Brainstem cavernous hemangioma is a relatively rare type of intracranial vascular malformation and accounts for 4–35% of cases . Brainstem cavernous hemangioma can occur anywhere in the brainstem but are more common in the posterior-midbrain region . However, the number of patients with brainstem cavernous hemangioma is so rare that it leads to a lack of understanding of the general features of brainstem cavernous hemangioma. The population counted in the SEER database was collected from most of the United States, representing approximately 48% of the U.S. population , which allowed us to investigate the general prevalence of brainstem cavernous hemangioma patients using the SEER database. In the SEER database study, we analyzed various factors that may be related to the prognosis of patients with brainstem cavernous hemangioma. Our report can explain, to some extent, the epidemiology and survival of patients with brainstem cavernous hemangioma in the United States.
First, the age-adjusted incidence rate was 0.0236 cases per 100,000 person-years between 2000 and 2019, which means that it is a very rare disease and may be the reason why there is less research related to the disease. The SEER database is a platform that allows us to analyze various variables. Among all variables considered, age was strongly associated with the occurrence and prognosis of the disease (P < 0.001). In Table 2 shows that age was a univariate and multivariate risk factor for disease. The best prognosis was observed in patients under 40 years of age and the worst in those over 60 (P < 0.001, Fig. 3C). This may be related to the time at which risk factors affecting the vasculature (e.g., hyperlipidemia, hypertension) play a role in the vascular branches supplying the brainstem. Moreover, the older the age, the longer the risk factors remain, and the greater the chance of causing brainstem cavernous hemangioma. This may also be related to the fact that people over 60 cannot tolerate surgery for treatment, have a low rate of surgical benefit, and have other brain diseases due to hypertension. However, these are only estimates, and the exact mechanism is not yet clear. In addition, brainstem cavernous hemangioma was found incidentally on MRI during the examination, and the final cause of death was brain diseases other than brainstem cavernous hemangioma . Therefore, people over 60 years of age are more likely to have a poor prognosis because they are more susceptible to other brain diseases or worse physical conditions.
As in other SEER studies, there was a higher incidence in white people [10, 11]; possibly because there are more white people in the geographic area, or white people are more susceptible than others. However, the number of cases is too small to determine the correlation, which future studies can investigate.
All brainstem cavernous hemangioma were benign in nature. Therefore, we speculate that the prognosis of brainstem cavernous hemangioma is generally good, and the poor prognosis is related to the size of the tumor as benign tumors usually affect patients with symptoms of occupational compression. However, tumor size was not significantly associated with prognosis in patients with brainstem cavernous hemangioma (P = 0.244, Fig. 3H). Most tumors (62.2%) were < 3 cm in size. These tumors have mild compression symptoms, but hemorrhagic seizures caused by brainstem cavernous hemangioma can lead to severe symptoms such as hemiparesis, respiratory dysfunction, and disorders of consciousness due to their dangerous location . In addition, the impact of brainstem cavernous hemangioma on quality of life is obvious . As shown in Fig. 3H, there was no significant relationship between the size of the tumor and the survival prognosis of the patients within four years; but after four years, the prognosis of patients with tumors less than 3 cm was significantly better than that of patients with tumors > 3 cm. It may be that the compression symptoms contributed to the poor prognosis four years later.
As brainstem cavernous hemangioma is a benign disease; many patients did not undergo surgery. Approximately 37.1% chose to undergo surgery, but the difference between those who underwent surgery and those who did not was not was not significant (P = 0.455, Table 2) according to the log-rank test, and the improvement in prognosis was not particularly significant. Nevertheless, patients who underwent GTR surgery had a better prognosis than STR and those who did not undergo surgery (P = 0.024, Fig. 3G). More interestingly, we divided patients into two groups (< 50 years, ≥ 50 years) according to the age at diagnosis (Fig. 4A), and analyzed their overall survival. As a result, patients who were diagnosed before the age of 50 and then underwent surgery had better prognosis than that of those after the age of 50 (P = 0.003, Fig. 4B). Although surgery is not effective for all patients with brainstem cavernous hemangioma, it is recommended for patients with indications for surgery and those requiring intensive care [12, 14]. Therefore, the earlier the disease is diagnosed and cleaner the tumor is resected, the better the prognosis of patients. However, surgery in the brainstem is not easy and full of risks .
The brainstem regulates vital activities in the body. Therefore, we suspect that diseases in this area are less suitable for surgical treatment because surgery causes greater damage compared to other treatments. However, few patients were treated with chemotherapy and radiation; therefore, we did not perform Kaplan-Meier analysis and log-rank tests for chemotherapy and radiation. Surgery remains the main treatment modality for patients with brainstem cavernous hemangioma . However, for brainstem cavernous hemangioma, surgical removal comes with great risks as it is difficult to remove from the surgical site or has important nerve tissue in the adjacent area that needs to be removed. Therefore, it is challenging for neurosurgeons to choose the best surgical approach and technique for the patient prognosis . According to recent studies, there is no specific recommended treatment for chemotherapy, and there are only examples of researchers using propranolol to treat brainstem cavernous hemangioma . When using radiation therapy, most current studies have been performed using gamma knife radiosurgery or stereotactic radiosurgery [19–21].
This study had some limitations. First, the disease is relatively rare, with few cases. Although the SEER database provides a large data platform, there is still very little data on brainstem cavernous hemangioma, and the conclusions drawn may be biased. In addition, the understanding of brainstem cavernous hemangioma is not well developed, its etiology and risk factors are unclear, and there is no unified indicator for how it develops and the prognosis of intervention after treatment, which needs to be studied by future researchers. Furthermore, this study only epidemiologically analyzed data from more than 200 people and only found that age and treatment modality may influence their prognosis; therefore, we hope we can continue to study more in the future with more data from the SEER database. Despite these shortcomings, the limited data may help clinicians and researchers in this area of research and help them better understand this disease.