Tina Young Poussaint MD, Presenter: Nothing to Disclose

Mehmet Kocak PhD, Abstract Co-Author: Nothing to Disclose

Sridhar Vajapeyam PhD, Abstract Co-Author: Nothing to Disclose

Richard L. Robertson MD, Abstract Co-Author: Nothing to Disclose

Russ Geyer MD, Abstract Co-Author: Nothing to Disclose

Daphne Adele Haas-Kogan MD, Abstract Co-Author: Nothing to Disclose

James Boyett PhD, Abstract Co-Author: Nothing to Disclose

Larry E. Kun MD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

 We report a retrospective analysis of MR findings in children with newly diagnosed BSG to test the effect of radiation therapy (RT) on imaging variables, to explore the change of the variables over time, and to investigate the association of these imaging variables with progression free survival (PFS) and overall survival (OS).  

Two multi-institutional clinical trials of children with newly diagnosed BSG combined RT with molecular targeted agents (PBTC-007: Phase I/II study of gefitinib and PBTC-014: Phase I study of tipifarnib). Brain MR scans (including perfusion and diffusion) were done pretherapy, every 2nd course during year 1 and every 3rd course until completion of therapy. Effects of RT on imaging variables were investigated using Wilcoxon Signed-Rank test, and Cox Proportional Hazard Models were used to investigate associations of imaging variables with progression free survival (PFS) or overall survival (OS).

72 patients (26 M/46F; median age 6.9 years) had 323 MR exams analyzed. RT & drug decreased tumor volume (TV) (p<0.0001) and tumor diffusion values(tDV) (p<0.0001) and increased tumor perfusion values(tPV) (p=0.034). Pre-RT and post-RT changes in TV and tDV were positively rank-correlated (p=0.003). Baseline TV, change in TV during RT, and longitudinal change in TV as a time-dependent covariate were found to be associated with PFS in a multivariable Cox model (p-values are <0.0001, 0.006, and <0.0001, respectively). Pre-RT tDV and the change in tDV during RT were associated with OS (p-values are 0.009, 0.003, respectively), which suggested that patients with larger tDV pre-RT or who had smaller drop in tDV after RT had shorter survival. Patients with no change or less than 25% drop in TV after RT progressed sooner (p= 0.003) and had shorter survival (p=0.0075). Change in tDV was found to be associated with neither PFS nor OS, while change in TV was found to be associated with both PFS and OS.   

 Treatment of BSG with RT & molecular targeted agents led to decreased TV, decreased tDV, and increased tPV. Patients with smaller decrements in TV progressed sooner. Patients with at least a 25% drop in TV during RT had longer PFS and OS. Validation of such results requires analysis across BSG protocols ongoing in PBTC.   

MR imaging variables can be used for the evaluation of pediatric BSG clinical trials and may be indicative of outcome.

Poussaint, T, Kocak, M, Vajapeyam, S, Robertson, R, Geyer, R, Haas-Kogan, D, Boyett, J, Kun, L, et al, , A Cross Protocol Analysis of MR Neuroimaging Findings in Children with Newly Diagnosed Brainstem Gliomas (BSG): A Report from the Pediatric Brain Tumor Consortium (PBTC).  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6008817.html