OBJECTIVE: To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment. METHODS: This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions. RESULTS: MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area. CONCLUSIONS Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.
Humans ; Lymphoma/radiotherapy* ; Central Nervous System Neoplasms/pathology* ; Retrospective Studies ; Prospective Studies ; Neoplasm Recurrence, Local/drug therapy* ; Combined Modality Therapy ; Brain/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Methotrexate

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System

OBJECTIVE: To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL). METHODS: Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m RESULTS: There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed. CONCLUSION The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.
Antineoplastic Combined Chemotherapy Protocols ; Central Nervous System ; Central Nervous System Neoplasms/drug therapy* ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Methotrexate/therapeutic use* ; Retrospective Studies ; Rituximab/therapeutic use* ; Temozolomide/therapeutic use* ; Treatment Outcome

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma outside the lymph nodes. At present, high-dose chemotherapy based on methotrexate is the standard induction therapy for newly diagnosed PCNSL, but the effective therapy of relapse/refractory and elderly PCNSL is still unclear. With the progress of clinical trials, new drugs and combined treatment method appear constantly, such as rituximab and ibrutinib, the remission rate of refractory and relapsed patients increased, while lenalidomide showed a good activity in the maintenance treatment of elderly patients. This review summarized briefly the recent advances of research on immunocheckpoint inhibitors, immunoregulatory agents, bruton tyrosine kinase (BTK) and PI3K/AKT/mTOR pathway inhibitors.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Central Nervous System ; Central Nervous System Neoplasms/drug therapy* ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local ; Phosphatidylinositol 3-Kinases

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult ; Astrocytoma ; Brain ; Brain Neoplasms ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Lomustine ; Oligodendroglioma ; Radiotherapy ; World Health Organization

Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Dexamethasone/therapeutic use* ; Humans ; Lenalidomide/therapeutic use* ; Lymphoma/drug therapy* ; Neoplasm Recurrence, Local ; Rituximab/therapeutic use* ; Treatment Outcome

PURPOSE: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). METHODS: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). RESULTS: The median follow-up duration was 84 (range, 8–171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076–4.746; p = 0.031). CONCLUSION: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.
Brain ; Breast Neoplasms ; Breast ; Central Nervous System Neoplasms ; Central Nervous System ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Mastectomy ; Multivariate Analysis ; Neoplasm Metastasis ; Quality of Life ; Radiation Oncology ; Radiotherapy ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Survival Rate ; Trastuzumab

In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma. The recent literature in pediatric neuro-oncology was reviewed, and a summary of the major findings are presented. Meaningful sub-classifications of these tumors have arisen, placing children into discrete categories of disease with requirements for targeted therapy. While the mainstay of therapy these past 30 years has been a combination of central nervous system irradiation and conventional chemotherapy, now with the advent of high resolution genetic mapping, targeted therapies have emerged, and less emphasis is being placed on craniospinal irradiation. In this article, the present and future perspective of pediatric brain malignancy are reviewed in detail. The progress that has been made offers significant hope for the future for patients with these tumours.
Adult ; Biology ; Brain Neoplasms ; Brain ; Central Nervous System ; Child ; Classification ; Craniospinal Irradiation ; Drug Therapy ; Ependymoma ; Glioma ; Hope ; Humans ; Medulloblastoma ; Molecular Biology

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ≤1 year of age and represent approximately 1–2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.
Brain ; Brain Neoplasms ; Central Nervous System ; Child ; Chromatin Assembly and Disassembly ; Drug Therapy ; Epigenomics ; Humans ; Phosphotransferases ; Protein-Tyrosine Kinases ; Radiotherapy ; Stem Cells ; Tyrosine

5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy.
Ammonia ; Brain Diseases, Metabolic ; Central Nervous System ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; Drug Therapy* ; Fluorouracil* ; Humans ; Hyperammonemia ; Leucovorin ; Neutropenia ; Thrombocytopenia