June 25, 2022

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Brain metastasis from lung cancer does not mean death!

Brain metastasis from lung cancer does not mean death! Immunotherapy may become a new hope for treatment.

 

Brain metastasis from lung cancer does not mean death! Although the current prognosis of patients with lung cancer and brain metastases is still poor, immune checkpoint inhibitors have shown a certain effect. The combined application of immune checkpoint inhibitors and traditional intracranial radiotherapy is expected to bring better prognosis for patients.

The brain is one of the most common distant metastatic sites of non-small cell lung cancer, and brain metastasis is also the main cause of death from advanced lung cancer.

The location, number, and size of brain metastases from tumors are closely related to concurrent symptoms and survival. Because brain metastases can seriously affect patients’ cognition, survival time, and quality of life, patients with central nervous system symptoms have a poor prognosis.

 

 


▌The hindering reason for brain metastasis treatment: blood-brain barrier

The goal of brain metastasis treatment is to improve survival and quality of life, and to prioritize the preservation of neurocognitive function.

The special structure of the brain, the “Blood-Brain Barrier” is a natural barrier that uses plasma and cerebrospinal fluid to form a moat to block most harmful substances to protect the safety of the brain.

Some people may ask, why do cancer cells enter the brain? Isn’t there a blood-brain barrier?

 

The cerebrovascular and vertebral arteries share vascular branches, so that lung cancer cells can migrate directly from the heart and carotid arteries to the brain without filtering through pulmonary capillaries. In other words, cancer cells enter the brain directly without passing through the blood-brain barrier.

In order for therapeutic drugs to enter the brain tissue, they need to pass through the blood-brain barrier to enter the brain. Chemotherapy drugs are too large to enter the brain or even cannot enter the brain. The moat that was originally used for protection has instead cut off the way forward. The biggest obstacle.

For example, after the common chemotherapy drug pemetrexed is used in patients with brain metastases, the concentration of the drug in the brain is only 1/10 of that in the peripheral blood, which is far from reaching the therapeutic concentration. This is the brain metastasis of chemotherapy drugs. The reason for the poor efficacy of the patient.

 

 

▌Immunotherapy becomes a new hope for brain metastasis treatment?

With the development of science and technology, medical technology continues to make breakthroughs, and immunotherapy has become the treatment method of modern medicine. In simple terms, the principle of immunotherapy is to reactivate the immune cells of the body’s defense mechanism, similar to initializing immune cells, allowing immune cells to be undisturbed, successfully identifying cancer cells and effectively killing them.

With the continuous development of PD-1 and PD-L1 inhibitors and corresponding combination therapies, immune drugs have become an important choice for patients with brain metastases from non-small cell lung cancer. By activating suppressed immune cells, and then play an anti-tumor effect, so immunosuppressants do not need to have a high blood-brain barrier passage rate.

In recent years, tumor immunotherapy represented by PD-1 and PD-L1 inhibitors has confirmed the therapeutic effect of immune checkpoint inhibitors on non-small cell lung cancer.

Although there is no clear pharmacokinetics to confirm that immunosuppressants can penetrate into brain metastases through the blood-brain barrier, clinical data show that immunosuppressants have a certain permeability to the blood-brain barrier of intracranial tumors, and PD-1 is found Inhibitors can improve the prognosis of patients with lung cancer brain metastasis to a certain extent, and the patients can tolerate it.

The relevant research of “Lung Cancer” shows:

When nivolumab (O drug) is applied to intracranial lesions of non-small cell lung cancer, the objective remission rate is similar to that of extracranial lesions, and it is hardly affected by the blood-brain barrier, and the control rate of intracranial lesions is 51%;

Pembrolizumab (Drug K) also has a certain effect on patients with untreated or progressing lung cancer brain metastases, and the remission rate of intracranial lesions can reach 33%;

Some scholars have found that asymptomatic non-small cell lung cancer patients with brain metastases treated with atelizumab (T drug) have a longer overall survival than those receiving chemotherapy.

In addition, the study of the PACIFIC trial also showed that duvalizumab (I drug) is superior to placebo in objective remission rate, progression-free survival and overall survival, and is effective for brain metastases that seriously affect the prognosis. The rate of drug I was lower than that of placebo (6.3% vs 11.8%), which significantly reduced the occurrence of high-risk metastases.

 

 

▌Immunotherapy combined with other treatments is effective?

Immunotherapy combined with radiotherapy, chemotherapy and anti-angiogenic drugs will also have an important impact on the treatment strategies of non-small cell lung cancer and its brain metastases.

After observing 4 cases of small cell lung cancer and 38 cases of non-small cell lung cancer patients with brain metastases, the researchers found that those who received concurrent treatment or first immunotherapy followed by intracranial radiotherapy improved the local control rate compared with radiotherapy followed by immunotherapy , The trend of reducing the probability of emerging brain metastases.

According to the KEYNOTE-001 study, pembrolizumab (drug K) in the treatment of stage I patients with advanced non-small cell lung cancer, analysis of radiotherapy before immunotherapy found that 42 patients received radiotherapy, of which 38 received extracranial radiotherapy. 4 patients received intracranial radiotherapy and 55 patients did not receive radiotherapy. The progression-free survival times of patients receiving radiotherapy and those who did not receive radiotherapy were 4.4 months and 2.1 months, and the overall survival times were 10.7 months and 5.3 months, respectively.

It is proved that immunotherapy combined with radiotherapy can make patients with advanced non-small cell lung cancer have a longer survival period, and immunotherapy combined with radiotherapy play a synergistic effect.

In a retrospective study, the efficacy of immunotherapy combined with radiotherapy in non-small cell lung cancer metastasized to the central nervous system was analyzed. The study included 17 cases of non-small cell lung cancer receiving immunotherapy and radiotherapy: radiotherapy before or during immunotherapy The 6-month intracranial objective response rates for patients and those who received radiotherapy after immunotherapy were 57% and 0%, respectively.

It can be seen that the combination of immunotherapy and radiotherapy, especially receiving radiotherapy before or simultaneously with immunotherapy, can indeed control metastatic cancer of the central nervous system.

Other reports have shown that patients with brain metastasis lung cancer who received intracranial radiotherapy and PD-1 inhibitors had better overall survival and brain control rates for concurrent treatment than immunosuppressive therapy followed by radiotherapy.

Studies believe that simultaneous immunotherapy and radiotherapy can improve the overall survival of patients with central nervous system metastases and reduce the appearance of new intracranial lesions. It shows that immunotherapy combined with radiotherapy, especially concurrent therapy, has better anti-tumor activity, and we look forward to further verification by prospective studies.

However, it should be noted that there are still many challenges to be faced when exploring the treatment of lung cancer brain metastases. The development of immunotherapy is still in a new field, which makes the treatment more difficult.

Although a considerable number of patients can continue to benefit from immunotherapy, the adverse effects of immunotherapy are still worthy of attention. Some patients will develop immune pneumonia, and subsequent immunotherapy may cause inflammation of multiple organs, and the proportion reaches 15-70%. There may be some problems in future treatment, and it is necessary to communicate with the attending doctor during treatment to find a suitable treatment plan.

 

 

▌Conclusion

Although the current prognosis of patients with lung cancer and brain metastases is still poor, immune checkpoint inhibitors have shown a certain effect. The combined application of immune checkpoint inhibitors and traditional intracranial radiotherapy is expected to bring better prognosis for patients.

Combination therapy of immunotherapy has shown some effect in brain metastasis of some tumors (such as melanoma), but the application of brain metastasis of lung cancer is still in the exploratory stage.

But there is no doubt that with the emergence of more and more treatments, the emergence of immunotherapy has given patients with brain metastases a glimmer of hope. If combined with the combined treatment to have an additive effect, it will greatly improve the lung cancer brain. Survival rate of patients with metastases.

 

(source:internet, reference only)


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