Surgical outcome and indicators of postoperative worsening in intra-axial thalamic and posterior fossa pediatric tumors: Preliminary results from a single tertiary referral center cohort

Background: Shared indications about the best management of intra-axial thalamic (IAT) and posterior fossa (PF) pediatric tumors are still lacking. The aim of this study was to analyze neurosurgical outcome in these tumors and to investigate factors associated with postoperative worsening. Methods: A retrospective single-center study on IAT and PF pediatric tumor patients treated surgically over a 7-year period was conducted. The Lansky Scale (LS) was used to assess patients' functional status. Surgical complexity was graded with the Milan Complexity Scale (MCS). The following analyses were performed: a longitudinal analysis of the preoperative, discharge, and 3 months' follow-up (FU) LS, a comparison between improved/unchanged and worsened patients, and an analysis of the predictive value of single MCS items. Results: 37 cases were collected: 20 PF and 17 thalamic. Mean MCS score was 6 ± 1.7. Mean preoperative, discharge and FU LS were 80.8, 74.6 and 80.3 respectively. Surgical mortality was 0%.The longitudinal analysis showed a neurological worsening at discharge compared to preoperative status (p = 0.011) and an improvement at FU compared to discharge (p < 0.004), both statistically significant. None of the variables analyzed showed a significant predictive value of early postoperative change; however, higher MCS scores were associated with a greater risk of worsening. Conclusions: The surgical management of IAT and PF pediatric brain tumors remains challenging; early postoperative worsening is possible, but most deficits tend to improve at FU. The MCS seems to be a valuable tool to estimate the risk of early postoperative worsening and to facilitate parents' informed consent

Case report: Multiple brain intravascular papillary endothelial hyperplasia: incidence, diagnostic challenges, and management approach

Multiple hemorrhagic brain lesions are mainly diagnosed based on clinico-radiological features integrated with histological data. Intravascular papillary endothelial hyperplasia (IPEH), or Masson's tumor, is a very rare entity, particularly when localized in the brain. In this study, we describe a case of multiple recurrent brain IPEHs and provide details on the diagnostic phase, therapeutic approaches, and related challenges. A 55-year-old woman presented with a relapsing neurological deficit. Brain magnetic resonance imaging (MRI) revealed a hemorrhagic right frontal-parietal lesion. When new neurological symptoms occurred, subsequent MRI scans detected more bleeding cerebral lesions. She underwent a series of single hemorrhagic lesion debulking. For any samples that underwent histopathological examination, the first results were not informative; the second and the third results revealed hemangioendothelioma (HE); and the fourth results led to the IPEH diagnosis. Interferon alpha (IFN-α) and subsequently sirolimus were prescribed. Both were well tolerated. Clinical and radiological features remained stable 43 months after starting sirolimus therapy and 132 months after the first diagnosis. To date, 45 cases of intracranial IPEH have been reported, mostly as single lesions without parenchymal location. They are usually treated by surgery and sometimes by radiotherapy upon recurrence. Our case is notable for two main reasons: because of the consecutive recurrent multifocal exclusively cerebral lesions and the therapeutic approach we used. Based on multifocal brain recurrence and good performance, we propose pharmacological therapy, including IFN-α and sirolimus, to stabilize IPEH

Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Quality of Life, Disability, Well-Being, and Coping Strategies in Patients Undergoing Neurosurgical Procedures: Preoperative Results in an Italian Sample

Background. The aim of this paper is to present the preliminary results of QoL, well-being, disability, and coping strategies of patients before neurosurgical procedure. Methods. We analysed data on preoperative quality of life (EUROHIS-QoL), disability (WHODAS-II), well-being (PGWB-S), coping strategies (Brief COPE), and functional status (KPS score) of a sample of patients with brain tumours and cerebrovascular and spinal degenerative disease admitted to Neurological Institute Carlo Besta. Statistical analysis was performed to illustrate the distribution of sociodemographic and clinical data, to compare mean test scores to the respective normative samples, and to investigate the differences between diagnoses, the correlation between tests, and the predictive power of sociodemographic and clinical variables of QoL. Results. 198 patients were included in the study. PGWB-S and EUROHIS-QoL scores were significantly lower than normative population. Patients with spinal diseases reported higher scores in WHODAS-II compared with oncological and cerebrovascular groups. Finally sociodemographic and clinical variables were significant predictors of EUROHIS-QoL, in particular PGWB-S and WHODAS-II. Conclusion. Our preliminary results show that preoperatory period is critical and the evaluation of coping strategies, quality of life, disability, and well-being is useful to plan tailored intervention and for a better management of each patient

IMMU-01. TEM-GBM: AN OPEN-LABEL, PHASE I/IIA DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND EFFICACY OF GENETICALLY MODIFIED TIE-2 EXPRESSING MONOCYTES TO DELIVER IFN-A WITHIN GLIOBLASTOMA TUMOR MICROENVIRONMENT

Abstract Temferon is a macrophage-based treatment relying on ex-vivo transduction of autologous HSPCs to express immune-payloads within the TME. Temferon targets the immune-modulatory molecule IFN-a, to a subset of tumor infiltrating macrophages known as Tie-2 expressing macrophages (TEMs) due to the Tie2 promoter and a post-transcriptional regulation layer represented by miRNA-126 target sequences. As of 31st May 2021, 15-patients received Temferon (D+0) with follow-up of 3 – 693 days. After conditioning neutrophil and platelet engraftment occurred at D+13 and D+13.5, respectively. Temferon-derived differentiated cells, as determined be the number of vector copy per genome, were found within 14 days post treatment and persisted albeit at lower levels up to 18-months. Very low concentrations of IFN-a in the plasma (8.7 pg/ml-D+30) and in the CSF (1.6 pg/ml-D+30) were detected, suggesting tight regulation of transgene expression. Five-deaths occurred at D+322, +340, +402, +478 and +646 due to PD, and one at D+60 due to complications following the conditioning regimen. Eight-patients had progressive disease (range: D-11 to +239) as expected for this tumor type. SAEs include GGT elevation (possibly related to Temferon) and infections, venous thromboembolism, brain abscess, hemiparesis, seizures, anemia and general physical condition deterioration, compatible with ASCT, concomitant medications and PD. Four-patients underwent 2ndsurgery. Recurrent tumors had gene-marked cells and increased expression of ISGs compared to first surgery, indicative of local IFNa release by TEMs. In one patient, a stable lesion had a higher proportion of T cells and TEMs within the myeloid infiltrate and an increased ISGs than in the progressing lesion, detected in the same patient. Tumor-associated clones expanded in the periphery. TME characterization by scRNA and TCR-sequencing is ongoing. To date, Temferon is well tolerated, with no DLTs identified. The results provide initial evidence of Temferon potential to activate the immune system of GBM patients, as predicted by preclinical studies

Diagnostic and surgical management of primary central nervous system angioleiomyoma: A case report and literature review

Angioleiomyoma (ALM) is a benign smooth muscle neoplasm that mainly occurs in lower extremities subcutaneous tissue and generally affects middle-aged adults. This tumor histotype may rarely localize intracranially, although only a few cases have been described in the literature. We report a case of intracranial ALM, whose differential diagnosis has been particularly challenging, and firstly provide a comprehensive radiological and intra-operative evaluation of a such rare entity. This represents also the first report of the use of intraoperative confocal microscopy in ALM and the first documented short-term recurrence. At this regard, a scoping literature review has been conducted with the aim of presenting the major clinical and diagnostic features along with the proposed therapeutic strategies

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389