title: MRI as a central component of clinical trials analysis in brainstem glioma: a report from the Pediatric Brain Tumor Consortium (PBTC).
abstract: We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression. Reduced tumor volume (P < .0001) and tumor diffusion values (P <.0001) were apparent on the first post-RT/drug studies. Decreases in tumor volume correlated with pre-RT volume (P < .0001) and pre-RT diffusion values (P < .0001); larger decreases were noted for tumors with higher volumes and diffusion values. Patients with larger pre-RT tumors had longer progression-free survival (P < .0001). Patients with ≥ 25% decrease in tumor volume and diffusion values after RT had longer progression-free survival (P = .028) and overall survival (P = .0009). Enhancement at baseline and over time was significantly associated with shorter survival. Tumor diffusion values with baseline enhancement were significantly lower than those without (P = .0002). RT of BSG is associated with decreased tumor volume and intralesional diffusion values; patients with ≥ 25% decrease in values post-RT had relatively longer survival intervals, apparently providing an early imaging-based surrogate for relative outcomes. Patients with larger tumors and greater decreases in tumor volume and diffusion values had longer survival intervals. Tumor enhancement was associated with shorter survival, lower tumor diffusion values (increased cellularity), and a smaller drop in diffusion values after RT (P = .006). These associations justify continued investigation in other large clinical trials of brainstem glioma patients.
authors.affiliation: Department of Radiology, Children's Hospital Boston, Boston, MA 02115, USA. tina.poussaint@childrens.harvard.edu
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Sridhar
authors.initials: S
authors.lastname: Vajapeyam
authors.forename: Roger I
authors.initials: RI
authors.lastname: Packer
authors.forename: Richard L
authors.initials: RL
authors.lastname: Robertson
authors.forename: Russell
authors.initials: R
authors.lastname: Geyer
authors.forename: Daphne
authors.initials: D
authors.lastname: Haas-Kogan
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmerman
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Patay
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004058:Diffusion; D005260:Female; D000077156:Gefitinib; D005910:Glioma / Q000175:diagnosis* / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011799:Quinazolines / Q000008:administration & dosage; D015363:Quinolones / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D012107:Research Design; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D015363:Quinolones; C402769:tipifarnib; D000077156:Gefitinib