ReTEECA Trial. Rescue TransEsophageal Echocardiography for In-Hospital Cardiac Arrest.

This trial is aimed at studying the utility and interventional outcomes of rescue transesophageal echocardiography (RescueTEE) to aid in diagnosis, change in management, and outcomes during CPR by using a point of care RescueTEE protocol in the evaluation of in-hospital cardiac arrest (IHCA). This is an interventional prospective convenience sampled partially blinded phase II clinical trial with primary outcomes of survival to hospital discharge (SHD) with RescueTEE image guided ACLS versus conventional ACLS.

An open-label, single-arm, multi-center, phase II clinical trial of single-dose [131I]meta-iodobenzylguanidine therapy for patients with refractory pheochromocytoma and paraganglioma

Objective In this phase II study, we aimed to investigate the efficacy and safety of single-dose [131I]meta-iodobenzylguanidine (131I-mIBG) therapy in patients with refractory pheochromocytoma and paraganglioma (PPGL). Patients and methods This study was designed as an open-label, single-arm, multi-center, phase II clinical trial. The enrolled patients were administered 7.4 GBq of 131I-mIBG. Its efficacy was evaluated 12 and 24 weeks later, and its safety was monitored continuously until the end of the study. We evaluated the biochemical response rate as the primary endpoint using the one-sided exact binomial test based on the null hypothesis (≤ 5%). Results Seventeen patients were enrolled in this study, of which 16 were treated. The biochemical response rate (≥ 50% decrease in urinary catecholamines) was 23.5% (90% confidence interval: 8.5–46.1%, p = 0.009). The radiographic response rates, determined with CT/MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1 and 123I-mIBG scintigraphy were 5.9% (0.3%–25.0%) and 29.4% (12.4%–52.2%), respectively. The most frequent non-hematologic treatment-emergent adverse events (TEAEs) were gastrointestinal symptoms including nausea, appetite loss, and constipation, which were, together, observed in 15 of 16 patients. Hematologic TEAEs up to grade 3 were observed in 14 of 16 patients. No grade 4 or higher TEAEs were observed. All patients had experienced at least one TEAE, but no fatal or irreversible TEAEs were observed. Conclusion A single dose 131I-mIBG therapy was well tolerated by patients with PPGL, and statistically significantly reduced catecholamine levels compared to the threshold response rate, which may lead to an improved prognosis for these patients.

CTNI-28. VOLUMETRIC AND DOSIMETRIC PATTERNS OF FAILURE ANALYSIS OF A PHASE II CLINICAL TRIAL OF 18F-DOPA-PET DIRECTED DOSE ESCALATED RADIOTHERAPY FOR GLIOBLASTOMA

While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( >95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 > 7.8cc, MRI-defined GTV76 > 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p< 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 > 2.17 cc who had biopsy only (median PFS 3.2 months, p< 0.001). Patients with 18F-DOPA-PET-defined GTV51 > 50 cc had the highest risk of grade 3+ radionecrosis (p< 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.

RTID-07. AN INVESTIGATOR-LEAD PHASE II CLINICAL TRIAL OF ACCELERATOR-BASED BNCT FOR REFRACTORY AND RECURRENT HIGH-GRADE MENINGIOMA

BACKGROUD Boron neutron capture therapy (BNCT) is tumor-selective particle radiation. We applied this unique technique and achieved excellent clinical results for recurrent and refractory high-grade meningiomas (HGM) using reactor neutron sources (Neuro-Oncology, in press, doi:10.1093/neuonc/noab108). Recently accelerator-based neutron sources (ABNS) was approved for medical device in Japan for refractory H&N cancers. PURPOSES Based on these situations, we proposed “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent HGM” for AMED in Japan which is similar to NIH in USA. This proposal was successfully accepted. DESIGN We prepared 2 study groups, BNCT test treatment group and control best supportive care group, for RCT. PFS and OS were set-up as primary and secondary endpoints, respectively. Rescue BNCT is allowed for control group patients, if they showed PD during observation. The trial started in August 2019. METHODS Twelve BNCT and 6 control subjects will be included. Patients’ eligibility criteria is recurrent HGM after some radiotherapy. Cyclotron-based ABNS system is used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. PROGRESS As of March 2021, 13 subjects were included, 9 for BNCT treatment group, 4 for control best supportive care group. All 4 control subjects showed PD during 2 months while 8 out of 9 subjects showed SD or PR during observation period and there is a statistical significance in both groups, by Log-rank and Wilcoxon analyses with p=0.0012 and 0.0020, respectively. CONCLUSION We started this RCT and will introduce the interim report of this clinical trial in the meeting. At the SNO meeting we will present further detail of this trial.