Abstract
BACKGROUND
Standard of care for patients with large brain metastases (BMs) suitable for surgery is surgical resection followed by radiosurgery in single or multifractions (SRS/HSRS) on tumor ...bed. Although a satisfactory local control is obtained, an increasing rates of leptomeningeal disease (LMD) related to surgery, and symptomatic radionecrosis related to SRS/HSRS have been observed. In the last years the employ of preoperative SRS/HSRS has been investigated in retrospective studies. Advantages seem to be: better target delineation to intact lesion, reduction of normal brain irradiated considering useless of margins, potential prevention of any cells spilled during resection, greater oxygenation ratio of intact region, sterilization effect, and resection of majority of irradiated tissues. Preoperative HSRS versus postoperative ones will be investigated in multicentric randomized phase III trial. Primary endpoint is rate of leptmeningeal disease secondary endpoints, local control, symptomatic radiation necrosis, surgical morbidity, quality of life (QoL) and neurocognitive functions assessment between the two modalities; brain distant progression (BDP), and overall survival (OS) will be evaluated too.
MATERIAL AND METHODS
Inclusion criteria are: patients aged 18-80 years, diagnosed malignant primary tumor, KPS≥70, oligometastatic disease, limited brain metastases (up to 4), large BM suitable for surgery. Exclusion criteria are: prior WBRT, SCLC, or germinal cell tumour or Lymphoproliferative disease, prior neurosurgery, and incompatibility to perform MRI. Stratification factors will be: histology of primary tumor (Breast, NSCLC, Melanoma, Other) and BMs location (sovra-or infra-tentorial). In Arm A (experimental) patients undergo preoperative HSRS, 27 Gy in 3 fractions, followed by surgery. In Arm B (control): patients undergo surgical resection followed by postoperative HSRS at the same doses. Outcome evaluation will be assess using MRI, total body CT scan and/or CTPET, neuropsychological and Quality of life assessment before and after treatments. For distinguish RN occurrence and disease progression delayed-contrastMRI, and perfusion MRI will be employed. Considering that estimated 1 year LMD is 10% for postoperative HSRS, and ≤ 2% for preoperative enrolment of 146 patients is expected (73 per Arm).
RESULTS
Enrollment started at April 2023 and among first patients included the treatment has proven to be safe.
CONCLUSION
Preoperative HSRS in large BMs suitable for surgical resection need prospective evaluation aiming to improve outcome, and reduced treatments side effects.
We discuss a CMS eXtension for Studying Energetic Neutrinos (CMS-XSEN). Neutrinos at the LHC are abundant and have unique features: their energies reach out to the TeV range, and the contribution of ...the {\tau} flavour is sizeable. The measurement of their interaction cross sections has much physics potential. The pseudorapity range 4<|{\eta}|<5 is of particular interest since leptonic W decays provide an additional contribution to the neutrino flux from b and c production. A modest detector of 4.1x\(10^{27}\) nucleons/cm\(^{2}\), placed in the LHC tunnel, 25 m from the interaction point, around the focusing magnet (Q1) closest to CMS, can cover that region. The hadronic calorimeter HF and the CMS forward shield will protect it from the debris of pp collisions. With a luminosity of 300/fb, foreseen for the LHC run in the years 2021-2023, the detector can observe over a thousand {\tau} neutrino interactions, and a hundred TeV-neutrino interactions of all flavours. Several backgrounds are considered. A major source can be prompt muons from the interaction point. However, the CMS magnetic field and the structure of the Forward Shield make the estimation of their flux in the location of interest uncertain. Besides, machine induced backgrounds are expected to vary rapidly while moving along and away from the beam line. We propose to acquire experience during the 2018 LHC run by a brief test with a small Neutrino Experiment Demonstrator, based on nuclear emulsions.
The CMS muon barrel drift tubes system commissioning Abbiendi, G.; Amapane, N.; Battilana, C. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2009, 2009-1-00, Letnik:
598, Številka:
1
Journal Article
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The CMS muon barrel drift tubes system has been recently fully installed and commissioned in the experiment. The performance and the current status of the detector are briefly presented and discussed.
The World Health Organization (WHO) 2021 classification of central nervous system (CNS) tumors classified astrocytoma isocitrate dehydrogenase-mutant (A IDHm) with either microvascular proliferation ...and/or necrosis or homozygous deletion of CDKN2A/B as CNS grade 4 (CNS WHO G4), introducing a distinct entity and posing new challenges to physicians for appropriate management and prognostication.
We retrospectively collected information about patients diagnosed with A IDHm CNS WHO G4 at three reference neuro-oncological Italian centers and correlated them with survival.
A total of 133 patients were included. Patients were young (median age 41 years) and most received post-operative treatment including chemo-radiation (n = 101) and/or temozolomide maintenance (n = 112). With a median follow-up of 51 months, the median overall survival (mOS) was 31.2 months, with a 5-year survival probability of 26%. In the univariate analysis, complete resection (mOS: 40.2 versus 26.3 months, P = 0.03), methyl-guaninemethyltransferase (MGMT) promoter methylation (mOS: 40.7 versus 18 months, P = 0.0136), and absence of telomerase reverse transcriptase (TERT) promoter mutation (mOS: 40.7 versus 18 months, P = 0.0003) correlated with better prognosis. In the multivariate models, lack of TERT promoter mutation hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.07-0.82, P = 0.024 and MGMT methylation (HR 0.40, 95% CI 0.20-0.81, P = 0.01) remained associated with improved survival.
This is the largest experience in Western countries exploring the prognostic signature of patients with A IDHm CNS G4. Our results show that MGMT promoter methylation and TERT promoter mutation may impact clinical outcomes. This may support physicians in prognostication, clinical management, and design of future studies of this distinct diagnostic entity.
•Novel studies specifically addressing astrocytoma IDH mutant WHO G4 are needed.•In this large multicenter experience, patients showed a median survival of 31.2 months.•Both MGMT promoter methylation and TERT promoter mutation seem to be associated with clinical outcomes.
We discuss an experiment to investigate neutrino physics at the LHC in Run 3, with emphasis on tau flavour. As described in our previous paper arXiv:1903.06564v1, the detector can be installed in the ...decommissioned TI18 tunnel, about 480 m downstream the ATLAS cavern, after the first bending dipoles of the LHC arc. In that location, the prolongation of the beam Line-of-Sight from Interaction Point IP1 to TI18 traverses about 100 m of rock. The detector intercepts the intense neutrino flux, generated by the LHC beams colliding in IP1, at large pseudorapidity eta, where neutrino energies can exceed a TeV. This paper focuses on optimizing global features of the experiment, like detector mass and acceptance. Since the neutrino-nucleon interaction cross section grows almost linearly with energy, the detector can be light and still collect a considerable sample of neutrino events; in the present study it weighs less than 3 tons. The detector is positioned off the beam axis, slightly above the ideal prolongation of the LHC beam from the straight section, covering 7.4 < eta < 9.2. In this configuration, the flux at high energies (0.5-1.5 TeV and beyond) is found to be dominated by neutrinos originating directly from IP1, mostly from charm decays, of which about 50% are electron neutrinos and about 5% are tau neutrinos. The contribution of pion and kaon decays to the muon neutrino flux is studied by means of simulations that embed the LHC optics and found small at high energies. The above studies indicate that with 150 /fb of delivered LHC luminosity in Run 3 the experiment can record a few thousand very high energy neutrino charged current interactions and over 50 tau neutrino charged current events.
ieCTs historically excluded HGG patients (pts) due to unavailability of serial bioptic sampling, use of corticosteroids, concerns on activity of immunotherapy in central nervous system, and rapid ...clinical deterioration.
Data of all recurrent HGG pts enrolled into ieCTs at the Humanitas Cancer Center Phase I Unit between 2014 and 2019 were retrospectively reviewed. Disease control rate (DCR) according to RANO criteria, six-months progression-free and overall survival (PFS-6; OS-6), and treatment-related adverse events (TRAEs), were evaluated. A control-cohort (CC) of patients treated with standard therapies (temozolomide, fotemustine, lomustine and procarbazine, bevacizumab) matched (1:1) for sex, age, line of treatment, MGMT methylation status, and IDH mutational status, was selected for comparison. A huge series of clinical and laboratory variables with an established prognostic relevance for solid tumors pts treated into ieCTs were studied through univariate analysis.
Only 5 out 23 ieCTs allowed inclusion of HGG pts. The experimental cohort (EC) consisted of 25 pts (M/F: 16/9; median age: 50 years): 22 (88%) glioblastoma, 3 (12%) anaplastic astrocytoma. 17 pts (68%) required steroid therapy, with a median baseline dexamethasone dose of 2mg (range 1-6). The median number of prior systemic therapies was 1 (range 1-2). 12 pts (48%) received monotherapies (anti PD-1, anti CSFR-1, anti TGF-ß, anti cereblon), 13 (52%) combination regimens (anti PD-L1 + anti CD38, anti PD-1 + anti CSFR-1). DCR was 40% in both EC (1 CR+2 PR+7 SD) and CC (1 PR+9 SD). 4 pts (16%) in EC had grade ≥3 TRAEs (1 neutropenia, 1 pneumonia, 2 hepatitis). With a median follow-up (FU) of 14 months PFS-6 were 35% and 16% (p=0.075), in EC and CC respectively, while OS-6 was significantly improved in the EC (82% vs 44%, p=0.004). With limitations due to small sample size, short FU and few events recorded, none of the parameters analyzed resulted prognostic.
Survival of our HGG pts treated into ieCTs compared favorably with a matched CC. Inclusion of HGGs pts into ieCTs should be encouraged. Clinical selection factors predicting which pts may benefit most still lack.
The authors.
Has not received any funding.
M. Simonelli: Advisory / Consultancy: AbbVie. A. Santoro: Advisory / Consultancy: BRISTOL-MYERS-SQUIBB; Advisory / Consultancy: SERVIER; Advisory / Consultancy: GILEAD; Advisory / Consultancy: EISAI; Advisory / Consultancy: BAYER; Advisory / Consultancy: MERCK SHARP & DOHME; Speaker Bureau / Expert testimony: TAKEDA; Speaker Bureau / Expert testimony: BRISTOL-MYERS-SQUIBB; Speaker Bureau / Expert testimony: ROCHE; Speaker Bureau / Expert testimony: ABBVIE; Speaker Bureau / Expert testimony: AMGEN; Speaker Bureau / Expert testimony: CELGENE; Speaker Bureau / Expert testimony: SERVIER; Speaker Bureau / Expert testimony: GILEAD; Speaker Bureau / Expert testimony: ASTRAZENECA; Speaker Bureau / Expert testimony: PFIZER; Speaker Bureau / Expert testimony: ARQULE; Speaker Bureau / Expert testimony: LILLY; Speaker Bureau / Expert testimony: SANDOZ; Advisory / Consultancy: PFIZER. All other authors have declared no conflicts of interest.
The goal of the current study was to clarify treatment outcomes for adult patients with rhabdomyosarcoma (RMS). Published series have reported definitively worse results for adults with RMS compared ...with children with RMS. This finding casts doubt on whether RMS is the same disease in adults as it is in children.
Of 190 patients with RMS who were age 18 years or older and whose cases were recorded over a 25-year span in the pathology database of the Istituto Nazionale Tumori (Milan, Italy), 171 could be analyzed retrospectively for treatment outcome. The authors attempted to stratify patients according to the degree to which they had been treated appropriately, based on current treatment guidelines for childhood RMS.
The overall rate of response to chemotherapy was 85%. For the entire series, 5-year event-free survival and 5-year overall survival (OS) were 28% and 40%, respectively. Among the 110 patients with embryonal, alveolar, or 'not otherwise specified' RMS, 5-year OS was 46%; however, 5-year OS was 61% for patients within this group (39% of the total) who had high scores for appropriate treatment.
The current series parallels other published series in that it confirms the finding of a relatively poor long-term outcome for adult patients with RMS. However, for patients whose treatment adhered to the current guidelines for treatment of children, outcome was similar to what has been reported in pediatric series. In addition, the rate of response to chemotherapy for the entire series was similar to the rate typically observed among children. These findings suggest that adults and children with RMS should receive similar treatment. Treatment protocols adopted from pediatric programs but tailored to adults could increase adults' chances of receiving appropriate treatment; prospective studies are needed to test this idea.
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