Fig. 5.

Verteporfin survival studies in primary and recurrent GBM models. (A) Experimental setup (top) and Kaplan-Meier survival analysis (bottom) of Verteporfin treatment alone or in combination with standard chemoradiation therapy, Temozolomide plus Radiation (TMZ + RT) in the recurrent GBM G-16302 PDX model, gender-matched (VP = 10 mg/kg IP beginning on day 14, TMZ = 5 mg/kg days 21-22, two fractions of whole brain 3Gy RT days 21-22). Combined VP + TMZ + RT treatment confers survival benefit over vehicle (*P = .02 VP + TMZ + RT vs VEH; P = .72 VP vs VEH; P = .55 TMZ + RT vs VEH; P = .76 TMZ + RT vs VP; P = .26 VP + TMZ + RT vs VP; P = .23 VP + TMZ + RT vs TMZ + RT; chi-square log-rank test; n = 9 mice/treatment condition, median survival 45.5/40.5/42.5/62 days for VEH/VP/TMZ + RT/VP + TMZ + RT, respectively). (B) DNA methylation analysis of human MGMT comparing cell line (G-16302, n = 3 technical replicates (dots)) and the survival cohorts of G-16302 PDX tumors at end stage (n = 5 PDX mice (dots) per treatment group, *P < .05 by Student t test). (C) Representative hematoxylin and eosin (H&E) images of tumor necrosis in PDX tumors of TMZ + RT and TMZ + RT + VP-treated mice. Scale bar = 1 mm. T, tumor; N, necrosis. (D) Pathological scoring of percentage necrosis stratified into 2 groups based on longest and shortest survival (n = 10 mice (dots) per treatment group, 2-4 sections per mouse, *P < .05 by Student t test, lines in box-and-whisker plots represent mean, bars represent min/max; ns, not significant). (E) Experimental setup (top) and Kaplan-Meier survival analysis (bottom) of Verteporfin vs vehicle treatment in G-13063 orthotopic PDX mice (*P = .02 by chi-square log-rank test; n = 9 mice/treatment condition, median survival 171/211 days for VEH/VP, respectively; tumors confirmed in all mice included in the analysis). Abbreviations: GBM, glioblastoma; PDX, patient-derived orthotopic xenograft; RT, radiation therapy; TMZ, Temozolomide; VEH, vehicle; VP, Verteporfin.