Central Nervous System TumourPROTON MINDNCT07836478
Neurocognitive Integrity After Proton Therapy for Brain Tumor
An observational study of Central Nervous System Tumour, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Radiation therapy remains a cornerstone in the management of both benign and malignant intracranial tumors, either as monotherapy or combined with surgery and/or chemotherapy. Despite its therapeutic benefits, it is frequently associated with potential long-term adverse effects, with neurotoxicity posing a major… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Tumour
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2026to 1 Jul 2036
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients affected by primary central nervous system tumors and eligible for protontherapy as adjuvant or radical treatment
Who may be able to join
- Primary tumors of Brain Tumor (CNS), benign and malignant
- Age ≥ 18 years
- Patients able to speak and read the local language(s) fluently
- Acceptance and signature of informed consent
- Radiological diagnosis, biopsy, or previous surgery
- Concomitant medical therapy is allowed
Who cannot join
- Previous brain radiotherapy (any form)
- High-grade gliomas
- Patients with concomitant neurological or psychiatric disorders.
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Prospective Evaluation of Neurocognitive Integrity After Proton Therapy for Brain Tumor
Radiation therapy remains a cornerstone in the management of both benign and malignant intracranial tumors, either as monotherapy or combined with surgery and/or chemotherapy. Despite its therapeutic benefits, it is frequently associated with potential long-term adverse effects, with neurotoxicity posing a major challenge, especially in young patients affected by benign primary tumors.
Read the detailed description
In the brain, late radiotoxicities typically manifest as cognitive dysfunction, leukoencephalopathy, brain atrophy, brain tissue necrosis, cerebrovascular complications, endocrinopathies, and/or secondary malignant neoplasms.
Radiation-induced hippocampal injury, in particular, significantly contributes to cognitive impairment, while broader central nervous system effects arise through multiple mechanisms, including vascular injury, neuronal depletion, chronic inflammation, demyelination, and tissue necrosis.
The severity of cognitive dysfunction depends on multiple factors, including the location and the volume of the tumor, the total radiation dose administered, the fractionation regimen, and the individual susceptibility of the patient, as well as comorbidities (e.g., diabetes, etc.) and concomitant drugs.
The distinct physical characteristics of proton therapy, such as a reduced entrance dose, an eliminated exit dose, and a Bragg peak, provide clear dosimetric advantages over conventional photon treatments. Pencil-beam scanning further improves on earlier passive scattering approaches by delivering modulated proton beamlets for superior target conformality and reduced neutron scatter, thereby limiting low- and intermediate- dose exposure to cranial organs at risk (OARs) while preserving adequate dose coverage within the target volume.
From a radiobiological standpoint, these properties suggest that proton therapy may present a more favorable risk-benefit balance compared to photon-based modalities, particularly for long-term clinical outcomes. It achieves a drastic reduction in the integral dose, offering substantial benefit in decreasing radiation-induced second malignancies, making it mandatory for children when available.
Proton therapy is well established for treating pediatric tumors, CNS tumors such as low-grade gliomas (LGG) and meningiomas, especially if near the optic pathway or brainstem, and all the benign tumors in young patients. In these cases, the primary goal extends beyond curing the disease to preserving neurological and cognitive functions.
- Conditions
- Central Nervous System Tumour
- Keywords
- Primary benign and malignant tumors of CNS, Protontherapy
What is being measured
The primary outcome is the main question the study is designed to answer.
The presence of cognitive impairment
The primary endpoint will be the presence of cognitive impairment during the first 5 years after enrollment, as measured by a comprehensive neuropsychological assessment.
Measured: From the end of Protontherapy through study completion, an average of 1 year.
Secondary outcomes (13)
Perceived cognitive impairment
For Functional Assessment of Cancer Therapy-cognition (FACT-cog) 37 items will be completed (score 1-4)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Depressive symptoms
At Beck Depression Inventory-II (BDI-II) 21 items will be completed (score 0-3)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Anxiety
For State-Trait Anxiety Inventory (STAI) 40 items will be completed (score 1-4)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Quality of Life data (QoL) - EORTC QLQ C30 questionnaires.
For EORTC QLQ C30, 30 items will be completed (score 1-4).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Sleep quality
For Pittsburgh Sleep Quality Index (PSQI) 24 items will be completed (score 0-3)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Cognitive Reserve
For Cognitive Reserve Index questionnaire (CRIq) 20 items will be completed (core 0-1)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Global functioning
For Montreal Cognitive Assessment (MoCA) 30 items will be completed (score 1-5).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Learning and Verbal Memory
For Rey Auditory Verbal Learning Test (RAVLT) 15 items will be completed (score 0-4).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Working memory
For Corsi Span backward/forward 18 items will be completed (score 0-4).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Visual memory
For Rey-Osterrieth complex figure -recall 18 items will be completed (score 0-2).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Visuospatial abilities
For Rey-Osterrieth complex figure -copy 18 items will be completed (score 0-2).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Executive function
For Frontal Assessment Battery (FAB) 30 items will be completed (score 0-3).
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Attention
For Symbol digit modalities test (SDMT) 110 items will be completed (score 0-1)
Measured: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2026
- Study startSep 2026 (estimated)
- Primary completion1 Jul 2031 (estimated)
- Study completion1 Jul 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System TumourStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07836478
- Sponsor's protocol ID
- UID 5445
- Other IDs
- L2-684
- Acronym
- PROTON MIND
- Status last verified
- Aug 2026
- First submitted
- 14 Sep 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Neurocognitive Integrity After Proton Therapy for Brain Tumor
- ClinicalTrials.gov ID
- NCT07836478
- Acronym / sponsor ID
- PROTON MIND / UID 5445
- Conditions
- Central Nervous System Tumour
- Keywords
- Primary benign and malignant tumors of CNS, Protontherapy
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- 1 Jul 2031 (estimated)
- Study completion
- 1 Jul 2036 (estimated)
- First posted
- 23 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Radiation therapy remains a cornerstone in the management of both benign and malignant intracranial tumors, either as monotherapy or combined with surgery and/or chemotherapy. Despite its therapeutic benefits, it is frequently associated with potential long-term adverse effects, with neurotoxicity posing a major challenge, especially in young patients affected by benign primary tumors.
Detailed description
In the brain, late radiotoxicities typically manifest as cognitive dysfunction, leukoencephalopathy, brain atrophy, brain tissue necrosis, cerebrovascular complications, endocrinopathies, and/or secondary malignant neoplasms.
Radiation-induced hippocampal injury, in particular, significantly contributes to cognitive impairment, while broader central nervous system effects arise through multiple mechanisms, including vascular injury, neuronal depletion, chronic inflammation, demyelination, and tissue necrosis.
The severity of cognitive dysfunction depends on multiple factors, including the location and the volume of the tumor, the total radiation dose administered, the fractionation regimen, and the individual susceptibility of the patient, as well as comorbidities (e.g., diabetes, etc.) and concomitant drugs.
The distinct physical characteristics of proton therapy, such as a reduced entrance dose, an eliminated exit dose, and a Bragg peak, provide clear dosimetric advantages over conventional photon treatments. Pencil-beam scanning further improves on earlier passive scattering approaches by delivering modulated proton beamlets for superior target conformality and reduced neutron scatter, thereby limiting low- and intermediate- dose exposure to cranial organs at risk (OARs) while preserving adequate dose coverage within the target volume.
From a radiobiological standpoint, these properties suggest that proton therapy may present a more favorable risk-benefit balance compared to photon-based modalities, particularly for long-term clinical outcomes. It achieves a drastic reduction in the integral dose, offering substantial benefit in decreasing radiation-induced second malignancies, making it mandatory for children when available.
Proton therapy is well established for treating pediatric tumors, CNS tumors such as low-grade gliomas (LGG) and meningiomas, especially if near the optic pathway or brainstem, and all the benign tumors in young patients. In these cases, the primary goal extends beyond curing the disease to preserving neurological and cognitive functions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients affected by primary central nervous system tumors and eligible for protontherapy as adjuvant or radical treatment
Key inclusion criteria (6 listed)
- Primary tumors of Brain Tumor (CNS), benign and malignant
- Age ≥ 18 years
- Patients able to speak and read the local language(s) fluently
- Acceptance and signature of informed consent
- Radiological diagnosis, biopsy, or previous surgery
Key exclusion criteria (4 listed)
- Previous brain radiotherapy (any form)
- High-grade gliomas
- Patients with concomitant neurological or psychiatric disorders.
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The presence of cognitive impairment
Time frame: From the end of Protontherapy through study completion, an average of 1 year.
The primary endpoint will be the presence of cognitive impairment during the first 5 years after enrollment, as measured by a comprehensive neuropsychological assessment.
13 secondary outcomes
Perceived cognitive impairment
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Depressive symptoms
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Anxiety
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Quality of Life data (QoL) - EORTC QLQ C30 questionnaires.
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Sleep quality
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Cognitive Reserve
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Global functioning
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Learning and Verbal Memory
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Working memory
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Visual memory
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Visuospatial abilities
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Executive function
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Attention
Time frame: At baseline (pre - Protontherapy), 6 and 12 months post-treatment, and then annually for 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Central Nervous System Tumour, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gabriella Pravettoni (+39 0257489207, Gabriella.Pravettoni@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The presence of cognitive impairment (time frame: From the end of Protontherapy through study completion, an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.