Devices implanted into brain tumors during surgery may guide treatment
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An implantable microdevice designed to test treatments in patients with gliomas during standard-of-care surgery has been easily and safely incorporated into surgical practice.
A study assessing the device — published in Science Translational Medicine — details its development and use by researchers at Brigham and Women’s Hospital.
“The current strategies for figuring out what drugs work in certain cancers are very inferential — we do genomic studies of the tumors and, depending on what mutations are found, we assume those tumors would be sensitive to drugs that target those mutations,” Pier Paolo Peruzzi, MD, PhD, assistant professor in the department of neurosurgery at Brigham and Women’s Hospital and Harvard Medical School, told Healio. “This has proven to be accurate — or at least partially accurate — in certain cancers, such as breast cancer, but much less so for other cancers — particularly the one that is my area of focus, brain cancer.”
Peruzzi spoke with Healio about the device his team developed, how it is used and its potential to accurately predict treatment success in individuals with brain cancer.
Healio: What prompted the development of this device?
Peruzzi: We published a paper in the Journal of Clinical Oncology showing the early results of a clinical trial where patients with glioblastoma — the worst type of brain cancer — were treated with different drugs based on the genomic analysis of the tumor. The outcomes showed that there was absolutely no effect from those drugs. We assumed that looking at these genetic differences would enable us to sort out which patients will respond to those specific targeted therapies. However, that is not the case. That is why we thought we needed a more direct readout to figure out what works and what doesn’t. We also wanted an approach that could be specific to every patient.
Healio: How does this device work?
The device, invented at Brigham and Women’s Hospital by the team of Oliver Jonas, PhD, a co-lead investigator of this trial, consists of multiple reservoirs — up to 30 — condensed into a tiny device that has the shape and size of a grain of rice. Each reservoir is filled with very, very small amounts of specific drugs we’re interested in studying. Once we position the device into the tumor, it releases the drugs, and then the readout happens when we take the sample out and back to the lab. We then analyze the tissue that has been exposed to the different drugs.
In the current study, the device was studied in six patients. To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation. The first thing we do is implant the device. We then continue the surgery as per normal routine. That surgery usually lasts for about 2 to 3 hours, and during this time the device remains in the living tumor, and then in the last step of the surgery, we remove the part of the tumor that contains the device, and then close. This way, we have been able to integrate the use of this device without changing our standard routine.
The only downside of that is, of course, we can’t prolong the surgery just so we can keep the device there longer. That’s why the incubation time has been limited to about 2 and a half hours.
Healio: How well has the device performed?
Peruzzi: The two most important things we wanted to know from a clinical trial perspective were that it is completely safe, and, at the same time, it provides tissue that can be then analyzed in the lab. Both objectives have been met with flying colors.
But, in addition to that, we’ve seen a few interesting things. The first is that having included a specific drug called temozolomide in these devices, we could establish a very strong correlation between how the tumor responded to that drug in the tissue associated with the microdevice, and how the patient responded to the same drug when this was administered systemically.
The other important piece of data is that we can compare the differential effect of the different drugs that are in the same device, in the same tumor. After surgery, when we analyze that specific piece of tumor, we can then evaluate how the cells respond. We can look for evidence of DNA damage and apoptosis. If we’re looking at 10 different drugs, for example, we can see which of those 10 drugs are most effective at killing the tumor. That is why we’re calling it high throughput, because we can test many drugs at the same time. This isn’t something that has been possible so far — right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug. We can only do this with one drug at a time. With our new approach based on the microdevice, we can really scale it up. The current device we are using has about 32 slots for different drugs.
Healio: Could this type of device be useful in studying drug effects in other tumor types?
Peruzzi: There are ongoing pilot trials in other cancers, including lung, breast and prostate cancer. But so far, our study is the only one that has shown molecular and clinical evidence that this approach can work.
Healio: What do you have planned for further research in this area?
Peruzzi: We have questions we want to explore going forward. One question is whether 2 and a half hours is enough time. We definitely can see a good signal — the signal seems to be very predictive. However, we need to increase the number of patients. We also want to compare this with a different strategy, which is to leave the device in place for 3 days. This gives more time for the drugs to work so we can see how each affects the immune system. Over the last few years, anti-tumor immunity has been a big focus in cancer therapy but has not produced much in terms of results in the brain cancer field. One theory is that the drugs normally used to treat tumors are also impairing the immune system. One thing we want to look at is which drugs can kill the tumor without killing the immune system as well. That would be a big step forward in this research.
Healio: What do you hope will be the long-term implications of this research?
Peruzzi: Our goal is for the placement of these devices to become an integral part of tumor surgery. Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient. That is the long-term goal. We’re getting data from the current clinical trial. The provision is that if there is a drug that is really showing an effect and there is equipoise, then we are going to try that specific drug and see how the tumor responds.
References:
- Peruzzi P, et al. Sci Transl Med. 2023;doi:10.1126/scitranslmed.adi0069.
- Rahman R, et al. J Clin Oncol. 2023;doi:10.1200/JCO.23.00493.
For more information:
Pier Paolo Peruzzi MD, PhD, can be reached at 60 Fenwood Road 1st Floor, Boston, MA 02115; email: pperuzzi@bwh.harvard.edu.
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