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Chest wall resections for lung cancer treatment remain difficult to plan using standard 2-dimensional computed tomography. Although virtual reality headsets have been used in many medical contexts, they have not been used in chest wall resection planning. We compared preoperative planning of a chest wall surgical resection for lung cancer treatment between senior and resident surgeons who used an immersive virtual reality device and a 2-dimensional computed tomography. Chest wall resection planning was more accurate when surgeons used virtual reality vs computed tomography analysis (28.6% vs 18.3%, P =.018), and this was particularly true in the resident surgeon group (27.4% vs 8.3%, P =.0025). Predictions regarding the need for chest wall substitutes were also more accurate when they were made using virtual reality vs computed tomography analysis in all groups (96% vs 68.5%, P <.0001). Other studied parameters were not affected by the use of the virtual reality tool. Virtual reality may offer enhanced accuracy for chest wall resection and reconstruction planning for lung cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite evidence of its advantages in many cancers, brachytherapy (BT) remains clinically underused and understudied in the pre-clinical setting due to a lack of versatile RT-compatible in vitro tools that can emulate the tumor microenvironment and radiobiology of various cancers. Microfluidic devices use conventional cell culture methods in 3D-tumor models, are radiocompatible and can integrate radiobioassays. However, they are seldom used in pre-clinical BT research. This project engineered the first microfluidic tool for in vitro testing of BT, with applications in translational radiobiology. PDMS microfluidic chips were engineered to grow and culture concentric rows of hypoxic spheroids, and to allow the insertion of a clinical iodine-125 BT seed at the center of the device. FaDu (hypopharyngeal squamous cell carcinoma), SK-LMS-1 (leiomyosarcoma) and HCT116 (colorectal carcinoma) cell lines were selected for their clinical relevance and ability to form spheroids. Presence of hypoxia in spheroids was assessed by immunofluorescence (IF) staining for hypoxic protein CAIX. On-chip dose distribution was calculated using clinical TG-43 parameters and compared to EBT-XD radiographic film. Target dose criteria was fixed at 8 Gy in the center of the first row of spheroids. Treatment response was quantified by DNA damages (γH2AX IF, comet assay) and cell survival (clonogenic assay). Response of hypoxic and normoxic regions of spheroids will be compared in IF. A total of 15 spheroids that are 750µm or larger can be cultured in our device, arranged as 5 rows of 3 spread from 1.5mm to 7.5mm away from a central iodine-125 seed. 48h after cell seeding, hypoxic cores were observed in spheroids derived from FaDu (50 ± 4% of cross-section, N = 3) and SK-LMS-1 (46 ± 4% of cross-section, N = 3) cells, results are pending for HCT116. TG-43 formula predicts that the center of each row receives 8 Gy, 2.6 Gy, 1.2 Gy, 0.7 Gy and 0.4 Gy respectively. Radiographic film analysis confirms on-chip TG-43 calculated doses (N = 5, R2 = 0.999). Similarly, tail moment from comet assays follows predicted dose trends (n>60, N = 3). There was no statistical difference between 8 Gy BT and 8 Gy GammaCell (8 Gy BT vs 8 Gy GammaCell, p = 0.8758), with a statistical difference between 8 Gy BT (8 Gy BT vs 2.6 Gy BT,1.2 Gy BT,0.7 Gy BT,0.4 Gy BT,0 Gy, p < 0.0001), 2.6 Gy BT (2.6 Gy BT vs 1.2 Gy BT,0.7 Gy BT,0.4 Gy BT,0 Gy, p < 0.05) or 8 Gy GammaCell (8 Gy GammaCell vs 2.6 Gy BT,1.2 Gy BT,0.7 Gy BT,0.4 Gy BT,0 Gy, p < 0.0001) and other lower BT doses. For the first time, brachytherapy can be easily integrated on-chip and its effects evaluated on relevant 3D-tumor models. Our system allows simultaneous quantification of BT efficacy on normoxic and hypoxic cells treated at various doses. On-chip combination of BT with antitumor drug will be explored in future work. We hope this device will serve as further proof of the potential of BT/RT-on-chip systems for better drug development, treatment planification and theranostics. [ABSTRACT FROM AUTHOR]

Le « gold standard » pour la prise en charge des médiastinites est actuellement l'utilisation de la thérapie par pression négative suivi d'un lambeau musculaire qui peut entraîner des complications à type de douleur, perte de force du membre supérieur, instabilité sternale... L'implantation d'un dispositif médical (DM) est classiquement contre-indiquée due au risque d'infection. Par ailleurs, la diffusion des antibiotiques est mauvaise au niveau du médiastin et du sternum et encore plus lorsque les artères mammaires internes ont étés prélevées, limitant l'efficacité d'antibiotiques avec des volumes de distribution faibles. Nous avons développé un DM chargé en antibiotique permettant un relargage local et ainsi une optimisation des concentrations et une protection de l'implantation. Nous avons utilisé une prothèse sternale en alumine poreuse chargée en gentamicine seule ou en association avec de la vancomycine. Le but est de remplacer mécaniquement le sternum tout en protégeant l'implantation avec l'antibiotique. Ce DM a été implanté chez 4 patients avec des destructions sternales nécessitant un remplacement. L'antibiotique n'ayant qu'un rôle prophylactique, une antibiothérapie par voie systémique était prescrite classiquement. À noter que chez le patient #4, le S. epidermidis en cause était résistant à la gentamicine (CMI : 384 μg/mL) et à la vancomycine (CMI : 8 μg/mL). Il s'agissait de 4 hommes (67,6 ans) ayant présenté une médiastinite dans les suites d'une chirurgie cardiaque. Le délai moyen entre le début de l'infection et l'implantation était de 9,5 mois. Lors de l'implantation la bactériologie était toujours positive. Les concentrations locales d'antibiotiques étaient largement supérieures à celles nécessaires (Cmax/CMI > 1500 pour la gentamicine et ASC/CMI ∼16000 pour la vancomycine) et les concentrations sanguines pendant 48 h étaient indétectables. L'administration locale des antibiotiques a permis de retrouver des paramètres pharmacologiques témoignant d'une « resensibilisation » du S. epidermidis à la gentamicine et la vancomycine grâce à l'administration locale. La cicatrisation était obtenue en moins de 10 jours. Chez les 3 patients dont la flore était sensible à l'antibiotique, il n'y a pas eu de récidive de l'infection (> 18 mois de recul). Chez un patient il y a eu un changement radical de flore entre les derniers prélèvements réalisés et l'implantation, avec un passage de totalement sensible à complètement résistant à la gentamicine. Le DM a dû être retiré après 19 mois, mais les tissus cicatriciels ont permis de ne pas remettre de matériel. L'utilisation de cette céramique chargée en antibiotique permet de reconstruire la cage thoracique et de protéger son implantation. Le relargage local permet d'obtenir des concentrations locales efficaces qui complètent le débridement, protègent le DM d'une infection bactérienne et diminue le risque de toxicité systémique. Cela permet d'optimiser les concentrations locales et de récupérer des résistances « pharmacologiques ». [ABSTRACT FROM AUTHOR]

Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100 mg/day ( n = 5) or 150 mg/day ( n = 25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III–IV extra hematological toxicities (skin ( n = 1), and diarrhea ( n = 3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML. [ABSTRACT FROM AUTHOR]