Central nervous system cancers Brem, Steven S; Bierman, Philip J; Brem, Henry ...
Journal of the National Comprehensive Cancer Network
9, Številka:
4
Journal Article
Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 ...consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (
P
< .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio OR, 1.03; 95 % CI, 1.002-1.060;
P
= .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97;
P
< .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13;
P
= .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.
Abstract
Brain metastases comprise the majority of central nervous tumors in adults and confer poorer survival for patients with primary cancer. Systemic disease control is improving with advances in ...treatment for primary tumors and the complexity of brain metastases management is increasing with multimodality approaches incorporating combinations of surgery, radiotherapy, chemotherapy, targeted therapies, and immunotherapy. Accordingly, the Society for Neuro-Oncology established an annual brain metastases conference to unite colleagues from multiple disciplines with content spanning a range of timely topics relevant to improving our understanding of brain metastases and how they are optimally treated. The inaugural meeting on August 16–17, 2019 was very successful with 163 impactful presentations being delivered to a large multidisciplinary audience on current research advances in the field of neuro-oncology. This review summarizes the major themes of the meeting and highlights the main findings presented.
Inhibiting kinases in malignant gliomas Chi, Andrew S; Wen, Patrick Y
Expert opinion on therapeutic targets,
20/4/1/, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Advances in the understanding of glioma pathogenesis have led to increasing interest in the development of targeted molecular agents, and especially kinase inhibitors, for treatment of malignant ...gliomas. Protein kinases are a large family of enzymes that function as key regulators of cellular signaling pathways governing diverse functions, such as cell proliferation, growth, differentiation, invasion, angiogenesis and apoptosis in malignant gliomas. Preliminary clinical results with kinase inhibitors suggest that they are generally well-tolerated but have shown only modest activity. However, valuable information was obtained from these early clinical trials that will help the future development of these agents. This article reviews the important protein kinases in malignant gliomas, summarizes the existing clinical development of kinase inhibitors and discusses strategies to improve their effectiveness.
Spin-echo echo planar (EP) perfusion weighted imaging (SE-PWI) has been demonstrated to be more selective than gradient-echo EP PWI for blood volume in microvessels the size of glioma neocapillaries, ...but it has not been comprehensively studied in human clinical use. We assessed whether SE-PWI before and after initiating chemoradiation can stratify patients with respect to progression free survival (PFS) and overall survival (OS). Sixty-eight patients with newly diagnosed glioblastoma (mean age 58.3, 36 males) were included in analysis. SE EP cerebral blood volumes (SE-CBVs) in enhancing and nonenhancing tumor, normalized to contralateral normal appearing white matter (SE-nCBV), were assessed at baseline and after initial chemoradiation. SE-nCBV parameters predictive of PFS and OS were identified in univariate and multivariate Cox proportional hazards models. Multivariate analysis demonstrated that baseline tumor mean SE-nCBV was predictive of PFS (
p
= 0.038) and OS (
p
= 0.004). Within the patient sample, baseline tumor mean SE-nCBV <2.0 predicted longer patient PFS (median 47.0 weeks,
p
< 0.001) and OS (median 98.6 weeks,
p
= 0.003) compared with baseline mean SE-nCBV >2.0 (median PFS 25.3, median OS 56.0 weeks). Exploratory multi-group stratification demonstrated that very high (>4.0) tumor SE-nCBV was associated with worse patient OS than intermediate high (>2.0, <4.0) SE-nCBV (
p
= 0.025). Baseline mean SE-nCBV can stratify patients for PFS and OS prior to initiation of chemoradiation, which may help select patients who require closer surveillance. Our exploratory analysis indicates a magnitude-dependent relationship between baseline SE-nCBV and OS.
This article briefly reviews the theory and modeling of single-surface multipactor discharge on a dielectric, focusing on recent studies on two-frequency RF-field-induced multipactor. A novel ...multiparticle Monte Carlo simulation model with adaptive time steps is used to investigate the time-dependent physics of multipactor discharge. Two-frequency RF operation is found to be effective in reducing multipactor strength compared with single-frequency RF operation with the same total RF power. Strong multipactor mitigation is also demonstrated for nonsinusoidal RF fields of multiple frequencies. Migration of multipactor trajectory is shown for different configurations of the two-frequency RF field. Frequency-domain analysis shows that multipactor-induced normal surface charging electric field consists of only even harmonics of the RF frequency for single-frequency RF operation, but is dominated by strong intermodulation products of the RF carrier frequencies for two-frequency RF operation.
Abstract
Background
Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated ...with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.
Methods
Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (>1.24 µm2/ms) or low (<1.24 µm2/ms) ADCL, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor.
Results
Baseline tumor volume (P = .3460) and ADCL (P = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADCL had a significant survival advantage in all patients (P = .0006), as well as BV (P = .0159) and BV+VB-111 individually (P = .0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume, and ADCL identified continuous measures of tumor volume (P < .0001; HR = 1.0212) and ADCL phenotypes (P = .0012; HR = 0.5574) as independent predictors of OS.
Conclusion
Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111.
Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low-grade ...gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neuro-oncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients. This report will briefly recount the proceedings of a workshop held in January 2013 and hosted by Accelerate Brain Cancer Cure (ABC(2)) on the subject of LGG. While much of the meeting covered recent insights into LGG biology, its focus remained on how best to advance the clinical management, whether by improved preclinical modeling, more effective targeted therapeutics and clinical trial design, or innovative imaging technology.
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