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Feasibility of Individualized, Model-guided Optimization of Proton Beam Treatment Planning in Patients With Low Grade Glioma

Phase 2
Recruiting
Conditions
Low Grade Glioma
Interventions
Other: model-guided optimization of treatment plan
Other: standard treatment plan, no optimization
Registration Number
NCT05964569
Lead Sponsor
University Hospital Heidelberg
Brief Summary

Low-grade glioma (LGG) represent typically slowly growing primary brain tumors with world health organization (WHO) grade I or II who affect young adults around their fourth decade. Radiological feature on MRI is a predominantly T2 hyperintense signal, LGG show typically no contrast uptake. Radiotherapy plays an important role in the treatment of LGG. However, not least because of the good prognosis with long term survivorship the timing of radiotherapy has been discussed controversially. In order to avoid long term sequelae such as neurocognitive impairment, malignant transformation or secondary neoplasms initiation was often postponed as long as possible

Detailed Description

Since patients with low grade glioma are expected to become long-term survivors, the prevention of long-term sequelae is particularly important. In addition to disease progression, also treatment related side effects such as decline of neurocognitive function, endocrine impairment or sensorineural deficits can have a negative impact on patient's quality of life.

Owing to the biophysical properties of protons with an inverse depth dose profile compared to photons and a steep dose fall of to the normal tissue, there is a strong rationale for the use of PRT in the treatment of patients with low-grade glioma. Although data from large randomized trials are still missing there is increasing evidence from smaller prospective trials and retrospective analyses that the expected advantages indeed transform into clinical advantages.

However, in about 20 % of all patients, late contrast-enhancing brain lesions (CEBL) appear on follow-up MR images 6 - 24 months after treatment. At HIT in Heidelberg and at OncoRay in Dresden, CEBLs have been observed to occur at very distinct locations in the brain and relative to the treatment field. Retrospective analysis has elucidated potential key factors that lead to CEBL occurrence. However, avoidance of CEBLs is hardly feasible using conventional treatment planning strategies. Model-aided risk avoidance denotes the use of model-based CEBL risk calculations as an auxiliary tool for clinical treatment planning: Model-based risk calculations and risk reduction via software-based optimization help the clinician to minimize risk of CEBL occurrence during treatment planning.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Age > 18 years
  • histologically proven low-grade glioma
  • indication for definitive or adjuvant radiotherapy
  • ability to understand character and personal consequences of the clinical trial
  • written informed consent
Exclusion Criteria
  • previous cerebral irradiation
  • contraindication for contrast-enhanced MRI
  • neurofibromatosis
  • participation in another clinical trial with competing objectives

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Optimized treatment planmodel-guided optimization of treatment planAllocated to Control Calculation of normal tissue complication probability (NTCP) Model-guided replanning. Replanning is performed with Raysearch Raystation. Optimizations objectives are: 1. the optimization objectives that control the maximum dose in the target volume employ a variable, LETd-dependent model for RBE that allows us to include the RBE-variations predicted by the NTCP model 2. the periventricular volume, defined as the volume closer than 4 mm to the ventricular wall, is included into the optimization with a constraint on its Equivalent Uniform Dose (EUD) and with the variable RBE model described above. Thereby, the combined effect of the RBE variation and increased sensitivity of the periventricular volume, as predicted by the NTCP model, is included. The effectiveness of the re-planning is verified by a second NTCP computation.
Standard treatment planstandard treatment plan, no optimizationModel-based NTCP is calculated after plan approval, however, no further adjustments are to be made to the approved treatment plan
Primary Outcome Measures
NameTimeMethod
incidence of contrast enhancing brain leasionsobserved within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain

the cumulative incidence of contrast enhancing brain lesions

Secondary Outcome Measures
NameTimeMethod
radiation-induced brain injuriesobserved within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain

incidence of radiation-induced brain injuries \> CTC°II

quality of life QLQ-BN20up to 24 months after completion of PRT

scores on the QLQ-BN20 questionare, scored 0 (absence) to 5 (fully present)

progression-free survivalobserved within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain

number of surviving patients without tumor progression

quality of life QLQ-C30up to 24 months after completion of PRT

scores on the QLQ-C30 questionare, scored 0 (absence) to 5 (fully present)

overall survivalobserved within 24 months after Proton Beam Therapy (PRT) measured by quarterly contrast enhanced MRI of the brain

number of surviving patients

patient reported outcomeup to 24 months after completion of radiotherapy

patient reported outcome according to points on the PRO-CTCAE questionaire, scored 0/1 for absent/present)

Trial Locations

Locations (1)

Department of Radiotherapy, University of Heidelberg

🇩🇪

Heidelberg, Germany

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