Evaluation of treatment results and factors affecting survival in high-grade glial tumor patients

Introduction: Brain and other central nervous system (CNS) tumors are the 8th most common cancer type in adults aged 40 and older. Gliomas make up 24% of all primary brain and CNS tumors; these tumors exhibit significant differences in histology, ranging from benign types to the highly aggressive and deadly Grade IV GBM. In recent years, a better understanding of the molecular characteristics of gliomas has aided in classifying patients based on genomic profiling. However, significant progress has not yet been made in clinical trial outcomes, and responses to new agents have been weak so far. The aim of our study is to retrospectively evaluate clinical symptoms, treatment outcomes, and prognostic factors by analyzing data from patients diagnosed with high-grade gliomas. With this data, we aim to provide insights for improving the future treatment and management of patients with different glioma types. Materials and Methods: This study included patients aged 18 and above who had been referred to the Medical Oncology Clinic of Akdeniz University Faculty of Medicine and were diagnosed with Grade 3 and Grade 4 Gliomas between January 2010 and December 2022. The study was planned retrospectively, and patient characteristics such as age at diagnosis, gender, ECOG performance score, histological subtype of the tumor, tumor localization, tumor size, administered treatments, type of surgical resection performed, receipt of adjuvant chemotherapy, and the number of cycles, radiotherapy status, relapse surgery status, comorbidity information were recorded by extracting data from patient records, hospital databases, and pathology reports. Factors influencing progression-free survival and overall survival in patients were assessed. Findings: The data of 324 patients diagnosed with high-grade gliomas were analyzed in this study. The mean age at diagnosis of the patients in the study was 54 years. The average overall survival (OS) was calculated as 36.92 months, the average progression-free survival-1 (PFS-1) was 19.85 months, and the average progression-free survival-2 (PFS-2) was 17.58 months. Univariate analyses revealed that the variables of age at diagnosis (p<0.001), having seizures at the time of admission (p=0.013), relapse surgery (p=0.001), re-radiation (p=0.017), receiving chemotherapy at relapse (p=0.013), Bevacizumab use (p<0.001), and the N/L ratio (p<0.001) were significantly associated with OS. In the multivariate analysis, age at diagnosis (p<0.001), receiving chemotherapy at relapse (p<0.001), and the N/L ratio (p=0.006) remained significantly associated with OS, while the significance of variables such as having seizures at the time of admission, relapse surgery, re-radiation, and Bevacizumab use disappeared. In the univariate analysis for PFS-1, a significant result was obtained for the variable of age at diagnosis. Patients aged 55 and above had a PFS-1 value 2.17 times worse than those aged below 55 (p<0.001). In the multivariate analysis for PFS-1, the significance of age at diagnosis continued, but no significant result was obtained from the other variables (p<0.001). For PFS-2, no significant difference was found in patients' survival times within the framework of variables such as relapse surgery, re-radiation, receiving chemotherapy at relapse, and Bevacizumab (p>0.05). In the multivariate analysis for PFS-2, a significant result was obtained for receiving chemotherapy at relapse. The likelihood of exitus for patients receiving chemotherapy at relapse was 0.478 times compared to those who did not receive chemotherapy (p=0.038). Conclusion: When examining our study data in conjunction with the literature, it becomes evident that surgery, radiotherapy, and chemotherapy are the standard treatment options for patients with high-grade gliomas. However, due to the limited treatment options currently available, aggressive disease progression, short survival rates, and early relapse periods continue to be observed in these patients. Although there has been some modest improvement in overall survival in recent years, the results obtained are still inadequate. In the context of contemporary regimens, concurrent radiotherapy with Temozolomide remains the cornerstone of treatment for patients diagnosed with high-grade gliomas. Histological subtypes and immunohistochemical markers have gained significant prognostic importance in today's context. There is a need for new and specific treatment modalities that significantly benefit survival. In the future, alongside morphological features, the evaluation of molecular analysis assessments in high-grade gliomas will contribute to the development of targeted therapies.