Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as BCL2 translocations to determine their impact on clinical outcome of LFL patients. The frequency of chromosomal deletions in 1p and 17p was comparable between LFL and SFL, while 6q deletions and BCL2 translocations more frequently occurred in SFL. A higher proportion of 1p deletions was seen in BCL2-translocation–positive LFL, compared with BCL2-translocation–negative LFL. Deletions in chromosomes 1p, 6q, and 17p predicted clinical outcome of patients with SFL in the entire cohort, while only deletions in chromosome 1p retained its negative prognostic impact in R-CHOP–treated SFL. In contrast, no deletions in one of the investigated genetic loci predicted clinical outcome in LFL. Likewise, the presence or absence of BCL2 translocations had no prognostic impact in LFL. Despite representing a genetic portfolio closely resembling SFL, LFL showed some differences in deletion frequencies. BCL2 translocation and 6q deletion frequency differs between LFL and SFL and might contribute to distinct genetic profiles in LFL and SFL

Clinical neuro-oncology for the neurologist.

Purpose of reviewNeuro-oncologic patients are routinely encountered in clinical practice. Neuro-oncology is a rapidly evolving field, so understanding the most classic paradigms and contemporary advances will optimize patient care.Recent findingsWe discuss the recent reclassification of tumors via molecular characteristics as it applies to direct clinical practice and review the contemporary standard of care for infiltrating gliomas, meningiomas, brain metastases, and CNS lymphoma.SummaryWe provide a straightforward primer on neuro-oncology with a focus on the brain tumors most commonly encountered by the adult neurologist and a clear emphasis on clinically relevant points including those which have recently become incorporated into our standard management. We cite key reviews to allow interested readers an opportunity to gain a more comprehensive understanding of specific topics

Analysis of thermal infrared directional anisotropy over different surface types

Measurements of surface temperature performed in the thermal infrared (TIR) domain display important directional anisotropy and significant 'hot spot' effects during daytime. These depend (1) on the surface structure which governs the temperature profiles inside the canopy via the coupled energy-radiative transfers simultaneously to the spatial distribution of the facets seen by the sensor, and (2) on the solar position. Characterizing the TIR directional anisotropy is important for several purposes : (1) access to the surface temperature of the different canopy layers for improving sensible heat flux estimates, (2) assimilation of multi-angular remotely sensed data in the surface models, (3) correction and normalization of large swath satellite sensors with the scope of analyzing temporal or spatial variability, and (4) definition of optimal viewing configurations and recommendations for future TIR spatial systems. Several experiments based on airborne measurements have been performed to characterize the TIR directional anisotropy over different types of surfaces: pine forests, vineyards, urban areas. The protocol is based on the use of a TIR camera equipped with wide-angle lenses and installed aboard a small aircraft flying different directions. It allows retrieving directional anisotropy (differences between oblique and nadir viewing temperatures) in a range of zenithal viewing angles up to 60° and in all azimutal directions. The possible sources of errors related to the instruments and the atmosphere are analysed and corrections proposed. Experimental results reveal significant directional anisotropy whatever the surface type. Measurements performed at different times of day and at different periods of the year show systematic hot spots in relation with the sun position. The impact of the surface structure is also illustrated. Over maritime pine stands it is shown that the size of the hot spot directly depends on the stand structure (i.e. size, geometry and spacing of trees on the stand), with values reaching ±2 K in the principal plane. Results obtained over vineyards reveal that anisotropy results from the combination of a 'macro structure' effect (orientation of rows) with a 'micro-structure' effect (hot spot of bare stony soil). The strong contrasts between dry bare soil and vegetation walls explain huge directional variations from -12 to 4 K in the principal plane. The impact of the size of buildings, the built-up ratio, and the vegetation ratio on the TIR anisotropy over urban areas is also illustrated from results obtained in the framework of the ESCOMPTE experiment performed at Marseille in 2001 which show ranges of variation between -5 K up to 7 K. An example of application for the correction of two temporal series of NOAA 14 and NOAA 16 data over the city is given. Finally we discuss the difficulty of assessing the contribution of angular variations in surface emissivity to the overall thermal anisotropy, and we briefly present a directional anisotropy modelling approach of surface temperature based on combining 3D canopy models with surface models

Disability outcomes in early-stage African American and White people with multiple sclerosis

Factors driving differences in disease burden between African American and White people with multiple sclerosis (pwMS) remain unclear. Here, we explored whether differences in disability outcomes could be observed after controlling for major sociodemographic factors and comorbidities, and assessed the presence of a possible interaction between MS and race

Practical guidance for telemedicine use in neuro-oncology.

While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations

INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (GBM): Interim results

2514 Background: Novel T cell-enabling therapies, in combination with checkpoint inhibition, may improve OS in GBM. INO-5401 (synthetic DNA plasmids encoding for hTERT, WT-1 and PSMA), plus INO-9012 (synthetic DNA plasmid encoding IL-12), with the PD-1 checkpoint inhibitor cemiplimab, is given to patients with newly-diagnosed GBM to evaluate tolerability, efficacy and immunogenicity of the combination. Methods: Phase I/II, single arm, 2 cohort study (A: MGMT unmethylated, B: MGMT methylated). The primary endpoint is safety; efficacy and immunogenicity are secondary. Nine mg INO-5401 plus 1 mg INO-9012 (every 3 weeks for 4 doses, then Q9W) is given with EP by CELLECTRA 2000 with cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over 3 weeks. TMZ is given with radiation (all patients), followed by maintenance (Cohort B only). Results: Fifty two subjects were enrolled: 32 in Cohort A; 20 in Cohort B. 35% women and 90% white. Median age 60 years (range 19-78 years). Common Grade ≥3 AEs reported were: platelet count decreased (11.5%), tumor inflammation (7.7%), seizure (7.7%), ALT increased (7.7%), lymphocyte count decreased (7.7.%). One Grade 5 unrelated event of urosepsis was reported. Of 69 SAEs reported there was only 1 related to the combination therapy, Grade 1 pyrexia. 48% of subjects reported irAEs, most frequently ALT increased (9.6%), AST increased (7.7%), diarrhea (7.7%), pyrexia (7.7%) and tumor inflammation (7.7%). 71% of the reported SAEs and irAEs occurred within the first 12 weeks of treatment. OS at 12 months was 84.4% (95% CI 67.2, 94.7) in Cohort A; Cohort B will be presented at ASCO. ELISpot assessments demonstrated T cell responses to INO-5401. Flow cytometry demonstrated evidence of activated INO-5401-specific CD8+T cells with lytic potential (CD38+Prf+GrzA+) when compared with baseline, post-treatment in the majority of patients assayed. Conclusions: INO-5401 + INO-9012 in combination with cemiplimab and RT/TMZ has an acceptable safety profile, is immunogenic and may show a survival advantage in patients with newly-diagnosed GBM. OS18 data will be presented later this year. Clinical trial information: NCT03491683

LTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Novel T cell-enabling therapies, in combination with checkpoint inhibition, may improve OS in GBM. INO-5401 (synthetic DNA plasmids encoding hTERT, WT-1, PSMA) plus INO-9012 (synthetic DNA plasmid encoding IL-12), and the PD-1 immune checkpoint inhibitor cemiplimab, is given to patients with newly diagnosed GBM to evaluate tolerability, efficacy and immunogenicity. METHODS Phase I/II, single arm, 2 cohort study (A: MGMT unmethylated, B: MGMT methylated). Primary endpoint is safety; efficacy and immunogenicity are secondary. Nine mg INO-5401 plus 1 mg INO-9012 (every 3 weeks x 4 doses, then Q9W) is given IM with EP by CELLECTRA® 2000 with cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over 3 weeks. TMZ is given with radiation (all patients), and adjuvantly (Cohort B only). RESULTS Fifty-two subjects enrolled: 32 in Cohort A; 20 in Cohort B. 35% women; median age 60 years (19–78 years). The adverse event profile is consistent with single-agent (INO-5401, INO-9012, EP and cemiplimab) reported events. OS at 12 months was 84.4% (Cohort A) and 85% (Cohort B). OS at 18 months in Cohort A is 50% (95% CI 31.9 - 68.1); median OS is 17.9 months (14.5 - NR); Cohort B OS18 and median OS will be presented. Tumor gene transcripts at diagnosis confirmed expression of INO-5401 antigens. Peripheral immune responses following INO-5401 revealed antigen-specific T cell responses by Interferon gamma ELISpot and flow cytometry, including cytokine production and expansion of antigen specific CD8+T cells with lytic potential. CONCLUSIONS INO-5401 + INO-9012, a novel DNA plasmid immunotherapy, demonstrates acceptable risk/benefit and generates robust systemic immune responses to encoded tumor antigens when administered with cemiplimab and RT/TMZ in newly diagnosed GBM patients. Overall survival is encouraging. Clinical trial information: NCT03491683