Abstract

Abstract BACKGROUND To identify the role of serum inflammatory markers and T1-gadolinium volume (T1GV) post-radiotherapy (RT), in the multidisciplinary approach to differentiate true tumor progression (TTP) from pseudo-progression (PsP) in high-grade glioma (HGG) patients. MATERIAL AND METHODS A retrospective cohort of HGG (WHO 2021) was consecutively enrolled from 2015 to 2021. Clinical, instrumental, and therapeutic data were collected at diagnosis, treatment and within 6 months after the end of RT.The response to treatment was assessed according to the modified RANO criteria; volumetry of suspected progression was performed on T1G and FLAIR. Blood tests also included the analysis of the neutrophil/lymphocyte ratio (NLR), systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI). Patients with suspected progression underwent a new MRI within 3 months of the first one.Any association between the clinicopathological factors and the presence of progression were analysed by Chi-square and Fisher’s exact test. Differences between group in continuous variables were assessed by independent sample-T test or Mann-Whitney U test, as appropriate. Prognostic factors for progression were investigated with a regression logistic model where predictors were log-transformed owing to their skewed distribution. Due to an existing multicollinearity in the common multivariate regression model between the variables “NLR” and “SII index”, two further separate binary regression models were set up, whereby in the “Multivariate Model NLR” the SII index was not considered and in the “Multivariate Model SII index” the NLR was not included. A Cox regression analysis was conducted to assess the impact of PsP- and TTP-related factors on overall survival (OS). RESULTS 39 patients (41.0% females) were included, 16 showed PsP and 23 TTP.NLR, SII and T1 gadolinium volume were higher in the TTP group than in PsP (respectively 4.7 vs 2.8, p= 0.002; 890.5 vs 546.5, p = 0.009; and 11.7 cm3 vs 2.2 cm3, p<0.001 ). Also absolute neutrophil counts and SIRI were higher in the TTP group than in PsP, but without reaching statistical significance.A multivariate “NLR” regression model showed NLR (OR 7.9, 95%CI: 1.4 to 45.3, p=0.020) and T1GV (OR 3.0, 95%CI: 1.4 to 6.7, p=0.007) as predictors of PSP; whereas the “SII model” confirmed the effect of T1GV [OR 2.7, CI 95% 1.3 to 5.5, p=0.006)] and SII [OR 4.2, 95%CI: 1.1 to 15.3, p=0.030].The OS was significantly worsened in patients with TTP compared to patients with PsP [HR 3.97, 95%CI: 1.59 to 9.93, p = 0.003]. At multivariate analysis other factors did not impact the overall survival. CONCLUSION Higher NLR, SII and T1GV showed good sensitivity and specificity to differentiate between PsP and TTP.Further studies with larger cohorts are needed to evaluate the inclusion of inflammatory indices and volumetry in the differentiation diagram of PsP from TTP.

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