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1.
Curr Opin Oncol ; 34(6): 691-697, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36170169

ABSTRACT

PURPOSE OF REVIEW: We review the diagnostic tools, treatment options, and clinical management for brain tumors diagnosed in pregnancy with consideration for management approaches that are best suited to preserve maternal and fetal health. RECENT FINDINGS: Women of child-bearing age are at risk of developing brain tumors and are at increased risk compared with male counterparts for tumors that are hormonally driven. Brain tumors are rare neoplasms, and diagnosis of brain tumors in pregnancy is uncommon, such that management guidelines and treatment recommendations are lacking for most tumor types. We discuss the standard treatment options for brain tumors and the relative risks and safety when these treatments are considered during pregnancy. We review the neoplasms most commonly affecting pregnant women and the existing literature and guidelines. SUMMARY: Pregnancy is a unique phase of life in which hormonal, immunologic, and vascular changes may impact tumor growth and presentation. Treatment decisions should consider the symptoms and stability of the pregnant patients, the gestational age and health of the fetus, and the location and behavior of the neoplasm.


Subject(s)
Brain Neoplasms , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Female , Humans , Male , Pregnancy
2.
J Neurooncol ; 158(1): 69-79, 2022 May.
Article in English | MEDLINE | ID: mdl-35437688

ABSTRACT

PURPOSE: Glioblastoma (GBM) is a devastating neuro-oncologic disease with invariably poor prognosis. Despite this, research shows patients have unrealistic perceptions of their prognosis, which may relate in part to communication patterns between patients, caregivers and oncologists. The purpose of this study was to examine communication processes and goals among patients, caregivers, and oncologists to elucidate drivers of prognostic understanding (PU) in the context of recurrent GBM. METHODS: This was a prospective, multi-center study enrolling adult patients with GBM, caregivers, and oncologists, who independently reported the content of a specific discussion involving the disclosure of GBM recurrence. Communication processes and goals were characterized for each participant, and concordance between all dyads and patient-caregiver-oncologist triads were calculated. RESULTS: Seventeen patient, caregiver, and oncologist triads were analyzed. At the individual level, three (17.6%) patients and 8 (47.1%) caregivers reported having discussed prognosis during the clinical encounter, as compared to ten oncologists (58.8%). Seven patients (41.2%) and 5 caregivers (29.4%), versus thirteen oncologists (76.5%) reported ever discussing prognosis or life expectancy at previous appointments. Generally, patient-caregiver concordance (i.e., both answered the same) regarding communication goals and processes was low. Triads showed limited concordant responses in discussing curability (n = 5), prognosis (n = 4), end-of-life treatment goals (n = 4), and ever discussing prognosis (n = 3). CONCLUSION: Patients, caregivers and oncologists had discordant views regarding communication processes and prognostic goals, even when recalling a single discussion. This study highlights the importance of clear and frequent communication about prognosis, and the need for further research on communication and PU in the neuro-oncology setting.


Subject(s)
Glioblastoma , Neoplasms , Oncologists , Adaptation, Psychological , Adult , Caregivers , Glioblastoma/therapy , Humans , Neoplasms/therapy , Physician-Patient Relations , Prognosis , Prospective Studies
3.
J Thromb Thrombolysis ; 53(2): 479-484, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34347201

ABSTRACT

The cumulative incidence of symptomatic venous thromboembolism (VTE) among patients with malignant gliomas (MG) is estimated to be as high as 36% during the course of therapy. Development of VTE is associated with an increased risk of hospitalization, delays in cancer treatment, and an increased risk of complications including intracranial hemorrhage as well as VTE specific symptoms. Despite the high risk of VTE and associated morbidity, there is no standard recommendations regarding long term outpatient VTE prophylaxis in patients with MG due to the lack of clinical trial evidence in this patient population. In this study, we treated ten patients with newly diagnosed MG with apixaban, 2.5 mg twice daily beginning 2-21 days after craniotomy and continuing for up to 6 months. Unacceptable toxicity was defined by ≥ grade 2 CNS or non-CNS hemorrhage, a thromboembolic event (i.e. stroke) or cardiovascular event requiring anticoagulation or anti-platelet therapy. There were no unacceptable toxicities to report and no treatment-related adverse events. None of the patients on the study were diagnosed with a VTE while receiving apixaban. We conclude that apixaban can be given safely to patients with primary MG shortly after craniotomy and should be considered for VTE prevention in these high-risk patients.


Subject(s)
Glioma , Venous Thromboembolism , Anticoagulants/therapeutic use , Glioma/complications , Glioma/drug therapy , Glioma/surgery , Humans , Pyrazoles , Pyridones/adverse effects , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
4.
Blood ; 133(5): 436-445, 2019 01 31.
Article in English | MEDLINE | ID: mdl-30567753

ABSTRACT

Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK) and has shown single-agent activity in recurrent/refractory central nervous system (CNS) lymphoma. Clinical responses are often transient or incomplete, suggesting a need for a combination therapy approach. We conducted a phase 1b clinical trial to explore the sequential combination of ibrutinib (560 or 840 mg daily dosing) with high-dose methotrexate (HD-MTX) and rituximab in patients with CNS lymphoma (CNSL). HD-MTX was given at 3.5 g/m2 every 2 weeks for a total of 8 doses (4 cycles; 1 cycle = 28 days). Ibrutinib was held on days of HD-MTX infusion and resumed 5 days after HD-MTX infusion or after HD-MTX clearance. Single-agent daily ibrutinib was administered continuously after completion of induction therapy until disease progression, intolerable toxicity, or death. We also explored next-generation sequencing of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) before and during treatment. The combination of ibrutinib, HD-MTX, and rituximab was tolerated with an acceptable safety profile (no grade 5 events, 3 grade 4 events). No dose-limiting toxicity was observed. Eleven of 15 patients proceeded to maintenance ibrutinib after completing 4 cycles of the ibrutinib/HD-MTX/rituximab combination. Clinical responses occurred in 12 of 15 patients (80%). Sustained tumor responses were associated with clearance of ctDNA from the CSF. This trial was registered at www.clinicaltrials.gov as #NCT02315326.


Subject(s)
Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Methotrexate/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Rituximab/therapeutic use , Adenine/analogs & derivatives , Adult , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/pathology , Circulating Tumor DNA/genetics , Female , Humans , Lymphoma/genetics , Lymphoma/pathology , Methotrexate/adverse effects , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Piperidines , Protein Kinase Inhibitors/adverse effects , Pyrazoles/adverse effects , Pyrazoles/pharmacokinetics , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , Rituximab/adverse effects , Treatment Outcome , Young Adult
5.
Curr Oncol Rep ; 22(8): 83, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32607727

ABSTRACT

PURPOSE OF REVIEW: Chimeric antigen receptor (CAR) T cells are a breakthrough therapeutic treatment for patients with relapsed and refractory hematologic malignancies. With two FDA-approved formulations and likely more to come, CAR T cell therapy is moving beyond clinical trials and into academic and community oncology practices throughout the country. Oncologists are tasked with understanding the indications for this treatment and the potential complications. RECENT FINDINGS: In this review, we focus on the neurological toxicities associated with CAR T cell therapy. Neurotoxicity affects approximately half of patients treated with CAR T cells and can cause severe morbidity. We discuss the incidence, pathophysiology, and management of neurological complications of CAR T cells. CAR T cells are a breakthrough treatment for hematologic malignancies with considerable neurological toxicity that requires attention and management.


Subject(s)
Hematologic Neoplasms/therapy , Immunotherapy, Adoptive/adverse effects , Neurotoxicity Syndromes/etiology , Receptors, Chimeric Antigen/immunology , Clinical Trials as Topic , Glioma/therapy , Humans , Neurotoxicity Syndromes/therapy
6.
Curr Opin Neurol ; 32(6): 857-863, 2019 12.
Article in English | MEDLINE | ID: mdl-31609738

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to discuss how a new treatment modality, tumor treating fields, may be incorporated into the oncologic care for patients with glioblastoma. RECENT FINDINGS: Tumor treating fields are a new treatment modality available to patients with newly diagnosed and recurrent glioblastoma. Alternating electric fields are delivered via a wearable, removable device affixed to the scalp of patients with supratentorial glioblastoma. With continuous use, the application of tumor treating fields combined with temozolomide chemotherapy has been shown to improve overall survival compared with temozolomide alone in patients with newly diagnosed glioblastoma. Adverse events attributable to the device are limited to localized skin reactions. Despite compendium guidelines in support of its use and Food and Drug Administration (FDA) approval, tumor treating fields have been slow to be adopted in the neuro-oncology community. Critics have raised concerns about the generalizability of the study data, patient quality of life, and mechanism of action of this therapy. SUMMARY: Tumor treating fields are available for the treatment of both newly diagnosed and recurrent glioblastoma and represent a new category of treatment modalities in oncologic therapy. This novel device has received FDA approval but has been slow to be adopted into clinical practice.


Subject(s)
Electric Stimulation Therapy/methods , Glioblastoma/therapy , Neoplasm Recurrence, Local/therapy , Supratentorial Neoplasms/therapy , Electric Stimulation Therapy/adverse effects , Electric Stimulation Therapy/economics , Electric Stimulation Therapy/instrumentation , Humans
7.
Muscle Nerve ; 2018 Jan 17.
Article in English | MEDLINE | ID: mdl-29342325

ABSTRACT

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018.

8.
Cancer Immunol Immunother ; 66(3): 379-389, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27942839

ABSTRACT

BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV). METHODS: Eleven patients with newly diagnosed glioblastoma were treated with radiation, TMZ, and BEV, following surgery. We measured immune-related PBMC subsets using multi-parameter flow cytometry and plasma cytokine and growth factor concentrations using electrochemiluminescence-based multiplex analysis at baseline and after 6 weeks of treatment. RESULTS: The absolute number of peripheral blood regulatory T cells (Tregs) decreased significantly following treatment. The lower number of peripheral Tregs was associated with a CD4+ lymphopenia, and thus, the ratio of Tregs to PBMCs was unchanged. The addition of bevacizumab to standard radiation and temozolomide led to the decrease in the number of circulating Tregs when compared with our prior study. There was a significant decrease in CD8+ cytotoxic and CD4+ recent thymic emigrant T cells, but no change in the number of myeloid-derived suppressor cells. Significant increases in plasma VEGF and placental growth factor (PlGF) concentrations were observed. CONCLUSIONS: Treatment with radiation, TMZ, and BEV decreased the number but not the proportion of peripheral Tregs and increased the concentration of circulating VEGF. This shift in the peripheral immune cell profile may modulate the tumor environment and have implications for combining immunotherapy with anti-angiogenic therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Glioblastoma/immunology , Glioblastoma/therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Bevacizumab/administration & dosage , Brain Neoplasms/blood , Brain Neoplasms/pathology , Chemoradiotherapy , Cytokines/blood , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Disease-Free Survival , Female , Glioblastoma/blood , Glioblastoma/pathology , Humans , Immunotherapy/methods , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/radiation effects , Male , Middle Aged , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/radiation effects , Temozolomide
9.
J Neurooncol ; 125(1): 183-90, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26275367

ABSTRACT

Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85% sensitivity and 79% specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69% sensitivity and 79% specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI.


Subject(s)
Brain Neoplasms/pathology , Contrast Media/metabolism , Glioblastoma/pathology , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Aged, 80 and over , Alkaloids , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Diffusion Magnetic Resonance Imaging , Disease Progression , Female , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , ROC Curve , Retrospective Studies , Temozolomide , Time Factors , Treatment Outcome
11.
Curr Treat Options Oncol ; 15(4): 551-66, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25173555

ABSTRACT

OPINION STATEMENT: Glioblastoma, an incurable, malignant, and highly vascular tumor, is a seemingly ideal target for anti-angiogenic therapies such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. Phase II trials in recurrent glioblastoma demonstrated bevacizumab was associated with clinical benefits, including decreases in brain edema and corticosteroids use resulting from reduced vascular permeability, as well as radiographic responses in 25 %-40 % of patients. In newly diagnosed disease, a phase III trial (AVAglio) showed adding bevacizumab to standard chemoradiotherapy improved progression free survival (PFS), with preservation of quality of life, and reduced corticosteroids use, but did not improve overall survival (OS). Another similar phase III trial (RTOG 0825) found similar PFS and OS trends, but suggested that the addition of bevacizumab resulted in more frequent cognitive decline compared with standard chemoradiotherapy. However, interpretation of those findings is limited by the fact that progressing patients were not evaluated, and patients remained longer on study in the bevacizumab arm. It is possible that the observed cognitive decline represented unrecognized tumor progression, rather than deleterious bevacizumab effects. Regardless, even if real, it is difficult to ascertain how improvements in PFS and quality of life compare with the associated economic costs and increased toxicities of bevacizumab, in the setting of no survival benefit. Further studies in recurrent disease are being conducted; preliminary results of a randomized trial showed favorable results with the combination with CCNU, and final results are awaited. Meanwhile, outside the realm of clinical trials, the current trend appears to be to reserve bevacizumab for use in recurrent disease, or for patients with moderate or severe neurologic symptoms, either in the newly diagnosed or recurrent setting. Further research efforts are needed to determine optimal candidates for this treatment from a molecular standpoint, as well as to develop imaging tools capable of accurately identifying response and progression, and to establish new drug combinations that could result in unquestionable clinical benefit and improved survival in these patients.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Biomarkers , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Glioblastoma/pathology , Glioblastoma/radiotherapy , Humans , Neovascularization, Pathologic/drug therapy , Prognosis , Treatment Outcome
12.
Clin Cancer Res ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995739

ABSTRACT

BACKGROUND: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK). We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary (PCNSL) or secondary CNS lymphoma (SCNSL). PATIENTS AND METHODS: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined cohort of 46 patients (31 PCNSLs, 15 SCNSLs). Patients received ibrutinib at 560mg or 840mg daily in the dose-escalation and 840mg daily in the expansion cohort. Median follow up was 49.9 and 62.1 months for patients with PCNSL and SCNSL, respectively. We sequenced DNA from available tumor biopsies and cerebrospinal fluid (CSF) collected before and during ibrutinib therapy. RESULTS: Tumor responses were observed in 23/31 (74%) PCNSLs and 9/15 (60%) SCNSLs, including 12 complete responses in PCNSL and 7 in SCNSL. Median progression-free survival (PFS) for PCNSL was 4.5 months (95%CI: 2.8-9.2) with 1y-PFS at 23.7% (95%CI: 12.4%-45.1%). Median duration of response (DOR) in the 23 PCNSL responders was 5.5 months. Median PFS in SCNSL was 5.3 months (95%CI: 1.3-14.5) with a median DOR 8.7 months for the 9 responders. Exploratory biomarker analysis suggests that mutations in TBL1XR1 may be associated with a long-term response to ibrutinib in PCNSL (p=0.0075). Clearance of circulating tumor DNA from CSF was associated with complete and long-term ibrutinib response. CONCLUSIONS: Our study confirms single-agent activity of ibrutinib in r/r CNS lymphoma and identifies molecular determinants of response based on long-term follow up. CLINICAL TRIAL INFORMATION: NCT02315326.

13.
Epilepsy Behav ; 29(2): 295-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24021495

ABSTRACT

Psychogenic nonepileptic seizures (PNESs) are paroxysmal events of altered behavior that outwardly resemble epilepsy but are caused by psychiatric disease. The diagnosis of probable PNESs can be made in the outpatient clinic prior to video-EEG monitoring by identification of specific PNES predictors and specific elements of seizure semiology from the clinical history. Since psychiatric disease may have distinct mechanisms between women and men, the objective of this study was to determine if gender-specific differences exist in PNES predictors and PNES semiology. Such differences could be used to optimize the accuracy of outpatient diagnosis of probable PNESs. Medical records of male and female patients with video-EEG diagnosis of definite PNESs were retrospectively reviewed for occurrence of PNES predictors. In addition, PNES semiology was analyzed de novo from video-EEG records and categorized into previously established semiology clusters. Eighty-six patients were included in the analysis (59 women and 27 men). We found significantly lower rates of reported physical and sexual abuse, lower rates of previous psychiatric diagnosis, and lower rates of chronic pain in male patients with no significant differences in rates of other PNES predictors. Furthermore, we found no difference in PNES semiology between men and women, with both groups experiencing similar rates of major motor, minor motor, and nonmotor semiology. In conclusion, our results lend support to the idea that distinct risk factor criteria but similar semiology criteria should be used for the diagnosis of probable PNESs in the outpatient clinic in men and women.


Subject(s)
Seizures/diagnosis , Sex Characteristics , Somatoform Disorders/diagnosis , Adult , Electroencephalography , Female , Humans , Male , Middle Aged , Outpatients , Retrospective Studies , Seizures/complications , Somatoform Disorders/complications , Young Adult
14.
Cancers (Basel) ; 15(12)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37370865

ABSTRACT

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan-Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.

15.
J Clin Oncol ; 41(3): 618-628, 2023 01 20.
Article in English | MEDLINE | ID: mdl-36288512

ABSTRACT

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.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Focal Adhesion Protein-Tyrosine Kinases/genetics , Focal Adhesion Protein-Tyrosine Kinases/therapeutic use , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/genetics , Meningeal Neoplasms/pathology , Meningioma/drug therapy , Meningioma/genetics , Mutation , Neoplasm Recurrence, Local/drug therapy
16.
Neurology ; 2022 May 06.
Article in English | MEDLINE | ID: mdl-35523586

ABSTRACT

Meningeal melanocytomas are an extremely rare, pigmented tumors of the central nervous system (CNS). They generally carry a favorable prognosis, although recurrence and transformation into the more aggressive malignant melanoma has been reported. We present a case of a patient who reported constipation and abdominal pain around the umbilicus, which progressed into cord compression with lower extremity weakness and gait instability. Spinal magnetic resonance imaging (MRI) revealed a tumor at the level of T11, and she underwent gross total resection of the mass. Pathology demonstrated a meningeal melanocytoma with intermediate features. She received post-operative radiation therapy and had stable disease for three years, at which time she developed new weakness and drop metastases. This case represents a rare presentation of a rare disease, in which a spinal cord tumor presented with constipation and abdominal distress. Intradural-extramedullary tumors of the thoracic spine are most commonly nerve sheath tumors or meningiomas, but rare entities such as melanocytomas can present in this location; even more rarely, these tumors can have an aggressive course with delayed recurrence.

17.
JCO Oncol Pract ; 18(1): 23-34, 2022 01.
Article in English | MEDLINE | ID: mdl-34339260

ABSTRACT

PURPOSE: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR). METHODS: This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested. RESULTS: The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care. CONCLUSION: Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact.


Subject(s)
Hematology , Neoplasms , Ambulatory Care , Humans , Medical Oncology , Neoplasms/therapy , Referral and Consultation
18.
J Neurosurg Case Lessons ; 2(11): CASE21436, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-35855300

ABSTRACT

BACKGROUND: Choroid plexus metastases are extremely rare from all types of malignancy, with only 42 cases reported in the literature thus far. Most of these originate from renal cell carcinoma and present as a solitary choroid plexus lesion; only two cases of multifocal choroid plexus metastases have been reported to date. OBSERVATIONS: The authors report the third case of multifocal metastases to the choroid plexus, that of a 75-year-old man who developed three measurable choroid plexus lesions approximately 3.5 years after undergoing total thyroidectomy and chemotherapy for papillary thyroid carcinoma. He underwent intraventricular biopsy of the largest lesion and subsequently died of hydrocephalus after opting for comfort care only. LESSONS: This is the third case of multifocal choroid plexus metastasis in the literature and the second case of multifocal metastasis from thyroid carcinoma. As such, the natural disease course is not well characterized. This case is compared with the previous eight reports of choroid plexus metastases from thyroid carcinoma, seven of which involved solitary lesions. The eight prior cases are evaluated with attention to treatment modalities used and factors potentially influencing prognosis, specifically those that might contribute to hydrocephalus, a reported complication for this pathology.

19.
Neuro Oncol ; 23(11): 1845-1858, 2021 11 02.
Article in English | MEDLINE | ID: mdl-34302487

ABSTRACT

BACKGROUND: Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. METHODS: In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population. RESULTS: The 386 respondents were predominantly female (58%) with a median age range of 40-49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field. CONCLUSIONS: The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.


Subject(s)
Benchmarking , Medical Oncology , Adult , Ethnicity , Female , Humans , Middle Aged , Societies , Surveys and Questionnaires
20.
Neurooncol Adv ; 3(1): vdab035, 2021.
Article in English | MEDLINE | ID: mdl-34007966

ABSTRACT

BACKGROUND: It remains unknown how the COVID-19 pandemic has changed neuro-oncology clinical practice, training, and research efforts. METHODS: We performed an international survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents, April 24-May 17, 2020. We assessed clinical practice and research environments, institutional preparedness and support, and perceived impact on patients. RESULTS: Of 582 respondents, 258 (45%) were US-based and 314 (55%) international. Ninety-four percent of participants reported changes in their clinical practice. Ninety-five percent of respondents converted at least some practice to telemedicine. Ten percent of practitioners felt the need to see patients in person, specifically because of billing concerns and pressure from their institutions. Sixty-seven percent of practitioners suspended enrollment for at least one clinical trial, including 62% suspending phase III trial enrollments. More than 50% believed neuro-oncology patients were at increased risk for COVID-19. Seventy-one percent of clinicians feared for their own personal safety or that of their families, specifically because of their clinical duties; 20% had inadequate personal protective equipment. While 69% reported increased stress, 44% received no psychosocial support from their institutions. Thirty-seven percent had salary reductions and 63% of researchers temporarily closed their laboratories. However, the pandemic created positive changes in perceived patient satisfaction, communication quality, and technology use to deliver care and mediate interactions with other practitioners. CONCLUSIONS: The pandemic has changed treatment schedules and limited investigational treatment options. Institutional lack of support created clinician and researcher anxiety. Communication with patients was satisfactory. We make recommendations to guide clinical and scientific infrastructure moving forward and address the personal challenges of providers and researchers.

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