Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma.
OBJECTIVE
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 IL1 3-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.
Parney
Ian F
IF
Department of Neurological Surgery, Brain Tumor Research Center, University of California at San Francisco, California 94143-0350, USA.
Kunwar
Sandeep
S
McDermott
Michael
M
Berger
Mitchel
M
Prados
Michael
M
Cha
Soonmee
S
Croteau
David
D
Puri
Raj K
RK
Chang
Susan M
SM
D036002:ADP Ribose Transferases / Q000008:administration & dosage*; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D002408:Catheters, Indwelling; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003937:Diagnosis, Differential; D018450:Disease Progression; D005098:Exotoxins / Q000008:administration & dosage*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D007260:Infusion Pumps; D036502:Infusions, Intralesional; D018793:Interleukin-13 / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D009460:Neurologic Examination / Q000187:drug effects; D011183:Postoperative Complications / Q000175:diagnosis; D011446:Prospective Studies; D037521:Virulence Factors / Q000008:administration & dosage*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018793:Interleukin-13; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A