CLRM-07. INCREASING EFFICIENCY IN EARLY PHASE MULTICENTER IMAGING BIOMARKER TRIALS: EMERGING STRATEGIES FROM THE GABLE (GLIOBLASTOMA ACCELERATED BIOMARKER LEARNING ENVIRONMENT) TRIAL

Validated biomarkers that more accurately predict prognosis and/or measure disease burden in patients with high-grade gliomas would help triage which treatment strategies are most promising for evaluation in Phase III multicenter trials. Multicenter trials to evaluate imaging biomarkers in this group face particular challenges; these trials have historically been slow to accrue and have not recently succeeded in validating new imaging biomarkers useful in treatment development. Due to variability in image acquisition protocols, scanner hardware, image analysis, and interpretive schemes, promising results obtained in single centers are poor predictors of success in the multicenter setting. Multicenter preliminary data to support further evaluation of imaging biomarkers is rarely available. The need for more efficient trial designs that bring multicenter data earlier into the process of biomarker development has become increasingly clear. In this presentation, the planning process within ECOG-ACRIN’s Brain Tumor Working Group for a platform multicenter trial called GABLE (Glioblastoma Accelerated Biomarker Learning Environment trial) designed to evaluate biomarkers for distinguishing pseudoprogression from true progression in patients with newly diagnosed GBM is described. In our planning process, it was determined that efficiencies can be gained from evaluating multiple biomarker types in parallel rather than serially; in the context of the proposed trial, not only conventional imaging biomarkers but plasma biomarkers and radiomic biomarkers can be evaluated simultaneously. Patient tolerance limits the feasibility of evaluating multiple non-standard-of-care imaging biomarkers in parallel. For this group of biomarkers, a “fast-switching” serial evaluation strategy using multiple interim analyses was developed to triage out biomarkers unlikely to succeed in identifying patient groups with clinically significant differences in median survival. For biomarker triage, an endpoint of event-free survival (events of either death or NANO progression) was proposed. Simulations were used to evaluate alpha and beta error using this evaluation strategy.

A Narrative Review of Cerebellar Malfunctions and Sleep Disturbances

Cerebellar malfunctions significantly impact the regulation of the sleep–wakefulness transition. The possible mechanism for this effect is still unknown. Evidence on the role of cerebellar processing in the sleep–wake cycle is derived mainly from animal studies, and clinical management of the sleep–wake cycle is also challenging. The purpose of this review is to investigate the role of cerebellar activity during normal sleep and the association between cerebellar dysfunction and sleep disorders. Large-scale, multicenter trials are still needed to confirm these findings and provide early identification and intervention strategies to improve cerebellar function and the sleep quality of patients.

Predicting of patient’s enrollment to multicentral international clinical trials of II–III phase

<p class="abstract">Many international multicenter trials ending by fail due to fail to recruitment of patients. Objective was to find the integrated and simple value for the assessing the possibility of recruitment in particular sites on the feasibility stage. Design consisted of retrospective review of the selected parameters since feasibility stage to final report of studies conducting in a few sites since 2008 to 2017 year. It was also selected empirical range of the sites. Collection of data was done from the private experience of authors. The integrated and simple values for the assessment of the possibility of recruitment in particular sites on the feasibility stage were calculated. Recruitment of patient as an integrated part of site’s work could be calculated as the beginning of running study on particular site which can lead to increasing of study success and could be used as an embedded value in artificial intelligence for both virtual and real studies. We titled this “calculated type of site on enrollment (CTSE)”.</p>

Use of an Extended Working Channel in High-Risk Transbronchial Biopsy: An Innovative Use of an Existing Modality to Minimize Bleeding and Hypoxia

Objective Bleeding is one of the main complications of transbronchial lung biopsy (TBBx) more so with conditions such as azotaemia and coagulopathy. Baseline hypoxia worsens the consequences of TBBx bleeding and can lead to escalation of care. In our experience, TBBx performed through a guide sheath (GS) using it as an extended working channel (EWC) helps minimize bleeding risk. We hypothesized that the EWC produces a tamponade effect in the close vicinity of the biopsy site, both reducing bleeding risk and restricting bleeding to a smaller segment. In this study, we assessed the impact of an additional EWC in high-risk (HR) patients undergoing TBBx, to reduce bleeding and enhance safety. Methods Retrospective study between January 2014 and December 2018 looking at the risk of bleeding following TBBx performed through a GS (EWC) in patients at high risk for bleeding-related complications. Bleeding incidence and consequent hypoxic events requiring escalation of care were noted. The specimen diagnostic yield was also analyzed. SPSS statistics were used—data are reported as mean and standard deviation for continuous variables, and number and percentage for discrete variables. Results Eight hundred four TBBxs were performed during the study period, and 105 (13.1%) procedures were done in the HR individuals using a GS as an EWC. No significant bleeding requiring escalation of care was seen with the use of EWC-GS. Histopathology revealed adequate sampling in all cases. Conclusions A GS as an EWC was used to reduce the bleeding risk, consequent hypoxia, and prevent escalation of care in TBBx in HR patients. Adequate tissue was obtained without any complications. Though prospective, randomized, multicenter trials using an EWC in HR-TBBx are important, they are challenging to do due to the HR population under study.

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.