Oncology research paves the way for patients with brain metastases

For many years, brain metastases have been lagging behind in oncology research, despite having a significant impact on the survival and quality of life of thousands of patients.

Manuel Valiente, a researcher at the National Cancer Research Center (CNIO) and one of the most authorities in the field, called for an immediate change: more clinical trials that include patients with brain metastases and provide treatments specifically designed for this condition.

Valiente analyzes why the brain remains a particularly complex frontier in oncology, the importance of early diagnosis, and how progress is (still not enough) even as new treatment options begin to emerge for a disease that already affects about 30% of cancer patients.

"Brain metastasis has been largely forgotten in oncological research and clinical trials for the last ten years. But the last eight years have seen more people investigating it from a laboratory perspective, and more interest in giving patients more options from a clinical perspective," the researcher said.

What often happens, he notes, is that with cancers that affect the brain, one of the problems that needs to be worked on more is that drugs don't cross the blood-brain barrier;"For this reason, diseases related to the brain have an additional complexity," he says.However, it is noted that over the past eight years, interest in these cases has increased.

For example, now, half of patients who relapse during immunotherapy have brain metastasis, "something that happens to many patients," he laments."The new treatment works well, but over time it begins to fail and metastases grow in the brain. From an oncology point of view, this slows the progress of many patients, so it is imperative to research brain metastasis," he emphasizes.

The importance of early diagnosis

In this case, another of his main "advantage" today, the researcher says, is the importance of early diagnosis in brain metastasis, as in other cancers. "Early treatment is always easier because the longer the tumor, the greater its complexity," he said.

In addition, he showed that, for example, immunotherapy is better for brain metastases that are smaller and do not require corticosteroids, but if it is more advanced, he says, the response rate can drop to 20%.

And the current reality is that the development of brain metastases in various cancer diseases is not monitored, it is not reported, when it is often common, especially in lung neoplasms, but also in breast cancer, melanoma, colorectal cancer, as has been proven in recent years.

"We need liquid biopsy biomarkers, non-invasive procedures that will allow us to detect cases of brain metastases. The good news is that these screening strategies are already starting to be published in scientific studies, they are being considered and, for example, last year a study was published which showed that by looking at a patient's blood in the case of very early lung tumors, it is possible to predict the epigenetic features of brain metastases in the blood. However, this is a study that, although conducted on patients, needs to be repeated in other groups and types of primary tumors," says ManuelValiente.

There are more and more cases

But, in addition, in recent years, the incidence of brain metastases has been increasing.Although, as Manuel Valente emphasized, "surprisingly, there are no epidemiological studies of brain metastases, the main phenomena are not clear in the world, there are no officially verified data, so we are talking about what are the trends we are seeing."

For this reason, he notes, more effort is needed to design clinical trials that include these patients, but this has not been done so far, and at the same time, work on ideas about how drugs penetrate the brain, which is currently unresolved, given that many are not equally effective in brain tumors.

In fact, he pointed out that ten years ago there was no test dedicated to analyzing the response of brain metastases to more modern drugs, including antibodies combined with chemotherapy, targeted therapy or immunotherapy when "it is a need for cancer today."

Specific therapy required

In an article published in "Trends in Cancer", which highlights the results of recent years of research on brain metastases, they complained that there is an unmet clinical need, namely that specific treatments should be found for brain metastases, since 30% of cancer patients develop them, especially in cases of breast, lung, skin, colon and rectum;And there is no current specific treatment for these people other than surgery and radiotherapy.

"Although there have been relative advances, there have been many advances in brain metastases surgery, and also in local radiation therapy; but it is not clear from a methodological point of view. Today, the concept of precision medicine is based on the type of primary tumor that occurs in the patient, but it does not take into account the changes in the metastasis, because there is not necessarily the same reaction as the primary treatments and the primary tumors. metastases, its application is not for the general population of thesepatients, but only for a small group of them", he explained.do

This reference explains that the working hypothesis for finding this specific drug is based on the fact that cancer cells have evolved to adapt to the new organ they need to grow, which includes metastases.

For this reason, Valiente insists that the current treatments must remain correct, but in his opinion the door should not be closed to other short-term treatments, "which should not be the same as those directed against the main tumor. Losing the chance of a cure," he says.

In fact, he claims that the presence of brain metastases often has other consequences, in addition to tumor growth, that impair the functionality of the organ.Which can cause a number of neurological problems, such as cognitive or personality changes, which significantly impair the patient's quality of life.Except for patients who generally have to follow fairly aggressive treatment.

“The challenge in clinical management of these patients is to care for the patient's quality of life.It is currently unknown why brain metastases occur with more severe functional damage in relation to the central nervous system when there are others that are not so affected.We are currently working to identify molecular and cellular mechanisms that can explain the heterogeneity of the functional effect of metastases or prevent the metastasis branch from turning towards them, which we will prevent the hand hypothesis with the hypothesis when they are already present,” concludes Manuel Valiente.