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We reviewed our Gamma Knife® Radiosurgery case mix to evaluate practice pattern changes across a 10 year period of time. In 2011 we completed 384 procedures with 782 lesions targeted. The majority of the treatments were for malignant disease with metastases representing the largest subgroup (n=245; 63.8%), A total of 117 (30.4%) benign pathologies were treated with benign tumors (n=63; 16.4%), functional cases and AVMs (each n=27; 7%) representing the most common cases treated with the remainder of cases represented by a variety of other pathologies. All treatments were completed using the Perfexion™ system. By 2021, we doubled our case volume completing (n=778) procedures, however, nearly tripled the number of targets treated (n=2317). Metastases again represented the largest cohort (n= 617 cases;79.3%), 84 (10.8%) benign tumors, 19 (2.4%) functional cases and 15 (1.9%) AVMs. In 2021, all cases were completed using the GK ICON™ System and 193 cases (24.8%) were performed using mask-based immobilization. There were also 16 anesthesia cases. Approximately 50% of the treated patients were from Ohio and 50% came from out of state. The above data demonstrates a growing volume of cases treated with GK at a single institution across a decade, with metastases representing the dominant and expanding cohort of cases treated (63.8% vs 79.3%). The associated nearly tripling of lesions treated likely reflects a willingness to treat patient with a greater number of brain metastases per session. Further, 24.8% in 2021 were treated with mask-based immobilization reflecting a work-flow change and expanded capabilities compared to treatments in the previous decade. [ABSTRACT FROM AUTHOR]

Introduction: Gamma-Knife radiosurgery (GKRS) is a well-established treatment for brain metastases (BM). The imaging features of BM can variably have either homogeneous and heterogenous enhancement, or cystic-like appearances. These features can represent different biological behaviors concerning the treatment of these lesions. Cystic BM (cBM) are perceived to be more resistant to treatment than solid BM (sBM). In this study, we sought to compare the response rates and overall survival of patients with cBM relative to sBM after GKRS. Method: Patients treated for BM with GKRS over a 2-year interval (2016-2017) were evaluated. GKRS dosing was delivered per RTOG 90-05 according to our standard protocol. Patients were divided in 3 groups: those with cBM only, sBM only, and both cystic and solid BM (csBM). Kaplan-Meier analysis with the log-rank test was used to calculate and compare overall survival (OS) between groups. Local control was analyzed utilizing RECIST criteria at 3, 6, and 12 months. Chi-square analysis compared the response rate for cBM and sBM. Result: 73 patients (59% female) with a mean age 67 years (range: 43-91) were analyzed. The most frequent pathologies were lung (54%) and breast (18%). KPS was ≥70 in 66 patients (90%). Prior to GKRS treatment, 22% of patients received WBRT, 71% chemotherapy, 22% had prior surgery, and 16% received immunotherapy. No significant differences were found in the clinical characteristics between patient groups. Mean OS was 20 months (2-38, 95% CI) for the cBM patient group, 17 months (12-22, 95% CI) for sBM patient group and 13 months (7-19, 95% CI) for csBM patient group (p = .967). Of the 416 lesions evaluated, 15% (n=62) were cBM and 85% (n=354) were sBM.cBM were significantly larger than sBM (p < 0.0001) and therefore cBM received significantly lower doses of radiation (p 0.001). No other significant differences were found between cBM and sBM. Local control at 6 months was 92% for cBM and 89% for sBMs (p =.49). Conclusion: Despite a perceived worse prognosis, our results suggest that patients harboring cBM treated with GKRS achieve similar oncologic outcomes when compared with patients with sBM. cBM are usually larger than sBM and therefore these lesions may be treated with less radiation dose than their solid counterparts. Regardless, cBM and sBM are suitable stereotactic radiosurgery targets with comparable local control rates. [ABSTRACT FROM AUTHOR]

(a) ∼20,000 ijs of four different commercial species of entomopathogenic nematodes were individually placed in vertically oriented PVC columns containing oven-dried sand. (b) Ijs were incubated for varying time periods depending on species as species move at different rates. (c) After incubation time, the top section (containing non-moving nematodes) and the bottom section (containing moving nematodes) of each PVC column was removed and rinsed in water to decant ijs from sand. (d) 500 ijs were sampled from the non-mover and mover ijs in each column. These ijs were exposed to a Galleria mellonella larva and allowed to infect the larva. After 24 hours, the larva was dissected and the number of ijs inside the insect was counted. (e) The percent invasion was compared between movers and non-movers using JMP® Pro 14.1.0 to determine if nematodes that move more have a higher infectivity rate than non-movers. [Display omitted] • Increased dispersal of EPNs may provide tradeoffs, such as risk of mortality in exchange for increased invasion potential. • Invasion of G. mellonella was assessed between the "movers" and "non-movers" of four species of entomopathogenic nematode. • S. carpocapsae movers were the only nematodes that did not show increased invasion potential. • H. indica , traditionally classified as a cruiser forager, had a movement index similar to an ambush forager. • EPNs classified as ambushers may not gain increased invasion success compared to EPNs who are cruisers or intermediates. Entomopathogenic nematodes (EPNs) are roundworms that parasitize insects with the aid of symbiotic bacteria. These nematodes have been used both as model organisms and for biological control of pests. The specialized third stage of an EPN, known as an infective juvenile (IJ) must forage to find a host with strategies varying from species to species (cruising, ambushing, and intermediate). Some IJs move more than others to find a host, despite an increased risk of predation and desiccation. This hints at potential underlying benefits (e.g., increased invasion) for EPNs that move more. We assessed whether EPNs that moved farther down a soil column also exhibit higher levels of invasion when compared to nematodes that remained at or near their point of origin. We found that movers in the cruisier and intermediate species: Steinernema riobrave, Heterorhabditis bacteriophora , and H. indica had higher invasion rates compared to their counterparts that did not move. S. carpocapsae , an ambusher, did not exhibit invasion differences between EPNs that moved versus those that did not. For the three cruiser/intermediate EPNs we tested, our results support our hypothesis that EPNs that tend to move more enjoy related benefits such as increased invasion potential. Further studies are required to explore other parameters that may interact with movement. The results of this study can potentially be used to develop EPN strains that move more and invade more, and thus can potentially be more effective biological control agents. [ABSTRACT FROM AUTHOR]

Background Pulsed reduced dose rate (PRDR) is a reirradiation technique that potentially overcomes volume and dose limitations in the setting of previous radiation therapy for recurrent central nervous system (CNS) tumors. Intensity modulated radiation therapy (IMRT) has not yet been reported as a PRDR delivery technique. We reviewed our IMRT PRDR outcomes and toxicity and reviewed the literature of available PRDR series for CNS reirradiation. Methods and materials A total of 24 patients with recurrent brain tumors received PRDR reirradiation between August 2012 and December 2014. Twenty-two patients were planned with IMRT. Linear accelerators delivered an effective dose rate of 0.0667 Gy/minute. Data collected included number of prior interventions, diagnosis, tumor grade, radiation therapy dose and fractionation, normal tissue dose, radiation therapy planning parameters, time to progression, overall survival, and adverse events. Results The median time to PRDR from completion of initial radiation therapy was 47.8 months (range, 11-389.1 months). The median PRDR dose was 54 Gy (range, 38-60 Gy). The mean planning target volume was 369.1 ± 177.9 cm 3 . The median progression-free survival and 6-month progression-free survival after PRDR treatment was 3.1 months and 31%, respectively. The median overall survival and 6-month overall survival after PRDR treatment was 8.7 months and 71%, respectively. Fifty percent of patients had ≥4 chemotherapy regimens before PRDR. Toxicity was similar to initial treatment, including no cases of radiation necrosis. Conclusion IMRT PRDR reirradiation is a feasible and appropriate treatment strategy for large volume recurrent CNS tumors resulting in acceptable overall survival with reasonable toxicity in our patients who were heavily pretreated. Prospective studies are necessary to determine the optimal timing of PRDR reirradiation, the role of concurrent systemic agents, and the ideal patient population who would receive the maximal benefit from this treatment approach. Summary Intensity modulated radiation therapy (IMRT) has not yet been reported as a pulsed reduced dose rate (PRDR) delivery technique for recurrent brain tumors and may allow for safe and comprehensive reirradiation for large volume tumors. We reviewed our IMRT PRDR outcomes and toxicity and reviewed the literature of available PRDR series for recurrent central nervous system tumors. We conclude that IMRT PRDR reirradiation is a feasible and appropriate treatment strategy for large volume recurrent brain tumors resulting in acceptable overall survival with reasonable toxicity in our patients who were heavily pretreated. [ABSTRACT FROM AUTHOR]

• Pheromone treated EPNs exhibited enhanced dispersal in soil columns. • Pecan weevils, and black soldier flies had lowest survival with pheromone treated EPNs. • Pheromones increase EPN dispersal and host mortality. Inconsistency in entomopathogenic nematode (EPN) efficacy is still one of the biggest challenges for the wider adoption of EPNs as biocontrol agents. Previous studies demonstrated that extracts from EPN-infected hosts enhance dispersal and efficacy, two key factors in success of EPNs. Some active components in the insect host cadavers responsible for dispersal, ascarosides, have been identified as nematode pheromones. We hypothesized that pheromone extracts increase dispersal of EPN infective juveniles (IJs) leading to increased efficacy. First, we determined whether pheromone extracts improved IJ movement/dispersal in soil columns baited with Tenebrio molitor larvae. We found that pheromone extracts induced higher numbers of Steinernema carpocapsae and Steinernema feltiae IJs to move towards T. molitor larvae in the bottom of the column compared to IJs treated with infected cadaver macerate and water, positive and negative controls, respectively. Furthermore, the number of S. carpocapsae IJs that invaded T. molitor larvae was higher for the pheromone extract treatment than the controls. S. feltiae IJs that were pretreated with pheromone extracts and macerate (positive control) infected T. molitor at the same rate but invasion was superior to IJs that were treated with water. Consistent with the soil column tests, both S. carpocapsae and S. feltiae IJs treated with pheromone extracts performed better in killing larvae of two economically important insect larvae, pecan weevil, Curculio caryae , and black soldier fly, Hermetia illucens , in greenhouse tests compared to IJs treated with water. We demonstrated pheromone-mediated behavioral manipulation of a biological control agent to enhance pest control potential. Conceivably, nematodes can be exposed to efficacy-enhancing pheromones prior to field application. [ABSTRACT FROM AUTHOR]

The internationalization of local Extension programs has long been a source of debate among Extension educators. Often, international work is seen as extravagant during difficult economic times. Extension also faces challenges attracting qualified young people into our profession. We report the results of a combined international Extension training and student education program. This program was popular with agents and students, improved student knowledge of Extension, and made long-term contributions to the programs of agents who participated. Building the cost for agent participation into study abroad courses may benefit students, Extension agents, and teaching faculty while controlling cost to Extension programs. [ABSTRACT FROM AUTHOR]

Purpose: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG.Methods and Materials: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed.Results: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016).Conclusions: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex. [ABSTRACT FROM AUTHOR]

Ascaroside pheromones stimulate dispersal, a key nematode behavior to find a new food source. Ascarosides produced by entomopathogenic nematodes (EPNs) drive infective juvenile (IJ) emergence from consumed cadavers and dispersal in soil. Without ascarosides from host cadavers, Steinernema feltiae (EPN) reduce dispersal substantially. To determine whether other Steinernema spp. exhibit the same behavior, we compared S. feltiae and S. carpocapsae IJs without host cadaver pheromones. Unlike S. feltiae, S. carpocapsae IJs continued to disperse. However, S. carpocapsae IJs exhibited a temperature-dependent quiescent period. The IJ quiescent period increased at ≤20 °C but did not appear at ≥25 °C. Consistent with this, S. carpocapsae IJ quiescence increased from 30 min to 24 h at ≤20 °C over 60 days. The quiescent period was overcome by dispersal pheromone extracts of their own, other Steinernema spp. and Heterorhabditis spp. Furthermore, S. carpocapsae IJ ambush foraging associated behaviors (tail standing, waving, and jumping) were unaffected by the absence or presence of host cadaver pheromones. For S. feltiae, IJ dispersal declined at all temperatures tested. Understanding the interaction between foraging strategies and pheromone signals will help uncover molecular mechanisms of host seeking, pathogenicity and practical applications to improve the EPN's efficacy as biocontrol agents. [ABSTRACT FROM AUTHOR]

Background Patients with single brain metastasis (SBM) have better outcomes after stereotactic radiosurgery (SRS). We analyzed our SRS database to evaluate possible prognostic factors in patients with SBM. Methods A total of 584 patients with SBM were treated with SRS at our institution (2000–2012). Study end points were overall survival (OS), and distant and local intracranial progression-free survival (DPFS and LPFS, respectively). Multivariable analysis was performed to develop prognostic models. Results Median OS was 10.8 months. A total of 196 patients (36.7%) had distant progression and 102 patients (19.2%) had local progression. New SBM prognostic indices (SPIs) were devised for OS, DPFS, and LPFS. Graded prognostic assessment, neurologic symptoms ( P = 0.01), and tumor volume ( P = 0.02) were independently associated with OS. The SPI for OS was defined: unfavorable (OS, 7.3 months), intermediate (OS, 10.6 months), and favorable (OS, 19.8 months). For DPFS, age ( P = 0.0029), tumor volume ( P = 0.0002), and previous whole-brain radiotherapy ( P = 0.027) were prognostic and were used to define SPI for DPFS: favorable (6-month cumulative incidence failure [CIF], 10.9%), intermediate (6-month CIF, 16.7%), and unfavorable (6-month CIF, 26.0%) ( P < 0.001). For LPFS, graded prognostic assessment ( P = 0.0012) and tumor volume ( P = 0.0004) were significant, and defined 2 groups in the LPFS SPI: unfavorable (6-month CIF, 12.3%) and favorable (6-month CIF, 6%) ( P < 0.001). Conclusions This is the largest series of patients with SBM treated with SRS analyzed for OS, LPFS, and DPFS. SPI was devised for end points. Tumor volume had a significant association with all 3 end points. Neurologic symptoms, age, and previous whole-brain radiotherapy were also found to be prognostic. [ABSTRACT FROM AUTHOR]

Abstract: Entomopathogenic nematodes (EPNs) are lethal insect parasites that develop inside the body of their insect host. The EPN Steinernema riobrave infects many different types of soil insects, including larvae of the invasive citrus root weevil, Diaprepes abbreviatus, which is a key pest in citrus production. Soil characteristics have a great impact on nematode foraging efficacy and therefore on the ability of EPNs to be used successfully in biological control programs. Our specific objectives were to: (1) survey for the presence of native EPNs in California citrus groves; and (2) identify soil parameters that would allow us to predict EPN efficacy. The long-term objective of this study is to develop biological control methods to address the invasion of the citrus root weevil, D. abbreviatus, into California using EPNs. We collected soils from 36 sites in California where citrus is produced commercially, sampled them for native nematode presence and tested the foraging efficacy (movement and host finding) of S. riobrave in these soils at three different soil depths; 100, 250 and 500mm. Soil textures and physical characteristics were analyzed. We found five isolates of endemic EPNs (Heterorhabditis spp.) from southern California. Three were identified as Heterorhabditis bacteriophora, and two as Heterorhabditis sonorensis, which were recorded for the first time in California. S. riobrave''s ability to infect hosts varied among soil types and depths. We also found significant correlations between soil characteristics (texture and physical characteristics) and S. riobrave foraging efficacy. Synthesis and applications. Our results and analyses can play a role in the prediction of S. riobrave success in various soil types. Perhaps more importantly, we suggest an approach to predict biological control potential based on soil characters that might be used with other insect pathogens. While soil texture is the main factor that affects EPN efficacy, we found that other parameters like organic matter level and dissolved solids are also important. [Copyright &y& Elsevier]

Purpose: To report on the development of visually significant maculopathy associated with blood–brain barrier disruption (BBBD) therapy for the treatment of central nervous system (CNS) lymphoma. Design: Retrospective case series. Methods: Chart review of 20 patients undergoing BBBD therapy for treatment of CNS lymphoma at the Cleveland Clinic. Patients with documented maculopathy were included in analysis. Results: Seven (54%) of 13 patients were identified with new macular retinal pigment epithelium (RPE) changes after BBBD treatment. The RPE changes consisted of fine clumps of hyperpigmentation in the foveal region associated with variable degrees of RPE loss. These changes were bilateral but often asymmetric. Two patients had decreased visual acuity resulting from maculopathy. One patient had documented progression of maculopathy after completion of treatment. Conclusions: Maculopathy is a frequent finding after BBBD therapy for CNS lymphoma. [Copyright &y& Elsevier]

Background: Single-session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2 cm) to determine the safety of preoperative SRS at escalating doses., Methods: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose-limiting toxicity was defined as grade III or greater acute toxicity., Results: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21 Gy. The maximum tolerated dose of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%., Conclusions: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Maintenance of an aggregated population structure implies within-species communication. In mixed-species environments, species-specific aggregations may reduce interspecific competition and promote coexistence. We studied whether movement and aggregation behavior of three entomopathogenic nematode species changed when isolated, as compared to mixed-species arenas. Movement and aggregation of Steinernema carpocapsae , S. feltiae and S. glaseri were assessed in sand. Each species demonstrated significant aggregation when alone. Mixed-species trials involved adding two species of nematodes, either combined in the center of the arena or at separate corners. While individual species became less aggregated than in single-species conditions when co-applied in the same location, they became more aggregated when applied in separate corners. This increased aggregation in separate-corner trials occurred even though the nematodes moved just as far when mixed together as they did when alone. These findings suggest that maintenance of multiple species within the same habitat is driven, at least in part, by species-specific signals that promote conspecific aggregation, and when the species are mixed (as occurs in some commercial formulations involving multiple EPN species), these signaling mechanisms are muddled., (© 2024 Glen Stevens et al., published by Sciendo.)