ESTRO 2025 Congress Report
By the Reirradiation Focus Group (report #1/5)

1. Implementation of the ESTRO "reirradiation of glioblastoma" guideline
   Meet-the-Experts
   Presenters: Nicolaus Andratschke, Astrid Elisabeth Heusel

The development of guidelines for glioblastoma (GB) reirradiation has become necessary due to the growing interest in central nervous system reirradiation and to the lack of sufficient data from retrospective and prospective studies. It is easy to obtain data about clinical parameters, endpoints, toxicities, patient quality of life, and target volumes. However, there is a lack of data on dosimetry, cumulative doses to organs-at-risk (OARs), volumetric overlap information, and types of reirradiation.

The ESTRO/European Association of Neuro-Oncology (EANO) guidelines on GB reirradiation were developed by formulating key clinical questions, which are listed below.

• KQ1: Patient Selection
  The decision to reirradiate a recurrent GB should be discussed within a multidisciplinary tumour board and risks, benefits, and therapeutic alternatives should be taken into account. Reirradiation should be considered when the patient has a Karnofsky performance status of ≥60 and the interval since the initial treatment is at least six months, regardless of patient age or 06-methylguanine-DNA methyltransferase methylation status.
• KQ2: Imaging for Recurrence
  To assess recurrence, especially in-field recurrence, contrast-enhanced MRI with T1-weighted sequences is required. Advanced MRI techniques or amino-acid PET (AA-PET) can be used to differentiate between pseudoprogression and radionecrosis. Currently, no technique or combination of techniques has proven superior to any other.
• KQ3: Target Definition
  For target definition, rigid image registration is required. The gross tumour volume (GTV) should include all contrast-enhancing lesions on T1-weighted imaging, new or progressive abnormalities on T2/fluid attenuated inversion recovery sequences, and all AA-PET-avid regions. The clinical tumour volume (CTV) margin is not mandatory but can include a 3-5mm margin from the GTV. A planning target volume (PTV) expansion of 3mm from the CTV is recommended. There is no consensus yet on whether or not to include suspicious perfusion areas seen on functional imaging.
• KQ4: Doses and Fractionation
  The total dose should have a biologically equivalent dose greater than 36Gy in 2Gy per fraction. Hypofractionated radiosurgery is preferred when the GTV is ≤3cm.
• KQ5: Planning and Delivery
  Advanced image-guided radiotherapy techniques should be used when delivering high-dose reirradiation. Dose should be recalculated in the equivalent dose in 2Gy fractions (EQD2). The minimum set of OARs that should be assessed comprises the brain, brainstem, chiasm, optic nerves, and cranial nerves near the PTV.
• KQ6: Cumulative Dose Constraints
  PTV prescription and modulation should be based on OAR safety.
• KQ7: Combined Treatments
  In combined treatments, the target definition, dose, and fractionation should not be changed. The use of systemic therapy during reirradiation for recurrent GB should be explored in prospective clinical trials. Combined treatment appears to be well tolerated but has not shown a benefit in rates of overall survival (OS).
• KQ8: Maintenance Systemic Therapy
  There is no indication of the need for adjuvant systemic therapy after reirradiation.

The performance of the DELPHI method resulted in 18 recommendations and nine statements, all of which achieved group consensus.

ESTRO/EANO recommendation on reirradiation of glioblastoma
Andratschke, Nicolaus et al.
Radiotherapy and Oncology, Volume 204, 110696

 

2. Reirradiation of gliomas: what are we learning from trials?
   Clinical Symposium
   Presenter: Anca-L Grosu

The management of recurrent glioblastoma (rGBM) is a major therapeutic challenge, with reirradiation emerging as a viable option in selected patients. The GLIAA trial—which was a multicentre study that involved 15 institutions and 200 patients—compared the efficacy of contrast-enhanced T1-MRI with that of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET-based delineation for reirradiation planning in patients with macroscopic disease (≤6cm) and prior radiotherapy completed ≥6 months earlier. All patients received 39Gy in 13 fractions (3Gy/fraction), with the CTV defined as GTV+3mm and PTV as CTV+1-2mm.

Results showed comparable outcomes between arms: progression-free survival (PFS) was 4.2 months, local control 6.5 months, and median OS 9.2 months, with no statistically significant differences. Radiation necrosis occurred in 25.5% (FET-PET) and 21.6% (MRI) of cases. Interestingly, median OS was longer in patients who developed radionecrosis (12 vs. 8 months, p = 0.006). A difference of ≥2ml in GTV between MRI and PET was noted in over 80% of cases, yet both imaging modalities were deemed equivalent for reirradiation. The GLIAA trial supports the hypothesis that reirradiation with 39Gy in small volume rGBM is feasible and well tolerated, with PTV margins of 5mm being appropriate.

These findings are consistent with the trial run by NRG Oncology and the Radiation Therapy Oncology Group named NRG Oncology/RTOG1205, in which treatment with bevacizumab alone was compared with that with bevacizumab + reirradiation. While OS rates did not differ significantly (9.7 vs. 10.1 months), PFS improved with reirradiation (3.8 vs. 7.1 months, p = 0.05), suggesting a benefit in disease control.

Meta-analyses further confirm the advantage of combining reirradiation with systemic therapy (e.g., chemotherapy, bevacizumab), as they report improved OS and PFS (hazard ratio ~0.7-0.5) and a lower risk of radionecrosis when bevacizumab is included (hazard ratio = 0.17, p < 0.0008). Experimental combinations with immunotherapy (e.g., nivolumab, ipilimumab) in early-phase trials have shown promising rates of OS (~15.6 months) in bevacizumab-naïve patients.

Biological studies reveal that recurrence patterns in gliomas are shaped by isocitrate dehydrogenase status and microenvironmental interactions, including mesenchymal transition and neuronal signalling, which may provide future therapeutic targets.

Current consensus recommends the selection of patients with good performance status, long PFS from initial radiotherapy, and recurrence outside eloquent brain areas. The EQD2 for cumulative dose should remain <100Gy, and a minimum interval of six months between radiotherapy courses is advised.

In conclusion, reirradiation represents a meaningful therapeutic strategy in well-selected rGBM patients. Further refinement using biological markers and advanced imaging is warranted to personalise therapy and improve outcomes.

3. Paediatric gliomas: survival benefits of reirradiation in DIPG/DMG
   Mini-Oral
   Presenters: Nisha Shariff et al.

In this large, retrospective study, the impact of reirradiation was evaluated in children with recurrent diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), two highly aggressive, incurable paediatric brain tumours.

Among 118 patients treated between 1998 and 2024, 39 received reirradiation after progression following an initial radiation course (commonly 54Gy in 30 fractions). The reirradiation regimens varied but commonly were 30.6Gy in 17 fractions or 20Gy in 10 fractions.

The children who underwent reirradiation had significantly better survival rates: median survival from progression was 6.9 months with reirradiation versus 2.7 months without. The six-month OS rate was 66% with reirradiation versus 22% without. Patients who received reirradiation more than one year after the first dose of radiation had the longest post-reirradiation survival (10.9 months vs. 5.5 months).

Multivariate analysis identified younger age and the omission of reirradiation as negative prognostic factors. Notably, histology and location of the tumour and use of systemic therapies were not significantly associated with survival rates.

These results underscore that reirradiation, although palliative, can extend survival in children with DIPG/DMG. Further research is needed to refine selection criteria and optimise timing.

Don't miss our upcoming reports in the reirradiation series. Still to come:

Dr Bartek Tomasik
Department of Oncology and Radiotherapy, Faculty of Medicine
Medical University of Gdańsk, Poland
Member of the ESTRO reirradiation focus group
ESTRO 2025 Social media ambassador for reirradiation
bartlomiej.tomasik@gumed.edu.pl
LinkedIn: Bartłomiej Tomasik
X: https://x.com/B_Tomasik (@B_Tomasik)

 

 

Dr Gian Marco Petrianni
Operative Research Unit of Radiation Oncology
Fondazione Policlinico Universitario Campus Bio-Medico
Rome, Italy
Member of the ESTRO reirradiation focus group
ESTRO 2025 Social media ambassador for reirradiation
g.petrianni@policlinicocampus.it
LinkedIn: Gian Marco Petrianni
X: Gian Marco Petrianni