The current recommended treatment for patients with newly diagnosed GBM is resection followed by adjuvant chemoradiotherapy. Based on the new histopathological criteria for glioma, the presence of IDH mutations was highlighted as important to the distinct prognosis of patients with GBM. However, it remains unknown whether total resection is beneficial for patients with wild type IDH GBM. The current study generated a risk scoring system that included information regarding clinical characteristics and IDH mutation status to evaluate the risk factors associated with the prognosis of GBM patients and to predict the survival outcomes at 12, 15, 18, and 24 months. It was determined that total resection, age < 60 years, received chemotherapy, and IDH mutation were independent factors associated with improved OS. Moreover, this study confirmed that totally removing the region of contrast-enhancement of GBM was beneficial for prolonging the OS of those with wild type IDH.
Total resection of the contrast-enhancement region of tumor has been proven the most beneficial factor for improving OS in patients newly diagnosed GBM patients.[1, 4, 19, 20] Removing more than 78% of contrast-enhancement of GBM has also been shown to be valuable for OS.[4] Moreover, Sawaya et al. recommended that more than 53.21% of the surrounding region of the T2-FLAIR abnormality beyond the 100% contrast-enhancement resection should be removed since that was able to bring more benefit for prolonging OS than only removing the region of contrast-enhancement.[15] Our findings were consistent with previous studies. In our risk scoring system, the impact coefficient of total resection was nearly twice that of other variables. Our findings re-verified that total resection was essential for improving OS of patients with GBM. Furthermore, referring to the literature review recently published, whether patients with GBM and wild type IDH have benefits associated with totally resection still unknown.[18] Our results confirmed that total resection would not only significantly prolong OS of patients with GBM and IDH mutations but also would prolong OS in patients with IDH wild type (supplemental part 2).
Radiation therapy plus chemotherapy is helpful for prolonging OS of patients with newly diagnosed GBM.[10, 11] Although the period of enrolled patients was too long to implement uniform treatment strategies for chemotherapy, having received chemotherapy was an independent favorable factor for OS. Hence, our findings suggest that chemotherapy was necessary for patients with newly diagnosed GBM. Additionally, our results showed that having received radiation therapy was not a significant beneficial prognostic factor for OS. However, our findings did not suggest that radiation therapy was unnecessary for the treatment of newly diagnosed GBM. As various previous studies have shown, [21–23] radiation therapy was undoubtedly beneficial for the OS of patients with GBM. In our study, almost all patients (nearly 90%) received radiation therapy. Hence, there was no significant difference in OS between the patients with and without radiation therapy. Hence, the variable of receiving radiation therapy was not selected to generate our risk system because all patients were recommended to receive radiation therapy after GBM resection at present.
Although the mutation rate in primary GBM was much lower than that in secondary GBM, IDH mutations were reported to have a strong positive correlation with OS in GBM.[24, 25] Our previous study showed that the IDH mutation status was able to predict the OS of patients with secondary GBM by using microRNA signature. In the current study, the IDH mutation status could be applied to classify the survival outcomes of newly diagnosed GBM patients. Using the criteria regarding histological tumors in neural central system (WHO 2016), it was recommended that molecular characteristics (IDH mutation, 1p/19q co-deletion) be used to diagnose different kinds of glioma.[3, 16] However, to our knowledge,[1, 6, 12, 26] our risk system was the first evaluative system, generated based on clinical characteristics, information regarding adjuvant treatment, and the IDH mutation status, to classify the survival outcomes of patients with GBM. Our findings remedied the lack of inclusion of molecular information in the evaluative systems that were previously recommended.
Our findings revealed that age > 60 years was significantly associated with decreased survival; similar findings have been shown in previous studies.[27–30] As has been previously demonstrated, elderly people may have a decreased ability to withstand neurological insults caused by the tumor, surgery, and/or adjuvant therapy.[27] In our study, there was no significant difference in the number of younger (≤ 60 years) and elderly (> 60 years) patients with total resection and chemotherapy. Consequently, we inferred that the reason that elderly age was still a negative prognostic factor because elderly people have fewer chances to undergo secondary surgical treatment or adjuvant therapy.[30] Moreover, we found a significant decline in the preoperative KPS score among elderly patients when compared with younger patients (p < 0.0001). This finding was consistent with those from previous studies, in which lower KPS scores were negatively associated with OS.[27, 31] These findings are likely explained by the fact that elderly patients may harbor tumors with different molecular profiles and resistance genes that confer more aggressive behaviors.[32]
The main advantage of our evaluative system was its stability; both the training and validation cohorts used the same cut-off values to classify survival outcomes. Moreover, the evaluative system was generated based on clinical characteristics and the IDH mutation status; these variables were processed in a binary manner. Our findings indicated that patients would possibly be able to live longer if they were younger than 60 years, received total resection and chemotherapy, and had an IDH mutation. Hence, our system will be efficient and accurate in assisting clinical neurosurgeons or oncologists to predict survival outcomes of patients. Additionally, we found that the AUC for survival prediction at 18 and 24 months was higher than that at 12 and 15 months in both the training and validation groups. This indicates that our system will be more advantageous for a long-term versus short-term survival prediction.
Although our system had some advantages for survival prediction, it was not externally validated to assess its robustness. In the future, multicenter trials will be performed to validate our risk system.