Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma.

BACKGROUND: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRA289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFRA289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma. PATIENTS AND METHODS: An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFRA289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFRA289mut on survival. RESULTS: One hundred twenty-eight patients were included and analyzed: 11% had EGFRA289mut glioblastoma (n = 14/128). EGFRA289mut glioblastomas had a relapse pattern that was more marginal than EGFRA289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFRA289mut group versus 1 in the EGFRA289wt group (P = 0.05). Half of the population with EGFRA289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap scoreVr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFRA289wt group, P = 0.035. EGFRA289mut did not influence survival. CONCLUSION: We highlighted a link between the EGFRA289 mutation and the relapse pattern in glioblastoma. The independent role of EGFRA289mut and its clinical implication should now be explored in further studies.

Usefulness of circulating tumor DNA from cerebrospinal fluid in recurrent high-grade glioma.

Molecular documentation at relapse of high-grade glioma is an urgent need for patient care. A prospective pilot study was conducted to assess the rate of mutation detection using targeted deep sequencing on circulating tumor DNA from cerebrospinal fluid (CSF) after chemo-radiotherapy based treatment. Fifteen patients were included: 13 patients with glioblastoma, 1 patient with gliosarcoma and 1 patient with anaplastic astrocytoma. At progression, 10/15 patients (67%) had detectable mutations in the CSF. Among them, 5/10 patients harbored at least one common mutation between initial tumor and ctDNA. CSF protein level and cfDNA concentration were higher, although not significant, in the ctDNA positive group versus ctDNA negative group (1.17g/L vs. 0.79g/L). Molecular documentation obtained from ctDNA in CSF at the time of relapse is informative in around two-thirds of the patients.

In vitro effect of tobacco smoke components on the functions of normal human polymorphonuclear leukocytes.

The function of polymorphonuclear leukocytes (PMNs) has previously been shown to be impaired in smokers in comparison with healthy nonsmokers. Potent inhibition of PMN chemotaxis has been achieved with whole tobacco smoke, the gas phase of smoke, and a water-soluble extract of whole smoke. In the present work several aspects of PMN function were studied after exposure to water-soluble fraction of the particle phase of tobacco smoke collected on glass fiber filters. These tests included capillary tube random migration, chemotaxis under agarose, phagocytosis of yeasts, Nitro Blue Tetrazolium dye reduction, and whole-blood bactericidal activity. The water extract of the particle fraction of smoke had a high content of nicotine when compared with the levels achieved in plasma of smokers and a much lower concentration of aldehydes when compared with the gas phase of smoke. It had no cytotoxic effect and did not affect phagocytosis, oxygen consumption, or bactericidal activity. Nitro Blue Tetrazolium reduction of both resting and stimulated PMNs was significantly decreased only with the most concentrated solution. The tested solutions exerted a dose-related depressive effect on capillary tube random migration, whereas the random migration measured in the agarose chemotaxis test was normal. Nevertheless, the chemotactic response to a caseine solution was significantly decreased. The same tests were performed in the presence of several concentrations of a nicotine solution and the only test to be affected was the capillary tube random migration, and, that only at a very high concentration. The results of this study contribute to the more precise delineation of the extent of the dysfunction of PMNs exposed to tobacco smoke components and indicate that deleterious products are released from the particle phase of the smoke, which deposits all along the respiratory tree.