Background
Diffuse large B‐cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG‐PET/CT for staging and end of treatment (EOT) response assessment, ...mid‐treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG‐PET/CT response assessment in DLBCL head‐to‐head.
Methods
We retrospectively included patients with DLBCL who underwent first‐line R‐CHOP(‐like) therapy (2013−2020). Interim and EOT FDG‐PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non‐CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SULpeak using PERCIST (PERCIST66).
Results
In multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non‐CMR at EOT with the Lugano classification and non‐CMR at EOT with PERCIST were predictive of progression‐free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS‐5 at interim, 87.6% for PERCIST66 at interim, 86% for non‐CMR with the Lugano classification at EOT and 83.3% for non‐CMR with PERCIST at EOT.
Conclusion
The Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non‐CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years.
Background
Several clinical prognostic models for diffuse large B‐cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National ...Comprehensive Cancer Network IPI (NCCN‐IPI), and models incorporating beta‐2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood.
Methods
We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry.
Results
A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN‐IPI performed better than the International Prognostic Indexes (IPI, age‐adjusted IPI, and revised IPI). Five‐year overall survival for high‐ and low‐risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN‐IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M‐NCCN‐IPI) by adding β2M to NCCN‐IPI (c‐index 0.708) with improved discriminatory ability compared to NCCN‐IPI (c‐index 0.698, p < 0.05) and 5‐year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high‐intermediate, low‐intermediate and low‐risk group, respectively.
Conclusion
International Prognostic Indices, except for NCCN‐IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN‐IPI and should be re‐evaluated in the development setting of future models for DLBCL.
Beta‐2 microglobulin (β2M) has been sporadically incorporated in prognostic models for diffuse large B‐cell lymphoma (DLBCL). We compared the prognostic discriminative ability of four existing DLBCL models with International Prognostic Indices. Moreover, we developed and validated a new model from the largest population investigating this marker so far, indicating the necessity to include β2M in future studies when analyzing prognostic markers in DLBCL.
Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations ...have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available.
Relapse involving the central nervous system (CNS) is an infrequent event in the progression of mantle cell lymphoma (MCL) with an incidence of approximately four percent. We report four cases of MCL ...with CNS relapse. In three of the four patients a large chromosomal copy-number alteration (CNA) of 1q was demonstrated together with TP53 mutation/deletion. These patients experienced brief response to ibrutinib, whereas a fourth patient harboring mutated ATM demonstrated a long-term effect to ibrutinib and no CNA. Although it is unclear whether chromosome 1q CNA contribute to specific phenotypes these reports may be of value as such lesions are uncommon features of MCL.
Background
Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple ...tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication.
Materials and methods
Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV
2.5
(SUV 2.5 cut-off) and MTV
41
(41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV
VAS
) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers.
Results
In the quantitative analysis, a ROC-determined MTV
2.5
cut-off (log-rank
p
= 0.11) seemed to outperform MTV
41
(log-rank
p
= 0.76) for PFS prediction. TLG2.5 (log-rank
p
= 0.14) and TLG41 (log-rank
p
= 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank
p
= 0.002, reviewer B log-rank
p
= 0.016, and reviewer C log-rank
p
= 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV
VAS
and eMTV were not consistently correlated with the outcome.
Conclusion
Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.
Models based on risk stratification are increasingly reported for Diffuse large B cell lymphoma (DLBCL). Due to a rising interest in nomograms for cancer patients, we aimed to review and critically ...appraise prognostic models based on nomograms in DLBCL patients. A literature search in PubMed/Embase identified 59 articles that proposed prognostic models for DLBCL by combining parameters of interest (e.g., clinical, laboratory, immunohistochemical, and genetic) between January 2000 and 2024. Of them, 40 studies proposed different gene expression signatures and incorporated them into nomogram-based prognostic models. Although most studies assessed discrimination and calibration when developing the model, many lacked external validation. Current nomogram-based models for DLBCL are mainly developed from publicly available databases, lack external validation, and have no applicability in clinical practice. However, they may be helpful in individual patient counseling, although careful considerations should be made regarding model development due to possible limitations when choosing nomograms for prognostication.
•An increasing number of prognostic models have been proposed for DLBCL patients.•Several models with nomograms for DLBCL patients have been recently proposed.•Most of them include gene-expression signatures derived from public databases.•Most of the current nomogram-based models lack optimal validation.•The clinical utility of nomogram models is prevented due to numerous limitations.
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•Primary central nervous system lymphoma (PCNSL) is an aggressive and rare disease.•Several prognostic models were developed for PCNSL on a limited number of PCNSL patients.•Older ...prognostic models, although externally validated, had variable prognostic significance in newer studies.•Newer prognostic models mainly lacked external validation and usage of appropriate methods for model comparison.•Further studies are needed to determine the optimal prognostic model for PCNSL patients.
Over the last decade, several prognostic models have been proposed for primary central nervous system lymphoma (PCNSL), but consensus on the optimal model for these patients is absent or lacking. This study aims to review available prognostic models for PCNSL and discuss their prognostic features. A comprehensive literature search performed in Pubmed/Embase identified ten studies with a variable number of analysed patients (range 32–3453), which proposed 12 prognostic models. Age and performance status were the most important prognostic factors in PCNSL and an integral part of the majority of the proposed models. However, there is no universally accepted prognostic model for PCNSL owning to a number of limitations such as a small number of patients, limited samples obtained for genetic analysis, retrospective nature of studies, single centre studies, and lack of validation. Future multicentre studies are necessary to determine the optimal prognostic model for PCNSL by combining different prognostic markers of significance.
Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in ...the era of positron emission tomography
(
PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.
Beta-thalassemia is an inherited blood disorder caused by reduced or absent synthesis of the beta chains of hemoglobin, resulting in decreased hemoglobin production. Symptoms depend on the type of ...beta-thalassemia ranging from no symptoms to severe illness. Ineffective erythropoiesis leads to a sequence of events responsible for bone marrow expansion, anemia, hemolysis, splenomegaly, increased iron absorption, and sometimes extramedullary hematopoiesis (EMH). We report an interesting case with EMH visualized on FDG-PET/CT and where FDG-PET/CT has also found the focus of a severe infection in a patient with beta-thalassemia.
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