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The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.
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Background: Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020. Methods: Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily. Results: The cohort age range was 21-74 years. Tumor types included astrocytoma (n = 14) and oligodendroglioma (n = 16), with most being grade 2 (n = 21). The best radiographic response in nonenhancing disease (n = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, n = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Conclusions: Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.
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PURPOSE: Brain tumours are associated with neurocognitive impairments that are important for safe driving. Driving is vital to maintaining patient autonomy, despite this there is limited research on driving capacity amongst patients with brain tumours. The purpose of this review is to examine MVC risk in patients with brain tumours to inform development of clearer driving guidelines. METHODS: A systematic review was performed using Medline and EMBASE. Observational studies were included. The outcome of interest was MVC or measured risk of MVC in patients with benign or malignant brain tumours. Descriptive analysis and synthesis without meta-analysis were used to summarise findings. A narrative review of driving guidelines from Australia, United Kingdom and Canada was completed. RESULTS: Three studies were included in this review. One cohort study, one cross-sectional study and one case-control study were included (19,135 participants) across United States and Finland. One study evaluated the incidence of MVC in brain tumour patients, revealing no difference in MVC rates. Two studies measured MVC risk using driving simulation and cognitive testing. Patients found at higher risk of MVC had greater degrees of memory and visual attention impairments. However, predictive patient and tumour characteristics of MVC risk were heterogeneous across studies. Overall, driving guidelines had clear recommendations on selected conditions like seizures but were vague surrounding neurocognitive deficits. CONCLUSION: Limited data exists regarding driving behaviour and MVC incidence in brain tumour patients. Existing guidelines inadequately address neurocognitive complexities in this group. Future studies evaluating real-world data is required to inform development of more applicable driving guidelines. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2023 CRD42023434608.
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Accidentes de Tránsito , Conducción de Automóvil , Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/epidemiología , Accidentes de Tránsito/estadística & datos numéricosRESUMEN
Both glioblastoma (GBM) and dementia are devastating diseases with limited treatments that are usually not curative. Having clinically diagnosed dementia with an associated biopsy-proven etiology and a coexisting GBM diagnosis is a rare occurrence. The relationship between the development of neurodegenerative dementia and GBM is unclear, as there are conflicting reports in the literature. We present two cases of simultaneous biopsy-proven dementia, one with Alzheimer's disease (AD) and GBM, and one with cerebral amyloid angiopathy (CAA) and GBM. We discuss how these diseases may be associated. Whether one pathologic process begins first or develops concurrently is unknown, but certain molecular pathways of dementia and GBM appear directly related while others inversely related. Further investigations of these close molecular relationships between dementia and GBM could lead to development of improved diagnostic tools and therapeutic interventions for both diseases.
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Patients with brain tumors will experience seizures during their disease course. While providers can use antiseizure medications to control these events, patients with brain tumors can experience side effects, ranging from mild to severe, from these medications. Providers in subspecialties such as neurology, neuro-oncology, neurosurgery, radiation oncology, and medical oncology often work with patients with brain tumor to balance seizure control and the adverse toxicity of antiseizure medications. In this study, we sought to explore the problem of brain tumor-related seizures/epilepsy in the context of how and when to consider antiseizure medication discontinuation. Moreover, we thoroughly evaluate the literature on antiseizure medication discontinuation for adult and pediatric patients and highlight recommendations relevant to patients with both brain tumors and seizures.
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Neoplasias Encefálicas , Epilepsia , Adulto , Humanos , Niño , Anticonvulsivantes/efectos adversos , Convulsiones/cirugía , Epilepsia/tratamiento farmacológico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/tratamiento farmacológico , Procedimientos NeuroquirúrgicosRESUMEN
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: Although CNS tumors are the most common pediatric cancer in the United States, most physicians caring for these patients are not formally certified in the subspecialty. To determine support for developing a formal certification process in pediatric neuro-oncology, the Society for Neuro-Oncology's Pediatrics Special Interest Track Training and Credentialing working group performed a cross-sectional survey-based study of physicians and patients/caregivers of children with a CNS tumor history. Methods: Surveys were built in Survey Monkey and were available for 3 months. The physician survey had 34 questions and was open to doctors currently caring for pediatric neuro-oncology patients. The patient/caregiver survey had 13 questions. Both surveys were completed anonymously. Results: The physician survey was completed by 193 participants, the majority of whom self-identified as oncologists. Only 5.6% of survey participants had ever been board-certified in neuro-oncology; the majority of participating physicians were either unaware that this certification existed or thought they were not eligible due to training in pediatrics rather than neurology or internal medicine. Almost half of the self-identified pediatric neuro-oncologists had not completed any specific clinical neuro-oncology training. Over 75% of physicians were supportive of the implementation of a formal certification process in pediatric neuro-oncology. A total of 30 participants completed the patient/caregiver survey. Although the majority of survey participants were highly satisfied with their oncologist, 70% would have been more comfortable if their oncologist had been specifically certified in pediatric neuro-oncology. Conclusions: There is support from physicians, patients, and caregivers to establish a formal certification process in pediatric neuro-oncology.
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Background: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized that reduced dose-WBRT (rd-WBRT) followed by a stereotactic radiosurgery (SRS) boost could provide durable disease control without significant adverse effects. Methods: We retrospectively reviewed PCNSL patients treated with rd-WBRT plus an SRS boost at Duke University between 2008 and 2021. Progression-free survival and overall survival (OS) were estimated using competing risk and Kaplan-Meier methods. Results: We identified 23 patients with pathologically confirmed PCNSL. Median age at diagnosis was 69 years (Q1Q3: 52-74) and median Karnofsky Performance Scale (KPS) was 80 (Q1Q3: 70-80). Median follow-up was 21 months. Median doses for rd-WBRT and SRS were 23.4 Gy (Q1Q3: 23.4-23.4) and 12 Gy (Q1Q3: 12-12.5), respectively. The cumulative incidence of intracranial progression at 2 years was 23% (95% CI: 8-42). Six patients (26%) developed distant radiographic progression while 2 patients (9%) developed both distant and local progression. Ten patients (44%) were alive without progression at last follow-up. By Kaplan-Meier estimate, the 2-year OS was 69% (95% CI: 46-84). There were no reported grade 3â +â radiation-induced toxicities. Conclusions: The combination of rd-WBRT with an SRS boost appears well-tolerated with durable intracranial control. This approach may represent a treatment option for select patients, such as those with progressive or refractory disease. Further prospective studies are needed to validate these findings and determine whether this approach could be incorporated into consolidation strategies.
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Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.
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BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas. METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles. The primary end point was imaging-based progression-free survival according to blinded assessment by an independent review committee. The key secondary end point was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was permitted on confirmation of imaging-based disease progression. Safety was also assessed. RESULTS: A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a median follow-up of 14.2 months, 226 patients (68.3%) were continuing to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P<0.001). The time to the next intervention was significantly improved in the vorasidenib group as compared with the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P<0.001). Adverse events of grade 3 or higher occurred in 22.8% of the patients who received vorasidenib and in 13.5% of those who received placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo. CONCLUSIONS: In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention. (Funded by Servier; INDIGO ClinicalTrials.gov number, NCT04164901.).
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Antineoplásicos , Glioma , Recurrencia Local de Neoplasia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Método Doble Ciego , Glioma/tratamiento farmacológico , Glioma/genética , Isocitrato Deshidrogenasa/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piridinas/efectos adversos , Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéuticoRESUMEN
Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined systemic therapy and SRS have contributed to a growing incidence of necrosis. The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway (cGAS-STING) represents a key biological mechanism linking radiation-induced DNA damage to pro-inflammatory effects and innate immunity. By recognizing cytosolic double-stranded DNA, cGAS induces a signaling cascade that results in the upregulation of type 1 interferons and dendritic cell activation. This pathway could play a key role in the pathogenesis of necrosis and provides attractive targets for therapeutic development. Immunotherapy and other novel systemic agents may potentiate activation of cGAS-STING signaling following radiotherapy and increase necrosis risk. Advancements in dosimetric strategies, novel imaging modalities, artificial intelligence, and circulating biomarkers could improve the management of necrosis. This review provides new insights into the pathophysiology of necrosis and synthesizes our current understanding regarding the diagnosis, risk factors, and management options of necrosis while highlighting novel avenues for discovery.
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INTRODUCTION: It has long been established that high-dose methotrexate is an essential part of therapy for primary central nervous system lymphoma. When regimens utilizing high-dose methotrexate were first studied, a dose of 8â g/m2 was used. More recently, reduced dosing strategies have been studied and adopted in attempts to reduce rates of adverse events. Studies utilizing 3.5â g/m2 of methotrexate have shown promising outcomes and improved rates of adverse events but there have never been any randomized head-to-head studies of differing dose levels of high-dose methotrexate. The purpose of this study was to compare efficacy and safety of different dosing strategies of high-dose methotrexate (HD-MTX) for primary central nervous system lymphoma (PCNSL). METHODS: This single center retrospective review was conducted between 07/01/2013 to 6/3/2020. The patient population was separated into two arms based upon dose of methotrexate. The high intensity (HiHD) arm was defined as patients who received doses > 3.5â g/m2, while the low intensity (LiHD) arm received ≤ 3.5â g/m2. The primary endpoint was overall response rate (ORR) and secondary endpoints include efficacy via 2-year overall survival (OS), progression to transplant, and utilization of consolidation or salvage therapy. Safety was assessed through monitoring of relevant laboratory studies. RESULTS: A total of 92 patients were included in this analysis. Baseline demographics were similar between groups, with the LiHD group trending toward older age. There were 78 patients eligible for assessment for ORR; there was no significant difference between the two groups (42.0% LiHD vs. 44.4% HiHD; p = 1.0). Rates of OS, progression to transplant and progression to consolidation chemotherapy were not different between groups. There were statistically significantly higher rates of renal and/or hepatic dysfunction with the first dose in the HiHD group compared with the LiHD group (11.5% LiHD vs. 64.3% HiHD; p ≤ 0.01). CONCLUSIONS: In this PCNSL patient cohort, there is no difference in terms of efficacy between HiHD LiHD methotrexate, but patients in the HiHD group had higher rates of renal and hepatic dysfunction. Limitations include small sample size and disparity between group sizes.
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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
Low-grade gliomas/glioneuronal tumors comprise one-third of all pediatric-type CNS tumors. These tumors are generally caused by activating mutations in the mitogen-activated protein kinase (MAPK) pathway. Targeted drugs, such as trametinib, have shown promise in other cancers and are being utilized in low-grade gliomas. A retrospective chart review was conducted to evaluate radiographic response, visual outcomes, tolerability, and durability of response in progressive circumscribed low-grade gliomas treated with trametinib. Eleven patients were treated with trametinib. The best radiographic response was 2/11 partial response, 3/11 minor response, 3/11 stable disease, and 3/13 progressive disease. In the patients with partial or minor response, the best response was seen after longer durations of therapy; 4 of 5 best responses occurred after at least 9 months of therapy with a median of 21 months. Patients with optic pathway tumors showed at least stable vision throughout treatment, with 3 having improved vision on treatment. Trametinib is effective and well-tolerated in patients with progressive low-grade glioma. Best responses were seen after a longer duration of therapy in those with a positive response. Patients with optic pathway lesions showed stable to improved vision while on treatment.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioma , Niño , Humanos , Adulto Joven , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Glioma/patología , Piridonas/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológicoRESUMEN
Venous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. We analyzed preoperative arterial blood, tumor tissue, and clinical-pathologic data (including next-generation sequencing data) from 258 patients with newly diagnosed World Health Organization (WHO) grade 2 to 4 adult-type diffuse gliomas. Forty-six (17.8%) experienced VTE. Tumor expression of tissue factor (TF) and podoplanin (PDPN) each positively correlated with VTE, although only circulating TF and D-dimers, not circulating PDPN, correlated with VTE risk. Gliomas with mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2 (IDHmut) caused fewer VTEs; multivariable analysis suggested that this is due to IDHmut suppression of TF, not PDPN. In a predictive time-to-event model, the following predicted increased VTE risk in newly diagnosed patients with glioma: (1) history of VTE; (2) hypertension; (3) asthma; (4) white blood cell count; (5) WHO tumor grade; (6) patient age; and (7) body mass index. Conversely, IDHmut, hypothyroidism, and MGMT promoter methylation predicted reduced VTE risk. These 10 variables were used to create a web-based VTE prediction tool that was validated in 2 separate cohorts of patients with adult-type diffuse glioma from other institutions. This study extends our understanding of the VTE landscape in these tumors and provides evidence-based guidance for clinicians to mitigate VTE risk in patients with glioma.
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Neoplasias Encefálicas , Glioma , Tromboembolia Venosa , Humanos , Adulto , Tromboembolia Venosa/genética , Tromboembolia Venosa/diagnóstico , Anticoagulantes/uso terapéutico , Glioma/complicaciones , Glioma/genética , Glioma/tratamiento farmacológico , Biomarcadores , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Isocitrato Deshidrogenasa/genética , MutaciónRESUMEN
PURPOSE: This guideline provides evidence-based recommendations for adults with isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma, as classified in the 2021 World Health Organization (WHO) Classification of Tumours. It includes indications for radiation therapy (RT), advanced RT techniques, and clinical management of adverse effects. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 4 key questions focused on the RT management of patients with IDH-mutant grade 2 and grade 3 diffuse glioma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management. CONCLUSIONS: Based on published data, the American Society for Radiation Oncology task force has proposed recommendations to inform the management of adults with IDH-mutant grade 2 and grade 3 diffuse glioma as defined by WHO 2021 classification, based on the highest quality published data, and best translated by our task force of subject matter experts.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Linfoma Folicular , Oligodendroglioma , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Glioma/genética , Glioma/radioterapia , Humanos , Organización Mundial de la SaludRESUMEN
Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains- physical, cognitive, nutritional, and psychological-at 2 time points prior to HCT-new patient evaluation (NPE) and sign-off (SO)-between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.