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

NCT ID: NCT05964569

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-11
• Study Completion Date: 2028-11-11

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.

Conditions

Low Grade Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard treatment plan

Model-based NTCP is calculated after plan approval, however, no further adjustments are to be made to the approved treatment plan

Group Type: ACTIVE_COMPARATOR

standard treatment plan, no optimization

Intervention Type: OTHER

original treatment plans are not optimized

Optimized treatment plan

Allocated 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.

Group Type: EXPERIMENTAL

model-guided optimization of treatment plan

Intervention Type: OTHER

original treatmant plans are optimized based on model-based NTCP

Interventions

model-guided optimization of treatment plan

original treatmant plans are optimized based on model-based NTCP

Intervention Type: OTHER

standard treatment plan, no optimization

original treatment plans are not optimized

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Juergen Debus

Department Head

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Radiotherapy, University of Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Semi Harrabi, MD

Role: CONTACT

semi.harrabi@med.uni-heidelberg.de

+496221 56 ext. 8201

Adriane Lentz-Hommertgen, Phd

Role: CONTACT

adriane.lentz-hommertgen@med.uni-heidelberg.de

+496221 56 ext. 8201

Facility Contacts

Juergen Debus, Prof. Dr. Dr.

Role: primary

juergen.debus@med.uni-heidelberg.de

+49 6221 56 ext. 8200

Adriane Hommertgen, Dr. med.

Role: backup

adriane.hommertgen@med.uni-heidelberg.de

0622156 ext. 34091

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

RadOnk-Indigo

Identifier Type: -

Identifier Source: org_study_id