EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi91-vi91
Author(s):  
Yeonju Kim ◽  
Terri Armstrong ◽  
Mark Gilbert ◽  
Orieta Celiku
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Tumor ◽  
Objective Response ◽  
Survival Rates ◽  
Maximum Tolerated Dose ◽  
Secondary Outcome ◽  
Patient Reported

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.

Treatment outcome of primary testicular non-Hodgkin’s lymphoma

2013 ◽  
Vol 154 (42) ◽  
pp. 1666-1673
Author(s):  
János László Iványi ◽  
Éva Marton ◽  
Márk Plander ◽  
Zoltán Vendel Engert ◽  
Csaba Tóth
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Treatment Outcome ◽  
Survival Rates ◽  
Testicular Lymphoma ◽  
Hodgkin's Lymphomas ◽  
Disease Free ◽  
Overall Survival Rates ◽  
Primary Testicular Lymphoma

Introduction: Primary testicular lymphoma constitutes a rare subgroup among extranodal non-Hodgkin’s lymphomas. Because of its aggressive clinical behaviour due to high grade histological features developing mainly in older population, patients with this disease usually have a poor prognosis. Orchidectomy followed by combination immunochemotherapy is a traditional treatment method with a rather inferior outcome. Aim: In this retrospective survey the authors analysed the clinical presentation, pathological features and treatment results of patients with primary testicular lymphoma diagnosed and treated in their haematology centre between 2000–2012 Method: During this period 334 patients with aggressive non-Hodgkin’s lymphomas were treated, of whom 8 patients (2.39%; age between 23 and 86 years; median, 60 years) underwent semicastration for primary testicular lymphoma (7 patients had diffuse, large B-cell lymphoma and one patient had Burkitt-like lymphoma). According to the Ann Arbor staging system a limited stage I-IIE was diagnosed in 7 patients and advanced stage was found in one patient. All but one patients were treated with rituximab added to CHOP regimen (6 or 8 cycles in every 21 or 28 days), whereas one patient received radiotherapy only. Central nervous system intrathecal prophylaxis was used in one case and no preventive irradiation of the contralateral testis was used. Results: With a median follow-up of 50 months complete remission was observed in 7 patients. However, two patients died (one due to progression and one in remission from pulmonary solid tumour). Complete remission rate proved to be 87.5%, disease-free survival was between 13 and 152 months (median 38 months) and overall survival rates were between 17 and 156 months (median 43 months). The 5-year disease-free and overall survival rates were 37.5 %. Conclusions: The relatively favourable treatment outcome could be mainly explained by the high number of patients with early-stage of the disease, early surgical removal of testicular lymphomas and the use if immunochemotherapy. This therapeutic regimen was effective to prevent localized and distant relapses. Despite omission of regular prophylaxis of the central nervous system, no relapse was detected. Orv. Hetil., 154 (42), 1666–1673.

scholarly journals Fotemustine-Based in Combination with Rituximab As First-Line Induction Chemotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma:a Prospective Phaseii Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Jingjing Wu ◽  
Fenghua Gao ◽  
Lei Zhang ◽  
Xin Li ◽  
Ling Li ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Objective Response ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival

Objective:To evaluate the safety, efficacy, and feasibility of rituximab, fotemustine, pemetrexed and dexamethasone (R-FPD) regimen for primary central nervous system lymphoma (PCNSL) patients. Methods:A prospective, single-center, single-arm, phase II clinical trial. Patients with newly diagnosed PCNSL diagnosed from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2020. R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100mg/m2 i.v. on D1) ,pemetrexed (600mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1).(NCT04083066) Results: 30 patients were included. After two cycles, the objective response rate(ORR) was 96.4%(27/28,26 PR,1 CR,0 SD,0 PD,2 Censored),the disease control rate(DCR) was 96.4%(27/28); After four cycles, the ORR was 71.4% (15/21, 5PR,10 CR,1SD,5PD,7NR,2 Censored),DCR was 76.2%(16/21). The median progression-free survival (PFS) was 20.3 months (95%CI:5.2--35.4),The median overall survival (OS) was 22.0 months (95%CI:16.1-27.9).The grade III-IV toxicities were mainly leukopenia(17.9%), thrombocypenia(25%) and anemia(10.7%). Conclusion: Fotemustine-based in combination with Rituximab chemotherapy can improve outcomes with the progress free survival and the overall survival benefits, as well as with better tolerability for newly diagnosed PCNSL patients. Keywords: rituximab; primary central nervous system lymphoma; pemetrexed; fotemustine; efficacy Disclosures No relevant conflicts of interest to declare.

scholarly journals Emerging Pharmacological Treatments for Cerebral Edema: Evidence from Clinical Studies

2020 ◽  
Vol 60 (1) ◽  
pp. 291-309 ◽  
Author(s):  
Jesse A. Stokum ◽  
Volodymyr Gerzanich ◽  
Kevin N. Sheth ◽  
W. Taylor Kimberly ◽  
J. Marc Simard
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Cerebral Edema ◽  
Clinical Studies ◽  
Central Nervous System Disease ◽  
Ancient Egypt ◽  
Nervous System Disease ◽  
Pharmacological Treatments ◽  
System Disease

Cerebral edema, a common and often fatal companion to most forms of acute central nervous system disease, has been recognized since the time of ancient Egypt. Unfortunately, our therapeutic armamentarium remains limited, in part due to historic limitations in our understanding of cerebral edema pathophysiology. Recent advancements have led to a number of clinical trials for novel therapeutics that could fundamentally alter the treatment of cerebral edema. In this review, we discuss these agents, their targets, and the data supporting their use, with a focus on agents that have progressed to clinical trials.

Motor deficits at presentation and predictors of overall survival in central nervous system lymphomas

2021 ◽  
Author(s):  
Yu Tung Lo ◽  
Ya Lyn Samantha Ang ◽  
Valerie Shiwen Yang ◽  
Dave Thevandiran Kanavathy ◽  
Sai Liang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Motor Deficits

scholarly journals EPID-18. TRENDS IN INCIDENCE AND SURVIVAL OF MALIGNANT PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS IN THE NETHERLANDS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii322-iii322
Author(s):  
Raoull Hoogendijk ◽  
Jasper van der Lugt ◽  
Dannis van Vuurden ◽  
Eelco Hoving ◽  
Leontien Kremer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
The Netherlands ◽  
Malignant Gliomas ◽  
Survival Rates ◽  
Tumor Patients ◽  
Netherlands Cancer Registry ◽  
Malignant Astrocytomas ◽  
Brainstem Tumors ◽  
The Impact

Abstract BACKGROUND Variation in survival of pediatric central nervous system (CNS) tumors is large between countries. Within Europe, the Netherlands had one of the worst reported survival rates of malignant CNS (mCNS) tumors during 2000–2007. METHODS Using the Netherlands Cancer Registry, we evaluated trends in incidence and survival of pediatric mCNS tumors (behavior /3, 5th digit in the morphology code) diagnosed between 1990–2017. RESULTS 839 newly-diagnosed mCNS tumor patients <18 years were registered between 1990–2017. Incidence of mCNS tumors remained stable (average incidence rate, 21.6 per million person-years). However, an increased incidence of malignant gliomas, NOS was found (Estimated Annual Percentage Change (EAPC) 11.6% p<0.001). This appears to be related to a registration shift between 1990–1999 and 2000–2009 as brainstem tumors increased (+25%, n=79) for astrocytomas and other gliomas but decreased (-31%, n=32) for unspecified intracranial and intraspinal neoplasms. Overall, 5-year observed survival (5Y-OS) of mCNS tumors increased from 51% in 1990–1999 to 61% in 2010–2017 (P-for-trend<0.001). This increase was not constant over time, as 5Y-OS for the period 2000–2009 was 47%. The only significant decrease in survival was found for malignant astrocytomas and other gliomas with a 5Y-OS of 56% in 1990–1999 decreasing to 48% in 2010–2017 (P-for-trend<0.001). CONCLUSION Between 1990–2017 incidence of mCNS tumors in the Netherlands remained stable and survival increased. However, a decrease in survival was seen for malignant astrocytomas and other gliomas, which is partially explained by the registration shift of brainstem tumors. The impact of this shift on survival for all mCNS tumors is subject to further research.

scholarly journals Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2934
Author(s):  
Sabine Seidel ◽  
Michelle Margold ◽  
Thomas Kowalski ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Prognostic Factors ◽  
Central Nervous System Lymphoma ◽  
Initial Response ◽  
Early Response ◽  
Multicenter Trial ◽  
High Dose ◽  
Therapeutic Trials

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

scholarly journals Convection-enhanced delivery to the central nervous system

2015 ◽  
Vol 122 (3) ◽  
pp. 697-706 ◽  
Author(s):  
Russell R. Lonser ◽  
Malisa Sarntinoranont ◽  
Paul F. Morrison ◽  
Edward H. Oldfield
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Convective Flow ◽  
Clinical Applications ◽  
Systemic Delivery ◽  
Convection Enhanced Delivery ◽  
The Central Nervous System ◽  
Real Time Tracking

Convection-enhanced delivery (CED) is a bulk flow–driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

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