Neuro-oncology practice最新文献

Background: Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy.

Methods: This series represents a single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival.

Results: Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15).

Conclusion: High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.

Background: Adult glioblastomas (GBMs), IDH-wildtype, WHO grade 4 with FGFR3::TACC3 fusion have a better prognosis than standard GBMs. Whether this extended survival leads to late biological consequences is unknown. Although constituting only 4% of all GBMs, FGFR3::TACC3 fusion-positive GBMs manifest recurrent morphological features that allow prediction of this subtype, possibly affecting trial eligibility and/or targeted therapies. However, we have previously shown that an identical histological pattern can be present in wildtype examples, and conversely, occasional FGFR3::TACC3 fusion-positive tumors lack this stereotypic morphology; thus, ultimately molecular characterization is required. We now report for the first time an adult with FGFR3::TACC3 fusion-positive GBM showing archetypal histological features who developed extracranial metastases to provide further insight into potential behavior of the GBM type.

Methods: Report of a 70-year-old man with left parietal GBM who developed 2 subsequent metastases, all 3 of which were assessed by next-generation sequencing (NGS) and DNA methylation.

Results: Biopsy-proven dural metastases occurred at 8 months and cervical lymph node metastasis at 12-month post-diagnosis before the patient succumbed at 23 months. By NGS, all 3 tumors showed FGFR3::TACC3 fusion as well as an additional PDZD2::TERT fusion of uncertain significance. DNA methylation profiling demonstrated mesenchymal subtype in the initial biopsy and RTKII subtype in subsequent dural and lymph node metastases, indicating intratumor spatial heterogeneity or temporal evolution.

Conclusion: Rarely, FGFR3::TACC3 fusion-positive GBM patients may develop dural and extracranial metastatic spread, the latter with subclass switching on epigenomic analysis.

Background: Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients.

Methods: A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures.

Results: Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies (n = 6138) evaluated OS and 5 studies (n = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review.

Conclusions: This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.

Background: Cancer in stroke patients is associated with higher levels of inflammatory biomarkers and unfavorable poststroke outcomes. We thus explored whether there is a link between cancer and stroke-associated infections.

Methods: Medical records of patients with ischemic stroke in 2014-2016 registered in the Swiss Stroke Registry of Zurich were retrospectively analyzed. Incidence, characteristics, treatment, and outcome of stroke-associated infections diagnosed within 7 days after stroke onset were tested for an association with cancer.

Results: Among 1181 patients with ischemic stroke, 102 patients with cancer were identified. Stroke-associated infections occurred in 179 and 19 patients (17% and 19%) without and with cancer (P = .60), respectively, among them pneumonia in 95 and 10 patients (9% and 10%) and urinary tract infections in 68 and 9 patients (6% and 9%) (P = .74 and P = .32). Use of antibiotics was similar between groups. Levels of C-reactive protein (CRP) (P < .001), erythrocyte sedimentation rate (ESR) (P = .014) and procalcitonin (P = .015) were higher and levels of albumin (P = .042) and protein (P = .031) were lower in patients with cancer than without cancer. Among patients without cancer, higher CRP (P < .001), ESR (P < .001) and procalcitonin (P = .04) and lower albumin (P < .001) were associated with stroke-associated infections. Among cancer patients with or without infections, no significant differences in these parameters were observed. In-hospital mortality was associated with cancer (P < .001) and with stroke-associated infections (P < .001). However, among patients with stroke-associated infections, cancer was not associated with in-hospital mortality (P = .24) or 30-day mortality (P = .66).

Conclusions: Cancer does not represent a risk factor for stroke-associated infections in this patient cohort.

In the United States, diagnosis of grade 3 or 4 glioma qualifies patients for Social Security disability benefits. Low-grade gliomas (LGGs) can be similarly debilitating, with at least 31% of patients presenting with cognitive deficits and 80% with tumor-related epilepsy. A diagnosis of LGG does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. We outline the American healthcare system process of medical documentation to support disability benefits, Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with LGG. The provider's role is not to simply "declare" a patient disabled, but to provide comprehensive documentation regarding diagnosis, treatment, disease status, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are 2 key sources of disability in LGG patients, selective referrals to neuropsychology and epileptology may improve patient care and bolster documentation of the patient's symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. We provide an extensive review for patient eligibility in the United States to receive disability. We map a comprehensive care process that may have relevance to multiple regions outside the United States. Providers are better able to help their patients navigate the disability application process when they understand how to address physical and cognitive changes for thorough care of their patient.

Background: To achieve patient-centric quality care in neuro-oncology, all aspects of the disease and its impact on quality survival need to be considered. This includes the psychological consequences of a brain tumor diagnosis and subsequent life-altering experiences. Far too often the voice of our patients is unheard. Empowering patients to advocate for their own psychological needs is essential.

Methods: Data were derived from four focus groups with adult patients with brain tumors (N = 15; M _age = 46 years, 53% female). A trained moderator led each 90-min group and posed semi-structured questions regarding patients' care needs throughout their neuro-oncological disease trajectory. Emphasis was placed on the quality of life and distress reduction. Common themes were identified via thematic content analysis using NVivo software. A high inter-rater reliability (M _kappa = 0.92, range = 0.85-0.93) was achieved. Two themes are presented here: Emotional Response to Stressors and Existential Considerations.

Results: Of the two themes presented, 14 codes emerged. Codes were classified into three broad categories: Fear, Despair, and Resilience. The frequency of each category ranged from 31.4% to 34.7%. Example quotes and a discussion of each category follows.

Conclusions: It is imperative that we include the patient perspective in the development of neuro-oncology programs, thereby considering the quality of survival in addition to quantity. Neuro-oncology quality care must be driven by our patients' experiences and should integrate support for emotional distress while promoting resilience throughout this life-threatening illness.

Knowledge about inherited and acquired genetics of adult diffuse glioma has expanded significantly over the past decade. Genomewide association studies (GWAS) stratified by histologic subtype identified six germline variants that were associated specifically with glioblastoma (GBM) and 12 that were associated with lower grade glioma. A GWAS performed using the 2016 WHO criteria, stratifying patients by IDH mutation and 1p/19q codeletion (as well as TERT promoter mutation), discovered that many of the known variants are associated with specific WHO glioma subtypes. In addition, the GWAS stratified by molecular group identified two additional novel regions: variants in D2HGDH that were associated with tumors that had an IDH mutation and a variant near FAM20C that was associated with tumors that had both IDH mutation and 1p/19q codeletion. The results of these germline associations have been used to calculate polygenic risk scores, from which to estimate relative and absolute risk of overall glioma and risk of specific glioma subtypes. We will review the concept of polygenic risk models and their potential clinical utility, as well as discuss the published adult diffuse glioma polygenic risk models. To date, these prior genetic studies have been done on European populations. Using the published glioma polygenic risk model, we show that the genetic associations published to date do not generalize across genetic ancestries, demonstrating that genetic studies need to be done on more diverse populations.