In our study, we reported that PNI score was an independent prognostic factor for survival in recurrent high-grade gliomas,and showed that patient with high PNI had better OS. Prognostic nutritional index (PNI) is an inflammation-based prognostic scoring system calculated by using two inflammatory markers, lymphocyte count and albumin. PNI has been originally used to assess the prognostic significance of nutritional and immunological status in malnourished cancer patients undergoing gastrointestinal surgery, and then it has been indicated as an independent and useful prognostic model for predicting survival in various tumors such as colorectal and genitourinary cancer9,22−24. Significance of preoperative PNI in patients with glioblastoma has been reported in the current literature. Zhou et al. showed that a PNI > 44.4 was an independent prognostic factor for better survival in patients with glioblastoma [HR: 0.47 (95%CI:0.23–0.97), p = 0.04)]17. Xu et al. revealed that PNI was an independent prognostic factor for survival [HR: 0.75 (95%CI:0.37–0.98), p = 0.03)] in their study, and low PNI value was significantly related with poor survival in patients who received adjuvant chemoradiotherapy18. Two other retrospective studies have been confirmed PNI as an independent prognostic factor for survival in newly diagnosed glioblastoma19–20. Conversely, Rigamonti et al. didn’t find any association between PNI and OS in their series of glioblastoma patients [HR = 0.79 (95%CI:0.61–1.03), p = 0.07]21. Studies about the clinical significance of PNI in patients with high-grade glioma are summarized in Table-4.
Recurrent high-grade gliomas generally have a poor prognosis. Despite local and systemic treatment options such as re-resection, re-irradiation, stereotactic radiosurgery, targeted therapy, and different chemotherapeutic agents, median overall survival is less than 12 months25–27. Several clinical and molecular prognostic biomarkers have been reported in different retrospective trials, which included patients with recurrence disease28. We found ECOG PS (HR: 3.4), gender (HR: 2.7), IDH status (HR: 0.2), ATRX status (HR: 3.3), and PNI (HR: 0.54) as independent prognostic markers for OS in our retrospective trial. Liau et al. shown that female sex associated with better survival in patients with recurrent GBM treated with bevacizumab [HR 2.1, 95%CI (1.24–3.93), p = 0.007]29. In another study, Tian et al. demonstrated that female patients with newly diagnosed GBM have a higher cancer-specific survival compared to male patients [HR 0.89, 95%CI (0.84–0.95), p < 0.001]30. IDH-1 mutation has been proven to be a prognostic factor in patients with high-grade glioma and was associated with better OS in a meta-analysis31. Chaurasia et al. indicated that wild type ATRX was significantly associated with better survival in their study which included a total of 163 GBM patients who underwent surgery32. Also, another study has shown that the ATRX mutation was related to poor survival in grade II glioma patients33. On the other hand, many other molecular and genetic markers such as MGMT methylation status, 1p/19 g deletion, PDGF, PTEN, EGFR, p53, and TERT have been identified as prognostic factors in high-grade glioma34. But, these molecular and genetic markers are limited used in many lower-middle-income countries due to the high economic cost. PNI is a more reliable, objective, simple, useful, and cheaper prognostic scoring model for recurrent high-grade gliomas to select the patients who underwent aggressive treatment strategies, and this was the rationale for our study. In the current study, we established that a high PNI value was associated with better survival in recurrent high-grade gliomas [HR = 0.54, (95% CI 0.30–0.97), p = 0.03]. Unlike other studies, our cohort consisted of recurrence high-grade glioma patients. To best of our knowledge, this is the first study to assess the prognostic value of PNI in recurrent high-grade gliomas.
Several studies have been reported preoperative NLR, SII, and PLR as independent prognostic factors for predicting survival in patients with newly diagnosed GBM35–38. But, we did not find an association between inflammatory-based indexes and survival outcomes in recurrent high-grade gliomas (HR for SII, PLR, and NLR: 1.08, 1.0, and 1.5, respectively). There is no previous study evaluating the association between these inflammation-based indices and survival in recurrent high-grade gliomas. We might conclude that the prognostic value of PNI is superior to other inflammation-based indexes for survival in patients with recurrent high-grade gliomas.
Our study has many limitations. First, this was a retrospective analysis with relatively small sample size, which may have caused some selection bias. Secondly, we were able to make PNI group-specific analysis according to only IDH1 and ATRX mutational status. Other genetic markers such as MGMT methylation status and 1p/19q co-deletion status could not be evaluated, because of the absence of data.