Neuro-oncology Research Articles

OS3.4 Karnofsky and WHO performance scores of brain tumour patients may limit inclusion in protocols though they depend on clinician status

Abstract BACKGROUND Inclusion criteria for oncological protocols often use the Karnofsky performance score (KPS) >=70 or the WHO performance score (PS) 0–2 as a cut-off value. Inclusion of neuro-oncology patients may be hampered, when general condition is preserved, while performance is decreased due to physical handicap. The goal of this study is to compare the KPS and PS assessments according to the status of the clinician. MATERIAL AND METHODS A cross-sectional survey was conducted through ANOCEF and EANO networks. Clinicians evaluated KPS and PS in 6 clinical situations concerning neuro oncology patients (from youngest and fittest to oldest, crippled with comorbidities). RESULTS The rate of PS <70 or PS> 2 increased significantly from case 1 to 6. Sex or nationality of the clinicians had no impact when adjusting on clinician characteristics. Conversely, speciality (residents/general practitioner vs neurosurgeons vs neurologists vs oncologists), impacted KPS or PS evaluations (p<.0001 and p=0.0046, respectively). Residents or general practitioner estimate KPS much lower than the others specialities. Neurosurgeons estimate PS more severely. Clinicians who were not used to including patients in clinical trials proposed lower KPS scores (p = 0.0008). This tendancy was not shown on PS. Eldest physicians significantly rated more severely than the youngest (p = 0.0459 and p <.0001 for KPS and PS, respectively). In a multivariate analysis, age and speciality were correlated with KPS and PS rating even if adjusted on cases. Discordant decision for protocol inclusion (i:e: (KPS) >=70 vs PS 0–2) showed little discrepancy in case 1 (2.3%), while discrepancy increased to respectively 16, 46, 39, 33 and 43% for cases 2 to 6: in nearly all cases, the KPS would have denied access to a trial, while WHO Ps would have allowed CONCLUSION Rating of KP and PS is subjective in neuro oncology patients: influenced by speciality, age and inclusion habit (for KPS) of clinicians, PS 0–2 allows usually more inclusion than KPS>=70 in more severely disabled patients. A Neuro oncology specific KPS and/or PS definition is warranted to allow more widely inclusion of patients with exclusive neurologic handicap.

Reply to ‘Assembling the brain trust: the multidisciplinary imperative in neuro-oncology’

Reply to ‘Assembling the brain trust: the multidisciplinary imperative in neuro-oncology’

État des lieux de l’activité de publications en neurochirurgie en France

Bibliometrics are methods used to quantitatively analyze the scientific literature. The application of bibliometrics in neurosurgery is emerging and has not yet been studied in the French neurosurgical community. In France, the most used statistical method is named SIGAPS; the scores are based on the position of the author and the impact factor of the journal. The SIGAPS score, which can be calculated for a research team or an individual, impacts the public financial support of university hospitals in France. We analyzed retrospectively the publication productivity and the SIGAPS score of university neurosurgery departments in France for the period 2009–2016. This was supplemented by a list of current academic research protocols granted by the Minister of Health. The SIGAPS score is higher in large university hospitals even though all teams are dedicated to publishing more in the traditional neurosurgery journals (Neurosurgery, Journal of Neurosurgery, World Neurosurgery, J Neuro-oncology, Neuro oncology, Eur Spine J). Of note, the national Neurochirurgie journal (publishing in French and English) is progressively improving its impact factor (0.8). The most common themes are functional neurosurgery, neuro-oncology and spine. There are 14 on-going national multicenter research programs, 4 of them focused on the health economics of treatment innovations. These data provide the most accurate available snapshot of the scholarly efforts of all the French university neurosurgery departments. It is based on a national statistics method (SIGAPS). For future evaluation, it should be combined with internationally available parameters such as the h-index and m-quotient. Publication productivity has broad implications for the success of both academic departments and individual faculty members and their financial support.

Reviewer Lists for Neuro-Oncology

Reviewer Lists for <i>Neuro-Oncology</i>

Survivorship in Neuro-Oncology.

Survivorship in Neuro-Oncology.

Survivorship in Neuro-Oncology: Improving Care by Advancing Science

Survivorship in Neuro-Oncology: Improving Care by Advancing Science

Developing a standardized process for oral chemotherapy management for neuro-oncology.

258 Background: Oral chemotherapies (OC) have transformed cancer care for millions of patients. While this has improved the patient experience, it presents significant challenges to safety of prescription, administration and side effect monitoring. While there are guidelines for documentation, there is not a best practices system for managing OC. This project identified areas of latent errors and implemented a standardized process for OC management. Methods: After review of the literature, we developed a process map for OC prescriptions at our institution. We then compared processes at three other neuro oncology clinics. We completed a hazard analysis and implemented several changes (see table). We identified binary measures in the medical record for every OC prescription that related to the process changes. Chart review of the 6 months prior to process change was used to create a baseline process mean for each variable. These same variables were monitored every 2 weeks after process change implementation using run charts. Successful process shift was defined as 7 consecutive 2-week averages that were continually on one side of the baseline process mean. Results: 5 months after process change was implemented, we had successfully reduced refills for OC and increased documentation of dose and dose calculation. There is a trend towards improvement in independently verified dose calculation and dedicated chemotherapy teaching visits, however these have not yet reached criteria for process change. Conclusions: This project used published studies, multi-institutional process mapping and hazard analysis to develop and implement a standardize process for OC. This process can be implemented for OC management in other oncology practices. [Table: see text]

P01.017 Geriatric Assessments in Neuro Oncology - a viable prospect

P01.017 Geriatric Assessments in Neuro Oncology - a viable prospect

P03.06 Introduction of post neuro oncology multidisciplinary team meeting clinic to improve patient pathway within a tertiary care centre

P03.06 Introduction of post neuro oncology multidisciplinary team meeting clinic to improve patient pathway within a tertiary care centre

Abstract 169: Identification of RNA aptamers selectively recognizing and affecting glioblastoma stem cells

Abstract Glioblastoma (GBM) is the most frequent and aggressive primary brain tumour in adults. Despite advances in surgical and medical neuro oncology, prognosis for GBM patients remains dismal, with a median survival of about 15 months. It has been demonstrated that the modest benefit of conventional therapies depends on a small population of cancer stem cells within the tumor, named Glioma Stem Cells (GSCs) that cause tumor relapse and chemoresistance and therefore could play a key role in GBM recurrence. Thus, the identification of new specific ligands for GSCs could be a fundamental challenge for the development of effective glioma therapies. Here, we developed an in vitro evolution based approach, named differential whole cellSELEX; it is used to generate nucleic acid ligands, named aptamers, with high affinity and specificity for GSCs. Aptamers, were obtained through the iterative evolution of a random pool of sequences using human primary GSCs as target. Among different potential candidates we focused on one sequence, named 40L. The 40L aptamer and its truncated form, 40S, were selective for human GSCs distinguishing them from tumor differentiated cells, obtained from the stem cells induced to differentiate. 40L revealed to be functionally active on target cells and able to inhibit stemness, cell growth and migration. 40s preserves binding ability of 40L sequence and it has further proven to strongly reduce tumor proliferation in in vivo experiment. Moreover, both 40L and 40s were able to rapidly internalize upon target binding and therefore may serve as selective vehicle for therapeutics.In conclusion, our results indicate that 40L and its short form 40s can selectively target GSCs both in vitro and in vivo. Given the crucial role of these cells in GBM recurrence and therapy resistance, 40L and 40s represent innovative drug candidates with a great potential in the GBM treatment. Citation Format: Alessandra Affinito, Cristina Quintavalle, Maurizio Albero, Claudia Vilardo, Francesco Palma, Giuseppina Roscigno, Lucia Ricci Vitiani, Roberto Pallini, Carla Lucia Esposito, Vittorio de Franciscis, Gerolama Condorelli. Identification of RNA aptamers selectively recognizing and affecting glioblastoma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 169.

A large, multicenter, retrospective study to identify a cutoff of MGMT methylation status by quantitative pyrosequencing approach in patients (PTS) with glioblastoma (GBM).

2012A LARGE, MULTICENTER, RETROSPECTIVE STUDY TO IDENTIFY A CUT-OFF OF MGMT METHYLATION STATUS BY QUANTITATIVE PYROSEQUENCING APPROACH IN PATIENTS (PTS) WITH GLIOBLASTOMA (GBM). Background: MGMT pr...

A comprehensive initiative to optimize accrual to neuro oncology clinical trials.

e18546Background: Access to cancer treatment clinical trials is a key measure for the delivery of quality cancer care. When available, cancer clinical trials should be offered up front and practice...

Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part I: therapeutic strategies.

Stereotactic radiosurgery can nowadays be considered not only as a potential adjuvant to surgical treatment of several neuro-oncological pathologies, including primary tumors and metastatic lesions, but in some cases also as a valuable alternative tailored option. In Part I of the review, we propose a dissertation focused on the different irradiation stereotactic radiosurgery techniques to date available for clinical indications more relevant to oncologists and oncologic surgeons, such as high-grade and low-grade gliomas, metastases and meningiomas. It is noteworthy that the most recent body of literature correlated with this topic shows that the therapeutic results presently achievable are revolutionizing the way patients are diagnosed and managed worldwide. As we sought to shed light on the current potentialities of stereotactic radiosurgery, we must consider that to exploit all the benefits provided by this shift in clinical practice, a profound awareness by all practitioners involved in the care of neoplastic patients is certainly warranted.

Bevacizumab alone at 5 mg/kg in an every-3-week schedule for patients with recurrent glioblastomas: a single center experience.

The use of bevacizumab is increasingly reported in neuro-oncology. The most common schedule is 10 mg/kg every 2 weeks. We retrospectively investigated the efficacy of a 3-week schedule of 5 mg/kg bevacizumab in patients with recurrent glioblastomas. Fourteen patients (median age, 46 years) were included in the study. The median number of bevacizumab cycles was 4 (range, 2-8). Five patients (36%) had a partial response, 7 (50%) had stable disease, and 2 (14%) had progressive disease. No grade III-IV toxicities were observed. The median progression-free and overall survival were 3.6 months and 6.4 months, respectively. Every-3-week low-dose single-agent bevacizumab showed substantial activity and a safe profile in patients with recurrent glioblastoma.

Reviewer Lists for Neuro-Oncology

Reviewer Lists for Neuro-Oncology

Extraneuraxial metastases from medulloblastoma: Single-institution outcome analyses

Introduction: Novel biological insights have led to consensus classification of medulloblastoma into four distinct molecular subgroups. It is widely accepted that medulloblastomas have a higher propensity for extraneuraxial metastases (ENM) compared to other primary brain tumors. We sought to review our own institutional experience of ENM from medulloblastoma. Materials and Methods: Patients with a histological diagnosis of medulloblastoma and ENM were identified from institutional neuro-oncology database. Patient-, disease-, and treatment-related details were retrieved by retrospective review of medical case records. Results: A total of 573 patients with medulloblastoma were registered from 2005 to 2016, of which 13 patients were detected with ENM. Median age of our study cohort was 17 years (range: 3–25 years) at index diagnosis. Ten (77%) patients had desmoplastic medulloblastoma, while 3 (23%) patients had large-cell/anaplastic histology. Five of 7 (71%) patients with known molecular subgroup affiliation belonged to sonic hedgehog subgroup, while the remaining two (29%) were subgroup 3 medulloblastoma. The median time to development of ENM was 13 months (range: 2–72 months) with common sites being bone (77%), bone marrow (62%), and lymph nodes (46%). Median overall survival after diagnosis of ENM was 2 months (range: 1–25 months) with 1-year survival probability of 23%. Patients with desmoplastic medulloblastoma had longer median overall survival compared to anaplastic histology (4.5 months vs. 1 month; P = 0.07). None of the other putative prognostic factors such as age at ENM, concurrent central nervous system involvement, visceral metastases, or time to relapse impacted overall survival. Conclusions: ENM from medulloblastoma, although rare, is frequently associated with desmoplastic histology. Bone, bone marrow, and lymph nodes are the most common sites of extraneuraxial involvement. Survival outcomes remain universally poor mandating the testing of newer agents and/or novel molecularly targeted therapies.

Targeting glioblastoma stem-cells: a recurrent challenge in neurooncology

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor in adults. To date, this tumor remains rapidly fatal despite treatment, median overall survival not exceeding 15 months from diagnosis (1).

Erratum to: Clinical PET/MRI in neurooncology: opportunities and challenges from a single-institution perspective

Erratum to: Clinical PET/MRI in neurooncology: opportunities and challenges from a single-institution perspective

A modified chemotherapy protocol with carboplatin and vincristine for pediatric brain stem low-grade gliomas

Objective To analyze the response and toxicity of a modified chemotherapy protocol with carboplatin and vincristine (CV) for pediatric low-grade gliomas (LGGs) in the brain stem. Methods Ten children with low-grade gliomas (LGGs) in the brain stem were administered the modified CV regimen at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University from August 2014 to August 2016, and the data were retrospectively reviewed. The conventional CV regimen was modified by changing the carboplatin dose or adding recombinant human endostatin(rhES). Carboplatin was administrated at a dose of 200~300 mg/m2 and the vincristine dose was 1.5 mg/m2 (maximum dose: 2 mg). Results Among the 10 children, 5 patients had objective response (1 had a complete response and 4 had a partial response); 2 got a minor response and 3 kept stable conditions. All patients' illnesses were effectively controlled. The median time for response to chemotherapy was 3 (1.5-8.0) months.The median time for follow-up was 14.5(4-26)months. Objective response was reported in 2 of 3 patients with recurrence. All 3 cases undergoing combination chemotherapy of carboplatin, vincristine and a novel antiangiogenic drug had objective response. Hematologic toxicity was a major side effect. The incidences of severe neutrocytopenia, decreased hemoglobin and thrombocytopenia were 8.8% (23/262), 5.3% (14/262) and 1.5% (5/262), respectively, which could resolve following symptomatic treatment. Conclusions A modified CV regimen seems effective for pediatric brain stem LGGs. Increasing carboplatin dose or adding rhES could help with the effect improvement of CV regimen and fast relief of the brain stem dysfunction. Those drug regimens were relatively well tolerated. Key words: Brain stem neoplasms; Glioma; Carboplatin; Vincristine; Child

Comparative genomic analysis for pediatric cancer patients evaluated in a California Initiative to Advance Precision Medicine Demonstration Project.

TPS10578 Background: California Kids Cancer Comparison (CKCC), a demonstration project for the California Initiative to Advance Precision Medicine, evaluates the utility of incorporating gene expression information into the genomic analysis of difficult-to-treat pediatric cancers. CKCC is a partnership between UC Santa Cruz and clinical genomic trials conducted by Children’s Hospital of Orange County, UC San Francisco (Pacific Pediatric Neuro Oncology Consortium), and Stanford University. Methods: CKCC compares each prospective tumor’s RNA sequencing profile to over 11,000 uniformly analyzed tumor profiles from pediatric and adult cancer patients. These comparisons are used to identify genes and pathways that are significantly over expressed in each patient’s tumor. The pathways are reviewed by data analysis for the potential for clinical impact and presented to the treating oncologist in a molecular tumor board setting.