Intraarterial Chemotherapy for Brain Tumors by Using a Spatial Dose Fractionation Algorithm and Pulsatile Delivery

Gobin, Y. Pierre; Cloughesy, Timothy F.; Chow, Kira; Duckwiler, Gary; Sayre, James W.; Milanese, Karen; Viñuela, Fernando

doi:10.1148/radiology.218.3.r01mr41724

Cited by 63 publications

(64 citation statements)

References 26 publications

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“…5,10 In brief, chemotherapeutic agents included melphalan, 2.5-7.5 mg, carboplatin, 30 -50 mg, and topotecan, 0.15-0.5 mg. The highest dose of chemotherapy administered in a session to a single eye was melphalan, 7.5 mg, ϩ carboplatin, 50 mg, ϩ topotecan, 0.5 mg.…”

Section: Balloon-assisted Infusionmentioning

confidence: 99%

“…The highest dose of chemotherapy administered in a session to a single eye was melphalan, 7.5 mg, ϩ carboplatin, 50 mg, ϩ topotecan, 0.5 mg. Dosage, combination of chemotherapy administered, and number of treatment sessions were determined by age, individual angioanatomy 10 of the OA and its branches, patient weight, extent of disease (with particular attention to the extent of vitreous seeding), and clinical response to previous intra-arterial treatments. Following each intra-arterial treatment session, tumor regression pattern, decrease in tumor size, improvement of tumor seeding (either diminution or calcification), and resolution of retinal detachment were used as objective measures to determine the effectiveness of individual treatment sessions.…”

Section: Balloon-assisted Infusionmentioning

confidence: 99%

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Intra-Arterial Chemotherapy as a Treatment for Intraocular Retinoblastoma: Alternatives to Direct Ophthalmic Artery Catheterization

Klufas¹,

Gobin

Marr³

et al. 2012

AJNR Am J Neuroradiol

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Section: Balloon-assisted Infusionmentioning

confidence: 99%

Section: Balloon-assisted Infusionmentioning

confidence: 99%

Intra-Arterial Chemotherapy as a Treatment for Intraocular Retinoblastoma: Alternatives to Direct Ophthalmic Artery Catheterization

Klufas¹,

Gobin

Marr³

et al. 2012

AJNR Am J Neuroradiol

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“…Then, chemotherapy was infused through the microcatheter using a pulsatile injection technique to avoid streamlining and heterogeneous delivery. 9 …”

Section: The Siac Proceduresmentioning

confidence: 99%

Spinal intraarterial chemotherapy: interim results of a Phase I clinical trial

Patsalides

Yamada

Bilsky

et al. 2016

SPI

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OBJECT Despite advances in therapies using radiation oncology and spinal oncological surgery, there is a subgroup of patients with spinal metastases who suffer from progressive or recurrent epidural disease and remain at risk for neurological compromise. In this paper the authors describe their initial experience with a novel therapeutic approach that consists of intraarterial (IA) infusion of chemotherapy to treat progressive spinal metastatic disease. METHODS The main inclusion criterion was the presence of progressive, metastatic epidural disease to the spine causing spinal canal compromise in patients who were not candidates for the standard treatments of radiation therapy and/or surgery. All tumor histological types were eligible for this trial. Using the transfemoral arterial approach and standard neurointerventional techniques, all patients were treated with IA infusion of melphalan in the arteries supplying the epidural tumor. The protocol allowed for up to 3 procedures repeated at 3- to 6-week intervals. Outcome measures included physiological measures: 1) periprocedural complications according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events; and 2) MRI to assess for tumor response. RESULTS Nine patients with progressive spinal metastatic disease and cord compression were enrolled in a Phase I clinical trial of selective IA chemotherapy. All patients had metastatic disease from solid organs and were not candidates for further radiation therapy or surgery. A total of 19 spinal intraarterial chemotherapy (SIAC) procedures were performed, and the follow-up period ranged from 1 to 7 months (median 3 months). There was 1 serious adverse event (febrile neutropenia). Local tumor control was seen in 8 of 9 patients, whereas tumor progression at the treated level was seen in 1 patient. CONCLUSIONS These preliminary results support the hypothesis that SIAC is feasible and safe.

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“…10 Superselective intraarterial injection of 99m Tc-hexamethylpropyleneamine oxime (Ceretec) into human cerebral arteries achieves a concentration of radiotracer in brain tissue 50 times higher than with intravenous injection. 16 In clinical studies of cerebral chemotherapy, the concentration delivered to the tumor via intraarterial injection versus intravenous injection of chemotherapeutic agents was 5 times higher with hydrosoluble drugs and up to 50 times higher with liposoluble drugs.…”

Section: Intraarterial Deliverymentioning

confidence: 99%

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain

Dashti

Spalding

Kadner

et al. 2015

PED

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Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.

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Intraarterial Chemotherapy for Brain Tumors by Using a Spatial Dose Fractionation Algorithm and Pulsatile Delivery

Abstract: Neurotoxicity of intraarterial cerebral chemotherapy can be minimized by using pulsatile injection and the described spatial dose fractionation algorithm.

Cited by 63 publications

References 26 publications

Intra-Arterial Chemotherapy as a Treatment for Intraocular Retinoblastoma: Alternatives to Direct Ophthalmic Artery Catheterization

Intra-Arterial Chemotherapy as a Treatment for Intraocular Retinoblastoma: Alternatives to Direct Ophthalmic Artery Catheterization

Spinal intraarterial chemotherapy: interim results of a Phase I clinical trial

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain

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