In this retrospective cohort study based on SEER database, we developed and verified a new prognostic model based on three clinical variables (histology, site, size) for the first time. Compared with clinical risk factors, our model can improve the prediction ability of prognosis in children and adolescents with CNS GCTs.
Our results show that GCTs histology, tumor site and size may be important predictors of CNS GCTs survival in children and adolescents. In addition, we also established a nomogram based on high-risk factors to predict the 5- and 10-year survival probability of children CNS GCTs, and verified the stability of the model through internal validation.
Consistent with other cancers, the histological type of intracranial germinoma has a significant influence on the prognosis of children. In our study, it was found that NGGCTs scored 76 points in the nomogram constructed based on multivariate regression analysis, which was significantly higher than GGCTs. Compared with other germ cell tumors, NGGCTs have higher invasiveness and malignancy, and poor prognosis. This is consistent with the findings of Matsutani et al., that germinoma with different histological characteristics has a significant impact on the prognosis of patients. In addition, the clinical treatment of NGGCTs generally requires the combination of surgery and postoperative radiotherapy and chemotherapy, and the treatment complications are also prognostic factors that cannot be ignored, which can be further explored in future studies.
In this study, the site of intracranial germinoma was only screened in LASSO regression but was not statistically significant in univariate COX regression (P = 0.087). This may be related to the incomplete statistics of the SEER database itself, as some tumors are present in multiple intracranial sites simultaneously. Intracranial germinoma usually occurs in the sellar region, pineal gland, basal ganglia and other parts. In our study, the number of germinomas in the pineal region was 48.2%, and Acharya et al. also reported that about half of CNS GCTs occurred in the pineal region. We found that tumor location was also an important factor affecting the prognosis of children. This may be due to the fact that the pineal region is located in an important intracranial anatomical site, which may cause increased intracranial pressure, diabetes insipidus, sleepiness and other changes in consciousness. In addition, because the pineal region is located deep in the brain, it is difficult to treat, resulting in a poor prognosis of tumors in this region.
Tumor size is known to be an important prognostic factor in many solid tumors. The variables screened by us through LASSO also included tumor size, indicating that the prognosis of CNS GCTs was significantly correlated with it. We found that the poor prognosis of CNS GCTs in children and adolescents was associated with tumor size, and the prognosis was worse as the number of tumors increased. This may be associated with a large germ cell tumor infiltrating the surrounding tissue and requiring craniotomy and postoperative chemoradiotherapy. And the treatment of small tumors jin only simple chemoradiotherapy. It is worth noting that craniotomy itself can cause great collateral damage to children, especially deep brain tumors. Therefore, in future studies, the size of the tumor needs to be further refined. Unlike previous studies, we did not find a correlation between age, sex, race, or treatment and the outcome of intracranial germinoma in children. This may be caused by a difference in the way we classify variables.
Currently, the impact of risk factors related to CNS GCTs on prognosis remains controversial. In addition, independent prognostic factors may be difficult to predict the prognosis of germinoma. A variable PI was calculated using the three risk factors, and the children were classified into high-risk and low-risk groups. The survival curve (Fig. 5, C and D) showed that there was a significant difference in survival time between the high-risk group and the low-risk group, and the difference between the development group and the validation group was statistically significant (P < 0.0001). We tested the stability and accuracy of the new prognostic nomogram model. The consistency index of the model in the development group and the validation group was 0.744 and 0.759, indicating that the model has the good predictive ability and can be used in clinical practice. In summary, the prediction model constructed by multiple factors has a more significant effect on prognosis than that of a single factor, and it is a very promising method for predicting prognosis in the future.
There are still limitations to the study. First, the SEER database is retrospective data with limited clinical information of patients, and there may be selection bias in inpatient data. Future randomized controlled trials are needed to validate prognostic risk factors for germinoma. Second, the current prognostic model is only validated based on internal data, and external validation is needed in the future. Nevertheless, our nomogram helps predict the prognosis of CNS germinoma in children with good accuracy.