Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma

Ian F Parney, Sandeep Kunwar, Michael McDermott, Mitchel Berger, Michael Prados, Soonmee Cha, David Croteau, Raj K. Puri, Susan M. Chang

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13-PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

Original languageEnglish (US)
Pages (from-to)267-275
Number of pages9
JournalJournal of Neurosurgery
Volume102
Issue number2
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

Convection
Interleukin-13
Cytotoxins
Glioma
Magnetic Resonance Imaging
Neoplasms
Magnetic Resonance Spectroscopy
Catheters
Research Personnel
Therapeutics
Exotoxins
Pseudomonas
Pseudomonas aeruginosa toxA protein
Neuroimaging
Brain Neoplasms
Biomarkers
Communication

Keywords

  • Convection-enhanced delivery
  • Glioma
  • Interleukin-13
  • Magnetic resonance imaging
  • Pseudomonas exotoxin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma. / Parney, Ian F; Kunwar, Sandeep; McDermott, Michael; Berger, Mitchel; Prados, Michael; Cha, Soonmee; Croteau, David; Puri, Raj K.; Chang, Susan M.

In: Journal of Neurosurgery, Vol. 102, No. 2, 02.2005, p. 267-275.

Research output: Contribution to journalArticle

Parney, IF, Kunwar, S, McDermott, M, Berger, M, Prados, M, Cha, S, Croteau, D, Puri, RK & Chang, SM 2005, 'Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma', Journal of Neurosurgery, vol. 102, no. 2, pp. 267-275.
Parney, Ian F ; Kunwar, Sandeep ; McDermott, Michael ; Berger, Mitchel ; Prados, Michael ; Cha, Soonmee ; Croteau, David ; Puri, Raj K. ; Chang, Susan M. / Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma. In: Journal of Neurosurgery. 2005 ; Vol. 102, No. 2. pp. 267-275.
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abstract = "Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13-PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.",
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AU - Parney, Ian F

AU - Kunwar, Sandeep

AU - McDermott, Michael

AU - Berger, Mitchel

AU - Prados, Michael

AU - Cha, Soonmee

AU - Croteau, David

AU - Puri, Raj K.

AU - Chang, Susan M.

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N2 - Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13-PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

AB - Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13-PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.

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