Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Animals , Dogs , Meningioma/genetics , Meningeal Neoplasms/geneticsABSTRACT
Background: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma. Methods: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected. Results: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH, and CHEK2 were most common (3/15, 20% each). BRCA1 variants occurred in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Prior cancer diagnosis was found in 5/15 patients (33%). Second-hit somatic variants were seen in 3/15 patients (20%) in NF1, MUTYH, and MSH2. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. 14/15 (93%) of patients discovered their pathogenic variant as a result of their paired glioma sequencing. Conclusions: These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further studies that can determine the role of variants in gliomagenesis and confirm the occurrence and types of pathogenic germline variants in patients with IDH wild type compared to IDH mutant tumors are necessary.
Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/drug therapy , Brain Neoplasms/therapy , Research Design , Data AnalysisABSTRACT
BACKGROUND: Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes. MATERIALS AND METHODS: A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected. RESULTS: Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131). CONCLUSION: This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.
Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Brain Neoplasms , Cholangiocarcinoma , Humans , Proto-Oncogene Proteins B-raf/genetics , Biliary Tract Neoplasms/genetics , Mutation , Brain Neoplasms/genetics , Retrospective Studies , Cholangiocarcinoma/pathology , Bile Duct Neoplasms/drug therapyABSTRACT
Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.
Subject(s)
Glioblastoma , Glioma , Humans , Glioma/genetics , Glioma/surgery , Mutation , Protein Kinase Inhibitors , Receptor, Fibroblast Growth Factor, Type 3/genetics , Microtubule-Associated ProteinsABSTRACT
Background: Chemical meningitis, a subtype of aseptic meningitis, as a complication of posterior fossa surgery is not a rare complication. However, the description of a severe protracted course following the surgical resection of an epidermoid cyst has not been described in the current literature. Chemical meningitis is thought to be associated with a hyperreactive inflammatory response, mediated in part by interleukin (IL)-10, IL-1ß, and tumor necrosis factor-α, to the postoperative keratin debris from the spontaneous leakage or surgical release of epidermoid contents into subarachnoid spaces, which ultimately can result in patient symptoms of meningitis and hydrocephalus. Often, this remains mild and the recommended management includes a short course administration of corticosteroids. Case Description: The authors report such a case in a patient who underwent a redoresection for a fourth ventricular epidermoid cyst. Postoperatively, the patient returned several times with symptoms of meningitis and hydrocephalus requiring multiple hospitalizations in the ensuing months. The patient required emergent cerebrospinal fluid diversion, further posterior fossa exploration and an extended high-dose corticosteroid treatment regimen. Conclusion: The authors summarize the current understanding of the biochemical processes involved for the rare presentation of postoperative chemical meningitis.
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A 25-year-old male presented with headaches 3 weeks after a car accident. His magnetic resonance imaging images showed a hemorrhagic vermis mass with fourth ventricle effacement. One month later, he underwent suboccipital craniotomy for removal of a pilocytic astrocytoma. A 3-month postoperative scan demonstrated a new area of medullary hyperintensity in the inferior olive, which was also present 7 months postoperatively consistent with hypertrophic olivary degeneration. This condition is caused by disruption to the dento-rubro-olivary pathway with magnetic resonance imaging enlargement of the inferior olivary nucleus and increased T2 signal. Hypertrophic olivary degeneration should be considered after cerebellar surgery and should not be mistaken for tumor recurrence.
Subject(s)
Astrocytoma , Neoplasm Recurrence, Local , Adult , Astrocytoma/complications , Astrocytoma/diagnostic imaging , Astrocytoma/surgery , Cerebellar Nuclei/pathology , Humans , Hypertrophy/etiology , Hypertrophy/pathology , Magnetic Resonance Imaging/methods , Male , Neoplasm Recurrence, Local/pathology , Olivary Nucleus/diagnostic imaging , Olivary Nucleus/pathologyABSTRACT
Background: Colloid cysts characteristically arise from the roof of the third ventricle near the foramen of Monro, causing symptoms from obstructive hydrocephalus. However, atypical locations have been reported with various clinical presentations, growth patterns, and displacement of surrounding anatomic structures. Case Description: Here, we describe the interesting case of a patient with a large hemorrhagic cavum vergae colloid cyst presenting with anterograde amnesia soon after starting antiplatelet therapy. The patient did not have hydrocephalus on presentation and his amnesia persisted after complete removal of the hemorrhagic mass through transcallosal interforniceal approach. Conclusion: To the best of our knowledge, this is the only reported instance of a colloid cyst presenting with amnesia in the absence of hydrocephalus. Pathophysiology as well as diagnostic and management strategies of hemorrhagic colloid cysts are discussed.
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While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.
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BACKGROUND: Intramedullary melanocytomas are exceedingly rare and their management is largely based on case reports and small clinical series. They have characteristic imaging and histologic findings that can aid in their diagnosis. Genetic testing may be required for definitive diagnosis and management guidance in ambiguous cases. CASE DESCRIPTION: We present the case of a thoracic intramedullary meningeal melanocytoma in a patient unable to undergo an MRI. CONCLUSION: This is the first reported S-100-negative case with genetic testing to support the diagnosis of a rare intramedullary melanocytoma.
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BACKGROUND: Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. METHODS: We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. RESULTS: We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). CONCLUSIONS: IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.
Subject(s)
Astrocytoma , Brain Neoplasms , Isocitrate Dehydrogenase , Venous Thromboembolism , Astrocytoma/complications , Astrocytoma/genetics , Brain Neoplasms/complications , Brain Neoplasms/genetics , Humans , Isocitrate Dehydrogenase/genetics , Mutation , Prospective Studies , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/geneticsSubject(s)
Brain Neoplasms , Lung Neoplasms , Brain Neoplasms/therapy , Cranial Irradiation , HumansABSTRACT
BACKGROUND: Age disparities among cancer clinical trial participants are pervasive and worsening over time. Identification of factors associated with age disparities is critical to improve enrollment of older patients on trials. The incidence and impact of trial eligibility criteria that exclude patients on the basis of age remains opaque. METHODS: ClinicalTrials.gov was queried for completed oncologic randomized controlled trials (RCTs). Phase 3 RCTs assessing a therapeutic intervention among adult cancer patients were included. Trial eligibility criteria were assessed using the ClinicalTrials.gov website as well as trial publications and protocol documentation. RESULTS: Seven hundred and forty-two trials met inclusion criteria, with a total combined enrollment of 449,720 patients. Upper age restriction enrollment criteria were identified for 10.1% of RCTs; the median age cutoff for restricted trials was 72â¯years (interquartile range 70-80â¯years). Linear regression modeling revealed decreasing incidence of age restriction criteria over time, at a rate of -1.1% annually (pâ¯=â¯.03); trials initiating enrollment in 2002-2005, for example, had a 16.1% rate of age-restrictive eligibility criteria, compared with 7.6% for trials initiating enrollment in 2010-2014. CONCLUSION: Use of eligibility criteria that explicitly exclude patients on the basis of age appears to be decreasing with time. Future efforts should aim to better characterize the relationship between eligibility criteria (such as those that exclude patients on the basis of specific organ function) and their association with age disparities among enrolled patients.
Subject(s)
Neoplasms , Aged , Aged, 80 and over , Clinical Trials as Topic , Humans , Incidence , Neoplasms/epidemiology , Neoplasms/therapyABSTRACT
BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.
Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Cohort Studies , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Male , Radiotherapy , Retrospective Studies , Temozolomide/therapeutic use , Treatment OutcomeABSTRACT
Importance: Seminal investigation 2 decades ago alerted the oncology community to age disparities in participation in cooperative group trials; less is known about whether these disparities persist in industry-funded research. Objective: To characterize the age disparities among trial enrollees on randomized clinical trials (RCTs) of common cancers in clinical oncology and identify factors associated with wider age imbalances. Data Sources: Phase 3 clinical oncology RCTs were identified through ClinicalTrials.gov. Study Selection: Multiarm RCTs assessing a therapeutic intervention for patients with breast, prostate, colorectal, or lung cancer (the 4 most common cancer disease sites) were included. Data Extraction and Synthesis: Trial data were extracted from ClinicalTrials.gov. Trial screening and parameter identification were independently performed by 2 individuals. Data were analyzed in 2018. Main Outcomes and Measures: The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was determined for each trial. Results: Three hundred two trials met inclusion criteria. The trials collectively enrolled 262â¯354 participants; 249 trials (82.5%) were industry-funded. For all trials, the trial median age of trial participants was a mean of 6.49 years younger than the population median age (95% CI, -7.17 to -5.81 years; P < .001). Age disparities were heightened among industry-funded trials compared with non-industry-funded trials (mean DMA, -6.84 vs -4.72 years; P = .002). Enrollment criteria restrictions based on performance status or age cutoffs were associated with age disparities; however, industry-funded trials were not more likely to use these enrollment restrictions than non-industry-funded trials. Age disparities were also larger among trials that evaluated a targeted systemic therapy and among lung cancer trials. Linear regression modeling revealed a widening gap between trial and population median ages over time at a rate of -0.19 years annually (95% CI, -0.37 to -0.01 years; P = .04). Conclusions and Relevance: Age disparities between trial participants and the incident disease population are pervasive across trials and appear to be increasing over time. Industry sponsorship of trials is associated with heightened age imbalances among trial participants. With an increasing role of industry funding among cancer trials, efforts to understand and address age disparities are necessary to ensure generalizability of trial results as well as equity in trial access.
Subject(s)
Neoplasms/therapy , Age Factors , Clinical Trials, Phase III as Topic/economics , Humans , Linear Models , Randomized Controlled Trials as Topic , Risk AssessmentABSTRACT
BACKGROUND: Papillary glioneuronal tumors (PGNTs) are rare World Health Organization grade I neoplasms that are characterized by a benign course and excellent response to surgical resection. A few reports exist of tumors with more aggressive clinical and histologic features. In this report we detail the case of an unusually aggressive PGNT in a 67-year-old woman. CASE DESCRIPTION: The patient had a 3-year history of seizures and was diagnosed with a frontoparietal mass on imaging. She underwent subtotal resection with a histologic diagnosis of PGNT. Less than a year after surgery, the patient experienced recurrence of disease and underwent reresection and adjuvant radiation treatment. The patient's disease continued to progress despite radiation treatment, so adjuvant temozolomide was initiated. Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. CONCLUSIONS: PGNTs, while typically benign, can rarely recur after surgery. Molecular testing should be performed on all PGNTs to help possibly identify more aggressive tumors and potentially reveal novel treatment options.
Subject(s)
Brain Neoplasms/pathology , Glioma/pathology , Neoplasm Recurrence, Local/pathology , Somatosensory Cortex/pathology , Aged , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Cyclin-Dependent Kinase Inhibitor Proteins/genetics , DNA Copy Number Variations , Female , Glioma/diagnostic imaging , Glioma/genetics , Glioma/therapy , Humans , Magnetic Resonance Imaging , Microtubule-Associated Proteins/genetics , Mutation , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/therapy , Neurosurgical Procedures , Oncogene Fusion/genetics , Promoter Regions, Genetic/genetics , Radiotherapy , Receptor, Fibroblast Growth Factor, Type 3/genetics , Somatosensory Cortex/diagnostic imaging , Somatosensory Cortex/surgery , Telomerase/genetics , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Optic pathway gliomas (OPGs) are relatively rare, and their presentation after the first decade of life is even less common. Although many treatment options exist, surgery is typically reserved for tumors significantly compressing surrounding structures. Pregnancy can complicate the management of these tumors, as fetal developmental considerations limit the ways in which they are imaged and treated. CASE DESCRIPTION: In this report we detail the case of a 27-year-old pregnant woman who was found to have an OPG during her third trimester. After a decline in this patient's vision and clinical status, a decision was made to induce labor at 31 weeks so that her disease could be more thoroughly addressed. CONCLUSIONS: While OPGs are typically benign tumors, pregnancy complicates their management significantly. Contrast media and anesthesia pose significant risks to the fetus, while pregnancy may contribute to increased rates of tumor growth and clinical deterioration. Managing OPGs in pregnant patients thus requires balancing the risks to the fetus and patient.
Subject(s)
Optic Nerve Glioma/diagnosis , Optic Nerve Glioma/surgery , Optic Nerve Neoplasms/diagnosis , Optic Nerve Neoplasms/surgery , Adult , Female , Humans , Optic Nerve Glioma/complications , Optic Nerve Neoplasms/complications , Pregnancy , Pregnancy Complications , Pregnancy Trimester, Third , Treatment Outcome , Vision Disorders/etiologyABSTRACT
BACKGROUND: Examine the potential effects of health disparities in survival of glioblastoma (GB) patients. METHODS: We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS). RESULTS: We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.