Short Term Outcomes After PRoton and PhotoN RadiOtherapy for IDH Mutated Grade 2 and 3 Gliomas (SOPRANO)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Radiotherapy; Complications
• Intervention / Treatment: Radiation: proton therapy; Radiation: photon therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Steven HJ Nagtegaal, MD PhD; Phone Number: +31(0)107042249; Email: s.nagtegaal@erasmusmc.nl
• Study Contact Backup: Name: Alejandra Mendez Romero, MD PhD; Phone Number: +31(0)107035829; Email: a.mendezromero@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: Steven Nagtegaal, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Proton group; Patients with grade 2 and 3 IDHmt glioma treated with proton therapy in Holland PTC, Maastro Clinic and UMC Groningen.	Radiation: proton therapy; Radiotherapy delivered with protons
Photon group; Patients with grade 2 and 3 IDHmt glioma treated with photon therapy in Erasmus MC, Haaglanden MC, LUMC, Amsterdam UMC locatie VUmc Site, Verbeeten Institute, Maastro Clinic, UMC Groningen, and Leuven University Hospital.	Radiation: photon therapy; Radiotherapy delivered with photons

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Next intervention-free survival	Time from the last day of radiotherapy until the start of a new next intervention. Next intervention is defined as either neurosurgical re-operation, re-irradiation, start of new chemotherapy (other than the standard adjuvant chemotherapy), start of VGEF inhibitors such as bevacizumab, or new start of dexamethasone for either tumor progression or radiotherapy effects.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Assessed and scored based on the Common Terminology Criteria for Adverse Events (CTCAEv5.0). Only grade 3, 4 and 5 adverse events will be recorded.	24 months
Overall survival	Measured from the last day of radiotherapy to death from any cause	24 months
Progression-free survival	Time from the last day of radiotherapy until progressive disease	24 months
Pseudoprogression-free survival	time from the last day of radiotherapy and the development of any transient contrast-enhancing lesion between the end of radiotherapy and disease progression, or any new contrast-enhancing lesion that remained stable over a period of 12 months	24 months

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Universitaire Ziekenhuizen KU Leuven; University Medical Center Groningen; Leiden University Medical Center; HollandPTC; Medical Center Haaglanden; Maastro Clinic, The Netherlands; Amsterdam University Medical Centre, VUmc Site; Institute Verbeeten
• Investigators: Principal Investigator: Alejandra Mendez Romero, MD PhD, Assitant Professor, Radiation Oncologist

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 22, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Proton therapy; Neuro-oncology; Photon therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: MEC-2023-0727

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No