[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

[Real world data in radiotherapy: A data farming project by Unitrad]. / Données de vie réelle en radiothérapie : le data farming du groupe Unitrad.

The aim of the data farming project by the Unitrad group is to produce and use large quantities of structured real-life data throughout radiotherapy treatment. Starting in 2016, target real world data were selected at expert consensus conferences and regularly updated, then captured in MOSAIQ© as the patient was treated. For each partner institution, the data was then stored in a relational database, then extracted and used by researchers to create real world knowledge. This production was carried out in a multicentre, coordinated fashion. When necessary, the raw data was shared according to the research projects, in compliance with regulations. Feedack was provided at each stage, enabling the system to evolve flexibly and rapidly, using the "agile" method. This work, which is constantly evolving, has led to the creation of health data warehouses focused on data of interest in radiotherapy, and the publication of numerous academic studies. It forms part of the wider context of the exploitation of real-life data in cancerology. Unitrad data farming is a collaborative project for creating knowledge from real-life radiotherapy data, based on an active network of clinicians and researchers.

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.

BACKGROUND: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). PATIENTS AND METHODS: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. RESULTS: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash. CONCLUSION: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

Flap delineation guidelines in postoperative head and neck radiation therapy for head and neck cancers.

INTRODUCTION: Reconstructive surgery in head and neck cancers frequently involves the use of autologous flaps to improve functional outcomes. However, the literature suggests that postoperative radiotherapy deteriorates functional outcomes due to flap atrophy and fibrosis. Data on patterns of relapse after postoperative radiotherapy with a flap are lacking, resulting in heterogenous delineation of postoperative clinical target volumes (CTV). Flap delineation is unusual in routine practice and there are no guidelines on how to delineate flaps. Therefore, we aim to propose a guideline for flap delineation in head and neck cancers to assess dose-effects more accurately with respect to flaps. MATERIAL AND METHODS: Common flaps were selected. They were delineated by radiation oncologists and head and neck surgeons based on operative reports, on contrast-enhanced planning CTs and checked by a radiologist. Each flap was divided into its vascular pedicle and its soft tissue components (fat, fascia/ muscle, skin, bone). RESULTS: Delineation (body and pedicle) of Facial Artery Musculo-Mucosal, pectoralis, radial forearm, anterolateral thigh, fibula and scapula flaps was performed. Based on information provided in operative reports, i.e. tissue components, size and location, flaps can be identified. The various tissue components of each flap can be individualized to facilitate the delineation. CONCLUSION: This atlas could serve as a guide for the delineation of flaps and may serve to conduct studies evaluating dose-effects, geometric patterns of failure or functional outcomes after reconstructive surgery. Changes in postoperative CTV definitions might be needed to improve risk/benefit ratio in the future based on surgery-induced changes.

Insight into Fluorocarbon Adsorption in Metal-Organic Frameworks via Experiments and Molecular Simulations.

The improvement in adsorption/desorption of hydrofluorocarbons has implications for many heat transformation applications such as cooling, refrigeration, heat pumps, power generation, etc. The lack of chlorine in hydrofluorocarbons minimizes the lasting environmental damage to the ozone, with R134a (1,1,1,2-tetrafluoroethane) being used as the primary industrial alternative to commonly used Freon-12. The efficacy of novel adsorbents used in conjunction with R134a requires a deeper understanding of the host-guest chemical interaction. Metal-organic frameworks (MOFs) represent a newer class of adsorbent materials with significant industrial potential given their high surface area, porosity, stability, and tunability. In this work, we studied two benchmark MOFs, a microporous Ni-MOF-74 and mesoporous Cr-MIL-101. We employed a combined experimental and simulation approach to study the adsorption of R134a to better understand host-guest interactions using equilibrium isotherms, enthalpy of adsorption, Henry's coefficients, and radial distribution functions. The overall uptake was shown to be exceptionally high for Cr-MIL-101, >140 wt% near saturation while >50 wt% at very low partial pressures. For both MOFs, simulation data suggest that metal sites provide preferable adsorption sites for fluorocarbon based on favorable C-F ··· M+ interactions between negatively charged fluorine atoms of R134a and positively charged metal atoms of the MOF framework.

RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study.

PURPOSE: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT). PATIENTS AND METHODS: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry. RESULTS: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ±â€¯16.0 Gy) and control patients (57.1 ±â€¯15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599]. CONCLUSION: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up.

Interfacial Water Features at Air-Water Interfaces as Influenced by Charged Surfactants.

The features of interfacial water at air-water interfaces of anionic sodium dodecyl sulfate (SDS) and cationic dodecyl amine hydrochloride (DDA) solutions were examined by combining sum frequency generation (SFG) vibrational spectroscopy measurements and molecular dynamics simulations (MDS). The SFG spectra revealed that interfacial water molecules for SDS solutions were highly ordered compared with those for DDA solutions. To elucidate this observation, in addition to agreement with the literature in regards to the interfacial electric field at the interfaces, we investigated the features of interfacial water molecules with respect to their network and their interaction with surfactant head groups. Our simulation analysis results revealed a higher number density, more strongly connected hydrogen bonding, and more orderly oriented interfacial water molecules at the interface of the SDS solutions as compared to the DDA solutions. The goal of this research is  to identify significant features of interfacial water for our improved understanding of such interfacial phenomena.

Microscopic Behaviors of Tri- n-Butyl Phosphate, n-Dodecane, and Their Mixtures at Air/Liquid and Liquid/Liquid Interfaces: An AMBER Polarizable Force Field Study.

In solvent extraction processes for recovering metal ions from used nuclear fuel, as well as other industrial applications, a better understanding of the metal complex phase transfer phenomenon would greatly aid ligand design and process optimization. We have approached this challenge by utilizing the classical molecular dynamics simulations technique to gain visual appreciation of the vapor/liquid and liquid/liquid interface between tri- n-butyl phosphate (TBP) and n-dodecane with air and water. In this study, we successfully reparameterized polarizable force fields for TBP and n-dodecane that accurately reproduced several of their thermophysical properties such as density, heat of vaporization, and dipole moment. Our models were able to predict the surface and interfacial tension of different systems when compared to experimental results that were also performed by us. Through this study, we gained atomistic understanding of the behaviors of TBP and n-dodecane at the interface against air and water, useful in further computational studies of such systems. Finally, our studies indicate that the initial configuration of a simulation may have a large effect on the final result.

Attachment, Coalescence, and Spreading of Carbon Dioxide Nanobubbles at Pyrite Surfaces.

Recently, it was reported that using CO2 as a flotation gas increases the flotation of auriferous pyrite from high carbonate gold ores of the Carlin Trend. In this regard, the influence of CO2 on bubble attachment at fresh pyrite surfaces was measured in the absence of collector using an induction timer, and it was found that nitrogen bubble attachment time was significantly reduced from 30 ms to less than 10 ms in CO2 saturated solutions. Details of CO2 bubble attachment at a fresh pyrite surface have been examined by atomic force microscopy (AFM) measurements and molecular dynamics (MD) simulations, and the results used to describe the subsequent attachment of a N2 bubble. As found from MD simulations, unlike the attached N2 bubble, which is stable and has a contact angle of about 90°, the CO2 bubble attaches, and spreads, wetting the fresh pyrite surface and forming a multilayer of CO2 molecules, corresponding to a contact angle of almost 180°. These MDS results are complemented by in situ AFM images, which show that, after attachment, CO2 nano-/microbubbles spread to form pancake bubbles at the fresh pyrite surface. In summary, it seems that CO2 bubbles have a propensity to spread, and whether CO2 exists as layers of CO2 molecules (gas pancakes) or as nano-/microbubbles, their presence at the fresh pyrite surface subsequently facilitates film rupture and attachment of millimeter N2 bubbles and, in this way, improves the flotation of pyrite.

Rate theory of ion pairing at the water liquid-vapor interface: A case of sodium iodide.

Studies on ion pairing at interfaces have been intensified recently because of their importance in many chemical reactive phenomena, such as ion-ion interactions that are affected by interfaces and their influence on kinetic processes. In this study, we performed simulations to examine the thermodynamics and kinetics of small polarizable sodium iodide ions in the bulk and near the water liquid-vapor interface. Using classical transition state theory, we calculated the dissociation rates and corrected them with transmission coefficients obtained from the reactive flux formalism and Grote-Hynes theory. Our results show that in addition to affecting the free energy of ions in solution, the interfacial environments significantly influence the kinetics of ion pairing. The results on the relaxation time obtained using the reactive flux formalism and Grote-Hynes theory present an unequivocal picture that the interface suppresses ion dissociation. The effects of the use of molecular models on the ion interactions as well as the ion-pair configurations at the interface are also quantified and discussed.

Li+ solvation and kinetics of Li+-BF4-/PF6- ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories.

Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li+ and the dissociation kinetics of ion pairs Li+-[BF4] and Li+-[PF6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found that the residence times of EC around Li+ ions varied from 60 to 450 ps, depending on the correction method used. We found that the relaxation times changed significantly from Li+-[BF4] to Li+-[PF6] ion pairs in EC. Our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influences the dissociation kinetics of ion pairing.

Rate theory of solvent exchange and kinetics of Li(+) - BF4 (-)/PF6 (-) ion pairs in acetonitrile.

In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li(+) and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li(+) in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li(+)-[BF4] and Li(+)-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li(+). We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li(+)-[BF4] and Li(+)-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.

Quantifying Dimer and Trimer Formation by Tri-n-butyl Phosphates in n-Dodecane: Molecular Dynamics Simulations.

Tri-n-butyl phosphate (TBP), a representative of neutral organophosphorous ligands, is an important extractant used in the solvent extraction process for the recovery of uranium and plutonium from spent nuclear fuel. Microscopic pictures of TBP isomerism and its behavior in n-dodecane diluent were investigated utilizing MD simulations with previously optimized force field parameters for TBP and n-dodecane. Potential mean force (PMF) calculations on a single TBP molecule show seven probable TBP isomers. Radial distribution functions (RDFs) of TBP suggest the existence of TBP trimers at high TBP concentrations in addition to dimers. 2D PMF calculations were performed to determine the angle and distance criteria for TBP trimers. The dimerization and trimerization constants of TBP in n-dodecane were obtained and match our own experimental values using the FTIR technique. The new insights into the conformational behaviors of the TBP molecule as a monomer and as part of an aggregate could greatly aid in the understanding of the complexation between TBP and metal ions in a solvent extraction system.

Computer Simulation of Methanol Exchange Dynamics around Cations and Anions.

In this paper, we present the first computer simulation of methanol exchange dynamics between the first and second solvation shells around different cations and anions. After water, methanol is the most frequently used solvent for ions. Methanol has different structural and dynamical properties than water, so its ion solvation process is different. To this end, we performed molecular dynamics simulations using polarizable potential models to describe methanol-methanol and ion-methanol interactions. In particular, we computed methanol exchange rates by employing the transition state theory, the Impey-Madden-McDonald method, the reactive flux approach, and the Grote-Hynes theory. We observed that methanol exchange occurs at a nanosecond time scale for Na(+) and at a picosecond time scale for Cs(+), Cl(-), and I(-). We also observed a trend in which, for like charges, the exchange rate is slower for smaller ions because they are more strongly bound to methanol.

Adsorption Kinetics in Nanoscale Porous Coordination Polymers.

Nanoscale porous coordination polymers were synthesized using simple wet chemical method. The effect of various polymer surfactants on colloidal stability and shape selectivity was investigated. Our results suggest that the nanoparticles exhibited significantly improved adsorption kinetics compared to bulk crystals due to decreased diffusion path lengths and preferred crystal plane interaction.

Hydrophobic and moisture-stable metal-organic frameworks.

Metal-organic frameworks (MOFs) have proved to be very attractive for applications including gas storage, separation, sensing and catalysis. In particular, CO(2) separation from flue gas in post-combustion processes is one of the main focuses of research among the scientific community. One of the major issues that are preventing the successful commercialization of these novel materials is their high affinity towards water that not only compromises gas sorption capacity but also the chemical stability. In this paper, we demonstrate a novel post-synthesis modification approach to modify MOFs towards increasing hydrophobic behaviour and chemical stability against moisture without compromising CO(2) sorption capacity. Our approach consists of incorporating hydrophobic moieties on the external surface of the MOFs via physical adsorption. The rationale behind this concept is to increase the surface hydrophobicity in the porous materials without the need of introducing bulky functionalities inside the pore which compromises the sorption capacity toward other gases. We herein report preliminary results on routinely studied MOF materials [MIL-101(Cr) and NiDOBDC] demonstrating that the polymer-modified MOFs retain CO(2) sorption capacity while reducing the water adsorption up to three times, with respect to the un-modified materials, via an equilibrium effect. Furthermore, the water stability of the polymer-functionalized MOFs is significantly higher than the water stability of the bare material. Molecular dynamic simulations demonstrated that this equilibrium effect implies a fundamental and permanent change in the water sorption capacity of MOFs. This approach can also be employed to render moisture stability and selectivity to MOFs that find applications in gas separations, catalysis and sensing where water plays a critical role in compromising MOF performance and recyclability.

Separation of polar compounds using a flexible metal-organic framework.

A flexible metal-organic framework constructed from a flexible linker is shown to possess the capability of separating mixtures of polar compounds (propanol isomers) by exploiting the differences in the saturation capacities of the constituents. Transient breakthrough simulations show that these sorption-based separations are in favor of the component with higher saturation capacity.