Neoplasms

Nervous System Diseases

All Conditions

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anticoagulants

All Drugs and Chemicals

Nitric Oxide Donors

Edetic Acid

Pentetic Acid

Diethylenetriamine

Patients will receive partial brain irradiation for malignant or benign brain tumors as standard of care. Patients will also have MRI (Magnetic Resonance Imaging) scans and neuropsychological/QOL (Quality of Life Questionnaire) tests prior during and after RT (Radiation Therapy).

Patients will receive whole brain irradiation for brain metastases as standard of care. Patients will also have MRI (Magnetic Resonance Imaging) scans and neuropsychological/QOL (Quality of Life Questionnaire) tests prior during and after RT (Radiation Therapy).

Whole Brain Irradiation

Partial Brain Irradiation

Neuropsychological Testing

Quality of Life Questionnaire

MRI Assessments include Diffusion Tensor Imaging (DTI)and Gd-DTPA (Diethylenetriamine Pentaacetic Acid - a radioactive tracer injected into the patient and viewed on images).

Magnetic Resonance Imaging (MRI) Assessments

Yue Cao, Ph.D.

This is a study to determine if Magnetic Resonance Imaging (MRI) techniques can detect early changes in white matter (in the brain) and the blood-brain barrier resulting from radiation therapy.

Patients will be assigned to one of two groups based on the type of radiation they will be receiving: whole brain irradiation or partial brain irradiation. Patients will undergo Magnetic Resonance Imaging (MRI) assessments, neurocognitive testing (Quality of Life and Neuropsychological assessments), and clinical evaluation.

MRI Study of Radiation-Induced Damage to White Matter and Blood-Brain-Barrier

Linear mixed models will be used to relate Magnetic Resonance Imagining (MRI) changes and radiation dose.

Changes in Magnetic Resonance Imagining (MRI) assessments will be compared graphically to changes in neurocognitive function and clinical symptoms. Parallel analysis will be conducted on each of the neurocognitive tests to determine if MRI assessments can identify patients at increased risk for later neurocognitive dysfunction.

University of Michigan Rogel Cancer Center

Mouth and Tooth Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Dental Caries

Neoplasm Metastasis

Neoplastic Processes

Quality of Life

Patients with five or more brain metastasis assigned by randomization to Stereotactic RadioSurgery (SRS) or Stereotactic Body RadioTherapy (SBRT) will be treated with a highly-conformal metastasis-directed single dose between 15 and 24 Gy or fractionated dose (e.g. 27 Gy in 3 fractions), respectively, depending on lesion size, while sparing clinically negative brain. The treatment will be delivered using five non-coplanar arcs and a mono-isocentric technique.

Patients with five or more brain metastasis assigned by randomization to Whole Brain Irradiation (WBI) will be treated using a 3D-Conformal RadioTherapy technique for a uniform dose delivery of 30 Gy in 10 daily/fractions to the target, that is entire brain.

To treat only brain metastasis identified through Magnetic Resonance imaging by means of stereotactic radiotherapy (experimental intervention) to determine if sparing of clinically uninvolved brain implies a better neurocognitive performance, quality of life and level of autonomy in activities of daily living respect to Whole Brain Irradiation (active comparator).

Stereotactic RadioTherapy

To irradiate the entire brain, site of at least 5 parenchymal metastasis.

Gianluca Ferini

Irene R. Cravagno, Chief Radiation Oncology Unit

Anna Viola, Radiation Oncologist

Gianluca Ferini, Chief Radiation Oncology Unit

Vito Valenti

Antonella Tripoli

Silvana Parisi

Stefano Pergolizzi

Antonio Pontoriero

Alberto Cacciola

Sara Lillo

Gianluca Mortellaro

Giuseppe Ferrera

This work aims to evaluate neurocognitive performance, daily activity and quality of life and local control among patients with brain metastasis (MBM) ≥ 5 due to solid tumors treated with Stereotactic RadioSurgery (SRS) or Whole Brain RadioTherapy (WBRT). This multicentric randomised controlled trial will be conducted at the Fondazione IOM (Viagrande) in collaboration with REM (Viagrande), Hospital G. Martino (Messina) and Hospital Civico ARNAS (Palermo). It will involve, within 5 years starting from 15 September 2020, the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy \> 3 months, histological confirmation of primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) of 20/30, Barthel Activities of Daily Living score 90/100, to be subjected to SRS on each brain lesion by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBRT (control arm). The primary endpoints are neurocognitive performance, quality of life and autonomy in daily-life activities variations, the first one assessed by Moca Score and Hopkins Verbal Learning Test - Revised, the second one through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and Brain Neoplasm (BN-20) questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatments frequency, acute and late toxicities, KPS decrease. It will be considered significant a statistical difference of at least 29% between the two arms (statistical power of 80% with a significance level of 95%). This trial has been approved by the local ethics committee on July 7th 2020 (record 70). Several studies debate what is the predominant factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiotherapy, especially if extended to the entire brain, or intracranial disease progression? Answer to this question may come from current opportunity, thanks to recent technological advancement, to treat, with significant time savings, improved patient comfort and at the same time minimizing the dose to healthy brain tissue, Multiple Brain Metastasis simultaneously, otherwise attackable only by panencephalic irradiation. The pursuit of a local control rate comparable to that obtainable with WBRT remains the fundamental prerequisite for the aforementioned related assessments.

WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)

WHOle Brain Irradiation and STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER): a Prospective Comparative Study of Neurocognitive Outcomes, Level of Autonomy in Daily Activities and Quality of Life

To assess how neurocognitive performance changes after SRS/SBRT compared to WBI

To assess how level of autonomy in activities of daily living changes after SRS/SBRT compared to WBI

To assess how quality of life changes after SRS/SBRT compared to WBI

Time between treatment and cerebral disease progression detected through Magnetic Resonance imaging

Time from the first day of treatment to exitus

Difference in needing further subsequent radiotherapy treatment between SRS/SBRT and WBI arms

Toxicities registered within three months from treatment

Toxicities registered after three months from treatment

Evaluation of how patient's performance status modifies after treatment

University of Messina

University of Palermo

Mediterranean Institute of Oncology

Antineoplastic Agents

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks, and a fixed dose of oral Temozolomide, 1h before each fraction of whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without adjuvant cycles of Temozolomide.

Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks

Whole brain irradiation

Carlos Gamboa-Vignolle, MD

RATIONALE

* Fractionated radiotherapy uses high-energy photons to kill, or damage tumor cells. High daily dose temozolomide combined with fractionated radiotherapy may make tumor cells more sensible to treatment.

PURPOSE

* This randomized phase II trial, assess in patients with brain metastases from solid tumors, whether the whole brain radiotherapy (WBRT) plus temozolomide is able to improve the results obtained with WBRT.

Primary Outcome Measures

* Objective Response Rates

Secondary Outcome Measures

* Survival Free of Brain Metastases progression
* Overall Survival
* Systemic Side effects

Objectives

Primary

* Compare objective response rates in both arms of treatment

Secondary

* Compare survival free of progression in both arms of treatment
* Compare Overall Survival in both arms of treatment
* Compare side effects

Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment

Phase II Randomized Study: Whole Brain Radiotherapy and Concomitant Temozolomide, Compared With Whole Brain Radiotherapy for Brain Metastases Treatment

Objective Response (OR) encompassed the number of participants with Complete Response (CR) and the number of participants with Partial Response (PR). CR is the disappearance of all brain metastases, assessed between two or more cranial MRI. PR is at least a 30% decrease in the sum of the longest diameter of the brain metastases, taking as reference the baseline sum longest diameter, assessed between two or more cranial MRI.

Objective Response Rate (ORR) is the ratio between the number of participants with objective response and the total number of participants.

Progression free survival of brain metastases is the survival of participants without progressive brain metastases or without neurological symptoms. The progressive brain metastases (PBM) were evaluated with cranial MRI. The PBM were defined as an increase of at least 20% in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new metastases.

Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.

AE, evaluated and graded according to the NCI common terminology criteria (NCI-CTCAE) v3.0

Grade 3 Severe AE.

Grade 4 Life-threatening or disabling AE.

Instituto Nacional de Cancerologia de Mexico

Radiation Oncologist

Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.

Whole brain irradiation, 1 fraction of 3 Gy x 5 days of each week for 2 weeks, Monday to Friday and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.

Whole Brain Irradiation and Temozolomide

Whole brain irradiation, 1 fraction of 3 Gy x 5 days each week for 2 weeks, Monday to Friday.

Total

Age, Categorical

Age Continuous

Sex: Female, Male

Mexico

Region of Enrollment

Our study had methodological limitations, such as the two temozolomide dose levels, which in future clinical trials may be adjusted to a single level.

Carlos Gamboa Vignolle/ Radiation Oncologist

Patients received Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks, and a fixed dose of oral Temozolomide, 1h before each fraction of whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without adjuvant cycles of Temozolomide.

Whole brain irradiation,at a dose of 30 Gy in 10 daily fractions over 2 weeks

Data on all enrolled participants were included in an intention-to-treat analysis.

Objective Response Rates. Assessed With Cranial MRI

Whole brain irradiation, at a dose of 30 Gy in 10 daily fractions over 2 weeks

Survival Free of Brain Metastases Progression (PFS of BM)

Overall Survival

Leukopenia

Lymphopenia

Nausea-Vomiting

Neutropenia

Platelets

Whole brain irradiation, Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks,and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.

Participants were assessed with a Complete blood count at the end of the first and second weeks of treatment. A standard biochemical profile was performed at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Participants also were evaluated clinically with the same periodicity .

Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment.

Overall Study

whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges

irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions

Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.

A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.

Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.

Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.

Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.

sector irradiation

For whole brain radiation the entire brain, the base of the skull and the meninges are included.

Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.

The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.

whole brain irradiation

Johannes Kerschbaumer, MD

Christian F Freyschlag, MD

Sabine Strauss, Mag

Marcel Seiz-Rosenhagen, MD, PD

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients.

To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Sector irradiation resembles a brain - tissue - sparing method by focusing the irradiation in the area of the tumor bed and a surrounding 1mm security margin.

The aim of this study is to investigate whether adjuvant "sector""-irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.

Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. Traditionally whole-brain irradiation is the treatment of choice following surgical resection. Whole brain irradiation has been the standard approach to minimize the risk of intracranial recurrence following resection of brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of resection of solitary metastases followed by whole brain irradiation compared with whole brain irradiation alone with regard to survival, local control, and length of functional independence. A following study by the same group failed to show a survival advantage for the addition of whole brain irradiation compared to surgical resection alone in patients with a solitary intracranial metastasis, although the likelihood of local and distant recurrence and death from neurological causes were significantly reduced by whole brain irradiation. Due to potential delayed neurocognitive effects associated with whole brain irradiation, investigators have evaluated the use of partial brain irradiation in the form of stereotactic radiosurgery instead of whole brain irradiation after resection of brain metastases. They showed that despite whole brain irradiation means superior control of brain recurrence in sites other than the resection bed, stereotactic radiosurgery after resection resulted in equivalent survival times and neurological preservation. In a retrospective series of 52 patients Karlovits et al. could show that stereotactic radiosurgery following surgical resection leads to equal local control compared to standard whole brain irradiation.

Study objective

The aim of this study is to investigate whether adjuvant "sector" -irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.

Hypothesis

1. Sector irradiation is equal to whole-brain irradiation in local tumor control after 3, 6, 12 and 36 months and
2. Sector irradiation" is superior to whole-brain irradiation in terms of quality of life and neurocognitive function

Patients and Methods

Patients with a single brain metastasis amenable to surgical resection fulfilling the inclusion criteria will be consecutively enrolled in this study. After microsurgical complete resection documented by early postoperative MRI within 72 hours and histological proven brain metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy and 6 and 12 months postoperatively. In case of local recurrence or developing further metastases a cross over to whole brain radiotherapy or focal irradiation is possible.

Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis

Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial

standardized assessment via "EORTC QLQ-C30/BN20" and the "FACT-Br" - questionary at 3, 6, 12 and 36 months after date of randomization

Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization

Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MRI Study of Radiation-Induced Damage to White Matter and Blood-Brain-Barrier	NCT01988675	Brain Neoplasms	Whole Brain Irr... Partial Brain I... Neuropsychologi... Quality of Life... Magnetic Resona...	18 Years -	University of Michigan Rogel Cancer Center
WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)	NCT04891471	Neurocognitive ... Quality of Life Activities of D...	Stereotactic Ra... Whole Brain Irr...	18 Years -	Mediterranean Institute of Oncology
Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment	NCT01015534	Brain Neoplasms	Temozolomide Whole brain irr...	18 Years - 80 Years	Instituto Nacional de Cancerologia de Mexico
MRI Study of Radiation-Induced Damage to White Matter and Blood-Brain-Barrier	NCT01988675	Brain Neoplasms	Whole Brain Irr... Partial Brain I... Neuropsychologi... Quality of Life... Magnetic Resona...	18 Years -	University of Michigan Rogel Cancer Center
Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment	NCT01015534	Brain Neoplasms	Temozolomide Whole brain irr...	18 Years - 80 Years	Instituto Nacional de Cancerologia de Mexico
Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis	NCT01667640	Metastatic Mali...	sector irradiat... whole brain irr...	18 Years - 80 Years	Medical University Innsbruck
MRI Study of Radiation-Induced Damage to White Matter and Blood-Brain-Barrier	NCT01988675	Brain Neoplasms	Whole Brain Irr... Partial Brain I... Neuropsychologi... Quality of Life... Magnetic Resona...	18 Years -	University of Michigan Rogel Cancer Center
Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis	NCT01667640	Metastatic Mali...	sector irradiat... whole brain irr...	18 Years - 80 Years	Medical University Innsbruck

Spots Global Cancer Trial Database for whole brain irradiation