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Editorial In summary, ESTRO clinical and other guidelines are soundly based, but always require validation, careful and consistent implementation, and focused education and training on their use, as well as local monitoring of that. As guidelines develop and older ones become superseded, there should be a clear mechanism to inform the community of the status of specific guidelines, especially when they have been replaced by new or updated versions. An important scientific aim for the future is to further advance guidelines and their individual statements into fully evidence-based instruments. These, in principle, could be directly linked to growing data-bases, allowing feedback mechanisms and thus continuous optimization. Another challenging research topic is the interplay of guidelines with growing opportunities and demands of personalized approaches of treatment.

This issue includes a perspective contribution by Lefresne et al. [1] on face-to-face scientific conferences versus virtual meetings and the implications for climate change. Generally, it is the policy of the Green Journal not to publish contributions with non-scientific content. In this specific case, the editors believe that the contribution by Lefresne and colleagues raises an important point that needs careful consideration and discussion in our scientific community. As scientists, we are at the forefront of research and strive to positively shape the future for humankind. Therefore, it is of key importance that the environmental impact of scientific activities is considered, and that our community develops and contributes to solutions to prevent further exacerbation of climate change with its substantial impact on health-related issues. This includes that pros and cons of face-to-face scientific meetings are carefully weighed.

A look through almost 2000 abstracts submitted for the upcom- ing ESTRO 2022 meeting together with a glance back on the 2021 papers published in Radiotherapy and Oncology gives one a good impression of the (current) key focus areas in radiation oncology: Almost all of this work relates to optimal delivery of radiation ther- apy in terms of technology, quality assurance and morbidity reduc- ing approaches. Thus, at present the research questions considered as most relevant for radiotherapy of e.g. lung and oesophageal can- cer are not related to tumour control, but to the late risk of cardiac disease in the patients who are lucky to survive their cancer long enough to develop such problems [1]. The same scenario is found in the patient cohort that constitutes the largest indication for radiotherapy in Europe: women with early breast cancer [2]. In these examples, and in many other situations where radiotherapy is applied with a curative intent, less focus has currently been given to the aim or indication of the treatment, namely the control of loco-regional malignant disease. Of course, since Holthusen’s seminal paper in 1936 [3] the overall aim of radiotherapy, as stated over and over again by all teachers in the field (including the authors of this editorial), is uncomplicated tumour control, i.e. loco-regional tumour control without severe normal tissue damage (therapeutic ratio). This implies that rigorous study of the effects of radiotherapy on normal, non-tumour, tissues is an absolute necessity. Yet, the prescription of radiotherapy in clinical practice is done to kill tumour cells for local and loco-regional control. If the effects of radiotherapy on tumours are shifting out of focus, it might be taken for granted that the indication, dose, fractionation, and potential multidisciplinary interactions in this field are fully understood, and what remains is the fine tuning of the associated risk of morbidity.

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At the annual conference of the Association for Radiation Research held in Oxford 26-28 June 2017, one session focused on the potential of targeting stem cells in radiation oncology. Cancer stem cells (CSCs) are highly tumorigenic cells capable to self-renew and to give rise to all other tumour cells. Emerging clinical evidence links CSCs to the risk of tumour relapse and suggests that therapeutic targeting of CSC populations in combination with radiotherapy might be a promising approach to improve local tumour control. This editorial outlines the concept of cancer stem cells in radiation biology and the main avenues for tumour radiosensitisation by anti-CSC therapies.

At the annual conference of the Association for Radiation Research held in Oxford 26-28 June 2017, one session focused on the potential of targeting stem cells in radiation oncology. Cancer stem cells (CSCs) are highly tumorigenic cells capable to self-renew and to give rise to all other tumour cells. Emerging clinical evidence links CSCs to the risk of tumour relapse and suggests that therapeutic targeting of CSC populations in combination with radiotherapy might be a promising approach to improve local tumour control. This editorial outlines the concept of cancer stem cells in radiation biology and the main avenues for tumour radiosensitisation by anti-CSC therapies.

The neuroendocrine responses to resuscitation with 7.5% hypertonic saline/6% Dextran-70 (HSD) following hemorrhagic hypotension were evaluated in conscious swine. Following hemorrhage, animals received 4 milliliters per kilogram of HSD (n=6) or 0.9% saline (n=8). Administration of normal saline did not alter cardiovascular function nor attenuate an increase in hormones, HSD rapidly improved cardiovascular function and acutely decreased ACTH, PRA (Plasma Renin Activity), cortisol, norepinephrine (NE), epinephrine (E), aldosterone and lysine vasopressin levels (LVP). The initial decrease in ACTH (adrenocorticotropic hormone), cortisol and aldosterone levels was due primarily to hemodilution associated with the expansion of plasma volume. The reductions in NE, E, LVP and PRA were greater than those attributed to hemodilution alone. Values for LVP, NE and E remained at values below those at the end of hemorrhage, but greater than basal levels, while PRA returned to values similar to these at the end of hemorrhage. (jg)

The effect of small-volume resuscitation (4 ml/kg) with hypertonic saline/dextran (HSD) (7.5% NaCL in 6% Dextran, n=6), hypertonic saline (HS) (n=8), dextran (n=6), or normal saline (0.9% sodium chloride, n=8) was evaluated in chronically instrumented, splenectomized conscious swine bled 37.5 ml/kg over 60 min. Hemorrhage resulted in a reduction in cardiac index, stroke volume index, and mean arterial pressure. Survival with HSD (66%) was better than the other three treatments. The survival rate due to HS (25%) was greater than that due to normal saline (0%) but was not different than that of dextran (17%). HSD and HS expanded plasma volume by 33 and 29%, respectively. Administration of HSD or HS acutely improved cardiac index and stroke volume, and decreased heart rate. The increases in cardiac index and stroke volume were greater following resuscitation with HSD and the improvement persisted over 3 h. Mean arterial pressure was acutely increased after administration of HSD but returned to post-hemorrhage values within 30 min. Plasma sodium cation concentration and osmolality were increased to a similar extent with HSD and HS, while plasma potassium cation levels were initially decreased, returning to control levels within 60 min. HSD appears to be a superior small-volume resuscitation solution compared to the other treatments with no detrimental effects noted in the present study of conscious swine.