Optimization of catheter’s implementation in the mold, in the case of vaginal HDR brachytherapy treatment

Background: The purpose of this study was to evaluate and compare results obtained in high dose rate (HDR) brachytherapy treatment of vaginal cancer. Different catheters distributions inside the custom mold were explored. The difference between those distributions is the position of the posterior catheter located near the rectum in the actual custom mold applicator used in different hospitals, each one having a catheter displacement of 0.5 which is equal to the length of a step position. The best catheters distribution offering an optimal dose distribution: better coverage of the clinical target volume (CTV), while reducing the dose received by organs at risk (OARs), were discussed. Materials and methods: A group of 60 patients treated with HDR brachytherapy, alone or in combination with external radiotherapy, was investigated. A custom mold is normally used for HDR brachytherapy vaginal cancer treatment. Three different geometrical positions of the catheters (G1, G2 and G3) and, consequently, 3 different dosimetries were simulated out for each patient on the CT images, using the Oncentra planning system. The coverage of the CTV was studied. Results: The average volume treated was 30.46 cc (min = 9.8 cc, max = 70.86 cc). The total prescribed dose, including external and internal radiotherapy, was 80 Gy. We evaluated conformity index (CI), dose homogeneity index (DHI) and conformality index (COIN) indices for the three implantation geometries to reach the same coverage criteria of the CTV. The D2cc parameter allowed the evaluation of the dose received by the OARs. For the rectum, a dose reduction of 9.67% (range 0.29–32.86) was obtained with the second geometry of implantation compared to 10.14% (range 1.43–28.33) with the third geometry. For the bladder, the second geometry of implantation showed a better preservation for this organ [15.93% (range 0.86–58.71) vs. 8.35% (range 0.33–30.43) with the third geometry]. The sigmoid was more protected using the second plan of implantation as well [6.33% (range 0.14–40.71) for the second implantation compared to 5.95% (range 0.33–36) for the third implantation]. Conclusions: G2 and G3 catheters’ distribution, having catheter position farther from the mold wall and so from the vaginal wall compared to the catheter position applied showed a better protection for the OARs while giving the same prescribed dose for the CTV

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma

Summary: Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care