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Background: Patients with high-grade glioma have high palliative care needs, yet few receive palliative care consultation. This study aims to explore themes on (1) benefits of primary (delivered by neuro-oncologists) and specialty palliative care (SPC) and (2) barriers to SPC referral, according to a diverse sample of clinicians. Methods: From September 2021 to May 2023, 10 palliative physicians and 10 neuro-oncologists were recruited via purposive sampling for diversity in geographic setting, seniority, and practice structure. Semistructured, 45-minute interviews were audio-recorded, professionally transcribed, and coded by 2 investigators. A qualitative, phenomenological approach to thematic analysis was used. Results: Regarding primary palliative care, (1) neuro-oncologists have primary ownership of cancer-directed treatment and palliative management and (2) the neuro-oncology clinic is glioma patients' medical home. Regarding SPC, (1) palliative specialists' approach is beneficial even without disease-specific expertise; (2) palliative specialists have time to comprehensively address palliative needs; and (3) earlier SPC enhances its benefits. For referral barriers, (1) appointment burden can be mitigated with telehealth, home-based, and embedded palliative care; (2) heightened stigma associating SPC with hospice in a population with high death anxiety can be mitigated with earlier referral to promote rapport-building; and (3) lack of neuro-oncologic expertise among palliative specialists can be mitigated by emphasizing their role in managing nonneurologic symptoms, coping support, and anticipatory guidance. Conclusions: These themes emphasize the central role of neuro-oncologists in addressing palliative care needs in glioma, without obviating the need for or benefits of SPC. Tailored models may be needed to optimize the balance of primary and specialty palliative care in glioma.
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CONTEXT: Early palliative care referral is recommended broadly in oncology. Yet, few patients with high-grade gliomas (HGG) - highly aggressive brain tumors - receive specialty palliative care consultation. OBJECTIVES: To delineate unique needs of HGG patients relative to other oncology patients according to perceptions of a diverse sample of US palliative medicine physicians and neuro-oncologists in each of the eight domains of palliative care; and to describe contrasts between physician specialties on indications for and timing of specialty palliative care referrals in HGG. METHODS: Between September 2021 and May 2023, we conducted semi-structured, 40-minute interviews with ten palliative medicine physicians and ten neuro-oncologists. Participants were recruited via purposive sampling for diversity in geographic setting, years in practice, and practice structure. Interviews were audio-recorded, professionally transcribed, and coded by two investigators. Data were analyzed thematically using a qualitative, phenomenological approach. RESULTS: The palliative care needs of HGG relative to other cancers across palliative care domains are distinguished by poor prognosis, physical and cognitive deficits, and neuropsychiatric symptoms. Themes on indications for palliative care referral differed between neuro-oncologists and palliative physicians. Neuro-oncologists favored selective referral for clinical indications such as high non-neurologic symptom burden requiring time-intensive management. Palliative physicians favored early referral of most HGG patients, to allow for maximal benefit across HGG trajectory. CONCLUSION: Patients with HGG have unique palliative care needs that affect palliative care delivery across care domains. Bidirectional education, enhanced collaboration, and consensus guidelines may help overcome barriers to specialty palliative care referral.
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Neoplasias Encefálicas , Glioma , Cuidados Paliativos , Derivación y Consulta , Humanos , Glioma/terapia , Neoplasias Encefálicas/terapia , Femenino , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Oncólogos , Actitud del Personal de Salud , AdultoRESUMEN
Background: Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data. Methods: We analyzed data on self-reported fatigue and neurocognitive outcomes from postoperative patients with glioma from the University of California San Francisco (nâ =â 100, UCSF) and Amsterdam University Medical Center (nâ =â 127, Amsterdam UMC). We used multiple linear regression models to assess associations between fatigue and seven (sub)domains of neurocognitive functioning and latent profile analysis to identify distinct patterns of fatigue and neurocognitive functioning. Results: UCSF patients were older (median age 49 vs. 43 years, Pâ =â .002), had a higher proportion of grade 4 tumors (32% vs. 18%, Pâ =â .03), and had more neurocognitive deficits (Pâ =â .01). While the number of clinically fatigued patients was similar between sites (64% vs. 58%, Pâ =â .12), fatigue and the number of impaired neurocognitive domains were not correlated (Pâ =â .16-.72). At UCSF, neurocognitive domains were not related to fatigue, and at Amsterdam UMC attention and semantic fluency explained only 4-7% of variance in fatigue. Across institutions, we identified four distinct patterns of neurocognitive functioning, which were not consistently associated with fatigue. Conclusions: Although individual patients might experience both fatigue and neurocognitive impairment, the relationship between the two is weak. Consequently, both fatigue and neurocognitive functioning should be independently assessed and treated with targeted therapies.
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This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6 min scan. Modified k-means clustering was performed for automatic brain tissue and lesion segmentation using distinct signal evolutions that contained mixed T1/T2/magnetization transfer properties. Multi-compartment modeling was used to derive quantitative multi-parametric maps for tissue characterization. Fourteen patients with contrast-enhancing gliomas were scanned with this sequence prior to the injection of a contrast agent, and their segmented lesions were compared to conventionally defined manual segmentations of T2-hyperintense and contrast-enhancing lesions. Simultaneous T1, T2, and macromolecular proton fraction maps were generated and compared to conventional 2D T1 and T2 mapping and myelination water fraction mapping acquired with MAGiC. The lesion volumes defined with the new method were comparable to the manual segmentations (r = 0.70, p < 0.01; t-test p > 0.05). The T1, T2, and macromolecular proton fraction mapping values of the whole brain were comparable to the reference values and could distinguish different brain tissues and lesion types (p < 0.05), including infiltrating tumor regions within the T2-lesion. Highly efficient, whole-brain, multi-contrast imaging facilitated automatic lesion segmentation and quantitative multi-parametric mapping without contrast, highlighting its potential value in the clinic when gadolinium is contraindicated.
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Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.
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Neoplasias Encefálicas , Neoplasias , Tromboembolia Venosa , Humanos , Anticoagulantes/efectos adversos , Tromboembolia Venosa/epidemiología , Hemorragia , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/tratamiento farmacológico , Administración OralRESUMEN
BACKGROUND: Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients. METHODS: We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950â +â poly-ICLC and varlilumab (Arm 1) or IMA950â +â poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines. RESULTS: A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment. CONCLUSION: The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.
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Anticuerpos Monoclonales Humanizados , Vacunas contra el Cáncer , Glioma , Péptidos , Humanos , Proyectos Piloto , Leucocitos Mononucleares , Estudios Prospectivos , Glioma/tratamiento farmacológico , Diferenciación Celular , Microambiente TumoralRESUMEN
Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as "Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A". Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.
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Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Niño , Persona de Mediana Edad , Anciano , Glioblastoma/genética , Glioblastoma/patología , Inhibidores de Puntos de Control Inmunológico , Homocigoto , Estudios Prospectivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Eliminación de Secuencia , Mutación/genética , Isocitrato Deshidrogenasa/genéticaRESUMEN
OBJECTIVE: Neurologic complications are among the most common and feared outcomes of cancer treatments. This review discusses the signs and symptoms, mechanisms, and management of the most common peripheral and central neurologic complications of chemotherapy, radiation therapy, and antiangiogenic therapy during cancer treatment and in survivors. LATEST DEVELOPMENTS: The landscape of cancer treatments is evolving to include more targeted and biologic therapies, in addition to more traditional cytotoxic therapies and radiation therapy. With increasingly complex regimens and longer survival for patients with cancer, the early recognition and management of neurologic complications is key to improving the morbidity and mortality of patients living with cancer. ESSENTIAL POINTS: Neurologists should be familiar with acute central and peripheral toxicities that can occur during cancer treatment and delayed toxicities that can occur years after exposure. Neurologists should be familiar with the clinical and radiologic presentations of these complications and strategies for management.
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Antineoplásicos , Neoplasias , Enfermedades del Sistema Nervioso , Humanos , Enfermedades del Sistema Nervioso/etiología , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Antineoplásicos/efectos adversosRESUMEN
Background: Epigenetic inhibition of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has emerged as a clinically relevant prognostic marker in glioblastoma (GBM). Methylation of the MGMT promoter has been shown to increase chemotherapy efficacy. While traditionally reported as a binary marker, recent methodological advancements have led to quantitative methods of measuring promoter methylation, providing clearer insight into its functional relationship with survival. Methods: A CLIA assay and bisulfite sequencing was utilized to develop a quantitative, 17-point, MGMT promoter methylation index. GBMs of 240 newly diagnosed patients were sequenced and risk for mortality was assessed. Nonlinearities were captured by fitting splines to Cox proportional hazard models and plotting smoothed residuals. Covariates included age, Karnofsky performance status, IDH1 mutation, and extent of resection. Results: Median follow-up time and progression-free survival were 16 and 9 months, respectively. A total of 176 subjects experienced death. A one-unit increase in promoter CpG methylation resulted in a 4% reduction in hazard (95% CI 0.93-0.99, Pâ <â .005). GBM patients with low levels of promoter methylation (1-6 CpG sites) fared markedly worse (HRâ =â 1.62, 95% CI 1.03-2.54, Pâ <â .036) than individuals who were unmethylated. Subjects with medium levels of promoter methylation (7-12 sites) had the greatest reduction in hazard (HRâ =â 0.48, 95% CI 0.29-0.80, Pâ <â .004), followed by individuals in the highest promoter methylation tertile (HRâ =â 0.62, 95% CI 0.40-0.97, Pâ <â .035). Conclusions: Our findings suggest that the relationship between the extent of MGMT promoter methylation and survival in GBM may be nonlinear. These findings challenge the current understanding of MGMT and underlines the clinical importance of determining its prognostic utility. Potential limitations include censoring, sample size, and extraneous mutations.
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PURPOSE: Adults with high-grade glioma (HGG), WHO grade III or IV, have substantial palliative care needs. Our aim was to determine occurrence, timing, and factors associated with palliative care consultation (PCC) in HGG at one large academic institution. METHODS: HGG patients receiving care between 08/1/2011 and 01/23/2020 were identified retrospectively from a multi-center healthcare system cancer registry. Patients were stratified by any PCC (yes/no), and timing of initial PCC by disease phase: diagnosis (before radiation), during initial treatment (first-line chemotherapy/radiation), second-line treatment(s), or end-of-life (after last chemotherapy). RESULTS: Of 621 HGG patients, 134 (21.58%) received PCC with the vast majority occurring during hospital admission [111 (82.84%)]. Of the 134, 14 (10.45%) were referred during the diagnostic phase; 35 (26.12%) during initial treatment; 20 (14.93%) during second-line treatment; and 65 (48.51%) during end of life. In multivariable logistic regression, only higher Charlson Comorbidity Index was associated with greater odds of PCC [OR 1.3 (95% CI 1.2-1.4), p < 0.01]; but not age or histopathology. Patients who received PCC prior to end of life had longer survival from diagnosis than those referred during end of life [16.5 (8, 24) months vs. 11 (4, 17); p < 0.01]. CONCLUSION: A minority of HGG patients ever received PCC, which primarily occurred in the inpatient setting, and nearly half during the end-of-life phase. Thus, only about one in ten patients in the entire cohort potentially received the benefits of earlier PCC despite earlier referral having an association with longer survival. Further studies should elucidate barriers and facilitators to early PCC in HGG.
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Glioma , Cuidados Paliativos , Adulto , Humanos , Estudios Retrospectivos , Glioma/epidemiología , Glioma/terapia , Derivación y Consulta , MuerteRESUMEN
Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.
Glioblastoma (GBM) is a very aggressive brain cancer. People who have GBM have trouble remembering things and are unable to do things they used to do. These changes can be very hard. Researchers are trying to better understand what it is like for people who take care of people with GBM (or caregivers). In this study, researchers created a new survey for caregivers. The survey included questions about what caregivers see happening in their loved one with GBM. Caregivers said that memory problems were common. Also, when the patient had more problems the caregiver had a harder time, too. Researchers hope to improve the survey and use it in the future for more studies.
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Disfunción Cognitiva , Glioblastoma , Adulto , Femenino , Humanos , Cuidadores/psicología , Glioblastoma/complicaciones , Glioblastoma/terapia , Glioblastoma/patología , Proyectos Piloto , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Encuestas y Cuestionarios , Calidad de VidaRESUMEN
Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDH glioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration of D-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1-97.6) and 91.1% (95% CrI, 72.0-97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of 'proneural' and 'stemness' gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDH LGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.
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Neoplasias Encefálicas , Glioma , Humanos , Piridinas/efectos adversos , Isocitrato Deshidrogenasa/genética , Glioma/tratamiento farmacológico , Glioma/genética , Mutación/genética , Preparaciones Farmacéuticas , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genéticaRESUMEN
PURPOSE: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS: Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION: Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Oligodendroglioma/patología , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodos , Glioma/patología , Astrocitoma/patología , Resultado del TratamientoRESUMEN
PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
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Neoplasias Meníngeas , Meningioma , Humanos , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Proteína-Tirosina Quinasas de Adhesión Focal/uso terapéutico , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/tratamiento farmacológico , Meningioma/genética , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
Glioblastomas (GBM) are lethal central nervous system cancers associated with tumor and systemic immunosuppression. Heterogeneous monocyte myeloid-derived suppressor cells (M-MDSC) are implicated in the altered immune response in GBM, but M-MDSC ontogeny and definitive phenotypic markers are unknown. Using single-cell transcriptomics, we revealed heterogeneity in blood M-MDSC from GBM subjects and an enrichment in a transcriptional state reminiscent of neutrophil-like monocytes (NeuMo), a newly described pathway of monopoiesis in mice. Human NeuMo gene expression and Neu-like deconvolution fraction algorithms were created to quantitate the enrichment of this transcriptional state in GBM subjects. NeuMo populations were also observed in M-MDSCs from lung and head and neck cancer subjects. Dexamethasone (DEX) and prednisone exposures increased the usage of Neu-like states, which were inversely associated with tumor purity and survival in isocitrate dehydrogenase wildtype (IDH WT) gliomas. Anti-inflammatory ZC3HA12/Regnase-1 transcripts were highly correlated with NeuMo expression in tumors and in blood M-MDSC from GBM, lung, and head and neck cancer subjects. Additional novel transcripts of immune-modulating proteins were identified. Collectively, these findings provide a framework for understanding the heterogeneity of M-MDSCs in GBM as cells with different clonal histories and may reshape approaches to study and therapeutically target these cells.
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Background: Monitoring lower-grade gliomas (LrGGs) for disease progression is made difficult by the limits of anatomical MRI to distinguish treatment related tissue changes from tumor progression. MR spectroscopic imaging (MRSI) offers additional metabolic information that can help address these challenges. The goal of this study was to compare longitudinal changes in multiparametric MRI, including diffusion weighted imaging, perfusion imaging, and 3D MRSI, for LrGG patients who progressed at the final time-point and those who remained clinically stable. Methods: Forty-one patients with LrGG who were clinically stable were longitudinally assessed for progression. Changes in anatomical, diffusion, perfusion and MRSI data were acquired and compared between patients who remained clinically stable and those who progressed. Results: Thirty-one patients remained stable, and 10 patients progressed. Over the study period, progressed patients had a significantly greater increase in normalized choline, choline-to-N-acetylaspartic acid index (CNI), normalized creatine, and creatine-to-N-acetylaspartic acid index (CRNI), than stable patients. CRNI was significantly associated with progression status and WHO type. Progressed astrocytoma patients had greater increases in CRNI than stable astrocytoma patients. Conclusions: LrGG patients in surveillance with tumors that progressed had significantly increasing choline and creatine metabolite signals on MRSI, with a trend of increasing T2 FLAIR volumes, compared to LrGG patients who remained stable. These data show that MRSI can be used in conjunction with anatomical imaging studies to gain a clearer picture of LrGG progression, especially in the setting of clinical ambiguity.
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OBJECTIVES: 2020 was marked by two racial pandemics-COVID-19-related attacks against Asians and the police brutality against Blacks that spurred the resurgence of the Black Lives Matter movement-calling attention to racial privilege and oppression in American society. The present study explores female Chinese transracial adoptees' unique lived experiences during this racially salient moment. METHOD: A phenomenological approach captured how 20 female Chinese transracial adoptees navigated and made sense of the dual racial pandemics and the subsequent impact on their racial awareness, identity development, and advocacy. Data were collected using semistructured individual Zoom interviews and coded using phenomenological analysis. RESULTS: Findings suggest the dual pandemics acted as catalysts for female Chinese transracial adoptees' racial consciousness and reevaluation of their positionality within the racial hierarchy. Three core themes emerged: female transracial adoptees' new self-understanding as racial beings; their perspective on their place within the White-Black dichotomy; and their role in promoting racial justice. CONCLUSIONS: Our findings contribute to the literature by highlighting the complexities of female Chinese transracial adoptees' racialized selves as children of color who have been raised in White families; their motivations to foster racial justice; and their ability to facilitate race talk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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BACKGROUND: Identifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation. Here, we compare the NDMI 850 to one we built using data from the Illumina Methylation 450K (NDMI 450). RESULTS: The NDMI 450 consisted of 22 loci, 15 of which were present on the NDMI 850. In adult whole blood samples, the linear composite scores from NDMI 450 and NDMI 850 were highly correlated and had equivalent predictive accuracy for detecting DEX exposure among adult glioma patients and non-glioma adult controls. However, the NDMI 450 scores of newborn cord blood were significantly lower than NDMI 850 in samples measured with both assays. CONCLUSIONS: We developed an algorithm that reproduces the DNA methylation glucocorticoid response score using 450K data, increasing the accessibility for researchers to assess this biomarker in archived or publicly available datasets that use the 450K version of the Illumina BeadChip array. However, the NDMI850 and NDMI450 do not give similar results in cord blood, and due to data availability limitations, results from sample types of newborn cord blood should be interpreted with care.