Jelena Jelicic

Objective: We examined the epidemiology of parotid gland lymphomas (PGL), the incidence, survival rates, clinical features, and association with primary Sjögren's syndrome (pSS).Methods: This retrospective nationwide cohort study analyzed data from Danish patients diagnosed with PGL between 2000 and 2020. Data were collected from medical records, the National Pathology Register, and the Danish lymphoma database. Statistical analyses included Kaplan–Meier curves, log‐rank tests, and Cox proportional hazards models.Results: A total of 433 patients were included. The incidence rate was 0.39 per 100,000 person‐years, with PGL constituting 1.9% of all non‐Hodgkins lymphoma in Denmark. The average annual incidence was 2.7% (incidence rate ratio = 1.027, p < 0.01). Follicular lymphoma (FL) was the most common subtype with 154 cases (35.6%), followed by large B‐cell lymphoma (LBCL) with 119 cases (27.5%), and extranodal marginal zone lymphoma (EMZL) with 84 cases (19.4%). The median overall survival (OS) for FL was 9.5 years (95% CI 6.9–10.2), with 5‐year and 10‐year OS rates of 70% and 44%, respectively. For LBCL, the median OS was 7.8 years (95% CI 5.0–8.8), with 5‐year and 10‐year OS rates of 59% and 33%. EMZL had a median OS of 12.8 years (95% CI 9.0–16.3), with 5‐year and 10‐year OS rate of 83% and 55%. EMZL was significantly associated with pSS, relative risk 21.97 (95% CI 2.81–171.53). Advanced age, B symptoms, and elevated LDH levels were significantly linked to poorer overall survival.Conclusion: This study offers new epidemiological, clinical, and prognostic insights, with a focus on their association with pSS.Level of Evidence: 3 Laryngoscope, 135:1391–1400, 2025

Objective: This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. Methods: This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. Results: The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2–12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren’s syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45–16.01). Conclusions: Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

Objectives: Recent front‐line clinical trials used the International Prognostic Index (IPI) to identify trial‐eligible patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL). However, many IPI‐like variants with improved accuracy have been developed over the years for rituximab‐treated patients.Methods: We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low‐risk IPI patients based on POLARIX/EPCORE DLBCL‐2 trial criteria.Results: We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN‐IPI assigned 33.3% and 11.9% of patients to the low‐risk group, respectively. Shorter 5‐year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low‐risk IPI group compared with low‐risk NCCN‐IPI group. Analyzed models failed to identify true high‐risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL‐2 trial eligibility criteria.Conclusion: True low‐risk patients are more optimal identified by NCCN‐IPI and should be excluded from front‐line clinical trials due to their excellent prognosis. However, additional high‐risk factors besides clinical prognostic models need to be considered when selecting trial‐eligible patients.

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.

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.

Diffuse large B-cell lymphoma is an aggressive disease occurring primarily in elderly patients. Despite high curative rates with doxorubicin-containing treatment, some elderly patients receive less intensive treatments, mainly due to advanced age, comorbidities, and concerns of cardiotoxicity from doxorubicin-containing regimens. We analyzed 1009 patients aged 75 years or older and 10,090 age- and sex-matched comparisons. We aimed to evaluate long-term cardiovascular side effects in elderly patients treated with doxorubicin. Approximately, 64% of patients received doxorubicin-containing treatment. These patients had a persistently increased risk of new-onset heart failure with a hazard ratio of 1.5 and 1.7 when conditioning on survival without heart failure to 6 and 24 months, respectively. Moreover, we observed an increased risk of venous thromboembolism during the first six months following the lymphoma diagnosis. On the contrary, no difference in risk of developing ischemic heart disease or stroke following doxorubicin-containing treatment was observed.

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0–90, 91–365, and +365-day survival. Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0–90 day period, but also up to one year after the diagnosis. For day 0–90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18–32 g/L) contributed to the worse prognosis. Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.