SCIDOT-43. FINAL DATA ANALYSIS OF A PILOT STUDY TESTING THE EFFICACY OF USING LASER INTERSTITIAL THERMAL THERAPY (LITT) TO INDUCE TEMPORARY DISRUPTION OF THE PERITUMORAL BLOOD BRAIN BARRIER (BBB) TO IMPROVE EFFECTIVENESS OF BBB-IMPERMEANT CHEMOTHERAPY IN RECURRENT GLIOBLASTOMA

Abstract

Abstract BACKGROUND Poor CNS drug delivery is a major limiting factor in GBM therapy. Since most recurrences occur peritumorally where infiltrating glioma cells reside, peritumoral BBB disruption may help improve drug delivery and efficacy. LITT, a minimally invasive cytoreductive treatment for brain tumors, may disrupt BBB as evidenced by post-ablation contrast enhancement. METHODS Patients with recurrent GBM were treated with LITT. The degree of post-LITT peritumoral BBB disruption was measured by the vascular transfer constant (Ktrans) in brain DCE-MRI. Serum levels of brain-specific enolase (BSE) were quantified as an independent measure of BBB disruption. Forty enrollments were planned with equal randomization to weekly low-dose doxorubicin, a BBB-impermeant chemotherapy, either during the BBB-permeable window (Early Dox) or after the resolution of disruption (Late Dox). The primary endpoint is 6-month PFS rate (6-PFS). RESULTS Peritumoral Ktrans peaked immediately post LITT, followed by a gradual decline for the next 4 weeks. Similarly, serum BSE concentrations peaked in 1–3 weeks after LITT before decreasing to baseline by 6 weeks. 41 patients were randomized to Early and Late Dox. 31 patients (14 Early and 17 Late Dox) were evaluable for the primary endpoint. MGMT promoter methylation rate was 28% and 47% in the Early and Late Dox arms, respectively. 6-PFS was 57.1% (8/14) in Early Dox compared to 35.3% (6/17) in Late Dox. PFS was 5.8 (95%CI: 4.1–6.3) months vs. 4.9 (95%CI: 2.4–6.3) months, while OS was 12.8 (95%CI: 7.8–14.5) months vs. 13.6 (95%CI: 10.2–17.1) months, for Early vs. Late Dox, respectively. The most common grade 3–4 toxicities were cytopenia observed in 6 (16%) patients. CONCLUSIONS LITT induces temporary peritumoral BBB disruption lasting 4–6 weeks, providing a rare opportunity to enhance local delivery of potentially efficacious but BBB-impermeant therapeutic agents. 6-PFS strongly favors dox given early during the window of BBB disruption, thus supporting the hypothesis.