ESTRO 2024 Congress report

We want to highlight different sessions and presentations that were focused on biological topics after our previous report on the biology pre-meeting course. In the field of biology, numerous exciting sessions and events were noticeable at ESTRO 2024. In this newsletter, we highlight the winners of best abstract and the interdisciplinary award, one of the interdisciplinary sessions (which was related to the planned joint bio-phys workshop) and the brachytherapy pre-meeting course.

Brachytherapy pre-meeting course: “Radiobiology and modelling in brachytherapy”

The brachytherapy pre-meeting course 2024, which was led by Jean-Michel Hannoun-Levi (radiation oncologist, France) and Frank-André Siebert (medical physicist, Germany), had a strong focus on biology and modelling. The faculty was interdisciplinary and comprised clinicians, physicists and physician scientists in biology. The morning sessions were focussed on biological basics such as radiosensitivity, repair, redistribution, repopulation, reoxygenation and reactivation of the immune response (the 6Rs) and the linear quadratic model and its implications for the planning and evaluation in brachytherapy. The concept of the 6Rs of fractionated radiotherapy is, in some respects, hard to transfer to brachytherapy, especially to low-dose-rate techniques, as continuous low-dose radiation or very small doses every hour are not usually covered by experimental data, and the linear quadratic model might be limited in this dose range. Alpha/beta values, which are crucial for the comparison of different fractionations, are derived either from in-vitro models (mostly 2D cell cultures) or from randomised clinical trials that have compared different fractionations and reported local control data and side effects. Different alpha/beta values have to be considered for the calculation of comparable doses (e.g. a tumour with a high alpha/beta ratio and late responding normal tissue with a low alpha/beta). These calculations become even more challenging when re-irradiation is discussed. Re-irradiation is a special focus in brachytherapy due to the advantageous spatial dose distribution. Special radiobiological challenges in brachytherapy include the comparison of biological effects among different brachytherapy techniques (low-dose-rate versus high-dose-rate), calculation of comparable doses between brachytherapy and external beam radiotherapy and the estimation of biological effects of the inhomogeneous dose distribution in the target volume that is typical for brachytherapy. During the second part of the course, clinical concepts for different sites that are typically treated with brachytherapy, and biological aspects of the respective treatments, were discussed.

Best abstract in biology: “Targeting serine/glycine metabolism improves radiotherapy response in non-small-cell lung cancer”

The best abstract in biology was focused on metabolism in cancer cells. Anais Sanchez-Castillo from Maastricht, The Netherlands, was awarded for her work on serine/glycine metabolism in cancer and possible ways to target this pathway with irradiation. Dr Sanchez-Castillo published her findings in 2023. She reported that in lung cancer, high levels of serine/glycine synthesis enzymes were associated with limited prognosis. Irradiation of in-vitro lung cancer cells led to decreases in intracellular levels of serine and glycine. The psychopharmacon sertraline was identified as a drug that might be repurposed to radiosensitise lung cancer cell lines. In an in-vivo model of Lewis lung carcinoma, treatment with irradiation and sertraline led to reduced tumour weight and an improved tumour immune microenvironment (https://pubmed.ncbi.nlm.nih.gov/38160212/). Additional unpublished data were shown for glioblastoma models, confirming the hypothesised mode of action.

Interdisciplinary award to Anthony Chalmers

The interdisciplinary award to Anthony Chalmers was based on a suggestion from the biology committee. The award is given for scientific contributions to a field other than the one trained in and for facilitation of interdisciplinary work. Anthony Chalmers is a prime example of a clinician who has done exceptional work in the field of radiobiology. In addition to his training as a clinical oncologist, he earned his PhD in radiation biology at the Gray Cancer Institute. His major projects focused on combinations of radiotherapy and DNA damage repair inhibitors, which he developed from preclinical research to clinical trials. He is active in a number of multidisciplinary radiotherapy research networks and is also very active in mentoring and supporting young researchers. In summary, he was awarded “for his strong bench-to-bedside research, tremendous work in the CRUK RadNet centres of excellence, establishment and running of the radiotherapy-drug combinations working group, and his work to recruit and support early career researchers into the radiotherapy research fields.”

Interdisciplinary symposium “Radiobiology and interdisciplinary aspects of hypofractionation”

Many exciting interdisciplinary sessions involved biology. One of them was focused on the biological and technical aspects of hypofractionated radiotherapy as well as clinical evidence. In the biology introduction by Martin Pruschy, several differences in the biological effects of normo-fractionated and hypofractionated radiotherapy were discussed. It was reported that irradiation with higher doses led to a shift in the repair mechanisms of DNA-double-strand breaks towards more error-prone mechanisms such as alternative end-joining, and thus to more chromosomal aberrations. In contrast to reoxygenation after normo-fractionated irradiation, irradiation with high doses even leads to enhanced tumour hypoxia; this is seen in preclinical models and imaging data taken from patients. Regarding anti-tumour immunity, higher radiation doses might lead to better “in-situ vaccination”. In conclusion, from a biology point of view, there is no clear preference for normo- or hypofractionation, but concepts must be tailored to respective clinical situations.

For higher radiation doses, technical developments must be focused on high precision in the application of radiotherapy (e.g. the integrated boost concept for a macroscopic tumour inside a clinical target volume) as discussed by Paul Keall. In addition to “conventional” hypofractionation, hypofractionation in the setting of spatially fractionated radiotherapy, mini beam or FLASH should be explored from a clinical as well as a biological point of view. Technical developments are also required to be implemented in the clinic, as discussed by Yolanda Prezado.

Evert van Limbergen presented how the use of moderate hypofractionation has become established for breast and prostate cancers. Interestingly, in prostate cancer, the modelling of alpha/beta values for normo-fractionated, moderately hypofractionated and ultra-hypofractionated treatments showed no consistent values; thus, biological equivalent doses should be calculated with caution.

Biological and technical aspects of hypofractionation will be discussed across disciplines in the joint physics-biology workshop on “Challenges and Opportunities in the Era of Hypofractionation”. The subtopics will include tissue responses in hypofractionated photon radiotherapy, hypofractionation with particle therapy and emerging technologies. The aim is to foster interdisciplinary discussions to identify research questions and establish an international expert group. The workshop is open for applications from radiation biologists, physicists and physician scientists (who have a focus on physics or biology) at all levels of their academic careers (from students to senior scientists). Biologists are very welcome to join this exciting interdisciplinary discussion. The application should be made through the web link:  Apply to Physics Workshop 2024

 

Franziska Eckert, MD

Deputy chair, Department of Radiation Oncology

Medical University of Vienna

Department of Radiation Oncology

Comprehensive Cancer Center Vienna

Austria

franziska.eckert@meduniwien.ac.at