Editor's Note: Radiation therapy plays a crucial role in the treatment of brain metastases from lung cancer. At the recent International Lung Cancer Conference (CLC 2024), Dr. Nan Bi from the Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College, delivered a keynote presentation titled "Advances in Precision Radiotherapy for Brain Metastases in Lung Cancer." The presentation focused on the necessity, safety, and technical challenges of using MRI-guided Adaptive Radiotherapy (MRIgART) for treating brain metastases. This article provides a brief overview of the report.Brain Metastases in Lung Cancer
Brain metastases are highly prevalent and often multiple, occurring throughout the course of lung cancer. They present a wide range of symptoms, have poor prognoses, and significantly impact patients’ quality of life. Radiation therapy plays a key role in treating brain metastases from lung cancer. With advances in precision medicine, new technologies such as stereotactic radiosurgery (SRS), MRI-guided adaptive radiotherapy (MRIgART), and artificial intelligence (AI) have improved the efficacy of brain radiotherapy while reducing toxicity. SRS has shown good control for small brain metastases. However, for large brain metastases, SRS is less effective in local control and carries a higher risk of toxicity. Large brain metastases treated with SRS are prone to radiation necrosis, making treatment for these patients a clinical challenge.
HFRT vs. SRS for Large Brain Metastases
Professor Jian-Ping Xiao from the Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College, was the first to propose and conduct a series of studies demonstrating that hypofractionated radiotherapy (HFRT) is more effective and less toxic than SRS for large brain metastases. Studies have shown that using 13-15 fractions of fractionated stereotactic radiotherapy (FSRT) for lesions larger than 3 cm in diameter, while adhering to the concept of adaptive radiotherapy, can significantly improve tumor control and reduce the risk of radiation necrosis.
Safety and Efficacy of MRIgART for Refractory Large Brain Metastases
In the era of chronic disease management for NSCLC, the treatment of large brain metastases requires enhanced radiotherapy efficacy and reduced toxicity to minimize its impact on quality of life (QoL). Achieving these goals involves reducing the dose to normal brain tissue and increasing the tumor irradiation dose, such as through the use of individualized adaptive radiotherapy (ART) techniques. Existing image-guided technologies cannot display real-time changes in the size and location of brain metastases, necessitating new imaging technologies that can adjust radiotherapy plans in real-time according to tumor size and location changes, achieving position adaptation (ATP) and shape adaptation (ATS). Could the advent of Precision Radiotherapy 3.0 for brain metastases break this impasse and offer patients a reprieve from brain metastases?
In 2019, Dr. Nan Bi and colleagues initiated the world’s first phase II trial (NCT06405256) using MRIgART to treat large brain metastases from lung cancer. The study aimed to evaluate the safety and efficacy of MRIgART for treating large brain metastases, analyze changes in lesion location and morphology between fractions, and guide the selection of ART indications, timing, and models. The study enrolled 19 patients with brain metastases ≥2 cm in diameter, a KPS ≥60, an expected survival time of over three months, and the ability to remain supine and still for 45 minutes. The trial results were as follows:
- 30% of patients showed significant changes in lesion location during radiotherapy, with all lesions shrinking to varying degrees; 8 lesions (47.1%) shrank by more than 20% in volume.
- After a median follow-up of 25.4 months, the control rate of irradiated brain metastases was 100%, with no grade 3 or higher late central nervous system (CNS) toxicity observed.
- T2-flair delineation of brain metastases was more consistent with T1+c than T2, suggesting the use of multiple sequences for delineation.
- HFRT for brain metastases revealed significant changes in tumor volume and location during treatment, especially for refractory lesions that were large, edematous before treatment, or located in functional areas, indicating the necessity of individualized adaptive radiotherapy.
- MR-LINAC treatment for brain metastases was found to be safe and effective, supporting its clinical application.
Additionally, there is a need to optimize the online ATS process; key issues include inaccurate target delineation, excessive time consumption, and a lack of objective indicators to trigger ATS. AI-assisted delineation on Daily MR images can improve ATS accuracy and efficiency. AI-based MRI online adaptive radiotherapy protocols can address these challenges and facilitate the clinical application of ATS.
This study was selected for oral presentation at the 2024 International MR-LINAC Alliance Meeting. Based on the above findings, there is still room to optimize the “MRIgART Process for Large Brain Metastases.” Future plans include conducting prospective dose-escalation trials for HFRT in refractory large brain metastases, as well as single-dose escalation trials, to further refine clinical workflows.
Dr. Nan Bi
- Chief Physician, Doctoral Advisor, Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College
- Postdoctoral Visiting Scholar, University of Michigan, USA
- Deputy Director of the Department of Radiation Oncology, Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College
- Chair of the Thoracic Oncology Group, Chinese Society of Radiation Oncology
- Vice Chair of the Youth Committee, Chinese Society of Radiation Oncology
- Vice Chair of the Youth Committee, Radiation Oncology Committee, China Anti-Cancer Association
- Board Member of CSCO, Member of the NSCLC/SCLC/Radiation Oncology Committees
- Lead Expert in the “Small Cell Lung Cancer Guidelines”
- Editorial Board Member of the Chinese Journal of Radiation Oncology
- Associate Editor of Cancer Clinical and Rehabilitation
- Recipient of the IASLC Developing Nation Award
- Recipient of the National Science and Technology Progress Second Prize
- Recipient of two Provincial/Ministerial Science and Technology Progress Second Prizes
- Recipient of the Beijing Outstanding Physician Award
- First/Corresponding author of papers published in Lancet Oncol., Ann Oncol., Mol Cancer, Clin Cancer Res., Cancer Res., JAMA Network Open, with achievements cited in guidelines from ASCO, ASTRO, ESMO, and CSCO, and included in ASTRO CME continuing education.
