Convection enhanced delivery for the treatment of malignant gliomas: symposium review

2005 ◽  
Vol 73 (1) ◽  
pp. 57-69 ◽  
Author(s):  
Michael A. Vogelbaum
Keyword(s):  
Malignant Gliomas ◽  
Convection Enhanced Delivery ◽  
Symposium Review

Current strategies for the treatment of malignant gliomas – experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw

2020 ◽  
Vol 92 (4) ◽  
pp. 1-5
Author(s):  
Grzegorz Turek ◽  
Tomasz Pasterski ◽  
Krzysztof Bankiewicz ◽  
Sebastian Dzierzęcki ◽  
Mirosław Ząbek
Keyword(s):  
Brain Tumors ◽  
San Francisco ◽  
Malignant Gliomas ◽  
High Grade ◽  
Current Standard ◽  
Convection Enhanced Delivery ◽  
Surgical Methods ◽  
High Grade Gliomas ◽  
Standard Medical Treatment ◽  
Intraoperative Electrical Stimulation

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. Material and methods: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management – from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. Results: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. Discussion: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

scholarly journals Neurocognitive functioning and quality of life in patients with recurrent malignant gliomas treated on a phase Ib trial evaluating topotecan by convection-enhanced delivery

2014 ◽  
Vol 1 (3) ◽  
pp. 94-100 ◽  
Author(s):  
Jennifer A. Oberg ◽  
Amie N. Dave ◽  
Jeffrey N. Bruce ◽  
Stephen A. Sands
Keyword(s):  
Quality Of Life ◽  
Disease Progression ◽  
Malignant Gliomas ◽  
Reliable Change Index ◽  
Response To Treatment ◽  
Neurocognitive Functioning ◽  
Convection Enhanced Delivery ◽  
Phase Ib ◽  
The Impact

Abstract Background Malignant gliomas are highly proliferative, invasive tumors that are resistant to conventional treatment, and disease progression is often accompanied by physical and mental debilitation. Neurocognitive functioning (NCF) and quality of life (QoL) were evaluated as part of a prospective phase Ib dose-escalation study of topotecan by convection-enhanced delivery (CED) for adult patients with recurrent malignant gliomas. Methods Sixteen patients were enrolled, and NCF and QoL were evaluated using the Cognitive Stability Index and SF-36 at baseline and monthly for 4 months post treatment. Descriptive analyses included the reliable change index for serial evaluations and correlations for associations between outcome variables and age, tumor volume, total topotecan dose, and treatment effect. Results Individual classifications of response to treatment indicated that a majority of patients reported stable scores over the follow-up period. Demographic and treatment-related variables were not associated with outcomes. Baseline processing speed scores were invalid for 6 subjects. Higher rates of valid scores were observed on subsequent administrations. Conclusions As the first study to use CED of any kind to evaluate the impact of CED on NCF or QoL, there was no evidence of severe detriment to either outcome. Long-term evaluation is necessary to track changes in NCF and QoL related to disease progression. Invalid scores suggest that computer-based assessments may not be suitable for all patients with malignant gliomas, especially those with cognitive deficits secondary to their disease. Future trials should include a wider range of sensitive measures to assess the impact of CED on patient NCF and QoL.

EFFECTS OF DRUG EFFLUX ON CONVECTION-ENHANCED PACLITAXEL DELIVERY TO MALIGNANT GLIOMAS

Neurosurgery ◽  
2007 ◽  
Vol 61 (4) ◽  
pp. E880-E882 ◽  
Author(s):  
Philipp G. Tanner ◽  
Markus Holtmannspötter ◽  
Jörg-Christian Tonn ◽  
Roland Goldbrunner
Keyword(s):  
Malignant Gliomas ◽  
Volume Of Distribution ◽  
Burr Hole ◽  
Neurological Deficits ◽  
Drug Efflux ◽  
Tumor Treatment ◽  
Convection Enhanced Delivery ◽  
Group 3 ◽  
Group 2 ◽  
And Diffusion

Abstract OBJECTIVE Convection-enhanced delivery (CED) is an approach in local brain tumor treatment. The spread of infusate in CED can be thought of as involving three phases: backflow, convection, and diffusion. Uncontrolled backflow may lead to efflux of the infusate outside the cranium. METHODS Based on an interim analysis of a clinical trial, the effects of drug efflux on convection were assessed. In a Phase I/II trial, eight patients with recurrent glioblastomas were treated with CED of paclitaxel. The first group of patients was treated with paclitaxel at a concentration of 0.5 mg/ml according to previously approved protocols. RESULTS These Group 1 patients developed severe skin necrosis due to an efflux of paclitaxel out of the cranium. The average volume of distribution (Vd) in these patients was 12.8 cm3. To prevent paclitaxel efflux, the burr hole was sealed with bone wax during and after CED in Groups 2 and 3. Surprisingly, patients in Group 2 showed a larger Vd (22.9 cm3 per catheter), exceeding the boundaries of the previous tumor, which led to subsequent neurological deficits. To allow a large Vd without severe side effects, the infusion volume was maintained, but the concentration of paclitaxel was reduced (paclitaxel concentration in Group 3, 0.25 mg/ml). CONCLUSION Vd remained high and no adverse effects were seen in Group 3. Sealing the burr hole during CED prevented efflux. The simple measure of sealing seems to increase Vd. These data demonstrate that uncontrolled backflow may have an important impact on CED and must be avoided.

scholarly journals P08.12 Tolerability and initial efficacy of convection-enhanced delivery of combinatorial IL-13RA2 and EphA2 targeted cytotoxins to dogs with spontaneous intracranial malignant gliomas

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii56-iii56 ◽  
Author(s):  
J. H. Rossmeisl ◽  
D. Herpai ◽  
J. L. Robertson ◽  
P. J. Dickinson ◽  
S. B. Tatter ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Convection Enhanced Delivery

scholarly journals STMO-04 LOCAL CONVECTION-ENHANCED DELIVERY OF CHEMOTHERAPY AS TREATMENT FOR BRAIN TUMORS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
Ryuta Saito ◽  
Masayuki Kanamori ◽  
Teiji Tominaga
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Malignant Glioma ◽  
Malignant Gliomas ◽  
Recurrent Malignant Glioma ◽  
Local Chemotherapy ◽  
Open Label ◽  
Convection Enhanced Delivery ◽  
Delivery Technique ◽  
Nimustine Hydrochloride

Abstract BACKGROUND Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last 2 decades. Applying this technique to treat brain tumors, we have been working to develop novel local chemotherapy against brain tumors. In the meanwhile, clinical trial against diffuse intrinsic brain tumor aiming at Japanese “shonin” approval is recruiting patients. In this study, potential of local CED based chemotherapy against supratentorial brain tumor is discussed. METHODS Until today, we have evaluated the safety and efficacy of local CED of nimustine hydrochloride against supratentorial malignant glioma patients in the three prospective, single institute, nonrandomized, open-label studies. Among those, one study recruited the recurrent malignant glioma patients whose enhanced tumor can be surgically resected. After the resection of the tumor, CED of ACNU was performed targeting the surrounding brain. Temozolomide was also given for 5 days during this trial. RESULTS Seven patients; 4 male and 3 female, age 33–71 y.o. (median 54 y.o.), were treated in this study. Five patients suffered glioblastoma and two suffered anaplastic astrocytoma. After the treatment, all seven patients lived longer than a year; one survived three years, one survived four and a half years, and one with glioblastoma is still alive after 5 years. DISCUSSION Potential efficacy of local chemotherapy delivering nimustine hydrochloride with CED against recurrent malignant glioma was suggested. Further study is required to pave the way for this strategy against supratentorial malignant gliomas.

CONVECTION-ENHANCED DELIVERY OF CINTREDEKIN BESUDOTOX (INTERLEUKIN-13-PE38QQR) FOLLOWED BY RADIATION THERAPY WITH AND WITHOUT TEMOZOLOMIDE IN NEWLY DIAGNOSED MALIGNANT GLIOMAS

Neurosurgery ◽  
2007 ◽  
Vol 61 (5) ◽  
pp. 1031-1038 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
John H. Sampson ◽  
Sandeep Kunwar ◽  
Susan M. Chang ◽  
Mark Shaffrey ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Gliomas ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Beam Radiation ◽  
Interleukin 13 ◽  
Grade 3 ◽  
Dose Limiting Toxicity ◽  
Final Cohort

Abstract OBJECTIVE Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13Rα2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 μg/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940–6100 cGy, 5 d/wk for 6–7 wk) with or without temozolomide (75 mg/m2/d, 7 d/wk during EBRT). Safety was assessed during an 11-week observation period after catheter placement RESULTS Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 μg/mL CB + EBRT [n = 3] and 0.25 μg/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 μg/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 μg/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION CB (0.5 μg/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted.

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