S378
Clinical - CNS
ESTRO 2026
Luca Ruffino 2 , Rosella Di Franco 4 , Simona Mercogliano 4 , Antonella Del Vecchio 5 , Matteo Muto 6 , Paolo Muto 4 , Anna Mondino 3,7 , Nadia Di Muzio 1,8 1 Radiation Oncology, IRCCS Ospedale San Raffaele, Milano, Italy. 2 Neurosurgery, IRCCS Ospedale San Raffaele, Milano, Italy. 3 Lymphocyte Activation Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milano, Italy. 4 Radiation Oncology, IRCCS Istituto Nazionale dei Tumori Fondazione G. Pascale, Napoli, Italy. 5 Medical Physics, IRCCS Ospedale San Raffaele, Milano, Italy. 6 Radiation Oncology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati, Avellino, Italy. 7 AIRC Foundation for Cancer Research, AIRC Foundation for Cancer Research, Milano, Italy. 8 Radiation Oncology, Università Vita Salute San Raffaele, Milano, Italy Purpose/Objective: Standard of care in Glioblastoma (GBM) is the Stupp protocol. However, it was observed that ultrahypofractionated RT (UHRT) is not inferior in selected patients. As relapses occur near the irradiated target volume, margin reduction and dose intensification could further improve local control. Neoadjuvant-UHRT may provide additional advantages, including optimal target definition on preoperative MRI, reduction in radionecrosis risk through removal of irradiated tissue, and enhanced immune activation. This trial investigates the safety and feasibility of neoadjuvant-UHRT with simultaneous integrated boost (SIB) in operable GBM. Material/Methods: This is an ongoing single-arm, multicenter, dose- escalation phase I trial designed to identify the maximum tolerated dose (MTD) of neoadjuvant-UHRT. A total dose of 30 Gy in 5 fractions is delivered to the planning target volume (PTV), with SIB escalation to the gross tumor volume (GTV) from 35 Gy up to 50 Gy in 5-patient cohorts. Escalation proceeds if ≤ 30% of patients experience cumulative ≥ G3 toxicity (CTCAE v5.0) one month after UHRT. Four weeks after neoadjuvant-UHRT completion, patients undergo MRI and surgical resection. Afoter four weeks another MRI is performed, followed by adjuvant temozolomide. Peripheral blood is collected before and after RT and up to 6 months for multiparametric immunophenotyping, to identify biomarkers of response and exploring synergistic integration with immunotherapy in GBM. Results: Up to October 2025, six patients have been treated; five at the first dose level (35 Gy SIB) and one at second dose level 40 Gy SIB. All patients completed RT as planned, with no ≥ G3 acute toxicity. Surgery was performed four weeks after UHRT, without intra- or postoperative complications. During the preoperative
work-up for one enrolled patient, four weeks afeter neoadjuvant-UHRT, a second, distinct lesion was detected on staging MRI. According to the trial protocol, only the primary lesion was treated with neoadjuvant-UHRT and subsequently resected, while the second lesion was managed after its complete excision with standard chemoradiation. At 10-month follow-up, the per protocol-treated cavity remains clean, free from recurrence, whereas the other lesion treated with standard therapy developed toxicity (edema) and the classic appearance where the diagnosis of recurrence/radionecrosis is difficult (Figure 1).
Figure 1 Conclusion:
Preliminary evidence indicates that neoadjuvant-UHRT with SIB is safe, well tolerated, and surgically feasible. The absence of high-grade toxicity and favorable postoperative outcomes support the safety of this paradigm, thus the trial continues. The interpretation of control MRIs is facilitated by the removal of irratiated tissue. Keywords: neoadjuvant RT, Glioblastoma, hypofractionated RT
Digital Poster 3234
Survival after normofractionated re-irradiation for recurrent glioblastoma - a retrospective analysis from the Comprehensive Cancer Center Vienna Vincent Dick, Leo Ulbrich, Martin Heilmann, Joachim Widder, Franziska Eckert
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