Abstract
BACKGROUND AND IMPORTANCE
Apraxia of speech is a disorder of articulatory coordination and planning in speech sound production. Its diagnosis is based on deficits in articulation, prosody, ...and fluency. It is often described concurrent with aphasia or dysarthria, while pure apraxia of speech is a rare entity.
CLINICAL PRESENTATION
A right-handed man underwent focal surgical resection of a recurrent grade III astrocytoma in the left hemisphere dorsal premotor cortex located in the posterior middle frontal gyrus. After the procedure, he experienced significant long-term speech production difficulties. A battery of standard and custom language and articulatory assessments were administered, revealing intact comprehension and naming abilities, and preserved strength in orofacial articulators, but considerable deficits in articulatory coordination, fluency, and prosody—consistent with diagnosis of pure apraxia of speech. Tractography and resection volumes compared with publicly available imaging data from the Human Connectome Project suggest possible overlap with area 55b, an under-recognized language area in the dorsal premotor cortex and has white matter connectivity with the superior longitudinal fasciculus.
CONCLUSION
The case reported here details a rare clinical entity, pure apraxia of speech resulting from resection of posterior middle frontal gyrus. While not a classical language area, emerging literature supports the role of this area in the production of fluent speech, and has implications for surgical planning and the general neurobiology of language.
OBJECTIVE Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors ...investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas. METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects. RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients. CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.
Resection of the T1 contrast-enhancing portion of glioblastoma multiforme (GBM) has been shown to increase patient survival, although whether GBM resection beyond these boundaries has an additional ...survival benefit is not clear. In this study, we examined the effect of resecting the enhancement and a margin of brain tissue surrounding the enhancement in patients with GBM of the temporal lobe.
We identified 32 consecutive patients with temporal lobe GBM who underwent initial resection between 2012 and 2015. Progression-free survival (PFS) and overall survival (OS) were analyzed based on the following categories: subtotal resection (STR; <99% of contrast enhancement removed), gross total resection (GTR; 100% of T1 contrast enhancement removed), and supramaximal resection (SMR; removal of T1 contrast enhancement plus removal of at least 1 cm of brain tissue surrounding the enhancement).
Patients undergoing SMR demonstrated a substantially improved median PFS (15 months) compared with those undergoing GTR (7 months) or those undergoing STR (6 months) (P < 0.003). A median OS advantage was also present in the SMR group (24 months) compared with the GTR (11 months) and STR (9 months) groups (P < 0.004). SMR significantly improved PFS (hazard ratio HR, 0.093; 95% confidence interval CI, 0.01–0.89; P = 0.039) and OS (HR, 0.169; 95% CI, 0.05–0.57; P < 0.004) when controlling for other variables. The complication rates did not differ among the resection groups (P = 0.66).
Achieving SMR substantially improved survival in patients with temporal lobe GBM compared with GTR of the enhancement alone.
•This is a retrospective series of 32 patients who underwent resection of temporal lobe glioblastoma multiforme comparing subtotal resection, gross total resection, and supramaximal resection (SMR).•Significantly improved progression-free survival was seen with SMR (P = 0.039).•Significantly improved overall survival was seen with SMR (P < 0.004).•Complication rates did not differ among the 3 resection groups (P = 0.66).
Metastasized cancer cells have an increased resistance to therapies leading to a drastic decrease in patient survival rates. However, our understanding of the cause for this enhanced resistance is ...lacking. In this study, we report that physically tight confinement during cancer cell migration triggers therapeutic resistance and induces cancer stem cell-like behavior including up-regulation in efflux proteins and in cancer stem cell related markers. Moreover, the re-localization of Yes-associated protein (YAP) to the cell nucleus indicated an elevated level of cytoskeletal tension. The increased cytoskeletal tension suggested that mechanical interactions between cancer cells and tight surroundings during metastasis is one of the factors that contributes to therapeutic resistance and acquisition of cancer stem cell (CSC) like features. With this system and supporting data, we are able to study cells with therapeutic resistance and CSC-like properties for the future purpose of developing new strategies for the treatment of metastatic cancer.
•Tight confinement during cancer cell migration triggers therapeutic resistance and induces cancer stem cell-like behavior.•Increasing efflux proteins and cancer stem cell markers associate with increased therapeutic resistance.•Re-localization of YAP to the cell nucleus indicates an elevated level of cytoskeletal tension during confined-migration.
Introduction
H3
K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to ...investigate the prognostic impact of different genetic alterations on survival of these patients.
Methods
We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan–Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).
Result
We included 30 studies with 669 H3-DMGs.
TP53
mutations were the most common second alteration among these neoplasms. In univariate Cox regression model,
TP53
mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143–1.829) whereas
ACVR1
(HR 0.712; 95% CI 0.518–0.976) and
FGFR1
mutations (HR 0.408; 95% CI 0.208–0.799) conferred prolonged survival. In addition,
ATRX
loss was also associated with a better OS (HR 0.620; 95% CI 0.386–0.996). Adjusted for age, gender, and tumor location, the presence of
TP53
mutations, the absence of
ACVR1
or
FGFR1
mutations remained significantly poor prognostic factors.
Conclusions
We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification.
Dysembryoplastic neuroepithelial tumors (DNETs) are rare tumors that present with seizures in the majority of cases. We report the results of a review of seizure freedom rates following resection of ...these benign lesions. We searched the English literature using PubMed for articles presenting seizure freedom rates for DNETs as a unique entity. Patient demographics, tumor characteristics, and operative variables were assessed across selected studies. Twenty-nine articles were included in the analysis. The mean age at surgery across studies was a median of 18 years (interquartile range 11–25 years). The mean duration of epilepsy pre-operatively was a median 7 years (interquartile range 3–11 years). Median reported gross-total resection rate across studies was 79 % (interquartile range 62–92 %). Authors variously chose lesionectomy or extended lesionectomy operations within and across studies. The median seizure freedom rate was 86 % (interquartile range 77–93 %) with only one study reporting fewer than 60 % of patients seizure free. Seizure outcomes were either reported at 1 year of follow-up or at last follow-up, which occurred at a median of 4 years (interquartile range 3–7 years). The number of seizure-free patients who discontinued anti-epileptic drugs varied widely from zero to all patients. Greater extent of resection was associated with seizure freedom in four studies.
The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated ...the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.
Background
Targeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)–TIE2 system may play a role in ...tumor survival under VEGF inhibition. We conducted a phase 2, double‐blinded, placebo‐controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM.
Methods
Patients ≥18 years of age with a Karnofsky performance status ≥70 and GBM or variants in first or second relapse were randomized to bevacizumab 10 mg/kg every 2 weeks plus trebananib 15 mg/kg every week or bevacizumab plus placebo. The primary endpoint was 6‐month progression‐free survival (PFS).
Results
After an initial 6‐patient lead‐in cohort confirmed the safety of combining bevacizumab and trebananib, 115 eligible patients were randomized to the control (n = 58) or experimental treatment (n = 57). In the control arm, 6‐month PFS was 41.1%, median survival time was 11.5 months (95% CI, 8.4‐14.2 months), median PFS was 4.8 months (95% CI, 3.8‐7.1 months), and radiographic response (RR) was 5.9%. In the experimental arm, 6‐month PFS was 22.6%, median survival time was 7.5 months (95% CI, 6.8‐10.1 months), median PFS was 4.2 months (95% CI, 3.7‐5.6 months), and RR was 4.2%. The rate of severe toxicities was not significantly different between arms.
Conclusion
The combination of bevacizumab and trebananib was well tolerated but did not significantly improve 6‐month PFS rate, PFS, or OS for patients with rGBM over bevacizumab alone. The shorter PFS in the experimental arm with a hazard ratio of 1.51 (P = .04) suggests that the addition of trebananib to bevacizumab is detrimental.
This phase 2, double‐blinded, placebo‐controlled trial in patients with recurrent glioblastoma (rGBM) through NRG oncology shows that the combination of bevacizumab plus trebananib—an angiopoietin (Ang) inhibitor—does not significantly improve 6‐month progression‐free survival (PFS) rate, PFS, or overall survival for patients with rGBM compared with bevacizumab plus placebo. The Ang1 blocking effects of trebananib may somehow counteract or negate the antitumor effects of the Ang2–vascular endothelial growth factor blockade.
Gangliogliomas are rare tumors that comprise up to 40% of lesional epilepsy. Seizure control represents an important quality-of-life determinant in patients with these tumors. Here we present results ...of a literature review addressing rates of seizure freedom in in patients with gangliogliomas. Across studies, seizure freedom occurred in 63%–100% of patients. Many studies included follow-up times of greater than 5 years, suggesting that the responses are durable. We discuss potential prognostic factors associated with seizure freedom, including the duration of epilepsy, patient age, frequency and semiology of seizures, tumor location, extent of surgical resection, and operative strategy, including surgical approach and use of invasive monitoring. Although significant differences in study populations and treatments preclude meta-analysis, we discuss prognostic factors identified in individual studies. Increased extent of resection, lesser duration of epilepsy, and younger age at surgery have been associated with increased seizure freedom rates in at least 2 studies each. Although all studies were retrospective in nature and are consequently limited by the weaknesses inherent to such investigations, the literature suggests that surgery is able to relieve most ganglioglioma patients—regardless of patient demographics, tumor characteristics, and operative variables—of seizures.
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described low-grade neuroepithelial tumor with an infiltrative growth pattern and oligodendrocyte-like cells that are ...CD34 immunopositive. Correlating histology and results from molecular testing is critical to correctly diagnosing PLNTY, as its histologic appearance is similar to oligodendrogliomas and shares genetic abnormalities common to other low-grade epilepsy associated tumors (LEATs). In this case report, we describe a 31-year-old female with intractable epilepsy found to have a temporal mass and diagnosed with PLNTY after histopathologic and molecular testing. We describe the radiographic, histologic, and genetic features in relation to the epileptic and oncologic outcomes for this patient. Then, we compare these features and outcomes to other cases of PLNTY described in the literature.