Radiation recall dermatitis induced by COVID-19 vaccination in breast cancer patients treated with postoperative radiation therapy

Background: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients. Methods: Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated. Results: A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs. Conclusions: Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling

Partial prostate re-irradiation for the treatment of isolated local recurrence of prostate cancer in patients previously treated with primary external beam radiotherapy: short-term results of a monocentric study

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Modelling, simulation and characterization of tunnel-fet devices for ultra-low power electronics

Dans les dernières années, beaucoup de travail a été consacré par l’industrie électronique pour réduire la consommation d’énergie des composants micro-électroniques qui représente un fardeau important dans la spécification des nouveaux systèmes.Afin de réduire la consommation d’énergie, nombreuses stratégies peuvent être adoptées au niveau des systèmes micro-électroniques et des simples dispositifs nano-électroniques. Récemmentle Transistor Tunnel `a effet de champ (Tunnel-FET) s’est imposé comme un candidat possible pour remplacer les dispositifs MOSFET conventionnels pour applications de tr`es basse puissance à des tensions d’alimentation VDD < 0.5V. Nous présentons un modèle Multi-Subband Monte Carlo modifié (MSMC) qui a été adapté pour la simulation de TFET Ultra Thin Body Fully Depleted Seminconductor on Insulator (FDSOIUTB) avec homo- et hétéro-jonctions et des matériaux semi-conducteurs arbitraires. Nous prenons en considération la quantification de la charge avec une correction quantique heuristique mais précise, validée via des modèles quantiques complets et des résultats expérimentaux.Le modèle MSMC a été utilisé pour simuler et évaluer la performance de FD-SOI TFET sidéealisées avec homo- et hétéro-jonction en Si, alliages SiGe ou composés InGaAs. Dans la deuxième partie de l’activité de doctorat un travail de caractérisation à basse températurea été réalisé sur les TFETs en Si et SiGe homo- et hétéro-jonction fabriqués par le centre de recherche français du CEA -LETI. L’objectif est d’estimer la présence de l’effet Tunnel comme principal mécanisme d’injection et la contribution d’autres mécanismes d’injection comme le Trap Assisted Tunneling.In the last years a significant effort has been spent by the microelectronic industry to reducethe chip power consumption of the electronic systems since the latter is becoming a majorlimitation to CMOS technology scaling.Many strategies can be adopted to reduce the power consumption. They range from thesystem to the electron device level. In the last years Tunnel Field Effect Transistors (TFET)have imposed as possible candidate devices for replacing the convential MOSFET in ultra lowpower application at supply voltages VDD < 0.5V. TFET operation is based on a Band-to-BandTunneling (BtBT) mechanism of carrier injection in the channel and they represent a disruptiverevolutionary device concept.This thesis investigates TFET modeling and simulation, a very challenging topic becauseof the difficulties in modeling BtBT accurately. We present a modified Multi Subband MonteCarlo (MSMC) that has been adapted for the simulation of Planar Ultra Thin Body (UTB)Fully Depleted Semiconductor on Insulator (FD-ScOI) homo- and hetero-junction TFET implementedwith arbitrary semiconductor materials. The model accounts for carrier quantizationwith a heuristic but accurate quantum correction validated by means of comparison with fullquantum model and experimental results.The MSMC model has been used to simulate and assess the performance of idealized homoandhetero-junction TFETs implemented in Si, SiGe alloys or InGaAs compounds.In the second part of the thesis we discuss the characterization of TFETs at low temperature.Si and SiGe homo- and hetero-junction TFETs fabricated by CEA-LETI (Grenoble,France) are considered with the objective to identify the possible presence of alternative injectionmechanisms such as Trap Assisted Tunneling.Negli ultimi anni uno sforzo significativo `e stato speso dall’industria microelettronica per ridurreil consumo di potenza da parte dei sistemi microelettronici. Esso infatti sta diventando unadelle limitazioni pi`u significative per lo scaling geometrico della tecnologia CMOS.Diverse strategie possono essere adottate per ridurre il consumo di potenza considerando ilsistema microelettronico nella sua totalit`a e scendendo fino a giungere all’ottimizzazione delsingolo dispositivo nano-elettronico. Negli ultimi anni il transistore Tunnel FET (TFET) si`e imposto come un possibile candidato per rimpiazzare, in applicazioni a consumo di potenzaestremamente basso con tensioni di alimentazione inferiori a 0.5V, i transistori convenzionaliMOSFET. Il funzionamento del TFET si basa sul meccanismo di iniezione purament quantisticodel Tunneling da banda a banda (BtBT) e che dovrebbe permettere una significativa riduzionedella potenza dissipata. Il BtBT nei dispositivi convenzionali `e un effetto parassita, nel TFETinvece esso `e utilizzato per poter ottenere significativi miglioramenti delle performance sottosogliae pertanto esso rappresenta una nuova concezione di dispositivo molto innovativa erivoluzionaria.Questa tesi analizza la modellizazione e la simulazione del TFET. Questi sono argomenti moltocomplessi vista la difficolt`a che si hanno nel modellare accuratamente il BtBT. In questo lavoroviene presentata una versione modificata del modello di trasporto Multi Subband Monte Carlo(MSMC) adattato per la simulazione di dispositivi TFET planari Ultra Thin Body Fully DepletedSilicon on Insulator (UTB FD-SOI), implementati con un canale composto da un unicosemiconduttore (omogiunzione) o con differenti materiali semiconduttori (eterogiunzione). Ilmodello proposto tiene il conto l’effetto di quantizzazione dovuto al confinamento dei portatoridi carica, con un’euristico ma accurato sistema di correzione. Tale modello `e stato poivalidato tramite una comparazione con altri modelli completamente quantistici e con risultatisperimentali.Superata la fase di validazione il modello MSMC `e utilizzato per simulare e verificare le performancedi dispositivi TFET implementati come omo o eterogiunzione in Silicio, leghe SiGe,o composti semiconduttori InGaAs.Nella seconda parte della tesi viene illustrato un lavoro di caratterizazione di TFET planari abassa temperatura (fino a 77K). Sono stati misurati dispositivi in Si e SiGe a omo o eterogiuzioneprodotti nella camera bianca del centro di ricerca francese CEA-LETI di Grenoble. Tramite talimisure `e stato possibile identificare la probabile presenza di meccanismi di iniezione alternativial BtBT come il Tunneling assistito da trappole (TAT) dimostrando come questo effetto `e,con ogni probabilit`a, la causa delle scarse performance in sottosoglia dei dispositivi TFETsperimentali a temperatura ambiente

Calibrated multi-subband Monte Carlo modeling of tunnel-FETs in silicon and III\u2013V channel materials

We present a semiclassical model for Tunnel-FET (TFET) devices capable to describe band-to-band tunneling (BtBT) as well as far from equilibrium transport of the generated carriers. BtBT generation is implemented as an add-on into an existing multi-subband Monte Carlo (MSMC) transport simulator that accounts as well for the effects typical to alternative channel materials and high-j dielectrics. A simple but accurate correction for the calculation of the BtBT generation rate to account for carrier confinement in the subbands is proposed and verified by comparison with full 2D quantum calculation

Toward computationally efficient Multi-Subband Monte Carlo simulations of nanoscale MOSFETs

We show how intense exploitation of multi-core architectures allowed us to cut by up to an order of magnitude the execution times of a Multi-Subband Monte Carlo (MSMC) simulator. The result brings simulations with the MSMC method out of the strictly academic domain and close to the execution time threshold for effective use in R&D departments of semiconductor research centres and industries

Electron-Hole Bilayer TFET: Experiments and Comments

We investigate Si/Si0.85Ge0.15 fully depleted-SOI tunnel FET (TFET) devices operated in the electron-hole bilayer (EHB) mode. The application of negative bias on front gate and positive bias on back gate results in confined hole and electron layers that are expected to enable vertical bandto- band tunneling (BTBT). The idea of the EHB-TFET device is to enhance the tunneling current by expanding the BTBT generation area from the narrow lateral source/channel junction to the entire channel region. Our systematic measurements on a variety of TFETs with variable geometry and channel materials do not offer support to this attractive concept. Self-consistent simulations confirm that the vertical BTBT transitions do not produce an appreciable current in our devices, due to sizeand bias-induced quantization, effective mass anisotropy, and incomplete formation of the bilayer. We examine the conditions for efficient vertical BTBT to occur and show that they cannot be met simultaneously, at least in Si or Si/SiGe devices

Acquired Resistance to Osimertinib in EGFR‐Mutated Non‐Small Cell Lung Cancer: How Do We Overcome It?

Osimertinib is currently the preferred first‐line therapy in patients with non‐small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutation and the standard second‐line therapy in T790M‐positive patients in progression to previous EGFR tyrosine kinase inhibitor. Osimertinib is a highly effective treatment that shows a high response rate and long‐lasting disease control. However, a resistance to the treatment inevitably develops among patients. Understanding the secondary mechanisms of resistance and the possible therapeutic options available is crucial to define the best management of patients in progression to osimertinib. We provide a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre‐treated with osimertinib and its future treatment applications

Bone Metastasis and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC): Microenvironment and Possible Clinical Implications

Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. We know that the presence of bone metastasis is a negative prognostic factor. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. This article reviews the most important pre-clinical and clinical scientific evidence on the reasons for this lower sensitivity to immunotherapy and the need to combine bone target therapies (BTT) with immunotherapy to improve patient outcome

Brain Metastases Management in Oncogene‐Addicted Non‐Small Cell Lung Cancer in the Targeted Therapies Era

The therapeutic landscape in patients with advanced non‐small‐cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene‐driven non‐small‐cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease. The intracranial activity of these drugs poses a crucial issue in determining the optimal management sequence in oncogene‐addicted non‐small‐cell lung cancer patients with brain metastases, with a potential change of paradigm from primary brain irradiation to central nervous system penetrating targeted inhibitors