bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Vaccination in Patients With Cancer and Patients Receiving HSCT or CAR-T Therapy: Immune Response, Real-World Effectiveness, and Implications for the Future
Authors: Hall Victoria G , Teh Benjamin W
Published: August 2023

Patients with cancer demonstrate an increased vulnerability for infection and severe disease by SARS-CoV-2, the causative agent of COVID-19. Risk factors for severe COVID-19 include comorbidities, uncontrolled disease, and current line of treatment. Although COVID-19 vaccines have afforded some level of protection against infection and severe disease among patients with solid tumors and hematologic malignancies, decreased immunogenicity and real-world effectiveness have been observed among this population compared with healthy individuals. Characterizing and understanding the immune response to increasing doses or differing schedules of COVID-19 vaccines among patients with cancer is important to inform clinical and public health practices. In this article, we review SARS-CoV-2 susceptibility and immune responses to COVID-19 vaccination in patients with solid tumors, hematologic malignancies, and those receiving hematopoietic stem cell transplant or chimeric-antigen receptor T-cell therapy.
Acinetobacter oleivorans IRS14 alleviates cold stress in wheat by regulating physiological and biochemical factors
Authors: Ali Ashif , Dindhoria Kiran , Kumar Rakshak
Published: August 2023

Aims

Climate change is responsible for extreme cold winters, causing a significant loss in crop yield and productivity due to chilling stress. This study aims to investigate the potential of psychrotrophic plant growth-promoting rhizobacteria (PGPR) strain to promote wheat growth under cold stress and explore the adaptive responses of wheat.

Methods and results

Wheat seeds and seedlings were inoculated with the psychrotrophic strain IRS14 and the plants were cultivated for five weeks at 6°C ± 2°C. The genetic, biochemical, physiological, and molecular analysis of the bacterium and plant was done to evaluate the effect of the PGPR strain in alleviating chilling stress. IRS14 possesses antioxidant activity and produced multiple phytohormones, which enhanced seed germination (∼50%) and plant growth (∼50%) during chilling stress.

Conclusions

Here, we reported that the application of IRS14 helps to regulate the biochemical and metabolic pathways in wheat plants. It alleviates chilling stress and increases plant growth rate and biomass. Strain IRS14 in wheat effectively increased chlorophyll content, antioxidants, carotenoid, proline, and endogenous phytohormones compared with untreated wheat.
Standardized ileal digestibility of amino acids in extruded full-fat soybean fed to non-gestating, gestating, and lactating sows
Authors: Wang Ya , Wang Ke , Zou Xiangyang , Jiang Xuemei , Zhuo Yong , Che Lianqiang , Wu De
Published: August 2023

This study was conducted to determine and compare the apparent ileal digestibility and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in extruded full-fat soybean (EFSB) fed to nongestating, midgestating, late-gestating, and lactating sows. Six EFSB samples were collected from different sources. Fourteen nongestating sows (Landrace × Yorkshire; parity 3 to 5) were fitted with a T-cannula at the distal ileum. After recovery, sows were assigned to a replicated 7 × 3 incomplete Latin square design. The diets included a nitrogen-free (NF) diet and six experimental diets (EFSB 1 to 6). Eight midgestating sows (Landrace × Yorkshire; parity 3; day 48 of gestation), eight late-gestating sows (Landrace × Yorkshire; parity 3; day 90 of gestation), and eight lactating sows (Landrace × Yorkshire; parity 3; day 6 of lactation) were all assigned to four dietary treatments in a repeated 4 × 3 incomplete Latin square design. The diets included a NF diet and three experimental diets (EFSB 4 to 6). Results showed that there were significant differences in the AID and SID of CP and other AA in nongestating sows (P < 0.05), the AID and SID values of EFSB 1 to 3 were higher than those of EFSB 4 to 6, and the value of EFSB 5 was the lowest. For midgestating sows, there were differences in the AID of methionine (EFSB 5 had a lower value than EFSB 4 and 6) (P < 0.01). For late-gestating sows, only the AID of methionine (EFSB 5 had a lower value than EFSB 4 and 6), tryptophan (EFSB 5 had a higher value than EFSB 4 and 6), and proline (EFSB 5 had a higher value than EFSB 4) was different (P < 0.05), and the SID of methionine (EFSB 4 had a higher value than EFSB 5) and tryptophan (EFSB 5 had a higher value than EFSB 4 and 6) was different (P < 0.05). The SID of histidine and valine was greater in lactation than in nongestation (P = 0.045 and P = 0.02, respectively). The SID of isoleucine was greater in lactation than in nongestation and gestation (P < 0.01). The SID of methionine in nongestation was lower than in gestation and lactation (P < 0.01). The SID of cysteine was the lowest in midgestation (P = 0.045), and the SID of proline was greater in midgestation than in lactation and nongestation (P < 0.01). In conclusion, the AA ileal digestibility of six EFSB samples from different sources was different, and the ileal digestibility of CP and most AA was not affected by the physiological stage of sows.
Data-mining-based identification of post-handover defect association rules in apartment housings
Authors: Kim Byeol , Lim Benson Teck Heng , Oo Bee Lan , Ahn Yong Han
Published: August 2023

With the increasing expectations of clients and the growing complexity of the built environment, property management teams are facing constant pressure to effectively manage and rectify defects for improved building operational efficiency and performance. This study aims to develop and validate a defect correlation evaluation model for project and property management professionals by specifically (i) examining the defect detection and management mechanisms of residential buildings and (ii) quantifying the mechanical characteristics of defects by using association rules mining (ARM) techniques. In addressing the limitations of current evaluation approaches, this study proposed an ARM evaluation model that integrated, contextualized, and operationalized building defects into work type, location, elements, and defect type. The association between these classifications was explored and mapped. Among the resulting 123 meaningful rules, rules occurred at a rate of about 62% of the same work type in the linked work type, nearly 193% of the same element in another element, and about 23% of the close location in the far location. In conclusion, this study informs project and property management professionals of the key and complex associations between defects of different characteristics and highlights the most common occurrence defects in residential apartment buildings. Thus, this helps reduce the ambiguity and subjectivity of prioritization in defect management and facilitates maintenance and repair planning.
Improving the signal quality of grades
Authors: Chilton Adam , Joy Peter , Rozema Kyle , Thomas James
Published: August 2023

We investigate how improving the signal quality of grades could enhance the matching of students to selective opportunities that are awarded early in academic programs. To do so, we develop methods to measure the signal quality of grades and to estimate the impact of changes to university policies on the identification of exceptional students for these opportunities. We focus on law schools, a setting where students are awarded important academic and professional opportunities after just one year of a three-year program. Using transcript data from a top law school over a 40-year period, we document large gains in identifying exceptional students if changes were made to certain personnel, course, and grading policies. Our findings provide motivation and a blueprint for how universities could leverage their internal records to ensure that fewer exceptional students miss out on selective opportunities.
Keep in touch: the soil–root hydraulic continuum and its role in drought resistance in crops
Authors: Affortit Pablo , Ahmed Mutez Ali , Grondin Alexandre , Delzon Silvain , Carminati Andrea , Laplaze Laurent
Published: August 2023

Drought is a major threat to food security worldwide. Recently, the root–soil interface has emerged as a major site of hydraulic resistance during water stress. Here, we review the impact of soil drying on whole-plant hydraulics and discuss mechanisms by which plants can adapt by modifying the properties of the rhizosphere either directly or through interactions with the soil microbiome.
X-ray emission from Westerlund 2 detected by SRG/ART-XC and Chandra: search for radiation of TeV leptons
Authors: Bykov A M , Uvarov Yu A , Kalyashova M E , Badmaev D V , Lapshov I Yu , Lutovinov A A , Mereminskiy I A , Semena A N
Published: August 2023

We present the results of current observations of the young compact cluster of massive stars Westerlund 2 (Wd2) with the Mikhail Pavlinsky ART-XC telescope aboard the Spectrum-Roentgen-Gamma (SRG) observatory which we analysed together with the archival Chandra data. In general, Wd2 was detected over the whole electromagnetic spectrum including high-energy gamma rays, which revealed a cosmic ray acceleration in this object to the energies up to tens of TeV. The detection of Wd2 with ART-XC allowed us to perform a joint spectral analysis together with the high resolution Chandra observations of the diffuse emission from a few selected regions in the vicinity of the Wd2 core in the 0.4–20 keV range. To fit the Wd2 X-ray spectrum above a few keV one needs either a non-thermal power-law emission component, or a hot plasma with temperatures ∼ 5 keV. Our magnetohydrodynamic modelling of the plasma flows in Wd2 shows substantially lower electron temperatures in the system and thus the presence of the non-thermal component is certainly preferable. A kinetic model of the particle acceleration demonstrated that the non-thermal component may originate from the synchrotron radiation of multi-TeV electrons and positrons produced in Wd2 in accordance with the TeV photons detection from the source.
An M dwarf accompanied by a close-in giant orbiter with SPECULOOS
Authors: Triaud Amaury H M J , Dransfield Georgina , Kagetani Taiki , Timmermans Mathilde , Narita Norio , Barkaoui Khalid , Hirano Teruyuki , Rackham Benjamin V , Mori Mayuko , Baycroft Thomas , Benkhaldoun Zouhair , Burgasser Adam J , Caldwell Douglas A , Collins Karen A , Davis Yasmin T , Delrez Laetitia , Demory Brice-Oliver , Ducrot Elsa , Fukui Akihiko , Muñoz Clàudia Jano , Jehin Emmanuël , García Lionel J , Ghachoui Mourad , Gillon Michaël , Chew Yilen Gómez Maqueo , Hooton Matthew J , Ikoma Masahiro , Kawauchi Kiyoe , Kotani Takayuki , Levine Alan M , Pallé Enric , Pedersen Peter P , Pozuelos Francisco J , Queloz Didier , Scutt Owen J , Seager Sara , Sebastian Daniel , Tamura Motohide , Thompson Samantha , Watanabe Noriharu , de Wit Julien , Winn Joshua N , Zúñiga-Fernández Sebastián
Published: August 2023

In the last decade, a dozen close-in giant planets have been discovered orbiting stars with spectral types ranging from M0 to M4, a mystery since known formation pathways do not predict the existence of such systems. Here, we confirm TOI-4860 b, a Jupiter-sized planet orbiting an M4.5 host, a star at the transition between fully and partially convective interiors. First identified with TESS data, we validate the transiting companion’s planetary nature through multicolour photometry from the TRAPPIST-South/North, SPECULOOS, and MuSCAT3 facilities. Our analysis yields a radius of $0.76\pm 0.02~\rm R_{Jup}$ for the planet, a mass of $0.34~\rm M_\odot$ for the star, and an orbital period of $1.52~\rm d$. Using the newly commissioned SPIRIT InGaAs camera at the SPECULOOS-South Observatory, we collect infrared photometry in zYJ that spans the time of secondary eclipse. These observations do not detect a secondary eclipse, placing an upper limit on the brightness of the companion. The planetary nature of the companion is further confirmed through high-resolution spectroscopy obtained with the IRD spectrograph at Subaru Telescope, from which we measure a mass of $0.67\pm 0.14~\rm M_{Jup}$. Based on its overall density, TOI-4860 b appears to be rich in heavy elements, like its host star.
Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis
Authors: Caravaca-Fontán Fernando , Stevens Kate , Padrón Maite , Huerta Ana , Montomoli Marco , Villa Juan , González Fayna , Vega Cristina , López Mendoza Manuel , Fernández Loreto , Shabaka Amir , Rodríguez-Moreno Antolina , Martín-Gómez Adoración , Labrador Pedro J , Molina Andújar Alicia , Prados Soler M Carmen , Martín-Penagos Luis , Yerovi Estefanía , Medina Zahonero Laura , De La Flor José Carlos , Mon Carmen , Ibernon Meritxell , Rodríguez Gómez Astrid , Miquel Rosa , Sierra Milagros , Mascarós Victoria , Luzardo Leonella , Papasotiriou Marios , Arroyo David , Verdalles Úrsula , Martínez-Miguel Patricia , Ramírez-Guerrero Gonzalo , Pampa-Saico Saúl , Moral Berrio Esperanza , Canga José Luis Pérez , Tarragón Blanca , Fraile Gómez Pilar , Regidor Dabaiba , Relea Javier , Xipell Marc , Andrades Gómez Cristina , Navarro Maruja , Álvarez Álvaro , Rivas Begoña , Quintana Luis F , Gutiérrez Eduardo , Pérez-Valdivia Miguel Ángel , Odler Balazs , Kronbichler Andreas , Geddes Colin , Anders Hans-Joachim , Floege Jürgen , Fernández-Juárez Gema , Praga Manuel
Published: August 2023

Background

The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear.

Methods

This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation.

Results

Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin–angiotensin system blockers were included. Proteinuria from baseline changed by –35%, –41%, –45% and –48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by –6%, –3%, –8% and –10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30–0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: –3.7 versus –5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good.

Conclusions

The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
A closer look at the role of iron in glioblastoma
Authors: Shenoy Ganesh , Connor James R
Published: August 2023

Glioblastoma (GBM) is among the deadliest malignancies facing modern oncology. While our understanding of certain aspects of GBM biology has significantly increased over the last decade, other aspects, such as the role of bioactive metals in GBM progression, remain understudied. Iron is the most abundant transition metal found within the earth’s crust and plays an intricate role in human physiology owing to its ability to participate in oxidation–reduction reactions. The importance of iron homeostasis in human physiology is apparent when examining the clinical consequences of iron deficiency or iron overload. Despite this, the role of iron in GBM progression has not been well described. Here, we review and synthesize the existing literature examining iron’s role in GBM progression and patient outcomes, as well as provide a survey of iron’s effects on the major cell types found within the GBM microenvironment at the molecular and cellular level. Iron represents an accessible target given the availability of already approved iron supplements and chelators. Improving our understanding of iron’s role in GBM biology may pave the way for iron-modulating approaches to improve patient outcomes.
BSBM-07 HIGH-DIMENSIONAL HISTOPATHOLOGIC EVALUATION OF THE HYPOXIC MICROENVIRONMENT IN GLIOBLASTOMA
Authors: Mansouri Sheila , Zaidi Mark , Singh Olivia , Karimi Shirin , Lombard Phoebe , Dvorkin-Gheva Anna , Velasquez Carlos , Ali Hafsah , Devaraja Kaviya , Sosa Julio , Patil Vikas , Wei QingXia , Wu Ronald , Li Mira , Cheung May , Voisin Mathew , Gao Andrew , Hedley David , Aldape Kenneth , Wouters Bradley , Zadeh Gelareh , Gandhi Shreya
Published: August 2023

Rapidly growing solid tumors such as glioblastoma (GBM) are characteristically hypoxic, displaying large areas of necrosis surrounded by hyperproliferative pseudopalisading cells. Intra-tumoral hypoxia develops over time in the three-dimensional space and the degree of tissue oxygenation is a dynamic process that varies continuously. Combined with the extensive inter- and intra-tumoral heterogeneity associated with GBM at the bulk and single cell level, hypoxia contributes to a gradient of molecular alterations that are specific to the different cell populations that make up the bulk of the tumor and reside in specific niches. To date, high dimensional histopathologic analyses of the hypoxic regions within GBM tissue have not been performed. Here, we took a combined spatial and single-cell proteomic profiling approach to investigate the histopathologic features of hypoxia by leveraging a unique clinical study where the exogenous hypoxia marker pimonidazole (PIMO) is administered to patients with GBM prior to surgery. Tissue specimens were subjected to imaging mass cytometry and serial immunohistochemistry using a panel of 27 markers associated with cellular hallmarks of hypoxia, metabolism, proliferation, stemness, angiogenesis, and immune cell types. We took high-resolution imaging and statistical approaches to explore the interplay of the different markers within hypoxic regions of primary and recurrent GBMs, in addition to IDH-mutant gliomas. Our findings elucidate the expression pattern of key biological markers relative to one another, altered composition of different cell types, along with differential proliferative, transcriptional, and translational activation states associated with each cell type within the hypoxic regions of GBM.
BSBM-10 CHARACTERIZATION OF A RADIATION-RESISTANT MODEL OF LUNG CANCER BRAIN METASTASIS
Authors: Wolford Cullen , Blethen Kathryn , Arsiwala Tasneem , Pecar Geoff , Fladeland Ross , Panchal Dhruvi , Kielkowski Brooke , Dykstra Leah , Blackburn Jillian , Dave Sahil , Lockman Paul
Published: August 2023

Lung cancer is the most common cancer to metastasize to the brain, with 50% of all brain metastases originating from lung primary tumors. Traditional therapy for lung cancer brain metastases includes surgical resection, radiation, and chemotherapy. Due to the presence of the blood-tumor barrier, penetration of therapeutics is significantly hindered. Even when used in combination, tumor recurrence and regrowth after initial chemoradiotherapy remain a significant issue. To recapitulate recurrent disease, we aim to characterize a radio-resistant preclinical model of brain metastasis to investigate its effect on growth, chemosensitivity, and drug permeation across the blood-tumor barrier. Herein, we have generated a human NSCLC cell line bearing EGFR exon 19 deletion (PC9) that has been serial passaged in mice to colonize brain (PC9-Br). PC9-Br cells were serially irradiated and allowed to proliferate for 10-14 days prior to re-irradiation. The total dose administered to PC9-Br cells was 60 Gy to generate a radioresistant population (PC9-Br-RR). Clonogenic, MTT, and SRB analysis indicates a significant increase in survival percentage of PC9-Br-RR compared to PC9-Br irradiation at 2, 4, 6, and 8 Gy. While PC9-Br-RR cells are more resistant to cisplatin than PC9-Br (IC50: 2.5 µM and 1.5 µM, respectively at 72 h), they are more sensitive to osimertinib in vitro (IC50: 6.9 nM and 33 nM, respectively at 72 h). In vivo, PC9-Br-RR tumors developed more rapidly in mice than PC9-Br and brain-to-body tumor burden analysis showed PC9-Br-RR cells have increased brain tropism. Collectively, this data supports the characterization of a radio-resistant brain metastasis model to investigate the role of acquired radio-resistance at the blood-tumor barrier.
BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Authors: Vilarino Noelia , de Rodas Miguel Lopez , Lu Benjamin Y , Goldberg Sarah , Schalper Kurt
Published: August 2023

BACKGROUND

Immune checkpoint inhibitors (ICI) can have activity in lung cancer brain metastases (LBM). However, the duration of responses is limited and most patients with LBM do not benefit from these therapies. Alterations in HLA class-I antigen presentation machinery via beta-2 microglobulin (B2M) downregulation and disruption of IFN-γ sensing were identified as mechanisms of immune evasion and ICI resistance in solid tumors. However, the expression and clinical significance of these pathways in LBM are poorly understood.

METHODS

Using multiplex quantitative immunofluorescence we measured the localized expression of B2M protein; and the IFN-γ pathway markers phospho-STAT1 (pSTAT1), and Interferon Regulatory Factor 1 (IRF-1) in 67 immunotherapy naïve LBM and 45 primary lung tumors (PLT), including 15 patients with paired samples represented in a tissue microarray. The markers were selectively measured in cytokeratin + tumor cells and in cytokeratin- stromal cells. Associations between the markers, PD-L1, TILs and clinicopathologic variables were compared between LBM and PLT.

RESULTS

LBM showed lower levels of B2M in both tumor and stroma compartments compared to PLT. In contrast, high tumor and stromal levels of pSTAT1 were observed in LBM and comparable levels of IRF-1 were found between both tumor sites. Consistently across LBM and PLT samples, pSTAT1 and IRF1 were strongly correlated, and a positive but weaker association was observed with B2M and TILs. Only in PLT high tumor-cell PD-L1 expression was associated with high levels of IRF-1. No statistically significant association was observed between the markers and clinicopathologic variables. Tumor B2M downregulation in PLT was associated with worse survival.

CONCLUSION

LBM show distinct immunomodulatory properties relative to PLT, characterized by reduced HLA class-I antigen presentation machinery, elevated IFN-γ signaling and reduced local adaptive immune responses. These results support differences in immune evasion mechanisms in LBM compared with the PLT, which may have biological and clinical implications.
BSLD-05 ESTABLISHMENT AND CHARACTERIZATION OF MOUSE MODELS OF LEPTOMENINGEAL METASTASIS
Authors: Derderian Camille , Guber David , Remsik Jan , Wang Helen , Li Min Jun , Tong Xinran , Cortesao Nobre Ana Rita Lobato , Osman Ahmed , Freret Morgan , Schneider Jenna , Wilcox Jessica , Chabot Kiana , Boire Adrienne
Published: August 2023

There is critical need to study leptomeningeal metastasis (LM), a fatal complication of cancer accompanied by severe neurological deficits. LM occurs when cancer cells enter the leptomeninges, float in the cerebrospinal fluid (CSF), and adhere to the surface of the brain and spinal cord. Understanding the molecular basis of LM requires reliable models of the disease that can recapitulate the complex microenvironment that supports LM cell growth. Here, we define a protocol for iterative in vivo selection of cancer cells competent to colonize the leptomeninges (LeptoM cells) from a larger population of primary tumor cells that stably express GFP and luciferase. We use these LeptoM cells to establish tractable models of leptomeningeal disease in both syngeneic and xenograft mice. With these models, we modulate disease severity and capture snapshots of hallmark LM characteristics over time. We demonstrate the fidelity of these mouse models to human disease in several dimensions: 1. Biochemically, through CSF proteomics and metabolomics; 2. Immunologically, via flow cytometry and cytokine profiling; 3. Transcriptionally through RNA sequencing; and 4. Neurologically by accumulation of neurological signs. They are freely available to the academic community. These models provide robust, reproducible tools for discovery and mechanistic dissection. They will enable identification of critical disease mechanisms, and assays of novel treatment modalities against LM.
CLRM-05 ADAPTATION OF NEW CLASSIFICATION OF ASTROCYTOMA IN LOW AND MIDDLE INCOME COUNTRY- HOW SMOOTH IS THE ROAD AHEAD?
Authors: Shrestha Roshani , Sapkota Simit , Adhikari Abish , Pandit Subhas , Jha Anjani , Karki Prakriti
Published: August 2023

BACKGROUND

The 2021 WHO CNS 5 classification made major changes with integration of immunohistochemistry, molecular profiling and sequencing in addition to histopathology to classify brain tumors. IDH mutation is mainstay for diagnosis of low grade glioma and 1p/19q testing required only to confirm oligodendroglioma but not in all cases. This integrated approach has favored prognosis, and diagnosis of disease as well as prediction of response to therapy.

METHODS

A retrospective study was conducted to analyze the molecular alterations in patients diagnosed with astrocytoma in 2021 in Kathmandu Cancer Center, Nepal. The demographic data were collected from the patients’ archived files from the medical record department. The patients were categorized as IDH: mutant and wild, and ATRX: retained and lost.

RESULTS

This study demonstrated IDH and ATRX mutation with 30.3% and 24.23% respectively. In our study, among grade 2 and 3 patients, 8 out of 11 (72.7%) were IDH mutant types. 2 patients of this group were IDH wild type, who ideally required further testing for correct classification but couldn’t be done due to financial constraints. IDH status of one patient in this group was unknown. 72.7% of the Grade 4 gliomas were IDH wild type and classified as Glioblastoma Multiforme. In 6 of the patients IDH status was unknown. Among 8 grade 2 and 3 tumors with IDH mutant, 2 had loss of ATRX and 6 had ATRX retained. Among these 6 patients only one had 1p/19q co-deletion done which was positive. Rests 5 were not properly classified.

CONCLUSION

In conclusion, higher percentage of IDH wild type was seen in Grade 4 gliomas. Similarly, the IDH mutant type predominated in Grade 2 and 3 gliomas. More pronounced investigations are still not feasible in low- and-middle income countries because of limited resources.
CLRM-07 RANO 2.0: PROPOSAL FOR AN UPDATE TO THE RESPONSE ASSESSMENT IN NEURO-ONCOLOGY (RANO) CRITERIA FOR HIGH- AND LOW-GRADE GLIOMAS IN ADULTS
Authors: Wen Patrick , Van Den Bent Martin , Youssef Gilbert , Cloughesy Timothy , Ellingson Benjamin , Weller Michael , Galanis Evanthia , Barboriak Danial , DeGroot John , Gilbert Mark , Huang Raymond , Lassman Andrew , Mehta Minesh , Molinaro Annette , Preusser Mattias , Rahman Rifaquat , Shankar Lalitha , Stupp Roger , Sul Joohee , Villanueva-Meyer Javier , Wick Wolfgang , Macdonald David , Reardon David , Vogelbaum Michael , Chang Susan
Published: August 2023

The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve the reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. Informed by data from a cohort of glioblastoma patients and other evaluations of RANO criteria that allowed evaluation of features of the different criteria, we propose updates to the RANO criteria (RANO 2.0). Based on the 2021 WHO classification of gliomas, we recommend a standard set of criteria for both high and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the post-radiotherapy MRI, rather than the post-surgical MRI, will be used as the baseline for future comparison. Since the incidence of pseudoprogression is high in the 12 weeks following radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, is required to define tumor progression. However, confirmation scans are not mandatory after this period nor for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement remains the maximum cross-sectional area of tumor (2-dimensional) but volumetric measurements are an option. For IDH-wildtype glioblastoma, the non-enhancing disease will no longer be evaluated. In IDH-mutated tumors with a significant non-enhancing component, clinical trials may require evaluating both the enhancing and non-enhancing tumor components for response assessment.
LMAP-05 BEVACIZUMAB AND GAMMA KNIFE RADIOSURGERY IN THE TREATMENT OF FIRST-RECURRENCE GLIOBLASTOMA
Authors: Zhang Jeff , Okai Bernard , Iovoli Austin , Goulenko Victor , Lim Jaims , Hess Ryan , Prasad Dheerendra , Fenstermaker Robert
Published: August 2023

Glioblastoma is the most common central nervous system malignancy in adults and remains a uniformly fatal disease despite two decades of developments in surgical management, radiation treatment, chemotherapy, and immunotherapy. There is currently no established standard of care for patients with recurrent glioblastoma following failure of initial Stupp protocol management. In this retrospective cohort study, we set out to determine if the use of bevacizumab and/or Gamma Knife radiosurgery in patients with recurrent disease could have an effect on prolonging progression-free survival (PFS) or overall survival (OS). Patients in the combined treatment group demonstrated longer post-recurrence mean PFS (9.1 ± 6.0 months) and OS (13.5 ± 8.6 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total OS (p=0.021), total PFS (p=0.057), post-recurrence PFS (p=0.034), and post-recurrence OS (p=0.017) compared to patients who received standalone bevacizumab or Gamma Knife treatment. This study demonstrates that the combined use of an antiangiogenic agent with stereotactic radiosurgery can have significant effects on improving patient survival in recurrent glioblastoma.
LMAP-08 MULTI-INSTITUTIONAL CLINICAL OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM GYNECOLOGIC MALIGNANCIES
Authors: Huang Christina , Leng Jim , Qazi Jamiluddin , Carpenter David , Chino Junzo , Ayala-Peacock Diandra , Stephens Sarah , Natarajan Brahma , Arshad Muzamil , Schultz Olivia , Moravan Michael , Reitman Zachary , Kirkpatrick John , Floyd Scott , Chmura Steven , Hong Julian , Salama Joseph , Mullikin Trey
Published: August 2023

Brain metastases (BM) are rare in patients with gynecologic (GYN) malignancies. We identified and analyzed all patients who completed a course of stereotactic radiosurgery (SRS) between 1/2015 and 12/2020 across two institutions. Demographic and clinical parameters were collected. Intracranial progression (ICP) was defined as any concern on post-SRS imaging for recurrence determined by multidisciplinary consensus. Clinical parameter distributions were compared across GYN and non-GYN patients utilizing chi-squared tests and t-tests. Overall survival (OS) and freedom from intracranial progression (FFICP) were estimated via the Kaplan Meier method. From a cohort of 1383 patients who completed SRS for BMs, 2.4% (n=33) had a BM from a GYN malignancy. Subsites included endometrial (n=19), ovarian (n=11), vulvar (n=2), cervical (n=1). There was no difference in age between GYN and non-GYN patients (mean 67.1 years vs. 63.0 years, p=0.06). GYN patients with BMs compared to non-GYN patients were more likely to have resection of BMs (48.5% vs. 25.6%, p=0.003), larger planned target volumes of all BMs (mean 23.6cc vs mean 15.2cc, p=0.02), and pre-SRS chemotherapy (72.7% vs. 49.6%, p=0.009). GYN patients were less likely to have whole brain radiation therapy prior to SRS (0 vs. 10.5%, p=0.049). GYN patients had worse OS compared to non-GYN patients (median 6.6 months (95% CI 3.3-12.4) vs. 10.0 months (95% CI 9.1-11.2), (HR 1.62 (95% CI 1.11-2.36), p=0.011)). Median FFICP for GYN patients was 9.5 months (95% CI 4.0-not reached) and for non-GYN patients was 8.7 months (95% CI 7.7-9.5). There was no difference in FFICP for GYN patients compared to non-GYN patients (HR 0.84 (95% CI 0.5-1.5), p=0.55). When comparing patients with BMs from endometrial cancer versus ovarian cancer, there was no difference in OS (p=0.13) or FFICP (p=0.58). These data may help guide treatment decisions and post-therapy surveillance in patients with BMs of GYN origin.
LMAP-10 RE-IRRADIATION FOR RECURRENT ADULT DIFFUSE GLIOMA
Authors: Zhou Jiangfen , Lai Mingyao , Cai Linbo
Published: August 2023

OBJECTIVE

To investigate the efficacy of re-irradiation and prognosticators for recurrent adult diffuse glioma diagnosed per 2022 WHO diagnostic criteria for central nervous system tumors.

METHODS

Patients older than 18 years with recurrent diffuse glioma confirmed by functional imaging or secondary surgical histopathology in Guangdong Sanjiu Brain Hospital from January 1, 2016, to December 31, 2022, were retrospectively analyzed. All patients were re-diagnosed per the 2022 WHO classification of central nervous system gliomas. All patients received re-radiotherapy after tumor recurrence, including conventional fractionation, hypofractionation, and stereotactic radiosurgery.

RESULTS

A total of 61 patients were included in this analysis, male to female ratio was 34:27, median age of 45 (ranging from 18-64) years. There were 35 cases of grade IV glioblastoma, 5 cases of grade IV astrocytoma, 3 cases of grade III astrocytoma, 13 cases of grade II astrocytoma, 3 cases of grade III oligodendroglioma, and 2 cases of grade II oligodendroglioma. Twenty-four patients (39.3%) underwent re-operative surgery after recurrence. Forty-one patients (67.2%) received concurrent re-irradiation and chemotherapy, and 26 (42.6%) received concurrent bevacizumab. The median interval from the first to the second radiotherapy was 19 months. The median overall survival (OS) of 61 patients was 47 months, and the median OS following re-irradiation was 13 months. Univariate analysis showed that WHO grading (p = 0.007), IDH status (p = 0.026), reoperation after recurrence (p = 0.019), re-irradiation with or without concurrent chemotherapy (p = 0.026), maintenance chemotherapy (p = 0.038), and antiangiogenic therapy (p = 0.011) were the significant prognosticators.

CONCLUSIONS

Re-radiotherapy is feasible and safe for recurrent adult diffuse glioma. Re-irradiation subsequent to the re-operative surgery after recurrence combined with other therapies are favorable prognosticators. Patients with IDH mutation could benefit more from re-irradiation after recurrence.
LMAP-20 EVIDENCE-BASED MULTIVARIATE NORMAL TISSUE COMPLICATION PROBABILITY (NTCP) STUDY OF DOMAIN-SPECIFIC COGNITIVE DECLINE AFTER PARTIAL BRAIN RT
Authors: Hopper Austin , Connor Michael , Salans Mia , Unnikrishnan Soumya , Huynh-Le Minh-Phuong , Tibbs Michelle , Qian Alex , Reyes Anny , Stasenko Alena , McDonald Carrie , Moiseenko Vitali , Hattangadi-Gluth Jona
Published: August 2023

Beyond the hippocampus, there are no evidence-based dose constraints for eloquent structures which subserve memory and attention/processing speed. We performed a multivariate normal tissue complication probability analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions in a prospective longitudinal clinical trial. 78 patients with primary brain tumors receiving fractionated RT completed a comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using validated automated segmentation parcellated individual white matter (WM) tracts, cortical regions, and hippocampi. Neurocognitive test performance was scored using reliable change indices adjusted for practice effects: negative scores indicate decline. Univariate logistic regression and multivariate model building were performed. On univariate analysis mean and max dose to multiple regions of the corpus callosum (CC) correlated with attention/processing speed decline including Dmax to anterior CC (p=0.011) and central CC (p=0.010), and Dmax/Dmean to mid-anterior CC (p=0.006 and 0.010). Dmean to left fornix was associated with memory decline (p=0.023), as were increasing age and chemotherapy. On multivariate analysis for attention, automated bootstrapped logistic regression showed the most frequently selected variable was Dmean to mid-anterior CC. Performance at nested cross-validation by AUC was 0.80 (0.75-0.84); LASSO model performance by AUC was 0.76 (0.72-0.81) with Dmean to the mid-anterior CC being the most frequent variable. The top five most important variables in Random Forest were Dmean to mid-anterior CC, all WM, combined CC and Dmax to CC and posterior CC. Model performance by AUC was 0.66 (0.60-0.71). We present the first, to our knowledge, multivariate NTCP model for decline in attention/processing speed, and dosimetric predictors of memory decline beyond the hippocampus. Dose to several eloquent ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.
LMAP-22 STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES FROM GASTROESOPHAGEAL PRIMARY CANCERS
Authors: Taori Suchet , Wei Zhishuo , Deng Hansen , Lunsford L Dade , Niranjan Ajay
Published: August 2023

BACKGROUND

Patients with brain metastases from gastroesophageal primary cancers have poor prognoses, and current management remains unclear. The authors present the largest single-institution experience of utilizing stereotactic radiosurgery (SRS) to treat patients with brain metastases from primary gastroesophageal cancers.

METHODS

A retrospective review of 71 patients (64 male, 90.14%) treated with Gamma Knife SRS from 2000 to 2022 for gastroesophageal primary cancers was conducted. Overall, 243 brain metastases were treated, and the median number of metastases per patient was 2 (range:1-21). The primary sites were esophagus (59 patients, 83.10%), gastric (7 patients, 9.86%), and gastroesophageal junction (5 patients, 7.04%). The median age at SRS was 66 years (range: 26-85), and the median KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76), and the median margin dose was 18 Gy (range: 11-20).

RESULTS

The median overall survival after SRS was 7 months (range: 1-64). At the last follow-up, 54 (76.06%) patients were deceased, and 8 (14.81%) patients died due to intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. On univariate analysis, > 2 brain metastases at SRS presentation (p=0.02, HR: 10.76, 95% CI: 1.48-78.40) was found to be the only significant predictor of local tumor progression. Ten patients (14.08%) experienced new tumor development at a median time of 4 months (range: 0-14) after SRS. On multivariate analysis, both the absence of concurrent systemic therapy (p=0.01, HR: 6.58, 95% CI: 1.55-27.0) and ≤ 2 tumors at SRS presentation (p<0.01, HR: 1.21, CI: 1.08-1.36) were found to be significant predictors of distant tumor control. The incidence of transient adverse radiation effects was 8.45%.

CONCLUSIONS

SRS can safely and effectively be used to treat primary gastroesophageal cancer brain metastases while allowing patients to focus on primary disease management.
NEIM-07 HARNESSING END-TO-END CLOUD-BASED WORKFLOWS AND MULTI-MODAL DATA ANALYTICS IN PEDIATRIC BRAIN TUMOR IMAGING AT THE CHILDREN’S BRAIN TUMOR NETWORK (CBTN)
Authors: Nabavizadeh Ali , Familiar Ariana , Kazerooni Anahita Fathi , Viswanathan Karthik , Kim Meen Chul , Lubneuski Alex , Heath Allison P , Vossough Arastoo , Storm Philip B , Resnick Adam C
Published: August 2023

Neuroimaging is an essential component of the standard of care in pediatric brain tumor patients. Developing efficient and agile workflows for image processing and integration of imaging with other data types to perform predictive analytics is an increasing need. At CBTN, we developed user-friendly workflows to support the entire imaging data lifecycle and to bridge access to multi-modal datasets with scalable analytics, to empower researchers to make breakthrough discoveries that will advance patient care. An automated deep learning-based brain extraction and tumor subregion segmentation model based on a multi-institutional dataset was developed that can reliably segment the treatment-naïve MRI scans of children across a variety of brain tumor histologies. This model was subsequently integrated into an end-to-end imaging pipeline for collecting, managing and analyzing clinically acquired radiology exams of the CBTN consortium with processing of 19,975 exams (1,443 subjects) to date. Critically, the constituent software tools enable the preparation of images for downstream AI analytics, from acquisition to feature extraction. A public website was also created to allow users to search and explore the dataset based on sequence labels, and clinical and imaging attributes. In addition, we established a scalable workflow and processes for de-identification, ingestion, quality control, and management of digital pathology slides for CBTN (over 8,000 slides to date). Finally, we evaluated the feasibility of interoperability between imaging (Flywheel) and molecular (CAVATICA) platforms deployed in cloud ecosystems which can allow streamlined, user-friendly workflows to ingest and harmonize files, perform cohort selection, prepare data using standard processing packages and cloud resources, and conduct analysis on extracted multi-modal feature sets. The described workflow lays the foundation for the broad use of imaging studies and access to multi-modal datasets and analytics, with the goal of empowering researchers to make breakthroughs in patient care.
NEIM-12 PRE- AND POST-TREATMENT RADIOLOGIC FEATURES AND VOLUMETRIC CHANGES LINKED TO TREATMENT RESPONSE OF BRAIN METASTASES AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT)
Authors: Sanvito Francesco , Telesca Donatello , Cho Nicholas S , Sayari Jessica T , Nagaraj Raksha , Raymond Catalina , Rana Shivam , Patel Kunal , Mozaffari Khashayar , Uterberger Ansley A , Khanlou Negar , Magaki Shino , Pouratian Nader , Everson Richard G , Yang Isaac , Kim Won , Ellingson Benjamin M
Published: August 2023

OBJECTIVE

To identify pre-treatment imaging features of brain metastases (BM) associated with lesion-specific progression free survival (PFS-L) after laser interstitial thermal therapy (LITT) and to report longitudinal volumetric changes following the treatment.

METHODS

Forty-seven BM treated with LITT were retrospectively examined. BM were followed until clinical progression, radiologic progression according to the modified RANO criteria, or censoring. The association between imaging features and PFS-L was assessed with survival analyses. Post-LITT volume shrinkage over time was fit to an exponential decay model.

RESULTS

Thirteen BM progressed after LITT (median time to progression 3.9 months), seventeen met radiologic criteria for response after LITT (median time to response 12.1 months), and seventeen were stable at time of censoring. Median follow-up duration for censored BM was 18.5 months. The probability of PFS-L at six months (PFS6) was 70.6% for the whole cohort. Pre-LITT enhancing volume <2.5 cc (p=0.0004) and sphericity ≥0.705 (p=0.0026) predicted longer PFS-L (PFS6=86.8%), and BM meeting both cutoffs showed a cumulative benefit (p<0.0001, PFS6=100%). Pre-LITT diffusion imaging did not predict PFS-L, while a subset of lesions (n=7) with highly perfused hotspots had worse PFS-L (p=0.0012). Immediate post-LITT volume was increased compared to pre-LITT (p<0.0001, median increase 80.3%). The percentage of volume increase was not a predictor of PFS-L (p=0.56). In fifteen responding BM (88.2%), the post-LITT volumetric shrinkage over time was described by an exponential decay (R2 ranging 0.92-1.0), and the kinetics of shrinkage was heterogeneous (half-life ranging 0.3-5.4 months).

CONCLUSIONS

Pre-treatment small size and high sphericity are ideal baseline features for BM considered for LITT treatment and could aid patient selection. Modeling longitudinal volumetric changes of BM responding to LITT is a potential approach to identify BM at risk for progression which deviate from a typical shrinkage pattern.
NEIM-14 PET/MRI DETECTS A RAPID DECREASE IN CEREBRAL BLOOD FLOW IN GLIOBLASTOMA FOLLOWING BEVACIZUMAB INFUSION
Authors: Thaw-Poon Serena , Zaharchuk Greg , Spielman Daniel , Recht Lawrence , Corbin Zachary
Published: August 2023

BACKGROUND

The impacts of bevacizumab on the vasculature and metabolism of glioblastoma have been understudied. Previous work has shown that perfusion measurements of lesions decrease weeks after infusion. Metabolic consequences, either direct or as sequelae of vascular changes, have also been proposed. The timing of both processes in humans, however, is unclear. We aimed to study changes to the vasculature and metabolism of glioblastoma after the administration of bevacizumab.

METHODS

Patients (n = 8) diagnosed with recurrent glioblastoma requiring bevacizumab were enrolled. Baseline scans were acquired with a GE Healthcare SIGNA PET/MRI scanner. Following the first infusion of bevacizumab (7.5 mg/kg), repeat scans were obtained within two days and two weeks. All scans were co-registered and analyzed using 3D Slicer. Cerebral blood flow (CBF) and standard uptake value (SUV) measures were normalized by taking the ratio of the mean tumor and contralateral region values, and the ratios at different time points were compared using Wilcoxon signed-rank tests.

RESULTS

A statistically significant decrease in tumor CBF was detected within two days of infusion (0.88 ± 0.36 vs. 0.79 ± 0.29, p = 0.01), but no significant decrease in SUV was detected within the same timeframe (0.89 ± 0.36 vs. 0.88 ± 0.39, p = 0.26). No statistically significant drop was detected at two weeks in our sample.

CONCLUSIONS

Our results provide evidence that bevacizumab decreases glioblastoma blood flow within two days of the infusion. The measure of tumor metabolism also trended downward, though not significantly. Taken together, these data support a model by which bevacizumab rapidly affects VEGF-mediated vascular changes within the tumor, withpotential effects on tumor metabolism over a longer timeframe. These findings enrich our understanding of the impacts on glioblastoma of bevacizumab, which has a continued high clinical utility that is underscored by its ubiquity in the neuro-oncology clinic.