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Simple Summary: Central nervous system lymphoma is a rarity among brain tumours. The clinical course depends on location and size of the tumour. Various established treatments, including chemotherapy, radiation, and stem cell transplantation, are available. The resection of intracranial lesions is still under discussion. In our retrospective analysis, we were able to show that compared to the sole confirmation of diagnosis through stereotactic biopsy, the resection of the lesion offered a significant advantage in patient survival. Especially for singular, easily accessible lesions, resection in addition to radiotherapy/chemotherapy could have a benefit. Our findings substantiate earlier research outcomes and shall lay the foundation for forthcoming prospective investigations. Background: Central nervous system lymphoma (CNSL) is rare form of brain tumour. It manifests either as primary CNS lymphoma (pCNSL) originating within the central nervous system or as secondary CNS lymphoma (sCNSL), arising as cerebral metastases of systemic lymphoma. For a significant period, surgical resection was considered obsolete due to the favourable response to chemotherapy and the associated risk of postoperative deficits. The objective of the present study was to demonstrate the benefits of resection in CNSL patients, including extended survival and improved postoperative function. Methods: A retrospective study involving patients diagnosed with either PCNSL or SCNSL that were surgically approached at our neurosurgical department between 2010 and 2022 was conducted. Patients were categorised into three subgroups based on their neurosurgical approach: (1) stereotactical biopsy, (2) open biopsy, (3) resection. We then performed statistical analyses to assess overall survival (OS) and progression-free survival (PFS). Additionally, we examined various secondary factors such as functional outcome via Karnofsky Performance Index (KPS) and prognosis scoring. Results: 157 patients diagnosed with PCNSL or SCNSL were enclosed in the study. Of these, 101 underwent stereotactic biopsy, 21 had open biopsy, and 35 underwent resection. Mean age of the cohort was 64.94 years, with majority of patients being female (54.1%). The resection group showed longest OS at 44 months (open biopsy = 13 months, stereotactic biopsy = 9 months). Calculated median follow-up was 34.5 months. In the Cox regression model, postoperative KPS 70% (p < 0.001) and resection vs. stereotactic biopsy (p = 0.040) were identified as protective factors, whereas older age at diagnosis was identified as a risk factor (p < 0.001). In the one-way analysis of variance, differences in postoperative KPS were found among all groups (p = 0.021), while there was no difference in preoperative KPS among the groups. Conclusions: Our data show a favourable outcome when resection is compared to either stereotactic or open biopsy. Additionally, the marginally improved postoperative functional status observed in patients who underwent resection, as opposed to in those who underwent biopsy, provides further evidence in favour of the advantages of surgical resection for enhancing neurological deficits. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary central nervous system (CNS) lymphoma (PCNSL), arising and remaining localized in the CNS, required the development of peculiar therapeutic strategies that deviate from those applied in systemic diffuse large B-cell lymphoma. To date, the optimal treatment approach for PCNSL consists in induction and consolidation/maintenance phases. Consolidation therapy with high-dose chemotherapy, followed by autologous stem-cell transplantation (HDC/ASCT), has demonstrated to be effective and safe in untreated and relapsed/refractory fit PCNSL patients; furthermore, it provides the preservation or improvement of cognitive function. This review offers scope to an overview of the experiences of HDC/ASCT as consolidation therapy in PCNSL patients, highlighting how conditioning regimens have changed over time. The progressive knowledge of CNS bio-availability of the single chemotherapy agents as well as of their efficacy and safety when used in different combinations has permitted to optimize the conditioning regimens with the unquestionable improvement of the outcome of the transplanted patients. Background: Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and represented the gold standard for many years, but at the expense of a high risk of neurotoxicity. Thus, alternative strategies are being investigated in order to improve disease outcomes and to spare the neurocognitive side effects due to WBRT. Methods: We reviewed published studies on PCNSL patients treated with HDC/ASCT, focusing on the efficacy and safety of the conditioning regimens. Prospective and retrospective studies, published in the English language from 1992 to 2022, in high-quality international journals were identified in PubMed. Results: Consolidation with HDC containing highly CNS-penetrating agents (thiotepa, busulfan or BCNU) followed by ASCT provided long-term disease control and survival in PCNSL patients. Two prospective randomized studies, comparing HDC/ASCT versus WBRT, reported similar progression-free survival (PFS) and similar results on the decline in neurocognitive functions in a substantial proportion of patients after WBRT but not after HDC-ASCT. A recent randomized study comparing HDC/ASCT versus non-myeloablative consolidation reported a longer PFS in transplanted patients. Conclusion: ASCT conditioned with regimens, including highly CNS-penetrating agents, represents, to date, the best choice among the available consolidation strategies for fit newly diagnosed PCNSL patients. [ABSTRACT FROM AUTHOR]

Simple Summary: We present a review of the most relevant epidemiological, diagnostic and therapeutic aspects of primary central nervous system lymphoma (PCNSL) in elderly patients. The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary central nervous system lymphoma is a rare disease with limited therapeutic options. A more profound understanding of the molecular mechanisms that underlie this disease has fostered the development of novel therapeutic approaches. Key developments for the treatment of primary central nervous system lymphoma were made in the field of small molecule inhibitors, i.e., drugs that were designed to specifically target the molecular backbone of cancer. Prominent examples include inhibitors of Bruton's tyrosine kinase or mammalian target of rapamycin, as well as immune modulatory thalidomide analogues. Along the same lines, another major strain of drug development for primary central nervous system lymphoma comprises of immune checkpoint inhibitors, i.e., monoclonal antibodies designed to unleash anti-cancer immune reactions. This review article discusses these ongoing clinical developments, including biological rationale as well as preliminary toxicity and efficacy, and provides an outlook for future developments. This review article outlines the current development of emerging treatment strategies for primary central nervous system lymphoma, a rare brain tumor with, thus far, limited therapeutic options. Small molecule targeted tyrosine kinase inhibitors, immunomodulatory agents, and immune checkpoint inhibitors will be discussed. The mechanisms of action, results of completed clinical studies, ongoing clinical trials, and future perspectives are summarized. Among the most promising clinical developments in the field of CNS lymphomas is ibrutinib, an inhibitor of Bruton's tyrosine kinase, which relays activation of nuclear factor kappa B upon integration of constitutive B cell receptor and Toll-like receptor signals. Down-stream of nuclear factor kappa B, the thalidomide analogs lenalidomide and pomalidomide exert immunomodulatory functions and are currently explored against CNS lymphomas. Finally, immune checkpoint inhibitors, such as drugs targeting the PD-1 pathway, may become novel therapeutic options to unleash anti-tumor immunity in patients with primary CNS lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: First line whole brain radiotherapy (WBRT) alone is a palliative treatment for patients with primary CNS lymphoma (PCNSL) not suitable for intensive multimodal therapy. Consolidating WBRT after chemotherapy with high-dose methotrexate WBRT has activity comparable to autologous stem cell transplantation (ASCT). However, dose-dependent toxicity of WBRT is a relevant limiting factor. With standard dose, WBRT rates of neuro-cognitive decline are high and should be taken into account. As an alternative, after complete response (CR) low-dose consolidating WBRT carries a lower risk for neurotoxicity and is a treatment option in patients not suitable for ASCT. For patients not achieving CR, the best combined treatment potentially involving focal radiotherapy remains to be determined. Background: Primary CNS Lymphoma is a rare and severe but potentially curable disease. In the last thirty years treatment has changed significantly. Survival times increased due to high-dose methotrexate-based chemotherapy. With intensive regimens involving autologous stem cell transplantation (ASCT), 4-year survival rates of more than 80% can be reached. However, this treatment regimen is not feasible in all patients, and is associated with some mortality. Methods: In this review, current evidence regarding the efficacy and toxicity of radiotherapy in PCNSL shall be summarized and discussed mainly based on data of controlled trials. Results: Being the first feasible treatment whole brain radiotherapy (WBRT) was initially used alone, and later as a consolidating treatment after high-dose methotrexate-based chemotherapy. More recently, concerns regarding activity and neurotoxicity of standard dose WBRT limited its use. On the contrary, latest evidence of some phase II trials suggests efficacy of consolidating WBRT is comparable to ASCT. After complete remission reduced dose WBRT appears as a feasible concept with decreased neurotoxicity. Evidence for use of local stereotactic radiotherapy is very limited. Conclusion: Radiotherapy has a role in the treatment of PCNSL patients not suitable to ASCT, e.g., as consolidating reduced dose WBRT after complete response. Local stereotactic radiotherapy for residual disease should be examined in future trials. [ABSTRACT FROM AUTHOR]