S3030
Invited Speaker
ESTRO 2026
simultaneously maintaining target coverage and respecting OAR constraints within each fraction. Although sarcoma-specific evidence remains limited, it is growing. MR-guided online adaptive SBRT has been shown to be feasible in cases of recurrent cardiac sarcoma, enabling dose escalation while protecting critical thoracic structures. Extrapolation from non- sarcoma sites, such as pancreatic, ultracentral thoracic and genitourinary tumours, consistently shows that ART improves PTV coverage daily, enables safe dose escalation and more reliably meets OAR constraints, with low rates of high-grade toxicity. However, the central unanswered question remains whether these dosimetric gains translate into meaningful outcomes such as local control, limb preservation, pathological response and quality of life. Defining which sarcoma subgroups would benefit most, integrating functional imaging into adaptive workflows and designing sarcoma-specific prospective
workflows, and patient populations change over time. Incorporating temporal validation and continuous performance monitoring allows models to be evaluated longitudinally, ensuring they remain reliable in practice. In this context, emerging approaches such as digital twins offer a framework to model patient- specific trajectories over time and to evaluate model performance within dynamic, evolving systems. Together, these developments support a shift towards learning health systems capable of continuously improving clinical decision-making. 5410 Radiotherapy for retroperitoneal sarcomas: Where are we now? Lisette M Wiltink Radiotherapy, LUMC, Leiden, Netherlands. Radiotherapy, NKI, Amsterdam, Netherlands This presentation will discuss the current state of radiotherapeutic management of retroperitoneal sarcomas. Key clinical trials that have shaped current practice in this field will be reviewed, and the implications of their results will be addressed. In addition, ongoing and upcoming studies will be highlighted, providing an overview of future developments and remaining challenges in the radiotherapeutic treatment of retroperitoneal sarcomas. 5412 Daily adaptation, better outcomes? The emerging role of adaptive radiotherapy in sarcomas Mateusz Jacek Spa ł ek Radiotherapy I, Maria Sk ł odowska-Curie National Research Institute of Oncology, Warsaw, Poland Soft tissue sarcomas present distinct radiotherapy challenges, including large tumours with complex geometry, proximity to critical organs at risk and substantial anatomical variability throughout treatment. These factors create an ongoing tension between achieving adequate target coverage and keeping toxicity to an acceptable level, a problem that conventional image-guided approaches only partially solve. Adaptive radiotherapy (ART), particularly online daily adaptation, offers a compelling solution. Although offline mid-course replanning can address cumulative anatomical change, it cannot accommodate day-to-day organ-at-risk mobility. Online adaptive platforms, whether MR- or CT-guided, enable re-optimisation of the anatomy on a per-fraction basis, while
trials remain the field's immediate priorities. Daily adaptive radiotherapy in sarcomas has
progressed from the conceptual stage to an early clinical reality. The challenge ahead is to build the evidence to confirm that adaptation truly yields better outcomes.
5413 Radiation-induced senescence as a driver of glioblastoma recurrence Bipasha Mukherjee, Sandeep Burma Neurosurgery, University Of Texas Health Science Center at San Antonio, San Antonio, USA Glioblastomas (GBM) are routinely treated with high doses of ionizing radiation (IR), yet these tumors inevitably recur, and the recurrent tumors are highly therapy resistant. Understanding mechanism(s) driving tumor recurrence after radiotherapy is an unmet need in the field of GBM therapy. During GBM therapy, both the tumor and the normal brain tissue surrounding the tumor are irradiated with up to 60 Gy of IR. IR is a potent inducer of senescence, and senescent stromal cells are known to promote the growth of neighboring tumor cells by secreting proteases, cytokines and growth factors that create a senescence-associated secretory phenotype (SASP). Our research has uncovered multiple mechanisms by which IR-induced senescence of both tumor cells as well as non-neoplastic cells in the tumor microenvironment (TME) promote GBM recurrence. Specifically, HGF secreted by senescent astrocytes after radiotherapy activates the MET receptor tyrosine kinase in surviving GBM cells, thereby promoting their growth and invasiveness. Furthermore, IL-6 secreted by senescent GBM cells activates the JAK-STAT pathway in their non-senescent counterparts, thereby
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