Rationale:

Proton beam therapy has recently become available for the treatment of patients with WHO grade 2 and 3 IDH mutated (IDHmt) glioma in the Netherlands. The dose distributions associated with proton therapy have substantially reduced the volume of the normal brain irradiated with low and intermediate radiotherapy doses. Whether this impacts rates of progressive disease or safety issues and how this compares with a similar population treated with photon therapy is currently unknown.

Objective:

To investigate short term outcomes after proton and photon radiotherapy for grade 2 and 3 IDHmt glioma.

Patients with grade 2 and 3 IDHmt glioma treated with proton therapy in Holland PTC, Maastro and UMC Groningen and referred Erasmus MC, Haaglanden MC, LUMC, Amsterdam UMC, Verbeeten Institute, Maastro, UMC Groningen, and Leuven University Hospital between 1st of January 2018 and the 30th of June 2022. The outcomes will be compared to those from patients with grade 2 and 3 IDHmt glioma treated with photon therapy in the same institutes and during the same period of time. The applied clinical target volume (CTV) margins and the chemotherapy are preferably similar for proton and photon therapy.

Retrospective data will be collected from the electronic records of each participating institute. For the primary outcome, data will be collected on interventions (radiotherapy, surgery, chemotherapy, medication) for either tumor progression or toxicity after radiotherapy. This will be used to calculate next intervention free survival as primary outcome.

For the secondary outcomes, data on survival, disease progression, pseudoprogression, and toxicity will be used to calculate overall survival, progression free survival, and pseudoprogression free survival, as well as toxicity incidence.

Inclusion Criteria:

• Histopathologically confirmed WHO grade 2 or grade WHO 3 IDHmt glioma
• Treatment with radiotherapy delivered between 1 of January 2018 and completed before or on the 30th of June 2022
• Treatment with chemotherapy delivered after radiotherapy (PCV or Temozolomide)
• Age ≥ 18 years

Exclusion Criteria:

• Prior cranial radiotherapy
• Contra-indication for MRI imaging
• Chemotherapy delivered before radiotherapy
• Dose and fractionation other that standard dose (50.4 Gy in 28 fractions for Grade 2 and 59.5 Gy in 33 fractions for Grade 3)
• Combination photon and proton therapy
• Patient has previously opted-out of the use of their data for research

Adult patients treated with proton radiation therapy for grade 2 and 3 IDHmt glioma referred to HollandPTC, Maastro and UMC Groningen from the 1st of January 2018 of and the 30th of June 2022. The photon group will consist of patients treated with photon radiation therapy within the same period in Erasmus MC, Haaglanden MC, LUMC, Amsterdam UMC, Verbeeten Institute, Maastro, UMC Groningen, and Leuven University Hospital. The reason for choosing this time interval is that the Dutch guideline for the treatment of glioma was updated regarding margins in December 2017. From January 2018 patients with grade 2 glioma were treated with a 5mm CTV margin to compensate for microscopic invasion. Patients with grade 3 IDHmt tumors were treated with 10mm CTV margins.