ESTRO 2025 - Abstract Book

S157

Invited Speaker

ESTRO 2025

4932

Speaker Abstracts ALK-driven NSCLC and radiotherapy - pro Gerard Walls Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom

Abstract:

Following the PACIFIC trial in NSCLC which led to immune checkpoint inhibitors being combined with chemoradiation for the first time in Oncology, the LAURA trial was another new paradigm for our discipline yet again spear-headed by thoracic oncologists. LAURA leveraged mutational testing to individualise the radiotherapy– drug combination for stage III non-small cell lung cancer, demonstrating that consolidation targeted therapy can vastly improve disease control in patients with a sensitising mutation, without the cost of unacceptable excess toxicity. The publication of this landmark trial was timely because evidence was emerging that immune checkpoint inhibitors have reduced benefit in NSCLC with specific actionable genetic alterations (AGAs). LAURA selected patients with common mutations in EGFR due to the availability of a well-tolerated and efficacious agent (osimertinib), but the findings of this study are likely to be transferable to other such settings. While AGAs affect the EGFR gene most commonly, appropriate targeted therapies have been successfully implemented in advanced disease for many other AGAs. Rearrangements of ALK , most often as fusions with EML4 , are also common in NSCLC, and second-generation oral targeted therapies have been identified. eg. brigatinib, alectinib. A small retrospective series published recently suggests that consolidation ALK -targeted therapy may be more beneficial than durvalumab and no treatment in the scenario where an ALK rearrangement has been identified in the tumour. Prospective evidence is awaited from the ongoing phase 2 BOUNCE trial and phase 3 HORIZON-1 trials, although some patients may ask about off-license use of ALK -targeted therapies in the interim. This presentation will discuss the completed and ongoing studies in the ‘ ALK -positive’ NSCLC chemoradiation setting and explore the implications of these data.

4933

Speaker Abstracts Thinking outside of the box to transform radiation sciences Marie-Catherine Vozenin radiation Oncology, HUG, Geneva, Switzerland. LiRR, UNIGE, Geneva, Switzerland

Abstract: Following the long tradition of innovation developed by the French school of Radiotherapy, with a continuous academic support in France, Switzerland and the USA, with the unique microenvironment created by ESTRO, the primary goal of my team has been and will continue to be dedicated to the discovery of innovative tools able to protect normal tissue and enhance tumor control. One of my most significant contribution to radiation oncology and radiation biology has been the development of FLASH which is a groundbreaking radiation therapy technique. The primary observation showing that FLASH spares normal tissue but not tumors has been performed in collaboration with Dr. Vincent Favaudon who pioneered the FLASH concept. With my team, we have successfully investigated the differential effect of FLASH in the brain, lung and skin and tested this new approach of radiotherapy on various species, including mice, zebrafish, mini-pigs, and cats. While we still don’t understand the specific mechanism underlying this differential effect, in less than ten years, FLASH has reactivated and transformed our community. FLASH has stimulated new collaborations between accelerator physicists, medical physicists, modelers, radiation chemists, radiobiologists and radiation oncologists. A new generation of young scientists has also been attracted, all are moved by a common goal, eradicate cancer.