Showing papers by "Jacoline E C Bromberg published in 2022"

European Association of Neuro-Oncology (EANO) Guidelines for Treatment of Primary Central Nervous System lymphoma (PCNSL).

Abstract: The management of primary central nervous system (PCNSL) is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the limited number of controlled studies available. In 2021, given recent advances and publication of practice-changing randomised trials, the European Association of Neuro-Oncology (EANO) created a multidisciplinary task force to update the previously published evidence-based guidelines for immunocompetent adult patients with PCNSL and added a section on immunosuppressed patients. The guideline provides consensus considerations and recommendations for treatment of PCNSL, including intraocular manifestations and specific management of elderly . The main changes from the previous guideline include strenghtened evidence for the consolidation with ASCT in first-line treatment, prospectively assessed chemotherapy combinations for both young and elderly patients, clarification of the role of rituximab even though the data remain inconclusive, of the role of new agents, and the incorporation of immunosuppressed patients and primary ocular lymphoma. The guideline should aid the clinicians in everyday practice and decision making and serve as a basis for future research in the field.

Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma

Abstract: To understand the clinical significance of the tumor microenvironment (TME), it is essential to study the interactions between malignant and non-malignant cells in clinical specimens. Here, we established a computational framework for a multiplex imaging system to comprehensively characterize spatial contexts of the TME at multiple scales, including close and long-distance spatial interactions between cell type pairs. We applied this framework to a total of 1,393 multiplex imaging data newly generated from 88 primary central nervous system lymphomas with complete follow-up data and identified significant prognostic subgroups mainly shaped by the spatial context. A supervised analysis confirmed a significant contribution of spatial context in predicting patient survival. In particular, we found an opposite prognostic value of macrophage infiltration depending on its proximity to specific cell types. Altogether, we provide a comprehensive framework to analyze spatial cellular interaction that can be broadly applied to other technologies and tumor contexts.

Rare central nervous system tumors in adults: a population-based study of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors

Abstract: Abstract Background Ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors occur relative frequently in children, but are rare central nervous system (CNS) tumors in adults. In this population-based survey, we established incidence, treatment, and survival patterns for these tumors diagnosed in adult patients (≥18 years) over a 30-year period (1989–2018). Methods Data on 1384 ependymomas, 454 pilocytic astrocytomas, 205 medulloblastomas, and 112 intracranial germ cell tumors were obtained from the Netherlands Cancer Registry (NCR) on the basis of a histopathological diagnosis. For each tumor type, age-standardized incidence rates and estimated annual percentage change were calculated. Trends in incidence and main treatment modalities were reported per 5-year periods. Overall survival was calculated using the Kaplan–Meier method, and relative survival rates were estimated using the Pohar-Perme estimator. Results Incidence and survival rates remained generally stable for pilocytic astrocytomas, medulloblastomas, and germ cell tumors. Increasing incidence was observed for spinal ependymomas, mostly for myxopapillary ependymomas, and survival improved over time for grade II ependymomas (P < .01). Treatment patterns varied over time with shifting roles for surgery in ependymomas and for chemotherapy and radiation in medulloblastomas and germinomas. Conclusions The study provides baseline information for highly needed national and international standard treatment protocols, and thus for further improving patient outcomes in these rare CNS tumors.

OS03.6.A Rituximab in primary CNS lymphoma - long term follow-up of the phase III HOVON 105/ALLG NHL 24 Study

Abstract: The efficacy of rituximab in Primary CNS Lymphoma (PCNSL) is still under debate. We performed an international randomized phase III study to investigate the efficacy of rituximab when added to methotrexate, BCNU, teniposide and prednisolone (MBVP) in PCNSL. The primary endpoint, event-free survival (EFS) at one year, was similar in both treatment groups and was previously reported (Bromberg et al, Lancet Oncology 2019; 20: 216-228). Here we present long-term follow up results after a median follow-up of 82 months. between August 2010 and May 2016 200 newly-diagnosed, non-immunocompromised patients with PCNSL aged 18-70 years and WHO performance status 0-3 were randomized between treatment with MBVP chemotherapy with (arm B) or without (arm A) rituximab. The rituximab was given weekly in the first MBVP cycle, fortnightly in the second (in total 6 rituximab administrations). Responsive patients received consolidation with high-dose cytarabine, and patients aged ≤ 60 were subsequently treated with low-dose WBRT if in CR/CRu; in case of PR with an additional boost on the tumor. Patients > 60 were not irradiated. All patients gave written informed consent. The modified intention-to-treat (m-ITT) population consisted of 199 eligible patients, 55% were men. The median age was 61 yrs (range 26-70), the median WHO performance status 1 (range 0-3). The primary endpoint EFS at one year was 49% (95% CI 39-58)(MBVP) vs 55% (95% CI 44-64) (R-MBVP). The EFS at 5 years was 25% (17-34) vs 36% (27-46) respectively, hazard ratio (HR) 0.85, 95% CI 0.61-1.18, p=0.33 (adjusted for age and WHO performance status). The progression-free survival (PFS) at one and 5 years were 58% (47-67) and 29% (21-39) (MBVP) and 65% (54-73) and 43% (33-53) (R-MBVP) ) (HR 0.73, 95% CI 0.52-1.02, p=0.07). 80 patients were still alive. Overall survival (OS) at 5 years for MBVP and R-MBVP was 49% (39-59) and 53% (43-63) respectively. A total of 111 patients had progression or relapse, 63 after MBVP and 48 after R-MBVP. 79% of these patients received further treatment. The median OS after progression/relapse was 9.7 months (5.9-19.9) in the MBVP arm, and 6.1 months (2.4-13.1) in the R-MBVP arm (HR 1.25, 95% CI 0.83-1.87, p=0.29). 119 patients died, 64 in the MBVP arm and 55 in the R-MBVP arm. Causes of death were PCNSL in 69% of the patients (both arms), complication of treatment (6% vs 5%), secondary malignancy (5% vs 2%) and other or unknown causes (20% vs 24%). Age was the strongest prognostic factor for EFS, PFS and OS in multivariate analysis. in the modified-ITT population we found no statistically significant benefit of the addition of rituximab to MBVP on EFS, PFS and OS in patients with PCNSL, even after a long follow-up of median 82 months. Therefore, the results of this study do not support the use of rituximab with MBVP in the treatment of primary CNS lymphoma.