Pulmonologist Dr. Lizza Hendriks (Maastricht UMC +) specializes in thoracic oncology and conducts research on the personalized prevention and treatment of brain metastases in lung cancer. “Doctors shouldn’t be too nihilistic, but on the other hand they should remain realistic.”
Brain metastases in lung cancer are far from rare, says lung specialist Lizza Hendriks. As a lung treatment specialist, she prefers to prevent brain metastases. “Prophylactic cranial irradiation (PCI) has been shown to significantly reduce the incidence of brain metastases. However, some of the patients develop neurocognitive disorders. This is why we want to be able to predict who is at high risk of brain metastases and neurocognitive disorders after CP, in order to make a personalized treatment decision together with the patient ”.
Predicting brain metastases
For stage III and IV small cell lung cancer, Hendriks and colleagues are investigating whether radiomics (advanced quantitative analysis of standard imaging) can predict who will develop brain metastases. “The idea is that the primary tumor is already preprogrammed to spread to the brain or not and we hope to be able to detect it with radiomic analysis. In a small series of 105 patients, we were able to reasonably predict who will not develop metastases. with a negative predictive value of 0.81. We are now evaluating the results internationally in a larger group of patients. If this is ultimately validated prospectively, it is possible to better educate patients about the usefulness of PCI. Now we are also trying to more systematically map risk factors for neurocognitive decline after PCI. Our previous review has shown that risk factors, such as some combination drugs and cardiovascular disease, are not always adequately considered. “
Prophylactic irradiation of the skull
Hendriks also focuses on locally advanced non-small cell lung cancer (NSCLC stage III). Standard treatment is chemoradiotherapy, followed by one year of immunotherapy. “Despite the curative intention, these people have about a 15% chance of brain metastasis. In the pre-immunotherapy era, PCI has been shown to reduce the incidence of brain metastases in this group, resulting in longer progression-free survival. The PCI has also proved convenient “. Due to the lack of survival benefit, PCI has not become the standard of care. The Dutch multicenter study NVALT28, with Hendriks and Prof. Dirk de Ruysscher (Maastro Clinic) as principal investigators, is now investigating whether adding low-dose PCI over adjuvant immunotherapy alone can reduce the rate of brain metastases by 15%. to 5%. “We opt for half the dose of radiation, because immunotherapy and radiation are mutually reinforcing. In this way we hope to maintain efficacy, with fewer side effects “.
Targeted therapy and local radiotherapy
Hendriks also focuses his research on patients with metastatic NSCLC. After all, a quarter of these patients already have brain metastases at the time of the first diagnosis. “There are also many new treatment options for this group. Targeted therapy can mean a lot to patients with specific mutations, others may benefit from immunotherapy, possibly in combination with chemotherapy. “
However, there are still many open questions. “For example, with targeted therapy, after a first response, brain metastases grow back, while the rest of the disease remains under control. Ideally, you want to treat brain metastases locally. The question is, is it necessary to temporarily stop targeted therapy to prevent the combination from causing further neurocognitive side effects? Or is it better to continue, so that the cancer does not grow back? We are now conducting a multicenter study in the patient group for which we choose to continue with targeted therapy. We conduct thorough memory tests, before and after radiation. If we do not find any indications on the harmful effects of the combination of radiation and targeted therapy, from now on we can safely continue with targeted therapy “.
Brain Metastasis Screening
Finally, Hendriks is interested in the desirability of screening for brain metastases in metastatic lung cancer. “American and European guidelines recommend it, preferably with MRI. However, it has never been proven that people live better or longer, “Hendriks notes.” At the same time, you do incriminating research on people and some of them have to live knowing that something is growing in their heads. We recently discussed this. problem in focus group with patients with asymptomatic brain metastases and relatives. This shows that patients appreciate MRI: even if diagnosis is difficult, most still want to know and even pay an MRI for it. Patients like the feeling. to be observed and hope that action can be taken before they develop headaches or epilepsy, for example. They may also better prepare for the future. The question remains whether screening is clinically meaningful and how exactly to define “clinical benefit.” set goals for this in the future together with the patient association “.
Not nihilism, but realism
When asked for a message to MedNet Oncology readers, Hendriks points out that the prognosis of lung cancer patients with brain metastases is often much better than before, thanks to targeted immunotherapy. “Doctors should therefore not be too nihilistic, but on the other hand remain realistic,” he advises. “People with a Karnofsky score below 70 who are not eligible for targeted therapy will very often have a short survival. The guidelines prescribe to provide only supportive care and I fully agree “, he says.” So, take a good look at the individual patient with all his characteristics and above all talk about the patient in an MDT to arrive at an optimal treatment plan ” .
