Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

the brain radiotherapy started within 1 month of almonertinib the brain radiotherapy here specifically refers to stereotactic radiotherapy

Brain radiotherapy was given within 3 months after brain progression during almonertinib treatment

Patients were randomly divided into two groups, experimental group (early intervention group of brain radiotherapy) : the brain radiotherapy started within 1 month of TKI treatment, the brain radiotherapy here specifically refers to stereotactic radiotherapy; Control group (brain radiotherapy late intervention group) : Brain radiotherapy was given within 3 months after brain progression during TKI treatment.

brain radiotherapy

Almonertinib

Likun Chen, Ph.D

Likun Chen

This is a prospective, multicenter, randomized, controlled clinical study of NSCLC patients with intracranial oligo-metastatic EGFR-sensitive mutations treated with EGFR-TKI Almonertinib , according to the implementation time of brain radiotherapy. Patients were randomly divided into two groups, experimental group (early intervention group of brain radiotherapy) : the brain radiotherapy started within 1 month of TKI treatment, the brain radiotherapy here specifically refers to stereotactic radiotherapy; Control group (brain radiotherapy late intervention group) : Brain radiotherapy was given within 3 months after brain progression during TKI treatment. The differences in OS,iPFS, PFS, iORR, safety, neurocognitive function and quality of life between the two groups were compared.

Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases

A Prospective, Multicenter, Randomized, Controlled Clinical Study of Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases

The time from randomization to death from any cause.

patients were randomized from the time of observation of intracranial disease progression or death from any cause

patients were randomized from the time of observation of systemic disease progression or death from any cause

proportion of patients with complete or partial response of intracranial lesions

Sun Yat-sen University

Professor of Medicine

Rare Diseases

Glioblastoma

Leukoencephalopathies

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

neurocognitive tests before and after radiotherapy

effect of cerebral radiotherapy on neurocognitive state

marie odile bernier, Dr

damien Ricard, Pr

Dimitri psimaras, Dr

georges Noel, pr

The survival time and the number of long time survivors after radiotherapy in brain cancer patients have increased for the last decades. Therefore the topic of late-delayed neurotoxic effects of this therapy gains more and more importance. Among these side effects, the main and most frequent one is the leukoencephalopathy, a diffused and progressive damage of the white matter characterized by myelin loss, loss of axons and vascular lesions. The incidence rate assessment, as well as the occurrence time, is based on retrospective studies with low numbers of patients, but seems to reach 30 to 50 % of the patients according to the follow-up. The risk seems to be increased during the first two years after the radiotherapy, but persists for decades.

To gain further insight in the radiation-induced leukoencephalopathy, the objective of this project is to study the onset and evolution of leukoencephalopathy in a 3-year prospective cohort of patients having undergone cerebral radiotherapy for glioma (stage 3-4), using specific cognitive tests, Magnetic Resonance Imagery (MRI) scans of the brain and predictive bio-markers of cognitive impairments.

Context The survival time and the number of long time survivors after radiotherapy in brain cancer patients have increased for the last decades. Therefore the topic of late-delayed neurotoxic effects of this therapy gains more and more importance. Among these side effects, the main and most frequent one is the leukoencephalopathy, a diffused and progressive damage of the white matter characterized by myelin loss, loss of axons and vascular lesions. The incidence rate assessment, as well as the occurrence time, is based on retrospective studies with low numbers of patients, but seems to reach 30 to 50 % of the patients according to the follow-up. The risk seems to be increased during the first two years after the radiotherapy, but persists for decades.

No complete characterization of this cognitive impairment has been done yet due to crucial discrepancies in the neuropsychological assessments that were used (namely missing of pre-treatment assessment), in the follow-up of patients and in the applied treatment. However, based on previous studies, it can be said that the short term memory and the frontal functions are mainly affected and the quality of life is exceedingly impaired. Irradiation schemes, in particular high doses and large irradiated volume, have been identified as risk factors of leukoencephalopathy. However, in spite of modified protocols that tended to limit the risk, the remaining occurrence of the disease suggests a high dependency on individual risk factors, that are still poorly known and make the individual sensitivity to develop these secondary effects unpredictable. Other factors such as cardio-vascular factors, smoking, old age and combined radio-chemotherapy are linked to leukoencephalopathy as well, although only few of these associations were proved in large studies. Moreover, some specific bio-markers could complete clinical examinations to predict risk of cognitive impairment in these patients. Several biomarkers could be of interest:

The protein S-100B is a protein synthesized mainly by glial cells and cells of Schwann. It is an intracellular protein regulating the cytosolic availability of calcium. Its concentration is 30-100 times brought up in the cerebral tissue that in the other tissues. Its plasmatic half-life is a 1 hour, its elimination is renal. So, the protein S-100B is a marker of traumatic brain injury, certain neurodegenerative disorders and malignant gliomas. The dosage maybe so realized in serum and urines.

* Growing evidence implicates oxidative/nitrative damage in the pathogenesis of neurodegenerative disorders. Subsequent studies were undertaken showing that specific isoprostanes (iPs) levels are elevated in urine and blood of Alzheimer Disease patients and that these values correlate with memory impairments. This suggests that iPs are useful biomarkers in neurological diseases. Their levels could be measured in urine and plasma of patients.
* Homocysteine is a sulfur-containing amino acid, derived from the metabolism of methionine. Higher levels of homocysteine were associated with worse memory performance in a large group of older subjects. While homocysteine is not a diagnostic test, it may represent a modifiable risk factor for dementia.

Highlighting neuropsychological disorders including at an early stage requires a reliable and reproducible assessment of the patient's cognitive state. However, a comprehensive neuropsychological assessment takes several hours and a qualified staff, making it difficult to implement in the conventional patient monitoring. The use of a simple and fast tool to detect cognitive impairment would help to develop a systematic approach for screening these disorders. A detection computerized neuropsychological standardized test (Computerized Cognitive Speed Test - CSCT) assessing processing speed of information, attention and working memory has been validated in multiple sclerosis patients compared to healthy volunteers. CSCT quickly detects patients with cognitive impairment, who could be then tested with more complete tests. It can be conducted by people with no neuropsychology training and the testing time is less than 2 minutes.

This study will allow a better understanding of the impact of cognitive sequelae in patients treated for glioma with current standard treatments, including radiation. The validation of a new screening test, the CSCT, in this disease will eventually detect earlier these effects and possibly initiate treatment before lesions are too advanced. Feasibility of the implementation of the CSCT in "routine" practice for all patients treated with brain radiotherapy will be tested.

• Objectives and methodology To gain further insight in the radiation-induced leukoencephalopathy, the objective of this project is to study the onset and evolution of leukoencephalopathy in a 3-year prospective cohort of patients having undergone cerebral radiotherapy for glioma (stage 3-4), using specific cognitive tests, MRI scans of the brain and predictive bio-markers of cognitive impairments.

Primary objective:

- To constitute a prospective cohort of patients treated for glioma (stage 3-4) with radiotherapy in order to estimate the incidence rate and occurrence time of the leukoencephalopathy at the end of the follow-up (3 years after first inclusion).

Secondary objectives:

* To validate the CSCT- Computerised Speed Cognitive Test to detect early cognitive impairment in this patients population compared with complete cognitive tests
* Estimate precisely the dose received by the different anatomical parts of the brain
* To study the relation between the risk of leukoencephalopathy and the received dose to the brain
* To analyze the prognostic risk factors of leukoencephalopathy (either linked to radiation treatment or to patients' clinical conditions) among patients with glioma (stage 3-4)
* To propose and test some bio-markers as predictive factors of cognitive impairment
* To study the radiological changes on MRI associated with neurological abnormalities
* To build a biological collection for patients treated in the Pitié Salpêtrière Hospital

Patients with a diagnostic of glioma (stage 3-4) treated with radiotherapy in 2 hospitals (Hospital Pitié Salpêtrière, Paris and Institut Paul Strauss, Strasbourg) will be eligible for the study.

Taking into account that about 100 patients with glioma are treated every year in the Radiation Oncologic department of the Pitié Salpêtrière Hospital and 50 in the Paul Strauss Institute, the inclusion of 200 patients will take about 2 years. Considering that the survival of these patients is rather short, median of 2 years for glioma 3-4, complete follow-up will be available for the majority of the highest glioma stages, those who are most likely to develop leukoencephalopathy.

The study will be mainly observational with a follow-up of patients based on classical monitoring. The only additional information collected will come from a CSCT test, a very simple and quick test (90 seconds) to identify mild cognitive dysfunction. A detailed neurological assessment by a neuro-psychologist will be performed before radiotherapy, at 12 and 36 months after radiotherapy and in case of abnormalities of the CSCT.

Methodology

* Study design: Observational prospective cohort of 200 patients, who will be followed every 2-3 months for a period of 3 years after enrolment.
* Eligibility:

Study population: Patients undergoing brain radiotherapy for glioma (stage 3 to 4) between April 2015 and April 2017 at the Mazarin Radiotherapy Department, Pitié-Salpêtrière University Hospital and in the Paul Strauss Institute, Strasbourg .

Before the radiotherapy:

* Description of the cancer: histological type, date of diagnosis, treatment of the cancer: type of surgery (total or partial resection), chemotherapy, etc...
* The radiotherapy planning record: type of radiotherapy (whole brain radiotherapy, stereotactic radiotherapy), total and fractionary delivered doses,
* Results of the CSCT test and of the detailed neuro-psychological tests before treatment Comorbidities will be collected from medical records: hypertension, diabetes, smoking habits, cardiovascular diseases, etc...

After radiotherapy, every 2-3 months:

During routine consultations with neuro-oncologists, the following information will be collected:

* Clinical examination: brain features: intracranial high pressure, progressive focal neurological deficit, epilepsia... and toxicity features: alert symptoms (amnesia, dysexecutive disorders, gait troubles, urinary dysfunction)
* MRI scan of brain: tumor features: progression, stability, response and toxicity features
* Results of the CSCT test

Additional data will be collected:

* Neurocognitive tests results performed during a dedicated consultation with neuropsychologist: before the radiotherapy and 12 and 36 months after the radiotherapy
* Blood samples : before the radiotherapy and 12 and 36 months after the radiotherapy In case of abnormal results at 2 consecutive CSCT tests (-1.5 Standard deviation (SD) of loss) with the exclusion of relapse at MRI, additional cognitive tests will be performed during a dedicated consultation with neuropsychologist. At the end of the follow-up, the vital status of the lost to follow-up patients will be assessed through the National Register for Identification of Physical Persons (RNIPP).

  * Outcomes:

Primary outcome Cognitive dysfunction due to leukoencephalopathy defined by both abnormal results at the CSCT test (confirmed by a complete cognitive test) and a MRI scan of the brain(exclusion of brain tumor relapse).

Secondary outcomes

* Overall death
* Death associated with leukoencephalopathy or cognitive dysfunction ● Data analysis: In this longitudinal study, survival analysis methods will be applied. Occurrence time of the leukoencephalopathy and incidence rates at different follow-up time points (month 6, 12, 18 and 36) will be considered. The Kaplan-Meier estimator will be used to estimate the leukoencephalopathy free survival function. For potential risk factors, hazard ratios associated with outcomes will be estimated using Cox models.

Specificity and sensitivity of the CSCT will be assessed in comparison with complete cognitive test (gold standard)

This project will involve the Neurology department and in the Radiotherapy department in the Pitié Salpétrière University Hospital and in the Paul Strauss Institute

* protéin S-100B, 8,12-iso-iPF2α-VI level, homocystéine
* micro RNAs (brain-miR-112, brain-miR-161, hsa-let-7d-3p, hsa-miR-5010-3p, hsa-miR-26a-5p, hsamiR-1285-5p, hsa-miR-151a-3p, hsamiR-103a-3p, hsa-miR-107, hsa-miR-532-5p, hsa-miR-26b-5p, hsa-let-7f-5p, ...).
* microparticules

Study of Neurological Complication After Radiotherapy for High Grade Glioblastoma

EPIBRAINRAD : Study of Neurological Complication After Radiotherapy for Glioblastoma High Grade

comparison of the CSCT result with the results of the complete neurocognitive evaluation.

collection of histograms of dose-volumes of specific organs and areas based on data from radiotherapy treatment plan.

levels of homocysteine, protein S100B,specific isoprostanes (8,12-iso-iPF2α-VI),micro RNA, microparticules

white matter abnormalities and cortical atrophy.The white matter lesion quantification will follow the procedure described by Wahlund et al (Wahlund 2001) using a 4 points scale (0: no lesion; 1: focal lesions; 2: beginning confluence of lesion; 3: diffuse involvement of the entire region). The cortical atrophy quantification will follow the procedure described by Pasquier et al (Pasquier 1996) using a 4 point scale (0: absence of atrophy; 1: mild atrophy; 2: moderate atrophy; 3: severe atrophy).

Centre National de la Recherche Scientifique, France

Sophie JACOB

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Hypersensitivity

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Crizotinib

Erlotinib Hydrochloride

Gefitinib

Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)

Brain Radiotherapy (stereotactic radiotherapy was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain )was used for more than 3 intracranial lesions);Molecular targeted therapy(according to the results of gene detection, targeted drugs were selected, such as EGFR mutation using the first generation of EGFR-TKI,ALK or ROS1 mutation using the first generation of ALK inhibitors)

if EGFR mutation is positive, (gefitinib, ecotinib, erlotinib）or ALK/ROS-1 positive（Crizotinib）

molecular targeted therapies

SRS was used for 1-3 intracranial lesions, and simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain)was used for more than 3 intracranial lesions

Brain Radiotherapy

Liu Anwen, Phd

Cai Jing, Phd

Anwen Liu, MD

Brain metastasis is the most common neurological complication in tumor patients, and lung cancer is the most common tumor with brain metastasis. The prognosis of patients with non-small cell lung cancer with brain metastasis is poor. If not treated, the median survival time was about 1 month, the median survival time for steroid therapy was about 2 to 3 months, and the median survival time for patients receiving whole brain radiotherapy was about 3 to 6 months. Studies have shown that the incidence of brain metastasis is not only related to tumor size, N stage and tumor cell type, but also more likely to occur in NSCLC patients with sensitive gene mutation. With the rapid development of NSCLC molecular targeted therapy and precise radiotherapy, the new main therapeutic methods for NSCLC brain metastasis in recent years include stereotactic radiotherapy for (SRT),. Based on intensity modulated technique, simultaneous modulated accelerated radiation therapy for Brain(SMART-Brain) and molecular targeted therapy were carried out. However, at present, the best treatment choice for NSCLC brain metastasis, especially for asymptomatic brain metastasis patients, is still controversial. The choice and combined application mode of individualized treatment for different patients is still a problem to be explored. Based on the synergistic effect of radiotherapy and molecular targeted therapy on the basis of cell and molecule, The purpose of this study was to prospectively compare the efficacy of radiotherapy combined with targeted therapy and targeted therapy alone in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutations, and subgroup analysis of different molecular targets and mutation sites. It is expected that this study will provide a basis for optimizing the curative effect of patients with NSCLC brain metastasis.

This is a randomized phase II clinical trial. The objective of the study is to assess efficacy and safety of brain radiotherapy combined with targeted therapy and simple targeted therapy in patients with asymptomatic NSCLC brain metastasis with gene sensitive mutation. Patients were randomized with equal allocation to Molecular targeted therapy alone or with brain radiotherapy. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent

The Role of Brain Radiotherapy in Patients With Asymptomatic Brain Metastasis in the Era of Targeted Therapy for NSCLC

A Randomized Phase II Trial of Brain Radiotherapy Combined With Targeted Therapy in Patients With Asymptomatic NSCLC Brain Metastasis With Gene Sensitive Mutation

time from the beginning of study to death due to any cause or last follow-up

Time from BM diagnosis to the first documentation of intracranial lesion progression or death with documented intracranial progression

ORR, proportion of patients with a best overall response of complete response or partial response (CR+PR)

The period from the start of treatment to the progression or death of a patient

the cumulative survival rate is 0.5, the corresponding survival time means that only 50% of the individuals can live through this time.

Number of patients with adverse events (AEs) as a measure of safety and tolerability

Nanchang University

Second Affiliated Hospital of Nanchang University

brain radiotherapy planned on synthetic CTs

Christoph Bert, Prof. Dr. rer. nat

Florian Putz, PD Dr. med.

The goal of this observational study is to show the feasibility of an MRI-only workflow in brain radiotherapy. The main question it aims to answer is:

* Is an MRI-only workflow based on deep learning sCTs feasible in clinical routine? Participants will be treated as in clinical routine, but treatment planning will be based on sCTs, that are generated from MRI images. The dosimetrical equivalence to the standard CT based workflow will be tested at several points in the study.

The purpose of this clinical study is to investigate the clinical feasibility of a deep learning-based MRI-only workflow for brain radiotherapy, that eliminates the registration uncertainty through calculation of a synthetic CT (sCT) from MRI data.

A total of 54 patients with an indication for radiation treatment of the brain and stereotactic mask immobilization will be recruited. All study patients will receive standard therapy and imaging including both CT and MRI. All patients will receive dedicated RT-MRI scans in treatment position. An sCT will be reconstructed from an acquired MRI DIXON-sequence using a commercially available deep learning solution on which subsequent radiotherapy planning will be performed. Through multiple quality assurance (QA) measures and reviews during the course of the study, the feasibility of an MRI-only workflow and comparative parameters between sCT and standard CT workflow will be investigated holistically. These QA measures include feasibility and quality of image guidance (IGRT) at the linear accelerator using sCT derived digitally reconstructed radiographs in addition to potential dosimetric deviations between the CT and sCT plan. The aim of this clinical study is to establish a brain MRI-only workflow as well as to identify risks and QA mechanisms to ensure a safe integration of deep learning-based sCT into radiotherapy planning and delivery.

Clinical Feasibility of Brain Radiotherapy Using Synthetic CTs in an MRI-only Workflow

Feasibility Study of an MRI-only Workflow: Use of Synthetic CTs Generated From MRI Data for MRI-based Radiotherapy

All criteria have to be met for the MRI-only workflow to be classified as successful:

Verification criteria that will be assessed:

1. Can the sCT be generated and is the sCT clinically utilizable?
2. Are the three rotations needed for CT-MRI registration each ≤ 3°?
3. Can a treatment plan be generated and verified using the sCT?
4. Is the dosimetric difference between sCT and CT based treatment plan in the planning target volume ≤ 3%?
5. Is the dosimetric difference between the sCT and CT based treatment plan in affected organs at risk (receiving \> 10% of prescribed dose) ≤ 3%?
6. Are the couch correction parameters during patient positioning in the rotational degrees of freedom ≤ 3°?

Presence (Yes/No) of individual reasons responsible for the unfeasibility of the MRI-only workflow, as assessed with a predefined checklist.

Paired difference in Dose-volume-histogram parameters (Target coverage, mean, median, near maximum and minimum dose) between MRI-only and standard radiotherapy treatment workflow.

Patient shift (vector magnitude) and rotational errors occuring during the course of MRI acquisition due to patient movement, as assessed by rigid registration of the last acquired MRI sequence in reference to the first sequence.

Similarity of organ at risk segmentations defined in MRI compared to reference segmentations defined in CT as assessed by the volumetric and surface Dice score, as well as mean surface and Hausdorff distances.

University of Erlangen-Nürnberg Medical School

Recurrence

Disease Attributes

Amino Acids

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib until brain tumor progression, then given brain radiotherapy, and continued to take Erlotinib till extracranial lesions progression.

Erlotinib with concurrent brain radiotherapy, and continued to take Erlotinib after radiotherapy until recurrence or termination for other reasons

Erlotinib

concurrent brain radiotherapy

secondary brain radiotherapy

Huanjun Yang, Master

Huanjun Yang

This project is aim to explore non-increased-intracranial-pressure symptomatic brain metastases of NSCLC, and if the OS of secondary brain radiotherapy after recurrence with Erlotinib is better than Erlotinib with concurrent brain radiotherapy. Treatment group are treated with Erlotinib until brain tumor progression, then gave brain radiotherapy, and continued to take Erlotinib till extracranial lesions progression. Control group are Erlotinib with concurrent brain radiotherapy, and continued to take Erlotinib after radiotherapy until recurrence or termination for other reasons.

Erlotinib With Concurrent Brain Radiotherapy and Secondary Brain Radiotherapy After Recurrence With Erlotinib in NSCLC Non-increased-intracranial-pressure Symptomatic Brain Metastases

Erlotinib With Concurrent Brain Radiotherapy and Secondary Brain Radiotherapy After Recurrence With Erlotinib in NSCLC Non-increased-intracranial-pressure Symptomatic Brain Metastases: A Prospective Multicenter Trial(TRACTS)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases	NCT05768490	Brain Metastase... Radiotherapy EGFR Activating...	brain radiother... Almonertinib	18 Years - 75 Years	Sun Yat-sen University
Study of Neurological Complication After Radiotherapy for High Grade Glioblastoma	NCT02544178	Leukoencephalop...	brain radiother...	18 Years -	Institut de Radioprotection et de Surete Nucleaire
The Role of Brain Radiotherapy in Patients With Asymptomatic Brain Metastasis in the Era of Targeted Therapy for NSCLC	NCT04193007	Non Small Cell ... Brain Metastase...	molecular targe... Brain Radiother...	18 Years - 80 Years	Second Affiliated Hospital of Nanchang University
Clinical Feasibility of Brain Radiotherapy Using Synthetic CTs in an MRI-only Workflow	NCT06106997	Brain Tumor, Pr... Brain Tumor - M...	brain radiother...	18 Years -	University of Erlangen-Nürnberg Medical School
Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases	NCT05768490	Brain Metastase... Radiotherapy EGFR Activating...	brain radiother... Almonertinib	18 Years - 75 Years	Sun Yat-sen University
Erlotinib With Concurrent Brain Radiotherapy and Secondary Brain Radiotherapy After Recurrence With Erlotinib in NSCLC Non-increased-intracranial-pressure Symptomatic Brain Metastases	NCT01763385	Non-small-cell ... Brain Metastase...	Erlotinib concurrent brai... secondary brain...	18 Years - 85 Years	Wu Jieping Medical Foundation

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