Previously, studies have shown that malignant brainstem gliomas in pediatric patients have a poor prognosis.[10, 11] Therefore, there is a need to discover a new complete prognostic scoring system for an accurate and useful prognosis assessment. A nomogram is a graphical representation of complex mathematical formulas.[12] The nomogram showed much more convenience and accuracy when used in clinical applications. A higher C-index means a better predictive value.[13, 14] The nomogram utility has been assessed in many fields, like bladder cancer,[15] esthesioneuroblastomas,[16] non-metastatic breast cancer,[17] or in neurosurgery of cancers like glioblastoma[18] and so forth. Of note, this is the first research to introduce nomogram into pediatric primary BSMG before the onset of therapies.
It is commonly believed that the prognosis of cancer patients depreciates with age. Previous studies of adult patients with brainstem gliomas have shown that younger age is a prognostic factor for improved survival.[19-21] Doyle et al. reported that those patients whose age was more than 50 years significantly signified a worse prognosis than younger cohorts.[22] However, in pediatric patients, the situation was different. Our study showed that the patients older than nine years had a better prognosis. In our opinion, this could be due to the patient's younger age, which decreased their tolerance to the disease and treatment measures. Notably, the research by Sun et al. supported our findings. Here, a significantly better prognosis was observed in patients whose age was more than ten years.[7]
Regarding the size of the tumor, the large size (defined as tumors with dimensions greater than 25mm) was an independent predictor of mortality in our patient cohort. Maxwell et al. established that the tumor size, which was larger than 34mm was a significantly worse predictor of mortality in his cohort.[11] Large size (>2 cm), enhancement, and invasion of adjacent brainstem structures on head MRI are signs of more aggressive tectal lesions[23]. Besides, the brainstem contained an extremely high density of critical structures.[24, 25] Nevertheless, as the tumor diameter increased, these critical structures are more likely to be compressed, which partly defined the surgiCal complexity.
Interestingly, pediatric BSMGs diagnosed after 2003 had a significantly better prognosis than that before 2003. It has been gradually recognized that brainstem gliomas comprise a heterogeneous group of tumors, and the patients could benefit from introducing the concept of precision and individualized therapeutic methods.[26] As the study progressed, a better understanding of the biology of BSMGs would improve treatment options and outcomes undoubtedly.[27] In previous studies, the biopsy is warranted in cases only when tumor progression.[28] Nevertheless, subsequent research suggested that brainstem stereotactic biopsy in children was a safe procedure and could alter the treatment recommendations.[29] There is minimal long-term benefit from chemotherapy, and the mainstay of treatment for BSMGs is radiotherapy. After 2003, it has been demonstrated that the use of radiochemotherapy may improve treatment efficacy.[30-33] All of the abovementioned facts can directly lead to better survival among pediatrics diagnosed after 2003.
According to the 2016 World Health Organization (WHO) of the Central Nervous System Grading Standard, gliomas are divided into four grades (I–IV), depending on the histological and molecular features.[34] High-grade gliomas (WHO grade III-IV) are more aggressive and invasive than low-grade (WHO grade I-II), and high-grade brainstem gliomas have shown poorer survival rates in pediatrics[35, 36], which is in line with our findings. Lesions with focal enhancement on head MRI in pediatric BSMGs were found mostly low-grade glioma.[37] Necrosis and inhomogeneous contrast enhancement were regarded as significant predictors of high-grade brainstem gliomas.[38] Recurrent mutations of a regulatory histone-H3F3A,[39] gain of H3K27 methylation at p16INKA4A,[40] and upregulation of MYCN in G34R/v mutated[41] were associated with carcinogenesis, tumor progression, and the risk of pediatric high-grade gliomas and had a significant effect on survival.
We divided pediatrics patients into low and high-risk groups according to their total points calculated from the nomogram. Kaplan Meier survival analysis showed significant differences in cancer-specific survival between low and high-risk groups. Thus, particular attention was given to these pediatric BSMGs with total points higher than 92.3 or tumor diameters larger than 2cm because of their poor outcomes.
In this study, we performed calibration and validation after the nomogram was constructed. Here, the receiver operating characteristics (ROC) were plotted using the calibration method, and the respective areas under the receiver operating characteristic curve (AUC) were calculated. The obtained calibration curve and high AUC values confirmed that our nomogram model was reliable, and its predicting capability was robust. Therefore, using these models, we can predict pediatric patients' survival with BSGM more accurately and provide the basis for individualized treatment for these patients. Finally, the DCAs of the nomogram in 1‐, 3‐, and 5‐year show that net benefits could be obtained in both the training and validation cohorts.
This study has some drawbacks. First, our study was based on the SEER database. This database lacks some vital information on tumor biological data, such as MGMT (O (6)-methylguanine-DNA methyltransferase),[42] promoter methylation, and IDH (isocitrate dehydrogenase) mutations,[43] or H3 K27M,[44] which have substantial prognostic value in pediatric patients suffering from glioma. Secondly, it has no detailed description of the relationships with neurovascular structures and the precise location of the lesions in the brainstem. Thirdly, this is a retrospective study and cannot define causality. However, compared to other reported studies, it has the largest sample size, a strength.