bluuebunny/crossref_metadata_2025 huggingface dataset:
INNV-06. DETECTION OF MUTANT P53 POSITIVE GLIOBLASTOMA CELLS IN CEREBROSPINAL FLUID (CSF) USING A MICROFLUIDIC BASED IMMUNOASSAY
Authors: Hsiao Steven , Pircher Tony , Sweed Nathan , Armijo Kaitlyn , Marrin Mikayla , Cho Leslie , Dugan Michael , Kesari Santosh
Published: November 2022

BACKGROUND

Metastatic involvement of the CSF by non-CNS neoplasms surpasses that of primary brain tumors, although conventional glioblastoma (GBM) can occasionally be identified in the CSF. Here, we apply Biocept’s CNSide test to examine a patient CSF sample with GBM, verified with an antibody against mutant p53. The p53 pathway is deregulated in 84% of glioblastoma patients and point mutations lead to expression of mutant p53 protein.

METHODS

A CSF sample from 65-year-old male patient, with GBM diagnosed by MRI & CT, and prior identified p53 mutation on R273C by NGS was collected into Biocept’s CSF collection tubes at Providence Saint John’s Health Center. CSF-cells were incubated, 2 days post collection, with a proprietary antibody cocktail, including anti-CD9, followed with a biotinylated secondary, which enables enrichment of capture antibody labeled cells in a streptavidin coated microfluidic device. Cells were fixed and permeabilized immunofluorescence was performed against mutant p53, CD45, fluorescently labeled streptavidin, for capture antibody detection, and DAPI. Microfluidic chips were scanned and analyzed on a Bioview system. The specificity of the mutant p53 antibody was verified using the same test on tumor cells with either wildtype p53 vs various p53 mutations.

RESULTS

CSF analysis by the CNSide platform detected 3 tumor cells / mL. Immunofluorescence confirmed strong expression of mutant p53 protein on about 1/3 of cells identified as tumor cells. Besides the patient R273C mutation, we demonstrated detection of P223L/V274F, E285K and Q331R mutations on tumor cell lines.

DISCUSSION

Our work suggests that a microfluidic based GBM capture test paired with appropriate biomarkers can be used as sensitive means to detect GBM cells in CSF and may be useful for diagnostics and treatment monitoring. Further, we demonstrated the utility of a mutant p53 antibody to identify tumor cells. Technical and clinical studies are needed to substantiate this hypothesis.
PATH-07. MULTIPLATFORM MOLECULAR ANALYSES REFINE CLASSIFICATION AND PROGNOSTICATION OF GLIOMAS ARISING IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1
Authors: Lucas Calixto-Hope , Sloan Emily , Jung Jangham , Gupta Rohit , Wu Jasper , Vasudevan Harish , Shai Anny , Whipple Nicholas , Bruggers Carol , Samuel David , Maher Ossama , Lu Rufei , Mirchia Kanish , Sullivan Daniel , Pekmezci Melike , Tihan Tarik , Bollen Andrew , Perry Arie , Banerjee Anu , Gupta Nalin , Mueller Sabine , de Groot John , Clarke Jennifer , Raleigh David , Phillips Joanna J , Reddy Alyssa , Chang Susan M , Berger Mitchel S , Diaz Aaron , Solomon David A
Published: November 2022

BACKGROUND

Gliomas arising in patients with neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade (LG) or high-grade (HG), and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 and epigenetic classification of these tumors remain limited.

METHODS

Next-generation sequencing and DNA methylation profiling was performed on gliomas from 47 NF1 patients and correlated with clinicopathologic features, treatment, and outcomes.

RESULTS

30 tumors demonstrated biallelic inactivation of NF1 without additional oncogenic alterations (“molecular LG subgroup”, median age 14 yrs). The remaining 17 tumors harbored additional oncogenic alterations beyond NF1 (“molecular HG subgroup”, median age 28), most frequently CDKN2A homozygous deletion (n=13), ATRX mutation (n=8), PIK3CA or PIK3R1 mutation (n=4), and TP53 mutation (n=3). Survival analysis showed significant differences in time to progression (137 vs 11 mos, p< 0.0001) and median survival time (undefined vs 37 mos, p > 0.0001) for molecular LG versus HG subgroups. DNA methylation profiles of the molecular LG subgroup resolved into a new epigenetic cluster closest to but divergent from the three existing reference classes of sporadic pilocytic astrocytoma. DNA methylation profiles of the molecular HG subgroup demonstrated most tumors epigenetically align with either HGAP or various subclasses of IDH-wildtype GBM.

CONCLUSION

NF1-associated gliomas stratify into two molecular subgroups. The “molecular LG subgroup” occurs primarily during childhood, harbors biallelic NF1 inactivation only, follows a more indolent clinical course, and has a unique epigenetic signature for which we propose the terminology “pilocytic astrocytoma, arising in the setting of NF1”. The “molecular HG subgroup” occurs primarily during adulthood, harbors additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, follows a more aggressive clinical course, and is epigenetically diverse. These findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.
NIMG-42. DURABLE OVERALL RESPONSE RATE (ORR) TARGETS FOR RECURRENT GLIOBLASTOMA (RGBM) CLINICAL TRIALS BASED ON THE HISTORIC ASSOCIATION BETWEEN ORR AND MEDIAN OVERALL SURVIVAL (MOS)
Authors: Ellingson Benjamin , Wen Patrick Y , Chang Susan , van den Bent Martin , Vogelbaum Michael , Li Gang , Li Shanpeng , Kim Jiyoon , Youssef Gilbert , Wick Wolfgang , Lassman Andrew , Gilbert Mark , de Groot John , Weller Michael , Galanis Evanthia , Cloughesy Timothy
Published: November 2022

Durable overall response rate (ORR) remains a meaningful endpoint in recurrent GBM; however, the target ORR for single arm recurrent GBM trials has not been based on historic information or tied to patient outcomes. The current study reviewed past trials in recurrent GBM in order to judiciously define target ORRs for use in recurrent GBM trials. After reviewing 69 treatment arms comprising 4,971 patients, ORR was 6.1%[95% CI 4.23; 8.76%] for cytotoxic chemotherapies (ORR=7.59% for CCNU, 7.57% for TMZ, 0.64% for CPT-11, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for immunotherapies (select trials), and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2=0.4078, P< 0.0001), biologics (R2=0.4003, P=0.0003), and immunotherapy trials (R2=0.8994, P< 0.0001), but not anti-angiogenic agents (R2=0, P=0.8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2=0.3164, P< 0.0001; mOS[weeks]=0.6xORR+28.9), suggesting an ORR >20% results in an mOS of > 40.9 weeks, which is double the survival estimate of a treatment with ORR=0% and ≥ 2 months longer than treatments with ORR=5%. Assuming an ineffective therapy (control) has ORR=5%, a trial of 32 patients with a target ORR=20% leads to the 95% confidence interval higher than the control group. We conclude that single arm phase II studies in recurrent GBM with ≥ 32 patients should have a target ORR ≥ 20%. This was associated with a median OS of approximately 1 year. Importantly, durability of response should also be considered and was not assessed in the current meta-analysis.
NIMG-83. MULTIMODAL PET/MRI RADIOMICS AND CLINICAL PARAMETERS FOR OVERALL SURVIVAL PREDICTION IN PATIENTS WITH IDH WILDTYPE GLIOBLASTOMA
Authors: Gutsche Robin , Bauer Elena , Kocher Martin , Werner Jan-Michael , Fink Gereon , Shah Nadim , Langen Karl-Josef , Galldiks Norbert , Lohmann Philipp
Published: November 2022

BACKGROUND

Currently, most radiomics studies on survival prediction in brain tumor patients are based on MRI only. The goal of our study was to evaluate multimodal radiomics derived from amino acid PET/MRI and clinical parameters for survival prediction in patients with newly diagnosed IDH wildtype glioblastoma.

METHODS

Sixty-three patients with newly diagnosed IDH wildtype glioblastoma were evaluated retrospectively. At initial diagnosis, all patients underwent structural MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET. Tumor volumes were automatically segmented using a deep learning-based tool followed by visual inspection. Predefined and deep radiomics features were extracted from both imaging modalities. Feature repeatability analyses and feature selection were performed to avoid overfitting. Cox regression models for overall survival were built from clinical parameters such as age or the extent of resection, radiomics features, and combinations thereof, and finally validated using 5-fold cross-validation. Further evaluation of the model in an external test dataset is ongoing.

RESULTS

The median overall survival was 12 months (range, 0-64 months). Higher age and larger FET PET tumor volumes were significantly correlated with shorter overall survival (age, r=-0.39, p< 0.001; volume, r=-0.31, p< 0.05). Models solely based on predefined FET PET or MRI radiomics features showed a similar mean concordance index (C-index) as the model based on clinical parameters (C-indices, 0.68±0.04; 0.64±0.03; and 0.69±0.08, respectively). Multimodal radiomics based on predefined and deep features yielded improved C-indices of 0.75±0.06 and 0.72±0.09, respectively. A model based on multimodal radiomics and clinical parameters achieved the best prognostic performance (C-index, 0.80±0.04).

CONCLUSION

Our results suggest an added clinical value of multimodal FET PET/MRI radiomics with clinical parameters for the non-invasive survival prediction in patients with IDH wildtype glioblastoma.
NCMP-04. COMBINATION BRAF/MEK INHIBITION IMPROVES SURVIVAL WITH LEPTOMENINGEAL DISEASE FROM MELANOMA IN A SINGLE INSTITUTIONAL REVIEW AT MOFFITT CANCER CENTER
Authors: Wallace Gerald , Kundalia Ronak , Imran Amna , Smalley Inna , Pina Yolanda , Forsyth Peter
Published: November 2022

Melanoma is third most common cancer to metastasize to the leptomeningeal space and confers a dismal prognosis. We retrospectively identified 87 cases of melanoma related leptomeningeal disease (M-LMD) diagnosed between 2011-2020 at Moffitt Cancer Center. The average age at diagnosis was 54 years (range 28-93 years) with a male predominance (50 men vs 36 women). There was a significant increase in median overall survival (OS) for patients with BRAF V600E mutation, but only if they were treated with combined BRAF/MEK inhibitors after diagnosis of LMD (5.54 months vs 1.39 months; p < 0.01). Immune checkpoint inhibitors also associated with a small but significant increase in OS when given after diagnosis of M-LMD (2.73 months vs 1.38mths; p < 0.01). There was no association between OS and gender (p > 0.05). The current data supports use of BRAF/MEK inhibitors for treatment of BRAF V600E mutated M-LMD. More work is needed to improve OS for these patients and patients without a targetable mutation and M-LMD.
NCMP-11. METASTATIC MENINGIOMA: AN UNUSUAL COURSE OF A COMMON DISEASE
Authors: Bazer Danielle , Zabrocka Ewa , Torres Marielle , Frontario Ariana , Kowalska Agnieszka
Published: November 2022

BACKGROUND

The most common central nervous system (CNS) tumor in adult patients is meningioma, accounting for 30% of all intracranial tumors. Despite this, extracranial meningioma metastases are exceedingly rare, accounting for 0.1% of cases, with common locations for metastases localized to the lungs, liver, lymph nodes, and bone.

RESULTS

We present a 55-year-old female with a past medical history of tobacco use, hypertension and depression, who initially presented due to a generalized tonic-clonic seizure. MRI brain revealed an intracranial lesion in the left occipital lobe with mass effect, requiring craniotomy and resection. Pathology was consistent with WHO grade I meningioma and post-operatively a small area of residual tumor remained. PET/CT found a left lung nodule, which was thought to be due to her smoking history and was followed with annual scans. Four years later, she had an increase in the size of the meningioma on surveillance MRI scans. The patient then required repeat craniotomy which redemonstrated pathology of WHO grade I meningioma, then treated with stereotactic radiation 14 Gy. The subsequent annual surveillance pulmonary scan showed a growth of left pulmonary nodule. She underwent a left lingual wedge resection and was found to have low grade spindle cell tumor, consistent with metastatic meningioma.

CONCLUSION

Although rare, metastatic meningioma should be included in the differential diagnosis of patients with concomitant extracranial lesions. Our case highlights the importance of annual, surveillance scans of extracranial lesions in meningioma patients.
NCMP-22. TREATING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) WITH PEMBROLIZUMAB: A SINGLE INSTITUTION EXPERIENCE
Authors: Hanna Sebastian , Thomas Alissa
Published: November 2022

BACKGROUND

PML is a rapidly progressive demyelinating disease, occurring in immunocompromised patients due to the opportunistic JC virus. The highest mortality rates are seen among patients with cancer treated with immunosuppressive therapy and for whom immune reconstitution is not possible. In 2019, the National Institutes of Health reported clinical benefit in patients with PML treated with pembrolizumab. We report our institutional experience with pembrolizumab for three patients with PML after exposure to rituximab and other chemotherapy. CASE PRESENTATION: The first patient was a 75-year-old woman with a history of psoriatic arthritis and bullous pemphigoid treated with rituximab. Eight months after rituximab exposure she presented with right hemiparesis and word-finding difficulty. PML was diagnosed based on positive JC virus DNA in cerebrospinal fluid by PCR. She received two doses of pembrolizumab with improvement in her neurological symptoms. Shortly after her second dose she contracted COVID-19 and died at her nursing home. The second patient was a 47-year-old man with a history of T cell/histiocyte large B-cell lymphoma treated with R-CHOP with salvage DHAP chemotherapy followed by BEAM and autologous stem cell transplant, with complete remission. Seven months post-transplant he presented with a rapidly progressive hemianopsia and aphasia, and PML was confirmed by brain biopsy. He received one dose of pembrolizumab but worsened and died of neurological deterioration secondary to PML. The third patient was a 73-year-old man with a history of mantle cell lymphoma previously treated with rituximab and bendamustine, who presented with acalculia and aphasia 14 months after rituximab exposure. PML was confirmed by brain biopsy, and he was treated with pembrolizumab with improvement in his neuro-cognitive functioning.

CONCLUSIONS

We observed neurological improvement following pembrolizumab treatment for PML in two of three patients, with one patient experiencing a durable response that is ongoing 3 years following PML diagnosis.
NCOG-29. INFLUENCE OF RADIATION DOSES TO HIPPOCAMPAL SUBVOLUMES ON MEMORY OUTCOMES IN PITUITARY TUMORS: DOES THE ENTIRE HIPPOCAMPUS NEED TO BE SPARED?
Authors: Dasgupta Archya , Thomas Ajay , Sahu Arpita , Agarwal Ujjwal , Chatterjee Abhishek , Goswami Savita , Gaikwad Utpal , Singh Vikas , Shetty Prakash , Moiyadi Aliasgar , Sahay Ayushi , Sridhar Epari , Jalali Rakesh , Gupta Tejpal , Goda Jayant Sastri
Published: November 2022

INTRODUCTION

In patients treated with radiation (RT), doses to hippocampus influence neurocognitive outcomes. However, the role of hippocampal subvolumes in memory functioning has not been reported, which prompted the current study.

METHODS

Adults ( > 18 years) with pituitary tumors treated with fractionated RT (45 Gy/ 25 fractions/ 5 weeks) were accrued in the prospective study. Hippocampus was delineated on T1-weighted 3D-FSPGR sequences with 1mm slice thickness. The head, body, and tail of hippocampus were drawn for the current study based on the consensus of two neuroradiologists. The anatomical landmarks were: head (basilar artery to interpeduncular cistern), body (interpeduncular cistern to superior colliculus), and tail (beyond superior colliculus). Memory assessment was done pre-RT and 18 months post-RT by dedicated neuropsychologist using Weschler Memory Scale. The dose-volume parameters (maximum, mean, D10-D100) were extracted from bilateral hippocampus and subvolumes individually, which were correlated with the memory outcomes. Binary endpoints of > 5% drop of memory quotient (MQ) or not at 18 months were used for analysis using an independent t-test or Mann Whitney test as appropriate.

RESULTS

Of 25 patients included in the analysis, 11 had drop of MQ > 5% at 18 months. The left and right hippocampus doses of D10, D20, and D30 were significantly higher in patients with higher memory decline. For the subvolumes, only dose to bilateral head had statistically significant impact on MQ. Mean doses for patients with > 5% MQ drop for left and right heads were 26 Gy and 24 Gy compared to 21 Gy and 19 Gy, respectively, for the other group.

CONCLUSION

Doses to bilateral hippocampus were shown to impact short-term memory. Of the subvolumes, only head appeared significant in memory functioning from the current pilot study, opening a window for exploring stricter dose constraints towards hippocampal head for primary or metastatic brain tumors.
NCOG-41. INTEGRATING NEUROPSYCHOLOGICAL CARE INTO A PEDIATRIC LONG-TERM SURVIVORSHIP CLINIC
Authors: Hess Colleen
Published: November 2022

Pediatric cancer survivors are vulnerable to neurocognitive deficits due to their treatment history including chemotherapy and radiation therapy. These treatments are associated with damage to the brain’s white matter pathways, contributing to neurocognitive “late effects” such as deficits in processing speed, working memory, executive function, visuospatial abilities, and fine motor skills. However, these neurocognitive deficits may go undiagnosed and therefore unsupported due to difficulties accessing neuropsychological care. This study seeks to improve survivors’ access to care, thereby increasing the likelihood of patients obtaining educational and therapeutic supports when needed, by integrating brief neuropsychological screenings into an existing medical clinic. During survivors’ annual oncology clinic visit, patients were administered a neurocognitive screening battery to assess their working memory, processing speed, and executive functions and thereby determine which patients would benefit from more comprehensive neuropsychological testing. The current sample of 22 patients (55% female) ranges from 6 to 21 years of age (M = 14). Based on testing performance, 23% of the sample (n = 5) demonstrated neurocognitive deficits according to the Neuropsychological Impairment Rule (NIR), and therefore was referred for more comprehensive neuropsychological assessment. Additionally, 9% of the sample (n = 2) was referred for further assessment, despite not meeting the NIR threshold, due to report of academic concerns. Importantly, 68% of the sample (n = 15) did not meet the NIR threshold and did not endorse neurocognitive concerns, and therefore did not require referral for further neuropsychological assessment. Current results demonstrate the utility of integrating neuropsychological care into long-term survivorship clinics via a neurocognitive screening battery as the majority of patients did not evidence significant deficits and therefore were adequately served from a neuropsychological lens without requiring additional assessment. In addition to increasing access to care, these efforts help to preserve families’ resources and reduce waitlists for patients in need.
EXTH-58. UNRAVELING THE MECHANISMS UNDERLYING THE THERAPEUTIC EFFICACY OF TIM-3 BLOCKADE IN DIPGS
Authors: Ausejo-Mauleon Iker , Labiano Sara , Laspidea Virginia , de la Nava Daniel , Marco-Sanz Javier , Tallón-Cobos Antonio , Becher Oren , Li Jiang , Filbin Mariella , Pastor Fernando , Alonso Marta M
Published: November 2022

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor and the leading cause of pediatric death caused by cancer. Despite great strides in the understanding of this disease, the survival is still dismal. One of the objectives of our lab is to modulate the tumor microenvironment (TME) towards a proinflammatory phenotype to render these tumors amenable to immunotherapy. TIM-3 is a member of the TIM-family of immunoregulatory proteins expressed on multiple immune cell types, including T-cells, NK, myeloid populations, and microglia, regulating adaptive and innate immunity. In silico assessment of TIM-3 expression in DIPG mRNA and single-cell datasets showed a robust expression of this gene in tumor cells and microglia uncovering this molecule as a potential target in DIPGs. In vivo studies showed that TIM-3 blockade with an antibody significantly increased the overall survival of two DIPG immunocompetent orthotopic models, led to long-term survivors (50%), and showed immune resident memory. TIM-3 inhibition resulted in a significant increase in the number and proliferative state of microglia, NK, and CD8+ cells and higher levels of IFNγ, GrzB and TNFα corresponding to NK and T-cell activate phenotypes. Interestingly, there was a decrease in the Treg population, which causes an increase in the pro-inflammatory CD8/Treg ratio. Chemokine studies demonstrated an augmentation of CCL5, CCL2 chemotactic cytokines, and CXCL10/IL-1β/IFN-γ pro-inflammatory axis in the tumor microenvironment of treated-mice. Additionally, DCs, CD4+, and CD8+ cells were increased in treated draining lymph nodes and of functional significance, expressed higher amounts of pro-inflammatory cytokines than in control mice. Interestingly, the depletion of the different immune populations did not completely abrogate the treatment efficacy indicating a residual although significant TIM-3 effect in the tumor. In conclusion, these data uncover TIM-3 as a potential target for the treatment of DIPG and its potential as an immune regulator of DIPG TME.
QLTI-03. AN INNOVATIVE APPROACH TO ACCESSIBLE INFORMATION FOR BRAIN TUMOUR PATIENTS AND THEIR LOVED ONES
Authors: Hurwitz Victoria , La Jessica , Hedges Sarah , Robinson Charlotte , Kostick Ellie , Suarez Aeron , Lavrador Jose , Bhangoo Ranjeev , Brazil Lucy
Published: November 2022

Patient information for cancer patients is acknowledged for its vital contribution to informed consent and a positive patient experience. It forms a measure to which UK oncology centres are held to account in the national cancer patient experience survey. It could be argued that this has driven the production of such information rather than it being designed to best meet the need of the neuro-oncology patient. With this in mind a YouTube channel was set up after consulting current High Grade Glioma patients on their preferred medium. Patients wanted short clips in a conversational style explaining aspects of their treatment and the pathway. They wanted it to be available in a medium that they were familiar with either s a podcast or YouTube shorts. The CNS team requested patients choose the name of the channel and began making short videos with patients and professionals on subjects suggested by patients. In twelve weeks, we have produced 23 videos, which have had 2282 views and 105 hours of watch time. The average person watches for two hours and forty-six minutes. It is possible to extrapolate from this that people are engaging with the content. The availability of information in this form has reduced the length of conversations and emails with the CNS’s pre-operatively. Patients have reported a greater sense of comfort from hearing other patient’s stories. The authors acknowledge there is not enough data available yet to formerly support this. In conclusion patient information should be designed to meet the needs of the patient not the guidance. It needs to be accessible to patients who have neurological impairments including changes in vision and concentration and provided in a medium that is current, visual and easily accessible.
QOL-09. NAVIGATING DISABILITY INSURANCE FOR PATIENTS DIAGNOSED WITH LOW-GRADE GLIOMA
Authors: Yogendran Lalanthica , Rudolf Mark , Yeannakis Drew , Fuchs Kathleen , Schiff David
Published: November 2022

Central nervous system tumors and their treatments can cause neurologic, cognitive, and psychiatric symptoms that restrict a patient’s ability to work. In the United States, a diagnosis of high-grade glioma (grade 3 or 4) medically qualifies a patient for disability benefits through Social Security. Low-grade gliomas can be similarly debilitating, with at least 50% of patients presenting with one or more cognitive deficits and 80% of patients with tumor-related epilepsy. In light of these serious symptoms, it is unsurprising at least half of patients with low-grade glioma do not return to work within one year of diagnosis. Yet a diagnosis of low-grade glioma does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. Thus, patients with low-grade glioma require special attention as they seek disability benefits. Here, we outline the process of medical documentation to support disability benefits, Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with low-grade glioma seeking disability benefits. The provider’s role is not to simply “declare” a patient disabled, but rather to provide comprehensive documentation regarding the patient’s diagnosis, treatment, response to treatment, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are two key sources of disability in low-grade glioma patients, referrals to neuropsychology and epileptology, among other sub-specialties, are key to improve patient care and bolster documentation of the patient’s symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. Providers are better able to help their patients navigate the disability application process when they understand how disability evaluations work and what key information evaluators seek.
QOL-10. NOVEL MULTIMODAL STUDY OF THREE COGNITIVE REHABILITATION INTERVENTIONS IN LOWER GRADE GLIOMA
Authors: Jamora Christina Weyer , Brie Melissa , Bracci Paige , Smith Ellen , Luks Tracy , Phan Stephanie , Braunstein Steve , Villanueva-Meyer Javier , Gehring Karen , Aguilera Adrian , Bush Nancy Ann Oberheim , Butowski Nicholas , Clarke Jennifer , Daras Mariza , de Groot John , Chang Susan M , Hervey-Jumper Shawn L , Taylor Jennie
Published: November 2022

BACKGROUND

Grade 2 and 3 glioma survivors (LrGG) are living longer, yet experience cognitive impairments with diminished quality of life (QOL). We present a novel multimodal study of three cognitive rehabilitation interventions in stable LrGG survivors.

METHODS

Participants were radiologically stable adult LrGG patients who were off medical treatment for ≥ 6 months with subjective and objective cognitive impairments ( >1SD in 2 or more domains). Patients were offered either In-person cognitive rehabilitation (strategy training including telehealth), or randomized to App-based cognitive rehabilitation (retraining and strategy training) versus Text messaging (strategy training). Intervention duration was 3 months. Neuropsychological testing (with parallel forms) and QOL assessments were conducted at baseline (T1), immediate post intervention (T2), and 6-month follow-up (T3), and analyzed with repeated measures regression or Wilcoxon signed rank tests.

RESULTS

Of the 33 analyzed (enrollment ongoing); 15/17 In-person, 5/8 App-based, and 8/8 Texting completed ≥ 80% or greater of interventions. Demographic and clinical characteristics were similar between cohorts. Median age was 48 years (range 27-63), 58% astrocytoma, 30% oligodendroglioma, 15% other (1 pilocytic astrocytoma, 4 diffuse glioma NOS), and 76% had prior radiotherapy. Rehabilitation interventions showed improvements in auditory working memory (T1-T2 In-person p= 0.02, eta2= 0.32-medium effect), verbal learning (T1-T3 App-based p= .06, eta2= 0.54-large effect; T1-T3 Texting p= .01, eta2= 0.75-large effect), and verbal memory (T1-T3 App-based p= .06, rho=0.31-medium effect).

CONCLUSION

Significant improvements in cognitive impairments were found with medium to large treatment effects within each cohort. Cognitive rehabilitation via In-person and Texting showed strongest feasibility and acceptability. In-person cognitive rehab showed earlier posttreatment improvements whereas treatment effects for App-based and Texting were noted, but took longer to realize gains. These interventions may show promise for addressing cognitive impairments in LrGG survivors and warrant further investigation.
SURG-15. MINIMALLY INVASIVE PREFRONTAL APPROACH FOR GLIOMAS: TECHNICAL DESCRIPTION AND ASSOCIATED COMPLICATIONS
Authors: del Pont Francisco Marcó , Merenzon Martin , Morell Alexis , Higgins Dominique , Patel Nitesh , Kader Michael , Eichberg Daniel , Shah Ashish , Silva Michael , Luther Evan , Lu Victor , Komotar Ricardo , Ivan Michael
Published: November 2022

INTRODUCTION

Classical prefrontal approaches exposed the lateral surface of the frontal lobe. Minimally invasive (MI) approaches achieved to reduce soft tissue damage and craniotomy size without affecting tumor resection grade. This is associated with shorter hospital stays and faster return to preoperative daily activities.

OBJECTIVE

To describe the MI prefrontal glioma resection technique developed in our department and to analyze our surgical results.

METHODS

We performed a retrospective review of patients who underwent prefrontal lobe glioma (WHO grade II-IV) resection using an MI approach in 2016-2021 at the University of Miami Hospital. Re-surgery, biopsy-only patients, multicentric tumors, and patients with less than four months of follow-up were excluded. Demographic and clinical data were collected. A 4-5 cm linear incision is done, starting at 1 cm lateral to the sagittal suture and extending towards the superior temporal line. An ellipsoidal-shaped mini-craniotomy is performed.

RESULTS

Thirty-four patients were included. The mean age was 50.2 years old, with 20 male subjects. Twenty-two patients had high-grade gliomas (HGG) and 12 patients had low-grade gliomas (LGG). On average, patients were discharged 1.97 days after surgery. The mean craniotomy area was 15,5 cm2 (7-43 cm2). The mean tumor volume was 64,5 cm2 ( 9 -165.8 cm2). Two wound infections and one case of aseptic meningitis were observed in patients with craniotomies > 15 cm2, while the group with craniotomies < 15 cm2 had no perioperative complications. In the HGG group, a supramaximal resection (SMR) was achieved in 8 patients, 9 HGG patients had gross total resection (GTR) or near-total resection (NTR), and 5 patients had subtotal resection (STR). In the LGG, GTR was achieved in 10 patients and STR in 2 patients.

CONCLUSION

MI prefrontal approach for frontal gliomas is safe and feasible with minor complications, short hospital stay, and without sacrificing tumor resection volume.
Evaluation of the Impact of HIV Serostatus on the Hepatitis C Virus Care Cascade and Injection Drug Use Among Persons Initiating Medication Treatment for Opioid Use Disorder
Authors: Lier Audun J , Vander Wyk Brent , Di Paola Angela , Springer Sandra A
Published: November 2022

Background

Persons who inject drugs are at increased risk for acquiring hepatitis C virus (HCV). Medications for opioid use disorder (MOUD) are associated with reduced injection drug use (IDU) frequency among persons with opioid use disorder (OUD). However, whether HCV treatment uptake or changes in IDU frequency differ by HIV serostatus among persons receiving MOUD is incompletely understood.

Methods

A secondary analysis was performed of data collected from 2 prospective cohort studies of participants with (PWH) or without HIV with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition–diagnosed OUD who were initiated on methadone, buprenorphine, or naltrexone.

Results

Of 129 participants, 78 (60.5%) were HCV antibody positive. PWH underwent increased HCV viral load testing (76.7% vs 43.3%; P = .028), but HCV treatment rates did not differ (17.6% vs 10.0%; P = .45) by HIV status. Participants without HIV reported a greater reduction in mean opioid IDU at 90 days (10.7 vs 2.0 fewer days out of 30; P < .001), but there were no group differences at 90 days. Stimulant use did not differ between groups. Urine opioid positivity declined from baseline to 90 days among the entire cohort (61.4% to 38.0%; P < .001) but did not differ by HIV serostatus.

Conclusions

PWH who received MOUD underwent higher rates of follow-up HCV testing, but HCV treatment rates did not significantly differ by HIV serostatus. Participants without HIV on MOUD reported a greater reduction in opioid IDU. Improved integration of concomitant OUD with HCV and HIV screening, linkage to care, and treatment are needed for persons without HIV.
Pointwise bounds for eisenstein series on Γ0(q)\SL2(ℝ)
Authors: Musicantov Evgeny , Zehavi Sa’ar
Published: November 2022

We construct pointwise bounds in the weight aspect for Eisenstein series on $X_0(q) = \Gamma_0(q)\backslash{} SL_2(\mathbb{R})$, with squarefree level q, using a Sobolev technique. More specifically, we show that for an Eisenstein series E on $X_0(q)$ of weight parameter n and type t, one has for all $x\in X_0(q)$: $|E(x,1/2 + it)| \ll_{\epsilon} q^{\epsilon}(1 + |n|^{1/2 + \epsilon} + |t|^{1/2 + \epsilon})\sqrt{y(x) + y(x)^{-1}}$, where y(x) is the Iwasawa y-coordinate of the point x.
In Search of Habitat
Authors: Chen Xuanjuan , Sun Zhenzhen , Yao Tong , Yu Tong
Published: November 2022

We perform portfolio-level analyses to understand insurance firms’ preferred habitat behavior in the government bond market. Based on portfolio durations and portfolio weights across maturities, we find that interest rate risk exposures of insurers’ portfolios are related to their operating liabilities and financing constraints. We show that this habitat behavior significantly affects bond pricing. During the “quantitative easing” era, bond purchases by the Federal Reserve have a larger impact on the yields of Treasury bonds with a higher habitat demand. (JEL E43, E52, G11, G12, G23)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Syrian Refugee Inflows, Health-Care Access, and Childhood Vaccination in Turkey
Authors: Erten Bilge , Keskin Pinar , Omurtak Miray , Ozen Ilhan Can
Published: November 2022

This study explores the impact of the arrival of Syrian refugees in Turkey on access to health-care resources and subsequent changes in infectious disease rates among native children. Employing a distance-based instrument, it finds that native children living in regions that received large inflows of Syrian refugees experienced an increase in their risk of catching an infectious disease compared to children in less affected regions. In contrast, there is no evidence of significant changes in the incidences of noninfectious diseases such as diabetes, cancer, or anemia. The findings also reveal that the number of health-care professionals and hospital beds per capita declined in provinces that received large refugee inflows. This study also documents a decrease in native children’s probability of being fully vaccinated in provinces that received large refugee inflows. Although contact with potentially infected refugees may increase disease spread among natives, the migration-induced supply constraints in health-care access may also worsen health outcomes in host countries.
The Practice Change and Clinical Impact of Lung-Protective Ventilation Initiated in the Emergency Department: A Secondary Analysis of Individual Patient-Level Data From Prior Clinical Trials and Cohort Studies*
Authors: Fuller Brian M. , Mohr Nicholas M. , Ablordeppey Enyo , Roman Olivia , Mittauer Dylan , Yan Yan , Kollef Marin H. , Carpenter Christopher R. , Roberts Brian W.
Published: November 2022

OBJECTIVES:

Mechanically ventilated emergency department (ED) patients experience high morbidity and mortality. In a prior trial at our center, ED-based lung-protective ventilation was associated with improved care delivery and outcomes. Whether this strategy has persisted in the years after the trial remains unclear. The objective was to assess practice change and clinical outcomes associated with ED lung-protective ventilation.

DESIGN:

Secondary analysis of individual patient-level data from prior clinical trials and cohort studies.

SETTING:

ED and ICUs of a single academic center.

PATIENTS:

Mechanically ventilated adults.

INTERVENTIONS:

A lung-protective ventilator protocol used as the default approach in the ED.

MEASUREMENTS AND MAIN RESULTS:

The primary ventilator-related outcome was tidal volume, and the primary clinical outcome was hospital mortality. Secondary outcomes included ventilator-, hospital-, and ICU-free days. Multivariable logistic regression, propensity score (PS)-adjustment, and multiple a priori subgroup analyses were used to evaluate outcome as a function of the intervention. A total of 1,796 patients in the preintervention period and 1,403 patients in the intervention period were included. In the intervention period, tidal volume was reduced from 8.2 mL/kg predicted body weight (PBW) (7.3–9.1) to 6.5 mL/kg PBW (6.1–7.1), and low tidal volume ventilation increased from 46.8% to 96.2% (p< 0.01). The intervention period was associated with lower mortality (35.9% vs 19.1%), remaining significant after multivariable logistic regression analysis (adjusted odds ratio [aOR], 0.43; 95% CI, 0.35–0.53;p< 0.01). Similar results were seen after PS adjustment and in subgroups. The intervention group had more ventilator- (18.8 [10.1] vs 14.1 [11.9];p< 0.01), hospital- (12.2 [9.6] vs 9.4 [9.5];p< 0.01), and ICU-free days (16.6 [10.1] vs 13.1 [11.1];p< 0.01).

CONCLUSIONS:

ED lung-protective ventilation has persisted in the years since implementation and was associated with improved outcomes. These data suggest the use of ED-based lung-protective ventilation as a means to improve outcome.
Identification of Escitalopram Metabolic Ratios as Potential Biomarkers for Predicting CYP2C19 Poor Metabolizers
Authors: Faraj Pari , Hermansen Astrid , Molden Espen , Hole Kristine
Published: November 2022

Background:

Escitalopram is metabolized by CYP2C19 to N-desmethyl escitalopram and escitalopram propionic acid. The primary aims of this study were to investigate the impact of the CYP2C19 phenotype on metabolic ratios of escitalopram in vivo and propose a biomarker for the CYP2C19 phenotype in patients treated with escitalopram.

Methods:

Median steady-state serum metabolite/parent drug ratio of N-desmethyl escitalopram and escitalopram propionic acid was investigated across CYP2C19 genotype-translated phenotype groups. The receiver operator characteristics method and the area-under-the-receiver-operator-characteristics curve was used to determine the best suited metabolic ratio for detecting CYP2C19 poor metabolizers (PMs).

Results:

A total of 441 patients were included in the study. The N-desmethyl escitalopram/escitalopram ratio was 67% and 44% lower in CYP2C19 PMs and intermediate metabolizers (IMs), respectively, than normal metabolizers. Furthermore, the ability of the ratio to predict CYP2C19 PMs was 92%. A metabolic ratio of <0.24 was detected in 8 of 8 PMs in the study, indicating that it is a promising biomarker of reduced CYP2C19 activity. The escitalopram propionic acid/escitalopram ratio was 77% and 48% lower in CYP2C19 PMs and IMs, respectively; however, the ability of the ratio to detect CYP2C19 PMs was only 87%.

Conclusions:

These findings suggest that DECT/ECT reflects CYP2C19 activity, and a metabolic ratio of <0.24 strongly predicts CYP2C19 PM phenotype. The ratio could be a valuable alternative to genotyping in personalized dosing of escitalopram and possibly other CYP2C19 substrates. The escitalopram propionic acid/escitalopram ratio was also associated with CYP2C19 activity; however, the ratio was inferior to the DECT/ECT at predicting PMs.
Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
Authors: Ghia Paolo , Pluta Andrzej , Wach Małgorzata , Lysak Daniel , Šimkovič Martin , Kriachok Iryna , Illés Árpád , de la Serna Javier , Dolan Sean , Campbell Philip , Musuraca Gerardo , Jacob Abraham , Avery Eric J. , Lee Jae Hoon , Usenko Ganna , Wang Min Hui , Yu Ting , Jurczak Wojciech
Published: November 2022

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.
The Burden of Respiratory Syncytial Virus Disease in Children and Adults Hospitalized in a Large Tertiary Hospital in the United Kingdom: A Retrospective Study
Authors: Knapper Francesca , Ellis Josephine , Bernatoniene Jolanta , Williams Philip
Published: November 2022

Respiratory syncytial virus (RSV) is an RNA virus spread via droplets. Children are predominately affected, with a significant burden in the under 1s. The burden of disease across both children and adults and management is rarely reported. We completed a retrospective study looking at the characteristics of all patients admitted with a positive RSV PCR throat swab were reviewed from a large tertiary hospital in the United Kingdom over the 2019/2020 season. Four hundred six paediatric patients and 81 adult patients were included. Ninety-four percent (76/81) of adult patients had comorbidities compared with 20% (81/406) of children. In adults Chest radiograph was normal in 46% (37/81). Thirty-six percent (29/81) showed consolidation. Viral coinfection was common among children 158 (39%). Forty (10%) of children were admitted to pediatric intensive care and 7 (9%) of adults were admitted to intensive care unit. No children and 6 (7%) of adults admitted with RSV died. RSV is associated with a significant morbidity. Mortality in adults admitted to Intensive Care Unit was high. Coinfection with other viruses is common in children. The use of antibiotics was higher than expected, although C-reactive protein and Chest radiograph suggested secondary bacterial infection is more common in adults.
Standardized Quantitative Sensory Testing to assess insufficient recovery of touch discrimination in free flap surgery in extremity reconstruction
Authors: Huber Julika , Scharberth Alina , Maier Christoph , Wallner Christoph , Wagner Johannes M , Dadras Mehran , Longaker Michael T , Lehnhardt Marcus , Behr Björn
Published: November 2022

Background:

With major advances in microsurgical techniques, free tissue transfer has become a widely adopted approach to treat complex soft tissue defects. However, sensory recovery is poor leaving the anaesthetic skin prone to injuries.

Methods:

28 patients with 22 anterior lateral thigh flaps and 6 latissimus dorsi flaps on their extremities participated in the study. Quantitative sensory testing and 2 points discrimination was performed in three test areas and one control on the contralateral unaffected extremity. Physical disability, mental health, quality of life and characteristics of pain were assessed by the painDetect, DASH, LEFS and sf12 questionnaires, respectively.

Results:

Somatosensory profiles of all flaps were characterized by an overall loss of nerve function. Small-fibre function was mostly recovered while large-fibre function and thus touch discrimination was severely impaired. Mechanical detection thresholds improved over time and from periphery to the centre. Reported pain was mild to moderate and correlated with decreased physical function.

Conclusion:

Standardized Quantitative sensory testing provides a useful tool kit to assess the sensory regeneration after surgical treatment of soft tissue defects. After free tissue transfer small-fibre function recovers with nerve ingrowth in a centripetal direction from the flap margins to the centre, likely via collateral axonal sprouting from the undamaged nerves surrounding the flap. Myelinated fibres recover slowly and inefficiently.