Satralizumab, an antibody against IL-6R, has been recently approved in Neuromyelitis optica spectrum disorder(NMOSD). Targeting IL-6 or IL-6 Receptor(like Satralizumab does) results in inhibition of ...both pro and anti-inflammatory pathways of IL-6. Sgp130FC(Olamkicept) is a monoclonal antibody that prevents only the proinflammatory pathway of IL-6 to be activated, and could represent a better way to target IL-6 pathway in Neuromyelitis optica spectrum disorder.
•Satralizumab, an antibody against IL-6R, has been recently approved in Neuromyelitis optica spectrum disorder(NMOSD).•Targeting IL-6 or IL-6 Receptor(like Satralizumab does) results in inhibition of both pro and anti-inflammatory pathways of IL-6.•Olamkicept is a monoclonal antibody that inhibits only the pro-inflammatory pathway of IL-6, and could represent a better way to target IL-6 pathway in NMOSD disorder.
•Latest therapies in SARS-CoV-2 infection.•Clinical trials in COVID-19 and controversial results.•Coagulation and inflammation: cross-talking.
SARS-CoV-2 is the agent responsible for COVID-19. The ...infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.
•Evidence of a role for IL-6 in the pathology of SARS-CoV-2 and COVID-19.•IL-6 pathways: the classic (anti-inflammatory) and the trans-signaling (pro-inflammatory)•SGP130Fc could block the IL-6 ...trans-signaling pathway(pro-inflammatory) in COVID-19.•Inhibition of the JAK/STAT pathway activated by IL-6: Ruxolitinib and Baricitinib.
Since the outbreak of COVID-19 many studies have been published showing possible therapies, here the author discusses the end of stage disease related drugs, like Tocilizumab which is currently being used in ARDS patients. In some patients, disease progression leads to an enormous secretion of cytokines, known as cytokine storm, among those cytokines IL-6 plays an important role. Here the author shows how IL-6 has both pro and anti-inflammatory properties, depending on the pathway of transduction: soluble (trans-signaling) or membrane-related (classic signaling), and suggests how targeting only the pro-inflammatory pathway, with SGP130Fc, could be a better option then targeting them both. Other possible IL-6 pathway inhibitors such as Ruxolitinib and Baricinitib are then analyzed, underlying how they lack the benefit of targeting only the pro-inflammatory pathway.
While Monte Carlo (MC) codes are considered as the gold standard for dosimetric calculations, the availability of user friendly MC codes suited for particle therapy is limited. Based on the FLUKA MC ...code and its graphical user interface (GUI) Flair, we developed an easy-to-use tool which enables simple and reliable simulations for particle therapy. In this paper we provide an overview of functionalities of the tool and with the presented clinical, proton and carbon ion therapy examples we demonstrate its reliability and the usability in the clinical environment and show its flexibility for research purposes. The first, easy-to-use FLUKA MC platform for particle therapy with GUI functionalities allows a user with a minimal effort and reduced knowledge about MC details to apply MC at their facility and is expected to enhance the popularity of the MC for both research and clinical quality assurance and commissioning purposes.
Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for ...application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both (4)He and (12)C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth-dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features.
Purpose
Only few centers worldwide treat intraocular tumors with proton therapy, all of them with a dedicated beamline, except in one case in the USA. The Italian National Center for Oncological ...Hadrontherapy (CNAO) is a synchrotron‐based hadrontherapy facility equipped with fixed beamlines and pencil beam scanning modality. Recently, a general‐purpose horizontal proton beamline was adapted to treat also ocular diseases. In this work, the conceptual design and main dosimetric properties of this new proton eyeline are presented.
Methods
A 28 mm thick water‐equivalent range shifter (RS) was placed along the proton beamline to shift the minimum beam penetration at shallower depths. FLUKA Monte Carlo (MC) simulations were performed to optimize the position of the RS and patient‐specific collimator, in order to achieve sharp lateral dose gradients. Lateral dose profiles were then measured with radiochromic EBT3 films to evaluate the dose uniformity and lateral penumbra width at several depths. Different beam scanning patterns were tested. Discrete energy levels with 1 mm water‐equivalent step within the whole ocular energy range (62.7–89.8 MeV) were used, while fine adjustment of beam range was achieved using thin polymethylmethacrylate additional sheets.
Depth‐dose distributions (DDDs) were measured with the Peakfinder system. Monoenergetic beam weights to achieve flat spread‐out Bragg Peaks (SOBPs) were numerically determined. Absorbed dose to water under reference conditions was measured with an Advanced Markus chamber, following International Atomic Energy Agency (IAEA) Technical Report Series (TRS)‐398 Code of Practice. Neutron dose at the contralateral eye was evaluated with passive bubble dosimeters.
Results
Monte Carlo simulations and experimental results confirmed that maximizing the air gap between RS and aperture reduces the lateral dose penumbra width of the collimated beam and increases the field transversal dose homogeneity. Therefore, RS and brass collimator were placed at about 98 cm (upstream of the beam monitors) and 7 cm from the isocenter, respectively. The lateral 80%–20% penumbra at middle‐SOBP ranged between 1.4 and 1.7 mm depending on field size, while 90%–10% distal fall‐off of the DDDs ranged between 1.0 and 1.5 mm, as a function of range. Such values are comparable to those reported for most existing eye‐dedicated facilities. Measured SOBP doses were in very good agreement with MC simulations. Mean neutron dose at the contralateral eye was 68 μSv/Gy. Beam delivery time, for 60 Gy relative biological effectiveness (RBE) prescription dose in four fractions, was around 3 min per session.
Conclusions
Our adapted scanning proton beamline satisfied the requirements for intraocular tumor treatment. The first ocular treatment was delivered in August 2016 and more than 100 patients successfully completed their treatment in these 2 yr.
Abstract
Background
The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical ...outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT).
Methods
We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan–Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes.
Results
After a median follow-up of 49 (range, 6–87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients.
Conclusions
Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC.
Key Points
• Proton and carbon ion therapy are effective and safe in skull base chordoma.
• Prognostic factors are GTV, organs at risk compression, and dose coverage.
• Dual particle therapy and customized strategy was adopted.
Introduction
Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying ...pathophysiologic mechanisms.
Objective
To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities.
Methods
Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted.
Results
A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors.
Conclusions
Our data support the evidence of a large overlap between FMD phenotypes.
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