A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells demonstrated. Convection enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma.

Purpose: To determine whether a multi-analyte liquid biopsy can improve the detection and staging of pancreatic adenocarcinoma (PDAC).

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard of care therapy for metastatic non-small cell lung cancer (mNSCLC) has not been explored. Experimental Design: A 500-gene next-generation sequencing (NGS) panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression free survival (PFS), and overall survival (OS).Results: Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range 1.9-52.5) and was significantly higher for patients achieving DCB compared to no durable benefit: 21.3 mut/Mb vs. 12.4 mut/Mb, P=0.003. For patients with pTMB >16 mut/Mb, median PFS was 14.1 vs. 4.7 months for patients with pTMB<16 mut/Mb (HR 0.30 [0.16-0.60]) P<0.001. Median OS for patients with pTMB>16 was not reached vs. 8.8 months for patients with pTMB<16 mut/Mb (HR 0.48 [0.22-1.03]) P=0.061. Mutations in ERBB2 exon 20, STK11, KEAP1, or PTEN were more common in patients with no DCB. A combination of pTMB>16 and absence of negative predictor mutations was associated with PFS (HR 0.24 [0.11-0.49]) P<0.001 and OS (HR 0.31 [0.13-0.74]) P=0.009. Conclusions: pTMB>16 mut/Mb is associated with improved PFS after first-line standard of care pembrolizumab-based therapy in mNSCLC. STK11/KEAP1/PTEN and ERBB2 mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies.

No abstract

Epilepsy is a common, disabling illness that is refractory to medical treatment in approximately one-third of patients, particularly among those with mesial temporal lobe epilepsy. While standard open mesial temporal resection is effective, achieving seizure freedom in most patients, efforts to develop safer, minimally invasive techniques have been underway for over half a century. Stereotactic ablative techniques, in particular, radiofrequency (RF) ablation, were first developed in the 1960s, with refinements in the 1990s with the advent of modern computed tomography and magnetic resonance-based imaging. In the past 5 years, the most recent techniques have used MRI-guided laser interstitial thermotherapy (LITT), the development of which began in the 1980s, saw refinements in MRI thermal imaging through the 1990s, and was initially used primarily for the treatment of intracranial and extracranial tumors. The present review describes the original stereotactic ablation trials, followed by modern imaging-guided RF ablation series for mesial temporal lobe epilepsy. The developments of LITT and MRI thermometry are then discussed. Finally, the two currently available MRI-guided LITT systems are reviewed for their role in the treatment of mesial temporal lobe and other medically refractory epilepsies.