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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. [ABSTRACT FROM AUTHOR]

• We examined group joining behavior among insect parasitic nematodes. • Steinernema glaseri joined conspecific groups and some heterospecific groups. • Groups that had experienced host contact were more attractive in some cases. Aggregations of foraging animals are key aspects of their ecology, driving spatial patterns, resource access, and successful resource exploitation. Entomopathogenic/insect parasitic nematodes demonstrate aggregated population structures. However, there are gaps in our understanding of how different behaviours affect aggregation. To understand joining behaviour as a mechanism of aggregation, we examined the group movement and joining behaviour of the EPN species, Steinernema glaseri, in conspecific (S. glaseri) and heterospecific (S. carpocapsae and S. feltiae) assemblages. We assessed group movement of S. glaseri using a glass olfactometer where nematodes were added to the central hub and allowed to disperse into six arms towards cues at the ends. We measured movement in the absence of external cues, when host cues were present but uniform, and in response to both con– and heterospecific entomopathogenic nematodes. S. glaseri dispersed in a highly aggregated fashion both in the presence and absence of host cues. When conspecific nematodes were present in the olfactometer ends, S. glaseri readily moved towards and joined conspecific groups, particularly if those conspecifics had experienced host contact 48 h previously. When heterospecific nematodes were present in the ends, S. glaseri only appeared to preferentially join groups of S. feltiae with prior host contact. S. glaseri exhibited no propensity to join groups of S. carpocapsae regardless of prior host contact. Findings demonstrate context-dependent joining behaviours that may underlie aggregation in EPNs. These behaviours may lead to more effective mass attack and regulate interspecific competition among these insect parasites. [ABSTRACT FROM AUTHOR]

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]

While soil resource heterogeneity and root herbivory can have significant direct influences on plant growth, soil heterogeneity may also have indirect effects by influencing the foraging behavior of root herbivores. We used sand-filled greenhouse pots to assess root herbivore foraging behavior and potential interactions between patch quality, herbivore foraging, and plant biomass production (yield). Individual pots were divided into four quarters: one fertilized, and three unfertilized, two of which were planted with tree seedlings. Two treatments were used to create fertilized quarters: high-organic manure fertilizer, and slow-release mineral fertilizer. Seedlings of red maple ( Acer rubrum L.) and Virginia pine ( Pinus virginiana L.) were used to create two single-species and one mixed-species treatments. Root-feeding beetle larvae were added to the pots and allowed to forage freely for ∼8 weeks. At harvest, root herbivores in organic-fertilized pots were strongly attracted to fertilized quarters despite their relatively low-root biomass. Herbivore distribution was significantly different in mineral fertilized pots, where larvae were most abundant in planted quarters, which is also where most of the plant roots occurred. Whole pot plant yield was significantly reduced by larvae; this effect was stronger in the mineral fertilized pots than organic fertilized pots. While one of the plant species appeared more sensitive to herbivory, root herbivores had a greater influence on yield in mixed-species pots than in single-species pots. Overall, these results suggest that patch quality influences on herbivore foraging may indirectly alter yield and plant community composition. [ABSTRACT FROM AUTHOR]

• While plant species respond differently to nutrient patches, the forces that drive this variability have not been extensively examined. In particular, the role of herbivory in modifying plant–resource interactions has been largely overlooked. • We conducted a glasshouse study in which nutrient heterogeneity and root herbivory were manipulated, and used differences in foraging among plant species to predict the influence of root herbivores on these species in competition. We also tracked the influence of neighborhood composition, heterogeneity, and herbivory on whole-pot plant biomass. • When herbivores were added to mixed-species neighborhoods, Eupatorium compositifolium, the most precise forager, was the only plant species to display a reduction in shoot biomass. Neighborhood composition had the greatest influence on whole-pot biomass, followed by nutrient heterogeneity; root herbivory had the smallest influence. • These results suggest that root herbivory is a potential cost of morphological foraging in roots. Root herbivores reduced standing biomass and influenced the relative growth of species in mixed communities, but their effect was not strong enough at the density examined to overwhelm the bottom-up effects of resource distribution. [ABSTRACT FROM AUTHOR]

• While plant species respond differently to nutrient patches, the forces that drive this variability have not been extensively examined. In particular, the role of herbivory in modifying plant–resource interactions has been largely overlooked. • We conducted a glasshouse study in which nutrient heterogeneity and root herbivory were manipulated, and used differences in foraging among plant species to predict the influence of root herbivores on these species in competition. We also tracked the influence of neighborhood composition, heterogeneity, and herbivory on whole-pot plant biomass. • When herbivores were added to mixed-species neighborhoods, Eupatorium compositifolium, the most precise forager, was the only plant species to display a reduction in shoot biomass. Neighborhood composition had the greatest influence on whole-pot biomass, followed by nutrient heterogeneity; root herbivory had the smallest influence. • These results suggest that root herbivory is a potential cost of morphological foraging in roots. Root herbivores reduced standing biomass and influenced the relative growth of species in mixed communities, but their effect was not strong enough at the density examined to overwhelm the bottom-up effects of resource distribution. [ABSTRACT FROM AUTHOR]

Fine-scale soil nutrient enrichment typically stimulates root growth, but it may also increase root herbivory, resulting in trade-offs for plant species and potentially influencing carbon cycling patterns. We used root ingrowth cores to investigate the effects of microsite fertility and root herbivory on root biomass in an aggrading upland forest in the coastal plain of South Carolina, USA. Treatments were randomly assigned to cores from a factorial combination of fertilizer and insecticide. Soil, soil fauna, and roots were removed from the cores at the end of the experiment (8-9 mo), and roots were separated at harvest into three diameter classes. Each diameter class responded differently to fertilizer and insecticide treatments. The finest roots (<1.0 mm diameter), which comprised well over half of all root biomass, were the only ones to respond significantly to both treatments, increasing when fertilizer and when insecticide were added (each P < 0.0001), with maximum biomass found where the treatments were combined (interaction term significant, P < 0.001). These results suggest that root-feeding insects have a strong influence on root standing crop with stronger herbivore impacts on finer roots and within more fertile microsites. Thus, increased vulnerability to root herbivory is a potentially significant cost of root foraging in nutrient-rich patches. [ABSTRACT FROM AUTHOR]

Focuses on fine root production and mortality, which are difficult to estimate accurately because some fine roots die within days of being produced, and many apparently healthy roots disappear rapidly with no obvious period of senescence. View that root dynamics are difficult to analyze without very fine-scaled temporal observations; Sampling of minirhizotron tubes in a Pinus palustris mill woodland; Findings suggest rapidly disappearing roots had relatively short life-spans; What monthly sampling of the same data set suggests about length production, median root life-span, and root loss; Suggestion that below-ground herbivory is the leading explanation for this rapid disappearance.

(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]

• 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]

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]

Objectives: To identify pretest characteristics of cerebrospinal fluid (CSF) specimens that will allow the rational use of flow cytometric analysis (FCA) in the diagnosis of hematologic malignancy. Methods: Retrospective data were collected on 501 consecutive CSF samples submitted for FCA. Results: A positive diagnosis of hematologic malignancy was made in 41 specimens (8.2%). Blasts or atypical lymphocytes were noted on Wright-stained slides in 98% of FCA-positive specimens (40/41), and a history of a hematologic malignancy was present in 89% of specimens (34/38). All FCA-positive specimens had atypical morphology or history of hematologic malignancy. Four hundred six specimens (81%) were FCA negative. Of FCA-negative specimens, 7% (30/406) had atypical morphology, and 3% (12/404) had future central nervous system involvement seen within 30 days. Conclusions: These data support a policy in which FCA of CSF is actively discouraged unless atypical lymphocytes or blasts are seen or a history of hematologic malignancy is present. [ABSTRACT FROM AUTHOR]

Reports on a case of brain-invasive solitary fibrous tumor of the meninges. Immunohistochemical findings; Focal infiltration into the underlying brain parenchyma; Implications on surgical pathology.

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]

Purpose: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG.Methods and Materials: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus.Results: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDHmut1p/19qcodel in 169 (35%), IDHmut1p/19qintact in 125 (26%), and IDHwt in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDHmut1p/19qcodel patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDHmut1p/19qintact (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDHwt classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008).Conclusions: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk factors for progression-free survival (PFS) in the molecular era among patients with low-grade glioma (LGG) who undergo gross total resection (GTR) followed by initial observation.Methods and Materials: We reviewed patients with World Health Organization grade 2 LGG treated at a single institution. We included only those who underwent magnetic resonance imaging (MRI)-confirmed GTR followed by initial observation. Molecular classification was obtained at either the time of diagnosis or pathology review. Cox proportional hazards regression, the Kaplan-Meier method, and the log-rank test were used. P values <.05 were considered statistically significant.Results: We included 144 patients who underwent MRI-confirmed GTR between 1994 and 2014 followed by initial observation. Median age was 29 years (interquartile range [IQR], 18-41), median tumor size was 2.7 cm (IQR, 1.8-4.0), and median follow-up was 81 months (IQR, 36-132). Molecular classification was 13% IDH-mutant 1p19q-codeleted; 21% IDH-mutant 1p19q-intact; 39% IDH1-R132H-wildtype; and 28% undetermined. For the entire cohort, 5- and 10-year PFS and overall survival were 71% and 53%, and 98% and 90%, respectively. On multivariate analysis, factors associated with worse PFS included increasing age at diagnosis (hazard ratio [HR], 1.05; 95% CI, 1.00-1.09; P = .03), increasing preoperative tumor size (HR, 1.07; 95% CI, 1.04-1.10; P < .0001), and IDH-mutant 1p19q-intact classification (HR, 3.18; 95% CI, 1.15-8.74, P = .025). Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively. Molecular classification was significantly associated with PFS (P < .0001) but not overall survival (P = .20).Conclusions: Among patients with LGG who undergo MRI-confirmed GTR and initial observation in the molecular era, increasing age, increasing tumor size, and IDH-mutant 1p19q-intact classification are associated with worse PFS. Because tumor progression is associated with adverse health-related quality of life, these factors may aid clinicians and patients in the shared decision-making process regarding goals of surgery and timing of postoperative therapy. Further study is required to elucidate why IDH-mutant 1p19q-intact LGGs are at higher risk for early progression. [ABSTRACT FROM AUTHOR]

Purpose: The incidence, risk factors, and outcomes of low-grade glioma patients who undergo malignant transformation (MT) in the era of temozolomide are not well known. This study evaluates these factors in a large group of World Health Organization grade 2 glioma patients treated at a tertiary-care institution.Methods and Materials: Patient, tumor, and treatment factors were analyzed using an institutional review board-approved low-grade glioma database. Characteristics were compared using χ2 and Wilcoxon signed rank tests. Time to event was summarized using proportional hazards models. Univariate and multivariate survival analyses were performed.Results: Of a total of 599 patients, 124 underwent MT; 76 (61.3%) had biopsy-proven MT. The MT incidence was 21%, and the median time to MT was 56.4 months. The 5- and 10-year progression-free survival rates were 30.6% ± 4.2% and 4.8% ± 1.9%, respectively, for MT patients and 60% ± 2.4% and 38% ± 2.7%, respectively, for non-MT patients. The 5- and 10-year overall survival rates were 75% ± 4.0% and 46% ± 5.0%, respectively, for MT patients and 87% ± 1.7% and 78% ± 2.3%, respectively, for non-MT patients. On multivariate analysis, older age (P = .001), male sex (P = .004), multiple tumor locations (P = .004), chemotherapy alone (P = .012), and extent of resection (P = .045) remained significant predictors of MT.Conclusions: MT affects survival. Risk factors include older age, male sex, multiple tumor locations, use of chemotherapy alone, and presence of residual disease. Our finding that initial interventions could affect the rate of MT is provocative, but these data should be validated using data from prospective trials. In addition to improving survival, future therapeutic efforts should focus on preventing MT. [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]

Background. Venous thromboembolism (VTE) is a complication of glioblastoma. Anticoagulating patients with glioblastoma carries a theoretical risk of intracranial hemorrhage (ICH). Methods. We performed a retrospective cohort study of consecutive glioblastoma patients (2007-2013) diagnosed with VTE. Results. The study population comprised of 523 glioblastoma patients of whom 173 (33%) had VTE events. Seventeen (10%) had ICH: 6 (35%) subdural hematomas and 11 (65%) intratumoral hemorrhages. In total, 4 patients with ICH required neurosurgical intervention. Enhancement in the area of subsequent intratumoral hemorrhage was noted in 9 of 10 with available pre-ICH scans. Multivariable regression did not show associations between ICH and tumor enhancement diameter or use of vascular-endothelial-growth-factor inhibitor. Fifteen (16%) patients receiving anticoagulation had ICH compared with 2 (2.6%) not receiving anticoagulation (P = .005). The method of anticoagulation was not associated with development of ICH. Median survival times from nondistal VTE diagnosis to death were 8.0 and 3.5 months (P = .05) in patients receiving anticoagulation and those not on anticoagulation, respectively. Conclusion. Patients with glioblastoma and VTE on anticoagulation have increased incidence of ICH. However, development of ICH was not associated with lower median survival from time of VTE. Intratumoral hemorrhage occurred within the enhancing portion of tumor; however, no relationship was identified between the development of ICH and (i) the median diameter of enhancement or (ii) type of anticoagulant used. However, patients with absence of enhancing tumor did not have intratumoral bleed, suggesting gross total resection may limit this adverse outcome. It is appropriate to initiate anticoagulation in glioblastoma patients with VTEs. [ABSTRACT FROM AUTHOR]

The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis. [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]

Purpose: The Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3–40.3 months). Median age was 65 (range, 42–85 years). Median KPS was 70 (range, 40–100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons. [Copyright &y& Elsevier]

Purpose: There have been conflicting reports in the literature regarding the prognostic significance of epidermal growth factor receptor (EGFR) amplification in patients with glioblastoma multiforme (GBM). The purpose of this study is to determine the prognostic significance of EGFR amplification in patients with GBM treated at the Cleveland Clinic Foundation. Methods and Materials: A retrospective review of GBM patients treated with surgery at the Cleveland Clinic Foundation was performed. Amplification of EGFR was evaluated with fluorescence in situ hybridization in a total of 107 patients diagnosed between December 1995 and May 2003. In addition to EGFR status, various prognostic factors were evaluated to determine the factors that influenced survival and radiographic response rate. The median follow-up was 9 months. Results: The overall median survival was 9.8 months, with a 1-year survival of 40%. Of the 107 patients in whom EGFR status was evaluated, 36 (33.6%) were found to have EGFR amplification. On multivariate analysis, median survival was found to be significantly improved for patients with age <60 (12.6 months vs. 8 months, p = 0.0061), patients with Karnofsky Performance Status ≥70 (12.1 months vs. 4.4 months, p < 0.0001), patients who had undergone subtotal resection or gross total resection (11.1 months vs. 4.1 months, p = 0.002), and patients who received a radiation dose ≥60 Gy compared with no radiation (12.7 months vs. 3 months, p < 0.0001). There was no association of EGFR amplification with survival. When stratified by age (<60 vs. ≥60), EGFR status still did not reach statistical significance in predicting for survival. For the 81 patients who had radiographic follow-up, the 1-year overall local control was 14%. On univariate analysis, only treatment with radiation (<60 Gy vs. ≥60 Gy vs. no radiation, p = 0.03) was found to predict for improved local control. Treatment with radiation did not remain statistically significant on multivariate analysis. Conclusion: Epidermal growth factor receptor amplification was not found to be a significant prognostic indicator of overall survival or radiographic local control in patients with GBM treated with surgery at the Cleveland Clinic Foundation. Further studies are needed to fully delineate the significance of this molecular marker in patients with GBM. [Copyright &y& Elsevier]

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas are a well-described type of low-grade B-cell non-Hodgkin lymphoma. They typically arise adjacent to mucosal surfaces in the gastrointestinal tract, lung and conjunctiva, and, less frequently, in the skin, salivary gland and thyroid gland. Unusual locations, such as the genitourinary tract, thymus and meninges, have also been reported. We recently encountered a case of an intracranial MALT lymphoma in a 53-year-old man who presented with persistent headaches and a seizure. The lesion developed as a mass within the lateral ventricle, appeared to be arising from the choroid plexus, and was not associated with meninges. Histologically, there was a vaguely nodular, dense lymphoid infiltrate with occasional benign follicles colonized by marginal zone lymphoma, suggesting derivation from a focus of prior inflammation. Translocations involving the MALT1 gene were not identified but karyotypic evaluation highlighted a complex cytogenetic profile with many chromosomal abnormalities. This rare case provides insight into the pathophysiology of MALT lymphomas. [ABSTRACT FROM AUTHOR]

: PurposeTo determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma.: Methods and materialsWe identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes.: ResultsThe median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834).: ConclusionDespite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population. [Copyright &y& Elsevier]

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]