performed a retrospective multicentric study from 4 cohorts of high-grades gliomas (POLA Network, TCGA, REMBRANDT and LGG-1p19q), totaling 900 gliomas. We performed N4 and WhiteStripe imaging corrections to standardize MRI intensities. We used ITK-SNAP to obtain a mask of the different habitats of the tumor. Then we used PyRadiomics to obtain 2616 radiomic features per sample. We used plsRcox for fitting several Cox model in high-dimensional settings. We assessed the performance of the difference Cox model with the Harrel’s concordance index. We used a Sparse Canonical Correlation analysis to analyze the spatial distribution of the tumors. RESULTS Radiomics features allow identification in an unsupervised manner IDH-mutant gliomas with a median AUC of 0.96 [0.92–0.98]. Interestingly, in the analysis of survival, radiomics features provided additional information to clinical or genetics covariates and the model with only radiomics features obtained a C-Index of 0.78 [0.72–0.82]. In addition, survival model with the best performance in the prediction of overall survival was the one combining radiomics, clinics and genetics features with a C-Index 0.85 [0.82–0.92] and was validated in the other cohorts. The analysis of spatial distribution showed a very strong distribution of 1p19q co-deleted oligodendrogliomas in the frontal lobes. CONCLUSION Radiomics features may provide additional relevant clinical information by improving the prognosis of LGG. Radiomics allow non-invasive prediction of the most relevant molecular alterations of LGG.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.