An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma

Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.

STMO-01 Cerebral edema and perioperative epilepsy due to placement of BCNU wafer for malignant glioma

Introduction: Cerebral edema is the most frequent adverse event of BCNU wafer, which is used as local chemotherapy of malignant glioma. However, predictive factor of this event is unknown. Moreover, there is no consensus about cerebral edema and perioperative seizure, which is often observed in glioma. Here, we report risk factor of cerebral edema with BCNU placement and relationship with perioperative seizure in malignant glioma cases. Material and Method: Thirty-one case of adult malignant glioma who underwent BCNU placement in our institute between March 2013 to March 2019 were investigated. The patients were dichotomized to two groups; patient with postoperative transient cerebral edema (CE+ group) and patient without postoperative transient cerebral edema (CE- group). Result: Postoperative cerebral edema associated with placement of BCNU was observed in 9 out of 31 patients (29%). Tumor malignancy was significant parameter for postoperative cerebral edema (p=0.003). Other factors such as, age, gender, laterality, tumor location, primary or recurrent, number of BCNU wafers, duration of recurrence were not significant for postoperative cerebral edema. Seizure was seen in 14 patients (45%), and cerebral edema was not significant parameter for seizure. Tumor malignancy was significant parameters for postoperative cerebral edema. Tumor malignancy was significant parameters for seizure (p=0.0004). Although postoperative seizure was observed in 4 patients (44%) with CE+ group, neither maximum volume (mean 61.1 ml) nor change ratio (mean 354%) of FLAIR-high-intensity region were not related with postoperative seizure. Conclusions: Tumor malignancy was important factor for patients who underwent placement of BCNU wafer with postoperative cerebral edema and seizure. On the other hand, there were no relationship between postoperative cerebral edema and perioperative seizure in patients treated with BCNU wafer.

ACTR-54. VIGILANT OBSERVATION OF GLIADEL WAFER IMPLANT (VIGILANT) REGISTRY: INTERIM ANALYSIS

INTRODUCTION The Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) was initiated to evaluate the use of BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular analysis. METHODS The VIGILANT registry is an observational study. Each patient receives usual care from treating physicians in routine quarterly visits, with no registry-specific visits required. The VIGILANT registry will enroll up to 500 patients at 35 US sites. Patients must be ≥18 years of age with no medical conditions increasing risk through participation. Patient follow-up will last 3 years. RESULTS The interim analysis is ongoing, with the following preliminary data. Of the 143 patients enrolled to date (mean age 59.8 ± 13.41 years, 60.1% male, 82.5% white), BCNU wafers have been implanted for newly diagnosed glioblastoma (GBM) in 49 (34.3%); for recurrent GBM in 48 (33.6%); for brain metastases in 28 (19.6%); for anaplastic oligodendroglioma in 4 (2.8%); and for other CNS tumors in 14 (9.8%). For patients with recurrent GBM, the median time from prior to current CNS tumor diagnosis was 341.5 days (IQR 88, 890). The majority of recurrent GBM patients had previously undergone systematic chemotherapy (87.5%) and radiation therapy (70.8%); only 8 (16.7%) had previously received BCNU wafers and only 4 (8.3%) had previously undergone alternating electric-field therapy. Of patients with brain metastases, 15 (51.7%) had previously undergone stereotactic radiosurgery. Of GBM patients with baseline biomarker assessments, MGMT promoter status was methylated in 52.1% (37/71), and IDH1 mutation status was positive in 15.9% (11/69). Median survival and contemporary practice patterns will be available at the time of presentation. CONCLUSIONS In the VIGILANT registry to date, BCNU wafers have been implanted most often and with equal frequency for treatment of newly diagnosed and recurrent GBM. Preliminary safety and efficacy data are pending.