Brain metastasis is one of the major causes of lung cancer treatment failure and death in lung cancer patients. In recent years, as the incidence of lung cancer increases, the incidence of brain metastasis of lung cancer has increased with the improvement of cancer treatment methods and the prolongation of patients’ survival. Brain metastasis from lung cancer greatly affects the quality and survival of patients. For most patients with brain metastases, although treatment cannot significantly prolong patients’ survival, patients’ quality of survival can be greatly improved.
I. Incidence
Lung cancer is the most common intracranial metastatic tumor. Small cell lung cancer (SCLC) is the most common intracranial metastasis, followed by undifferentiated large cell carcinoma, adenocarcinoma, and squamous carcinoma. About 10% of patients with small cell lung cancer have brain metastases at the time of diagnosis, and the incidence of brain metastases is as high as 80% for patients who survive for more than 2 years after treatment. About 1/3 of surgically resected non-small cell lung cancer (NSCLC) fails due to brain metastases, and up to 50% or more at autopsy, and mainly adenocarcinoma. Even for stage I NSCLC without intrathoracic lymph node metastasis confirmed by postoperative pathology, 5% of them showed brain metastasis symptoms within 3 months after surgery, suggesting the presence of asymptomatic microscopic brain metastases before surgery.
Mechanism of brain metastasis
The mechanism of intracranial metastasis of lung cancer is not fully understood. The route of intracranial metastasis is mainly through bloodstream metastasis. Lung cancer grows fast and the tumor is prone to necrosis and shedding due to insufficient blood supply. Lung tissue is rich in blood vessels, and cancer cells enter the body circulation through pulmonary veins, and then form metastases with the carotid artery or vertebrobasilar artery upstream to brain tissue.
Pathological characteristics of brain metastases
Brain metastases of lung cancer tend to be multiple. The multiple metastases account for 70% to 86%, while the single metastases account for only 14% to 30%. 80% to 85% of the metastases are located in the brain, the cerebellum accounts for 10% to 15%, and the brainstem accounts for only 2% to 3%. Meningeal invasion is less common than brain metastases and is more common in SCLC patients. Dural metastases are more common than soft meningeal metastases. The cancer cells spread to the soft meninges and spread through the cerebrospinal fluid, which can infiltrate the cortex, cranial and spinal nerves, and cause cerebrospinal fluid circulation disorders at the same time. The brain tissues around the metastases often have ischemic edema, necrosis and even hemorrhage due to local mechanical compression or insufficient blood supply. In larger tumors, necrosis and cystic degeneration are often present in the center.
Based on the patient’s history of primary lung cancer tumor, clinical symptoms and signs and relevant special examinations such as computed tomography (CT) or magnetic resonance imaging (MRI) to detect intracranial occupying lesions and exclude primary brain tumor and other tumors, the clinical diagnosis of lung cancer brain metastasis can be established. Brain metastasis mostly occurs within one year after treatment. Those who have a history of lung cancer and develop increased intracranial pressure and/or psychoneurological symptoms should first consider intracranial metastases. In the diagnosis and treatment of lung cancer, attention should be paid to asking whether there are clinical symptoms of intracranial metastasis and conducting corresponding neurological examination. If there is any abnormality, further CT or MRI examination should be performed. Preoperative staging examination must include cranial CT or MRI to exclude patients with lung cancer who have only pulmonary symptoms without any intracranial hypertension symptoms. After the diagnosis of brain metastasis of lung cancer is established, patients need to further clarify the scope of metastasis, and relevant examinations of the whole body, such as abdominal ultrasound and ECT scan, should be done at the same time to provide a basis for further treatment. The diagnosis of brain metastasis mainly relies on imaging.
1.CT Enhanced CT examination is one of the most reliable means to diagnose brain metastases at present. At present, the diagnosis and efficacy evaluation of most studies take CT as the standard. CT can clearly show the size, location and number of metastases. The typical presentation of brain metastases on CT plain scan is an isolated round-like mass, mostly isointense or slightly hypointense, which is related to the cellular composition of the tumor, the blood supply, the degree of necrotic cystic degeneration, and whether there is bleeding and calcification. Contrast injection to enhance the scan can make the lesion more clear. It is worth noting that the false-positive rate of cranial CT examination can be as high as 11%, so some people advocate that tumor biopsy should be performed after CT detection of intracranial lesions. In addition, CT is unsatisfactory for lesions smaller than 0.5 cm and subcurtain metastases. Therefore, repeat CT examination or further MRI examination is needed when necessary.
MRI is the best test to diagnose brain metastasis, which has the advantages of better soft tissue contrast and multi-planar and multi-directional display compared with CT, and can better distinguish the anatomical structures in the skull. Therefore, MRI is easier to detect brain metastases at an early stage than CT, and early metastases can be shown by MRI when CT does not show any abnormality; MRI can better show multiple foci, and many people with single foci on CT scan are diagnosed as multiple foci by MRI, and more foci and larger tumors are often found after enhancement. In particular, MRI is easier to diagnose than CT for subcurtain metastases.
3.Cerebrospinal fluid examination
The detection of cancer cells in cerebrospinal fluid is a reliable basis to confirm the diagnosis of soft meningeal involvement. Cerebrospinal fluid examination is easy to perform, and most patients are not contraindicated to undergo lumbar puncture except for those with severe intracranial pressure increase. However, a negative cerebrospinal fluid test cannot exclude meningeal metastases from the tumor. Cerebrospinal fluid examination can also be used to observe the effect of treatment. After treatment, malignant cells in cerebrospinal fluid may disappear and sugar in cerebrospinal fluid may increase or return to normal in some patients.
4.Other tests
Although stereotactic aspiration biopsy is an invasive test, it can accurately puncture the tumor site under CT guidance to obtain pathological evidence, exclude the primary intracranial tumor and avoid misdiagnosis and misdiagnosis. In addition, if the primary tumor has been cured for many years and it is difficult to exclude metastatic cancer from isolated intracranial lesions, or if the diagnosis of intracranial occupying lesions is unknown, surgical exploration can also be performed under selected conditions to confirm the diagnosis. Cerebral angiography was once the most common examination method in neurosurgery. It is difficult to be accepted by patients because it is painful, complicated, and dangerous. Cranial plain radiography is used to examine some brain metastases with cranial metastases. For metastases close to the skull, cranial bone destruction or even nodules can be seen on X-ray when the skull is invaded. There may be signs of cranial hypertension on the cranial X-ray. Chest radiography may reveal primary lung cancer. Other examination methods such as EEG, brain ultrasound and radioisotope examination also have certain reference value for the diagnosis of intracranial tumor.
IV. Differential diagnosis
When diagnosing brain metastases from lung cancer, attention should be paid to differentiate them from primary brain tumor, brain abscess and cerebrovascular disease to avoid misdiagnosis as metastases. If neurological symptoms are the first manifestation and a single occupying lesion is found on imaging, primary brain tumor should be excluded. 11% of single central nervous system nodal lesions are non-metastatic. Sometimes stereotactic puncture biopsy or post-surgical pathology is required to make a definitive diagnosis.
The clinical manifestations and CT examinations of the above mentioned lesions are sometimes not easily distinguished from brain metastases: severe cerebrovascular disease (e.g. intracerebral and subdural hematomas) can also occur in the late stage of cancer due to impaired coagulation mechanisms, brain softening can be caused by a large number of tumor emboli in the middle cerebral artery, and metastatic intratumoral abscesses can be formed by tumor emboli and septic emboli from lung cancer. Therefore, it may lead to delay in the diagnosis of brain metastases, and stereotactic aspiration biopsy, surgical exploration and cerebral angiography are feasible to confirm the diagnosis if necessary. Comprehensive examination should be enhanced in the diagnosis of primary tumors to exclude the possibility of other tumors such as breast cancer and malignant melanoma that are prone to brain metastases. It is worth noting that patients with small cell lung cancer may also have neurological symptoms, mainly dementia, psychiatric disorders, myasthenia gravis, etc. These symptoms may subside or remit after lung cancer resection or chemotherapy. In addition, psychoneurological symptoms may also appear in patients with water-electrolyte disorders, hypoglycemia and severe psycho-psychiatric diseases. It should be avoided to mistake the treatable concomitant and complications as advanced brain metastasis and give up the necessary efforts prematurely.
V. Treatment
Lung cancer brain metastasis is a common cause of treatment failure for lung cancer, and the natural survival of patients with lung cancer brain metastasis is only 1 month. In recent years, with the diagnosis of brain metastases, the improvement of surgical techniques and the application of stereotactic radiation technology, the use of active comprehensive treatment has further prolonged the survival period and improved the quality of survival for those with brain metastases only.
The aim of treatment for brain metastases is mainly to prolong the survival period and improve the quality of survival of patients. The treatment of brain metastases is part of systemic therapy, and the key to improving the survival rate of patients with brain metastases also lies in enhancing the control of extracranial systemic diseases. Treatment of brain metastases requires comprehensive consideration of the patient’s age, general condition, neurological status, primary tumor site, the presence of extracranial multiple metastases, and the number and location of brain metastases. The main treatment methods include symptomatic support therapy, surgery, radiotherapy and chemotherapy.
Radiotherapy, chemotherapy, surgical treatment and SRT have palliative effects on brain metastases. Simultaneous symptomatic supportive treatment can reduce complications and improve the efficacy. The choice of treatment modality should be based on the patient’s general condition, control of extracranial systemic diseases and the size, number and location of brain metastases, etc. to select the best treatment plan for the individual.