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Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence. Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure. In this review, we present the current status and the recent advances in PDAC treatment together with the biological and immunological hallmarks of this cancer entity. On this basis, we discuss new concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome – with a specific focus on protocols involving radio(chemo)therapeutic approaches.

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.

Background Different studies have proved in recent years that hypofractionated radiotherapy (RT) improves overall survival of patients affected by locally advanced, unresectable, pancreatic cancer. The clinical management of these patients generally leads to poor results and is considered very challenging, due to different factors, heavily influencing treatment delivery and its outcomes. Firstly, the dose prescribed to the target is limited by the toxicity that the highly radio-sensitive organs at risk (OARs) surrounding the disease can develop. Treatment delivery is also complicated by the significant inter-fractional and intra-fractional variability of therapy volumes, mainly related to the presence of hollow organs and to the breathing cycle. Main body of the abstract The recent introduction of magnetic resonance guided radiotherapy (MRgRT) systems leads to the opportunity to control most of the aforementioned sources of uncertainty influencing RT treatment workflow in pancreatic cancer. MRgRT offers the possibility to accurately identify radiotherapy volumes, thanks to the high soft-tissue contrast provided by the Magnetic Resonance imaging (MRI), and to monitor the tumour and OARs positions during the treatment fraction using a high-temporal cine MRI. However, the main advantage offered by the MRgRT is the possibility to online adapt the RT treatment plan, changing the dose distribution while the patient is still on couch and successfully addressing most of the sources of variability. Short conclusion Aim of this study is to present and discuss the state of the art, the main pitfalls and the innovative opportunities offered by online adaptive MRgRT in pancreatic cancer treatment.

Clinical outcomes for patients with pancreatic adenocarcinoma (PAC) remain dismal. Local recurrences, proportions of margin positive surgical resections, and overall survival outcomes remain inferior in PAC than any other solid tumor. This stems from a current standard of care management approach that needs to be inspired and transformed with modern treatment techniques and novel therapeutic options. Radiation therapy has historically been a central component in the treatment of pancreatic adenocarcinoma; however, the role of radiation therapy has been called into question based on the publication of clinical trials with conflicting results. We present an overview of the rationale for radiation therapy in resectable, borderline resectable, and unresectable pancreatic adenocarcinoma. We further present a summary of emerging clinical data and future directions to improve outcomes in this devastating malignancy.

Background Neoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients. Methods For six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose D pres  = 51Gy(RBE)] and the boost target [D pres  = 66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared. Results All treatment plans of each strategy fulfilled the prescribed doses to the targets (D pres(GTV,CTV)  = 100%, D 95%,(GTV,CTV)  ≥ 95%, D 2%,(GTV,CTV)  ≤ 107%). No significant differences for the conformity index were found ( p  > 0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets ( p  < 0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy ( p  < 0.045). Conclusion Based on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.

In this paper, the problems of effective implementation of large-scale projects of international sporting event tourism are considered. It has been shown that large-scale sports events in the system of event tourism play a significant role and have a steady dynamic of development, that is why they form a circle of scientific interests both in the sphere of international tourism marketing and in the field of project management. The features of sport large-scale events and their management are analyzed, which, as it is defined, requires the use of a complex of measures and instruments within the limits of macro-projects of international sports tourism. The concept of macro-projects of international sport tourism is defined, the necessity of application of criteria of effective realization of data of macro projects in accordance with the system of requirements for their effectiveness is revealed and substantiated. Particular attention is paid to the necessity of searching for scientifically grounded ways of providing organizers of large-scale projects of sport event tourism with the fullest implementation of project tasks in the process of organizing sport events, as well as on the formation of a scientific basis for the selection of projects of sports event tourism of a certain group of large-scale projects (macro projects), management of which, based on their specificity, significance, scale and number of structures involved in the organization, has certain features. On the basis of the conducted study of the results of holding a large event in Ukraine, the Euro-2012, a comparative analysis of this event and sports events that were implemented in other countries, the author identified a list of factors that influence the effective implementation of similar to the Euro-2012 events, problems of realization and ways of overcoming them.