Proof-of-Concept Study Assesses SSRS for Brain Metastases
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In an interview with Targeted Oncology, Rupesh Kotecha, MD, discusses the background of this phase 1 study and current options for patients with brain metastases.
Patients with brain metastases with 18F-fluciclovine had target lesions that demonstrated interval reduction in PET metrics after treatment with single-session stereotactic radiosurgery (SSRS), according to interim results of a phase 1, proof-of-concept study (NCT04689048).1
The study evaluated SSRS for the treatment of large brain metastases (> 2cm) and found it to lead to modest local control. Findings were presented at the annual American Society for Radiation Oncology (ASTRO) meeting.
There were 7 patients included in the study who completed baseline imaging and were treated with SSRS for 9 protocol-eligible target lesions. Additionally, 25 other bystander lesions were treated with SSRS. Among those enrolled, the median age of patients was 72 years, and 57% of patients were female.
Initial target lesion sizes varied, with median diameters of 2.16 cm (range, 1.76-3.22 cm) and volumes of 4.71 cc (range, 2.24-10.21 cc). The median baseline SUVmax, SUVpeak, and SUVmean values were recorded at 5.78 (range, 2.16-8.79), 3.33 (range, 0.5-2.72), and 1.75 (range, 1.22-5.16), respectively.
At interim scans, target lesion diameter and volume reductions were both 2%, and at the first follow-up, reductions were 30% for diameter and 43% for volume, respectively. At interim scans, SUVmax, SUVpeak, and SUVmean values showed reductions of 20%, 9%, and 14%. At the time of the first follow-up, values were 59%, 41%, and 21%, respectively. Further, bystander lesions (< 2 cm) treated with SSRS had smaller baseline sizes. At interim scans, they showed a 5% reduction in SUVmax and a 63% reduction at follow-up.
In an interview with Targeted OncologyTM, Rupesh Kotecha, MD, chief of radiosurgery and director of central nervous system metastasis with Baptist Health Miami Cancer Institute, discussed the background of this phase 1 study and current options for patients with brain metastases.
Brain cancer, 3D illustration showing presence of tumor inside brain: © Dr_Microbe - stock.adobe.com
Targeted Oncology: Can you start by discussing the prognosis for patients with large brain metastases?
Kotecha: Thinking about patients with large brain metastases, we have to consider not only the patient-related factors, but specifically, tumor-related factors as well as they are more challenging to control than the traditional smaller brain metastases. Typically, when we're thinking with stereotactic radiation therapy techniques, we can get control rates with stage radiosurgery of about 85%, although we don't know really what the long-term control with radiation alone is typically for the very large lesion. We would consider doing things like surgery, but for medically inoperable patients who can only have radiation therapy; that's where this type of research kind of fits into this space.
Can you discuss the standard of care utilized in this patient population?
The current standard of care for these patients is variable. We have traditionally used single fraction radiation or single doses of radiation. Essentially, the control rates have been poor, anywhere from 48% to 60%, maybe, in the best series. But when we think about staged radiosurgery approaches where we give 2 sessions of radiosurgery with an intervening time anywhere from 2 to 4 weeks, then we can improve those control rates to be at 85% or potentially a little bit higher. Another course of care is to give fractionated radiation therapy, fractionated radiosurgery, and that is when radiation is delivered between 3 to 5 sessions a treatment. That is also served with control. It's about 85 percent depending on the total lesion size and the histology.
Can you provide an overview of this phase 1 study presented at ASTRO?
The purpose of our research is really to identify if we can use an amino acid PET CT scan as a biomarker to see which patients would truly respond to the treatment, and we can identify that early on in their course. In this study, patients receive a baseline amino acid PET scan. Then at 4 weeks, they will receive another amino acid PET scan with their MRI scan. Then at their follow-up assessment, they also receive an amino acid PET scan, and we track the changes over time to potentially evaluate if we can use this as a biomarker to see who is truly responding to treatment or not. If you're the patient, telling you an 85% control rate doesn't mean a lot to you because either you are going to be controlled or you're not. As a patient, they are either 100% or 0%. Hopefully, we can identify that a little bit better using this amino acid PET scan as the focus of our research.
Patients in this study have to have at least a single lesion that is more than 2 cm in size on their baseline MRI scan. Essentially, they undergo the PET CT scan at baseline and with their first stage of treatment, and then with their follow-up. That's what's outside the standard of care, is to use this diagnostic imaging test the amino acid PET scan. Traditionally, patients with cancer think about obtaining a regular FDG [fluorodeoxyglucose] or a glucose-based PET scan, but that's not utilized in the brain, so we can't really see cancer in the brain with those traditional studies.
Our cancer center participated in a phase 2 trial to evaluate the use of amino acid PET scans in patients who had been treated previously with radiation to help differentiate recurrent disease or recurrent tumor from tumor-related change. That study actually showed that there was good diagnostic performance with that. What we are doing is taking that 1 step further, evaluating that at baseline, as well as with follow-up imaging to see if we cannot just use 1 time point, but potentially develop an ongoing biomarker to treat.
What findings were presented at the meeting?
At this meeting, we [presented] the early results from the first patients who are enrolled into this study. The total accrual will be 20 patients in total, and the data that has been presented at the ASTRO meeting is for the 5 patients who completed the entire treatment course, and for the 7 patients who had their baseline scans as well. Essentially, we compared the metrics of following patients with traditional MRI scans in which we looked at the lesion size over time and how that tumor reduces over time. We could also look at lesion volume over time to see how that reduces.
The interesting component to our study is we're looking at the PET metrics, the activity, and how that changes over time. At least in these initial results that were presented at the meeting, the PET metrics, which is the focus of our study, there was a change at a higher proportion than with the traditional MRI metrics. In other words, if you see a tumor that is shrinking over time, the actual reduction in the PET signal is a better biomarker, potentially of a response, than just looking at standard MRI measurements alone, which is what we're looking to see hopefully when we accrue the full 20 patients.
What are the next steps for this research?
What we'd like to do is to accrue the completion of our patients. This study is ongoing right now and we've accrued double than what we presented at the meeting as of now. Essentially, we are looking at doing additional studies to further fine tune and to develop this PET imaging biomarker response to treatment time point. A study that we have, which is in concept development, is going to be opening very soon at our facility and is going to be looking at patients with smaller brain metastases, those that are less than 2 cm, and patients will receive 2 PET scans, 1 at baseline and 1 at 8 weeks. Then, we are using that 8-week scan potentially as a biomarker for their ultimate response to treatment. We're already in the next stages of the next steps.
