As long-term cancer survival outcomes improve, the brain has increasingly become a site of refractory and recurrent disease.
At Memorial Sloan Kettering Cancer Center (MSK), neurosurgeon Nelson Moss, MD, Co-Director of the Multidisciplinary Brain Metastasis Program, and radiation oncologist and early drug development specialist Brandon Imber, MD, are investigating whether brachytherapy may be an effective treatment option for reducing local recurrence, lowering the risk of necrosis associated with standard radiation, and improving the quality of life for patients with brain metastases.
These MSK experts are currently conducting two prospective brachytherapy studies: one for patients with recurrent brain metastases after stereotactic radiosurgery (SRS), and one for patients with newly diagnosed metastatic brain tumors.
Standard Treatments for Brain Metastases
SRS is the preferred standard treatment for managing most small, asymptomatic or unresectable brain metastases and for lowering the risk of recurrence after resection of symptomatic, operable tumors.
“About 10% of all radiated brain metastatic lesions grow back, a significant proportion of those become big enough to require surgery, and about one-third to one-half of those resected after prior radiation will recur if we don’t give any additional radiation,” said Dr. Moss. “The issue is that giving more external beam radiation comes with an increased risk of necrosis.”
In 2021, Dr. Moss and colleagues published a large case series of MSK patients with recurrent brain metastases who received adjuvant SRS after salvage resection. The study demonstrated that local salvage therapies for this patient population are reasonable and beneficial. The local recurrence rate was 29% for patients who received salvage resection plus adjuvant SRS compared with 44% for those who received salvage resection alone. (1)
Further, while the addition of adjuvant SRS was associated with a 13% increased risk of radiographic necrosis at 12 months, the percentage of symptomatic necroses in the adjuvant SRS group was only 5.1%. Overall, the addition of post-salvage radiotherapy was well tolerated and resulted in a trend toward six- and 12-month local control compared to salvage resection alone. (1)
Brachytherapy for Treating Brain Metastases
MSK has been pioneering brachytherapy for brain tumors as an alternative to SRS since 2019. The radiation dose from the radioactive seeds is concentrated to the cavity and has a more rapid fall off than SRS, so there is less exposure to healthy tissue.
“Adjuvant radiation delivered via brachytherapy adds minimal operative time to resections,” said Dr. Moss. “As a one-time treatment, patients avoid the inconvenience of repeat visits that are necessary for SRS.”
Today, MSK is one of the highest users of GammaTile brachytherapy (GT Medical Technologies, Inc.) in the world. The device received U.S. Food and Drug Administration clearance for treating recurrent brain tumors in late 2018. (2) Recently, GT Medical Technologies, Inc. designated MSK a GammaTile Center of Excellence, recognizing MSK and its physicians for achieving a high level of clinical expertise and experience with the device and their dedication to improving patient outcomes.
The GammaTile implant is a collagen sponge embedded with titanium-encased cesium-131 seeds that look like grains of rice. The embedded format provides even seed spacing with no need for surgical glues or scaffolds compared to previous methods using unembedded seeds. (3)The radioactive isotope cesium-131 offers potential clinical and radiation protection advantages over historically-employed isotopes, such as iodine-125. (4)
Drs. Moss, Imber, and colleagues conduct the operations together. The surgical team places the tiles into the tumor cavities immediately after resection, and the radiation team oversees preparation of the radioactive material and ensures dosing and spacing are as intended. The tiles deliver targeted radiation for about 100 days. The collagen matrix is absorbed over time and the seeds remain in place after they lose radioactivity.
Drs. Imber and Moss conducted a prospective study of consecutive MSK patients with post-SRS brain metastases who underwent resection plus implantation of cesium-131 brachytherapy with GammaTiles. They published their findings in the Journal of Neuro-Oncologyin 2022. (4)
In total, 20 patients underwent 24 operations with cesium-131 implantation in 25 tumor cavities. A median of 16 seeds were implanted. The device was associated with favorable local control and toxicity profiles. At a median follow-up of 1.6 years for survivors, two tumors recurred resulting in a one-year progression incidence of 8.4%. Radiographic seed settling was observed in 7 of 25 cavities (28%), with one case of clinical migration and no instances of clinical sequelae. There were eight cases of radiation necrosis, of which four were symptomatic. (4)
MSK-Led Trial: Surgery With or Without Brachytherapy for Recurrent Brain Metastases After SRS
Drs. Moss and Imber are leading a clinical trial that is evaluating the effectiveness of cesium-131 brachytherapy (GammaTile) in preventing recurrence in adults undergoing elective craniotomy for resection of previously irradiated brain metastases. Patients are randomized to brachytherapy or investigators choice of standard care without brachytherapy after surgery.
The phase 2 study (NCT04690348) seeks to enroll a total of 99 patients at MSK and Baptist Health South Florida in Miami. The primary outcome of the study is freedom from local progression at nine months post-surgery, as determined by contrast-enhanced magnetic resonance imaging. Read more.
The ROADS Trial for Patients with Newly-Diagnosed Brain Metastases
MSK is also participating in the national Radiation One-And-Done Study (ROADS) clinical trial, which is comparing the safety and efficacy of intraoperative cesium-131 brachytherapy (GammaTile) versus standard-of-care SRS after metastatic brain tumor resection.
The phase 3 study (NCT04365374) seeks to enroll a total of 180 adults across 36 locations in the United States. Eligible patients with one to four newly diagnosed brain metastases are randomized to receive either GammaTile brachytherapy placed during surgery or SRS after surgery. Read more.
At MSK, the standard of care is to treat patients with SRS within a month, which provides a one-year control rate of 94%. (5) (6)“It will be hard for cesium-131 brachytherapy to outperform SRS in the upfront setting, especially in patients with multiple tumors,” said Dr. Imber. “However, if it shows a good efficacy rate, it will be a good treatment option, particularly for patients with single tumors.”
Advancing Care for Patients with Brain Metastases
“At MSK, our team of specialists within the Multidisciplinary Brain Metastasis Program provide excellent, comprehensive care to our patients,” said Dr. Moss. “We have a weekly tumor board, Dr. Imber and I conduct joint clinic visits, and every patient receives a customized treatment plan prepared in collaboration with their medical oncologist.”
“Our brachytherapy program has grown in size and intensity over the last couple of years, including providing second opinions,” said Dr. Imber. “Brachytherapy is an important tool in our toolbox, but it is one of many options we provide within our multidisciplinary program.”
For example, radiation oncology, neuro-oncology, and thoracic medical specialists at MSK are conducting three clinical trials of new SRS strategies in patients with lung cancer brain metastases. Read more.