Brain Metastasases

Cerebral radiation necrosis (CRN) is a severe complication of high-dose radiation for brain metastases (BM) or glioma, which can potentially cause significant neurologic symptoms leading to serious morbidity and impaired quality of life (QoL). The first-line therapy for symptomatic CRN (sCRN) is corticosteroids, primarily dexamethasone, which often leads to complications, refractory symptoms, and interference with anti-cancer treatment. Since 2017, bevacizumab, an antibody against Vascular Endothelial Growth Factor (VEGF), has been used in a second-line treatment setting for refractory sCRN. A small randomized clinical trial (RCT) has shown that bevacizumab significantly diminishes cerebral edema on MRI and decreases clinical symptoms of sCRN in irradiated glioma patients. Several non-randomized clinical studies demonstrated a beneficial radiological and clinical effect of bevacizumab in patients with sCRN after irradiation for BM. The optimal first-line treatment for sCRN is currently unknown. Effective and safe first-line treatment of sCRN will optimize the patient's well-being and health-related QoL. Furthermore, minimizing corticosteroid use will benefit the clinical treatment options and outcomes of concomitant or future anti-cancer treatment. This phase III multicenter, open-label, randomized clinical trial compares the clinical efficacy of first-line bevacizumab versus standard-of-care dexamethasone for sCRN in patients with high-grade glioma (HGG) or BM.

This is a prospective, single-centre feasibility study of CSF ctDNA conducted at the Sunnybrook Odette Cancer Centre (SOCC), Toronto, Canada, including multiple solid tumor, stratified into cohorts according to CNS disease involvement, including leptomeningeal disease (Cohort A), parenchymal brain metastases (Cohort B), and no evidence of CNS metastases (Cohort C).

This is an open-label, prospective, single-arm, multicenter phase II clinical trial. The aim is to explore the efficacy and safety of radiotherapy combined with cisplatin/carboplatin, adebrelimab, and bevacizumab in patients with triple-negative breast cancer and brain metastases.

The goal of this observational study is to learn about the effects of the timing of radiation therapy and immunotherapy in adults with non-small cell lung cancer (NSCLC) that has spread to the brain. The main questions it aims to answer are: 1. Does the timing of the two treatments change how long the brain tumor stays stable and how long participants live? 2. What medical problems do participants have when receiving these treatments at different times? 3. How does the timing of treatments affect the body's immune system? Researchers will compare participants who receive radiation and immunotherapy 30 days or less apart to those who receive them more than 30 days apart to see if the timing affects the treatment's success and safety. Participants already receiving radiation and immunotherapy as part of their regular medical care will: 1. Allow researchers to collect information about their treatment, health, and medical imaging during regular checkups. 2. Give a small blood sample during their routine blood draws. 3. Have standard magnetic resonance imaging (MRI) scans of their brain.

Conventional image-guided techniques (such as cone-beam CT) have poor soft tissue contrast and unsatisfactory treatment outcomes. MRgART offers high-resolution imaging of brain tissue and, by acquiring daily MR images, successfully achieves real-time image monitoring, displaying tumor position and volume changes during treatment. This may improve local control rates for brain metastases, reduce toxicities, and translate into survival benefits. Our research team has already conducted a phase II prospective study and achieved favorable results, with a 1-year local control rate of 100% for intracranial brain metastases, significantly superior to historical controls of conventional radiotherapy, no severe late toxicities, and real-time individualized precision treatment. Based on the phase II study results, this phase III single-arm prospective study was designed. This study aims to conduct a multicenter prospective study to establish an MR-guided adaptive radiotherapy (MRgART) technical platform, enabling real-time monitoring of tumor position and volume changes and individualized plan adaptation. Through technological innovation, we aim to significantly improve local control rates for large and complexly located brain metastases while reducing severe adverse effects such as radiation brain necrosis, thereby laying the technical foundation for precise and safe treatment. This study will establish a new technical system for adaptive radiotherapy (ART) for brain metastases based on per-fraction MR images acquired during radiotherapy, using adaptive radiotherapy to improve target dose coverage and reduce radiation doses to organs at risk such as normal brain tissue. It is anticipated to validate the phase II findings of high local control, low toxicity, and significantly prolonged survival. Based on the obtained results, combined with multicenter clinical practice and application experience, domestic and international expert symposiums and special sessions will be conducted, and a multicenter consensus on MRI-linac guided adaptive radiotherapy for brain metastases from lung cancer will be developed. Furthermore, this study recognizes that MRI generates high noise levels and that without appropriate hearing protection, repeated treatments may cause hearing damage to patients. Therefore, the study will simultaneously collect hearing-related scales from patients before, during, and after treatment (through pure-tone audiometry tests performed in the otolaryngology department or self-administered pure-tone screening via a mini-program) to explore the impact of performing or not performing strict hearing protection on changes in patients' hearing scales, as well as its effect on treatment interruption or repeated setup. Compared to conventional cone-beam CT-guided radiotherapy, MRI-guided adaptive radiotherapy still has some shortcomings. MR image acquisition is slow, and after each fraction's images are acquired, they require manual registration with CT images, followed by manual re-contouring and manual plan calculation, and finally, execution requires triple review by physicians, physicists, and therapists. Currently, each patient requires approximately 40 minutes to 1 hour from lying on the treatment couch to the end of treatment. If there are setup errors or significant target volume changes requiring adaptive re-contouring, even more time may be needed to complete the treatment, posing significant challenges to patients' physical strength and mental state, and limiting its potential application value in patients with altered consciousness, the elderly and frail, or those unable to cooperate. Additionally, it consumes substantial medical resources. To address this situation, our research group plans to develop an artificial intelligence-assisted system for target contouring, treatment planning, and treatment decision-making. Based on our center's previously published results, we aim to establish a full-process AI-assisted model for MRgART in the treatment of lung cancer brain metastases, and compare its efficacy and treatment time differences with manual-only radiotherapy delivery. On this basis, we will explore the feasibility of exempting a small subset of patients (approximately 10-20 patients) in the phase III study from conventional CT and MR simulation, contouring targets and generating plans on simulation CT and MRI images, and then directly using ATS (adaptive target shaping based on interfractional target deformation) to generate radiotherapy plans within the MRgART workflow and proceed with subsequent treatment.

To find a recommended dose of the combination of alpelisib and pembrolizumab that can be given to patients with metastatic breast cancer or melanoma.

This will be an open-label Phase 0/1 study that will enroll approximately 15 participants, 9 participants with recurrent WHO Grade 4 glioma (rGBM) and 6 participants with brain metastases, who will receive the investigational drug risvutatug rezetecan (GSK5764227), a B7-H3-targeted antibody-drug conjugate (ADC) with the GSK5757810 payload. The trial will consist of a Phase 0 component (subdivided into Arms A and B) and an Expansion Phase 1 component. Participants with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component will be eligible to enroll in the Expansion Phase to receive therapeutic dosing of risvutatug rezetecan.

Cerebral radiation necrosis (CRN) is a severe complication of high-dose radiation for brain metastases (BM) or glioma, which can potentially cause significant neurologic symptoms leading to serious morbidity and impaired quality of life (QoL). The first-line therapy for symptomatic CRN (sCRN) is corticosteroids, primarily dexamethasone, which often leads to complications, refractory symptoms, and interference with anti-cancer treatment. Since 2017, bevacizumab, an antibody against Vascular Endothelial Growth Factor (VEGF), has been used in a second-line treatment setting for refractory sCRN. A small randomized clinical trial (RCT) has shown that bevacizumab significantly diminishes cerebral edema on MRI and decreases clinical symptoms of sCRN in irradiated glioma patients. Several non-randomized clinical studies demonstrated a beneficial radiological and clinical effect of bevacizumab in patients with sCRN after irradiation for BM. The optimal first-line treatment for sCRN is currently unknown. Effective and safe first-line treatment of sCRN will optimize the patient's well-being and health-related QoL. Furthermore, minimizing corticosteroid use will benefit the clinical treatment options and outcomes of concomitant or future anti-cancer treatment. This phase III multicenter, open-label, randomized clinical trial compares the clinical efficacy of first-line bevacizumab versus standard-of-care dexamethasone for sCRN in patients with high-grade glioma (HGG) or BM.

When cancer spreads to the brain, doctors often use a precise type of radiation therapy called stereotactic radiosurgery (SRS) to treat these tumors. This treatment can effectively control brain tumors while helping protect healthy brain tissue. However, when brain tumors or the areas where tumors were surgically removed are larger, treatment outcomes in terms of side effects and tumour control can become worse. Specifically, standard SRS on larger areas can have lower tumour control and higher risk of side effects, particularly a condition called radiation necrosis, which can cause swelling and damage in nearby healthy brain tissue. Currently at Sunnybrook, large brain tumors are typically treated with SRS spread over 5 daily treatments using a machine called a linear accelerator. While this approach works well for many patients, it may be possible to improve results by combining two different types of radiation therapy machines - the linear accelerator and another specialized machine called the Gamma Knife. In this study, the investigators want to test a new treatment approach where patients first receive 4 daily treatments using the linear accelerator, followed by a 1-2 week break, and then a final treatment using the Gamma Knife. The break between treatments allows the study doctors to take new scans and precisely target any remaining tumor, which may shrink during the break, thereby potentially reducing the amount of healthy brain tissue exposed to radiation. The Gamma Knife is also particularly good at delivering very precise radiation while sparing nearby healthy tissue. Lastly, there may be unique biological mechanisms between the two technologies that could be taken advantage of, by combining the technologies in the participant's treatment plan, to improve cancer control. The investigators believe this combined approach might help achieve better tumor control while reducing the risk of side effects compared to using just the linear accelerator. This study will help the investigators understand if this new treatment strategy is safe and effective for patients with large brain tumors or surgical cavities, and whether it leads to better outcomes than the current treatment approach.

The purpose of this study is to improve outcome of breast cancer patients who develop brain metastases. This will investigate the benefits of early detection of brain metastases using brain imaging. In patients diagnosed and currently being treated for advanced or metastatic breast cancer, current guidelines do not recommend routine brain imaging. However, there is emerging evidence suggesting that patients diagnosed without symptoms of brain metastases may have a better outcome than those with symptoms such as headache, vomiting and weakness. In current practice, if signs and symptoms suggestive of brain metastases are to develop, then the doctor will arrange imaging of the brain, which may be a computerised tomography (CT scan) and/or a magnetic resonance imaging (MRI) scan. Should brain metastasis be detected, local radiotherapy, chemotherapy or targeted treatments will be offered. When initially diagnosed with metastatic or advanced breast cancer, participant will or would have undergone a brain scan by either MRI or CT during normal standard full-body CT scan (chest, abdomen and pelvis) imaging. In this study, each time participants have a regular full-body CT scans to assess treatment progress, they will also have an additional CT scan of the brain. Participants will have a total of 12 extra brain scans, with scans taking place every three months for the first 2 years, and every 6 months for the following years. These scans will occur at the same location as your current treatment. There will be no extra costs involved in the study and participants will be in the study for 4 years and following their follow-up details will be collected from medical records. Some participants who develop brain metastases during the followup will have neurosurgery to remove these metastases. The investigators will collect either fresh or archived tissues and a cerebrospinal fluid (CSF) sample at the time of surgery from those patients. If the treating investigators do not think neurosurgery is an option, they will ask participants to have a lumbar puncture for the collection of CSF. The purpose of this optional CSF collection is to take a liquid biopsy to check for markers (or biomarkers) potentially expressed by the breast cancer tumour cells in the brain. Participants will also be asked to provide a blood sample as well as old tumour from breast surgery (other metastatic tumour tissue). The information obtained from this component of the study will not impact a parcipants current management, but it will help researchers to develop better treatments for breast cancer brain metastases in the future.

A multicenter, single-arm, open-label study evaluating the safety and efficacy of AK112 combined with chemotherapy as first-line treatment for non-squamous NSCLC patients with BRAIN metastases and negative driver genes

The goal of this observational study is to extract the imaging features of brain lesions and primary lung lesions in NSCLC patients with brain metastases by deep learning, as well as common clinicopathological parameters, which are used to construct a multimode model that can accurately predict the treatment efficacy and survival of the third-generation EGFR-TKI treatment, and to use the model to assist in screening high-risk populations suitable for upfront cranial radiotherapy. Participants receiving third-generation EGFR-TKI treatment will be enrolled in our study and we will collect their regular contrast-enhanced chest CT and contrast-enhanced brain MRI for model construction.

This study was designed to evaluate the safety, efficacy and pharmacokinetics of JK-1201I in triple negative breast cancer patients with brain metastases.