Systemic Inflammatory Score Predicts Response and Prognosis in Patients With Lung Cancer Treated With Immunotherapy

Abstract

Aim: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. Patients and Methods: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. Conclusion: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.Lung cancer has the highest mortality rate worldwide of all cancer types (1, 2). In recent years, the emergence of molecular targeted drugs and immune checkpoint inhibitors (ICIs) has drastically changed the strategy for the treatment of advanced lung cancer. ICIs improve the overall survival (OS) of patients with lung cancer (3-5).The expression level of programmed death-ligand 1 (PD-L1) in tumor cells is determined through immunohistochemistry (IHC). PD-L1 is a significant predictive marker of ICIs; however, it is not a sufficient indicator of the efficacy of immunotherapy. Several serum-based parameters related to systemic inflammation and nutritional status of patients have been studied as predictive or prognostic markers during immunotherapy, such as the neutrophil-tolymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) (6-8). However, the unified cutoff points for these metrics and other parameters that are more sensitive than these markers are controversial.This study aimed to investigate factors of the efficacy of immunotherapy that are readily available via routine blood tests. We focused on the combination of hemoglobin (Hb) and serum albumin levels. Patients and MethodsThis retrospective study included consecutive patients with inoperable lung cancer who underwent monotherapy with ICIs,

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…It remained uncertain among six cohort studies on the association between pretreatment PNI and DCR for cancer patients treated with ICIs. Pooled analysis revealed that a higher PNI level was associated with greater DCR (pOR = 2.48, 95% CI = 1.87-3.29, Figure 4) (19,20,26,28,29,34). The combined analysis of three studies on the association between PNI and ORR showed that PNI higher than the cutoff indicated more favorable ORR (pOR = 2.17, 95% CI = 1.52-3.10, Figure 5) (26,28,34).…”

“…Five publications showed that PNI was an independent predictor of unfavorable PFS in cancer patients with immunotherapy (18,19,26,27,34), whereas five cohort studies detected no significant relationship between PNI and PFS (20,28,30,31,33). The combined analysis of ten studies that enrolled 1,282 participants showed that a higher PNI level was associated with worse PFS (pHR = 1.61, 95% CI = 1.37-1.88, Figure 3).…”

“…Five observational studies reported that PNI was an independent indicator for a shortened OS in cancer patients with immunotherapy (18,19,(26)(27)(28), while PNI was not considered as a prognostic factor for OS in seven studies (20,(29)(30)(31)(32)(33)(34). Pooled analysis of all selected publications revealed that the PNI values higher than the cutoff value predicted a poor OS (pHR = 2.24, 95% CI = 1.57-3.20, Figure 2) in advanced cancer patients treated with immune checkpoint inhibitors.…”

“…Kim et al identified that PNI greater than the cutoff was correlated with favorable progressivefree survival (PFS) and overall survival (OS) in advanced esophageal squamous cell cancer (ESCC) with immunotherapy (19). A study by Zaitsu et al showed that PNI was not a significant prognostic factor of immunotherapy in patients with lung cancer (20). Overall, the association between PNI and survival outcomes in cancer patients with immunotherapy remains obscure.…”

The prognostic value of prognostic nutritional index in advanced cancer receiving PD‐1/L1 inhibitors: A meta‐analysis

“…Eight studies 16,17,[19][20][21][22][23][24] consisting of 616 patients were included to analyze the association between PNI and PFS. The pooled results showed that patients with low PNI had shorter PFS (HR = 1.75, 95% CI 1.40-2.18, p = 0.000), with no significant heterogeneity (I 2 = 0%, p = 0.638) (Figure 2B).…”