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Older patients with glioblastoma appear to benefit more from treatment combining a shorter course (3 weeks rather than 6 weeks) of radiotherapy together with temozolomide than from radiotherapy alone. Glioblastoma is a fatal illness that is associated with a median survival of less than 2 years. Population studies of glioblastoma have shown that survival declines with increasing age, 1 , 2 and the incidence of glioblastoma is increasing, especially among the elderly. 3 Older patients have been underrepresented in most randomized trials, in which the average age of participants is approximately 55 years, as compared with the population-based median for patients with glioblastoma of 65 years of age. 2 In 2005, a phase 3 trial of radiotherapy alone (60 Gy over a period of 6 weeks) versus radiotherapy plus temozolomide showed longer survival . . .

Establishment of a detection platform for glioblastoma-dendritic cell (DC) vaccine preparation and to determine the efficacy of the vaccine in a clinical trial. Autologous glioblastoma-DC vaccine was prepared from a glioblast specimen procured from surgical resection. The specimen was used to enrich the vaccine with peripherally blood-derived DCs after heat-shock induced, glioblastoma apoptosis. The control group received conventional treatment of surgery and radio-chemotherapy post-operation. The therapeutic group received a combination of glioblastoma-DC vaccine and conventional therapy. A comparison of the functional immune parameters, including tumor control, rate live time, Karnofsky scores, and complications occurring in each group were observed and recorded. The proportions of peripheral CD3 + , CD3 + CD4 + , CD4 + /CD8 + , and NK cells were significantly higher after DC vaccination than the control group ( P  < 0.05). Serum levels of IL-2, IL-12, and IFN-γwere significantly higher after DC vaccination than in the control group ( P  < 0.05). Nine months after vaccination, tumor control rate is significantly improved in the DC group compared with the control group ( P  < 0.05); survival rate was significantly higher in DC group than in control group ( P  < 0.05) and the time to relapse was significantly longer in DC group than that in control group ( P  < 0.05). Karnofsky scores were better in DC vaccination group 6 and 9 months post-treatment compared with the control group ( P  < 0.05). The combination of glioma DC vaccine and radiotherapy/chemotherapy post-operatively enhances the immune function of patients, increases the tumor control rate, prolongs the survival time and relapse duration, improves the quality of life, and therefore provides a more effective intervention of treating glioblastoma.

High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age (<60 vs ≥60 years) and institution (Berlin vs Tübingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m 2) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m 2) on days 3–5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. 551 patients (median age 63 years, IQR 55–69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8–39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5–46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80–1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6–25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3–16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors. German Cancer Aid.

Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas, but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven. We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma. This open, randomised, phase 2 trial was undertaken in 24 centres in six countries. 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS, cranial nerves, or eyes, aged 18–75 years, and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were centrally randomly assigned by computer to receive four courses of either methotrexate 3·5 g/m 2 on day 1 (n=40) or methotrexate 3·5 g/m 2 on day 1 plus cytarabine 2 g/m 2 twice a day on days 2–3 (n=39). Both regimens were administered every 3 weeks and were followed by whole-brain irradiation. The primary endpoint was complete remission rate after chemotherapy. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00210314. All randomly assigned participants were analysed. After chemotherapy, seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission, with a complete remission rate of 18% (95% CI 6–30) and 46% (31–61), respectively, (p=0·006). Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response, with an overall response rate of 40% (25–55) and 69% (55–83), respectively, (p=0·009). Grade 3–4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects (three vs one). In patients aged 75 years and younger with primary CNS lymphoma, the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone. Swiss Cancer League.

Background Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children’s quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. Methods This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. Discussion This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. Trial registration This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Alectinib, a potent ALK tyrosine kinase inhibitor, was more effective and somewhat less toxic than crizotinib when used as primary therapy in patients with ALK -positive non–small-cell lung cancer. Importantly, it reduced the risk of CNS relapse.

Purpose Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. Methods PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. Results Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability ( p  = 0.02), while no significant differences were observed in radiological improvement/stability ( p  = 0.27) or steroid wean-off ( p  = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT ( p  = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). Conclusion Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

IntroductionTo assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients.MethodsIn the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable.ResultsIn univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01–1.08; OS 1.06 (95% CI 1.02–1.10) and as categorical variable HR (< 27 versus ≥ 27 for PFS 1.55 (1.02–2.35); OS 1.68 (1.05–2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value.ConclusionNeurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old.

Primary central nervous system lymphoma (PCNSL) is a diffuse large B cell lymphoma in which the brain, spinal cord, leptomeninges and/or eyes are exclusive sites of disease. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Other factors such as T cells, macrophages or microglia, endothelial cells, chemokines, and interleukins, probably also have important roles. Clinical presentation varies depending on the involved regions of the CNS. Standard of care includes methotrexate-based polychemotherapy followed by age-tailored thiotepa-based conditioned autologous stem cell transplantation and, in patients unsuitable for such treatment, consolidation with whole-brain radiotherapy or single-drug maintenance. Personalized treatment, primary radiotherapy and only supportive care should be considered in unfit, frail patients. Despite available treatments, 15–25% of patients do not respond to chemotherapy and 25–50% relapse after initial response. Relapse rates are higher in older patients, although the prognosis of patients experiencing relapse is poor independent of age. Further research is needed to identify diagnostic biomarkers, treatments with higher efficacy and less neurotoxicity, strategies to improve the penetration of drugs into the CNS, and roles of other therapies such as immunotherapies and adoptive cell therapies. This Primer summarizes the epidemiology, pathophysiology, diagnosis and treatment of primary central nervous system lymphoma. This Primer also reviews future research avenues and the effect that this disorder has on the quality of life of patients.

Background Chimeric antigen receptor T-cell (CAR-T) therapy is gradually reshaping the treatment paradigm for patients with central nervous system lymphoma (CNSL). However, the duration of remission (DOR) has remained the major challenge in existing studies. This study aimed to provide real-world long-term follow-up data on CAR-T therapy in CNSL patients and primarily investigate the impact of maintenance therapy on prolonging DOR. Methods This study evaluated the efficacy and safety of CAR-T therapy in 22 patients with CNSL, including 5 with primary CNSL and 17 with secondary CNSL (2025004, retrospectively registered). Maintenance therapy with programmed cell death protein-1 inhibitor (PD-1i) and Bruton’s tyrosine kinase inhibitor (BTKi) was initiated in responding patients, while subgroup analysis comparing maintenance versus non-maintenance was restricted to those who achieved complete remission after CAR-T therapy. Results The best overall remission rate was 90.9%, with the best complete remission rate of 68.2%. With a median follow-up of 20.7 months (range, 3.1–88.9 months), the estimated 2-year progression-free survival and overall survival rates were 59.1% and 71.6%, respectively. No patient suffered severe immune effector cell-associated neurotoxicity syndrome, and only 3 patients experienced severe cytokine release syndrome. Patients who underwent PD-1i and BTKi maintenance achieved a 2-year DOR rate of 100%, which was significantly superior to those without maintenance therapy (Log-rank, P  = 0.04). Conclusion Our findings suggested the promising efficacy and manageable toxicities of CAR-T therapy in patients with CNSL. This study preliminarily proposed the concept that maintenance therapy may improve the DOR after CAR-T therapy.