Proton therapy of a pregnant patient with nasopharyngeal carcinoma

Background and purpose: Radiotherapy during pregnancy is rarely administered due to lack of data and practical challenges. This is the first detailed report of proton therapy as cancer treatment for a pregnant patient with nasopharyngeal carcinoma. Materials and methods: Pencil beam scanning proton therapy was prescribed to a pregnant patient to a total dose of 70 Gy (RBE) to the therapeutic CTV and 54.25 Gy to the prophylactic CTV, delivered in 35 fractions with a simultaneous integrated boost technique. Results: Phantom measurements showed a thirty-fold decrease in fetal radiation dose when using proton compared to photon therapy, with a total fetal dose of 5.5 mSv for the complete proton treatment, compared to 185 and 298 mSv for the photon treatment with and without lead shielding, respectively. After adminstering proton therapy during pregnancy, at 39 weeks of gestation, a healthy boy with a birthweight on the 83th percentile was delivered. Pediatric follow-up at 2 months of age of the offspring showed normal growth and age-adequate motor development with no signs of neurological problems. MR follow-up of the tumor 3 months after the end of treatment showed complete remission. Conclusion: This case demonstrates the potential of proton therapy for treatment during pregnancy. Compared to photon therapy, proton therapy can significantly limit fetal dose, while simultaneously offering a more optimized treatment to the patient

Scanning probe microscopes go video rate and beyond

Quantum Matter and Optic

Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if >= 70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.Peer reviewe

The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer : An International Multidisciplinary Systematic Review

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

High Diagnostic Performance of Short Magnetic Resonance Imaging Protocols for Prostate Cancer Detection in Biopsy-naive Men: The Next Step in Magnetic Resonance Imaging Accessibility

Background: To make magnetic resonance imaging (MRI) more accessible to men at risk of high-grade prostate cancer (PCa), there is a need for quicker, simpler, and less costly MRI protocols. Objective: To compare the diagnostic performance of monoplanar (“fast” biparametric MRI [bp-MRI]) and triplanar noncontrast bp-MRI with that of the current contrast-enhanced multiparametric MRI (mp-MRI) in the detection of high-grade PCa in biopsy-naïve men. Design, setting, and participants: A prospective, multireader, head-to-head study included 626 biopsy-naïve men, between February 2015 and February 2018. Intervention: Men underwent prebiopsy contrast-enhanced mp-MRI. Prior to biopsy, two blinded expert readers subsequently assessed “fast” bp-MRI, bp-MRI, and mp-MRI. Thereafter, systematic transrectal ultrasound-guided biopsies (SBs) were performed. Men with suspicious mp-MRI (Prostate Imaging Reporting and Data System 3–5 lesions) also underwent MR-in-bore biopsy (MRGB). Outcome measurements and statistical analysis: Primary outcome was the diagnostic performance of each protocol for the detection of high-grade PCa. Secondary outcomes included the difference in biopsy avoidance, detection of low-grade PCa, acquisition times, decision curve analyses, inter-reader agreement, and direct costs. Results from combined MRGB and SB were used as the reference standard. High-grade PCa was defined as grade 2. Results and limitations: Sensitivity for high-grade PCa for all protocols was 95% (180/ 190; 95% confidence interval [CI]: 91–97%). Specificity was 65% (285/436; 95% CI: 61–70%) for “fast” bp-MRI and 69% (299/436; 95% CI: 64–73%) for bp-MRI and mp-MRI. With fast bp-MRI, 0.96% (6/626) more low-grade PCa was detected. Biopsy could be avoided in 47% for the fast bp-MRI and in 49% for the bp-MRI and mp-MRI protocols. Fast bp-MRI and bp-MRI can be performed in 8 and 13 min, respectively, instead of 16

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy

none38siContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).noneWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; MacLennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B LWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; Maclennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B

Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Systemic versus localized coagulation activation contributing to organ failure in critically ill patients

In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may not only be relevant for vascular atherothrombotic disease in general but has in certain clinical settings considerable consequences, for example in the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on an interleukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by physiological anticoagulant mechanisms and endogenous fibrinolysis. Interestingly, apart from the overall systemic responses, a differential local response in various vascular beds related to specific organs may occur