Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay.

BACKGROUND: Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last 3 decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment. METHODS: A modified 3D cell culture assay was validated to establish baseline parameters including drug concentrations, timing, and reproducibility. Live tumor tissue from HGG patients were tested in the assay to establish response parameters. Clinical correlation was determined between prospective ex vivo response and clinical response in ND HGG patients enrolled in 3D-PREDICT (ClinicalTrials.gov Identifier: NCT03561207). Clinical case studies were examined for relapsed HGG patients enrolled on 3D-PREDICT, prospectively assayed for ex vivo drug response, and monitored for follow-up. RESULTS: Absent biomarker stratification, the test accurately predicted clinical response/nonresponse to temozolomide in 17/20 (85%, P = .007) ND patients within 7 days of their surgery, prior to treatment initiation. Test-predicted responders had a median overall survival post-surgery of 11.6 months compared to 5.9 months for test-predicted nonresponders (P = .0376). Case studies provided examples of the clinical utility of the assay predictions and their impact upon treatment decisions resulting in positive clinical outcomes. CONCLUSION: This study both validates the developed assay analytically and clinically and provides case studies of its implementation in clinical practice.

A unique approach to neurostimulation in patients with previous two-segment spine surgery and obstruction of epidural access for spinal cord stimulation: a case series.

INTRODUCTION: Patients with extensive surgery in the lumbar and thoracic spine are often not considered for neurostimulation due to the inability to perform a conventional spinal cord stimulation (SCS) trial. We are presenting six such patients in which spinal-peripheral neurostimulation (SPN) was used via a caudal approach. METHODS: Six patients with intractable low back and leg pain following extensive lumbar and thoracic surgeries, up to at least the T10 level, underwent a stimulation trial with one caudal lead and one subcutaneous lead in order to achieve SPN. RESULTS: In five cases, the trial was successful with coverage of the pain area and at least satisfactory pain relief. All six patients were implanted with a paddle lead(s) and a subcutaneous lead using SPN with good pain control. CONCLUSION: SPN with a caudal lead appears to be a viable option for SCS trial in patients with no possibilities for conventional trial lead placement.

Organic synthesis using polymer-supported reagents, catalysts and scavengers in simple laboratory flow systems.

The use of appropriate combinations of polymer-supported reagents, catalysts and/or scavengers is a powerful approach, both for the synthesis of single organic compounds and for parallel syntheses. A further stage of development is the use of such reactants in flow systems. So far, it has been shown that a variety of flow formats afford excellent chemical yields and, where relevant, excellent enantiomeric excesses. The supports have a longer lifetime than in batch systems. 'Flow cascades' promise to be important in future.