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Glioblastoma is a cancer that affects the brain. There are several and in some cases it can have a poor prognosis and few treatment options. American researchers have tried a new approach: that of treating patients directly at the heart of brain cells.
A brain tumor, glioblastoma is classified into different grades. Considered benign for grades 1 and 2, it is severe when graded as grade 3 or 4 with few treatments currently available.
Main obstacle: the blood-brain barrier
For doctors trying to treat patients, the first hurdle is not so much the disease as the brain itself. Indeed, the blood-brain barrier (BBB) is, as its name suggests, a “barrier”. It prevents poisons, viruses and bacteria from the blood from entering the brain, but it also blocks most therapeutic substances.
Too much chemotherapy
Usually, sick patients are therefore operated on, to remove as much tumor tissue as possible, and then treated with radiotherapy and chemotherapy. The latter can in theory be delivered in high doses, in order to cross the blood-brain barrier.
But in fact, high-dose medications end up causing excessive side effects that patients cannot tolerate. As a result, the amount of chemotherapy that can be safely given to brain tumor patients is not enough.
“Tumors inevitably grow back“, explains Professor Jeffrey Bruce, professor of neurosurgery and lead author of the study.And when they do grow back, there’s no proven treatment for them.“.
Use a pump implanted directly in the brain
In an attempt to circumvent the BBB, neurosurgeons at Columbia University and New York Presbyterian are taking a more direct approach: using a fully implantable pump that continuously delivers chemotherapy through a tube inserted directly into the brain.
Initially, the first prototypes, which included an external pump attached to a catheter inserted into the skull, allowed only one treatment limited to a few days before running the risk of infection. Patients also had to stay in the hospital while hooked up to the pump.
Better prototypes developed
The two teams succeeded in designing a new prototype that has no external parts and can be left in place for as long as needed.
It is a small pump surgically implanted in the patient’s abdomen and connected to a thin, flexible catheter threaded under the skin. Stereotaxic imaging guides the surgical placement of a catheter precisely in the area of the brain where the tumor and residual cancer cells are located.
A one-month phase 1 study
The pumps were implanted in five patients with recurrent glioblastoma, for a phase 1 study, for one month. They were filled with topotecan, a chemotherapy drug used to treat lung cancer, and gadolinium, a tracer agent to track drug delivery.
Patients had four treatments over the course of a month. Each week, the pumps were on for two days and off for five days. The patients then continued their normal lives, at home, while the treatment diffused, drop by drop.
“The patients walked, talked, ate and did all their daily activities normally. They didn’t even know if the pump was on or not“explains Professor Bruce.
A “concentration of chemotherapy 1000 times higher”
“If you pump the drug very slowly, literally several drops per hour, it penetrates the brain tissue“says the specialist, who first tested the method extensively on animal models.
“The concentration of drug that ends up in the brain is 1,000 times greater than anything you’re likely to get from intravenous or oral administrationAdditionally, wireless technology is used to turn the pump on and off and control the flow, ensuring that the drug slowly seeps in and ‘saturates’ the tumor without leaking around the catheter.
“Most medications would be more effective if you could administer them long term without side effects” he adds. “The pump can stay in place for a long time, so we can deliver higher doses of chemotherapy directly to the brain without causing the side effects we get with oral or intravenous chemotherapy.”
Chemotherapy administered in this way “works”
At the end of this study, none of the patients presented serious neurological complications. And the MRI showed that the chemotherapy had saturated the area in and around the tumour.
And according to Professor Peter Canoll, professor of pathology and cell biology at Columbia who participated in this work, chemotherapy works: the number of actively dividing tumor cells has decreased significantly, while normal brain cells do not. were not affected.
Further studies should confirm these first results.
On the other hand, the fact that the trial has so far only involved five patients prompts Professor Bruce to be cautious: “This new approach has the potential to transform the treatment of patients with brain cancer, where the prospects for survival remain very poor. But more tests are needed in patients with early-stage tumors and with different types of chemotherapy“.
Further studies are planned to determine whether the treatment is also safe for patients with newly diagnosed glioblastoma and whether it can improve survival. Remember that the median survival of patients undergoing treatment for glioblastoma is just over 12 months. And once patients’ tumors come back, the prognosis is then usually only four to five months.