On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy

Abstract

BackgroundPrevious studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.MethodsAnalysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.ResultsLow baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0–2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.ConclusionsNLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.

Neutrophil‐to‐lymphocyte ratio as a prognostic marker for head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: Meta‐analysis

“…We screened the titles and abstracts of these studies and identified 24 potentially eligible studies. The full‐text versions of these 24 studies were then inspected according to the exclusion criteria, with 14 studies involving 929 patients determined to be eligible for inclusion in the present study 5,13–24 (Table 1). Two studies 15,23 contained overlapping data.…”

“…The HRs for OS were reported in 11 studies comprising 710 patients 5,13,14,17–21,23–25 and ranged from 0.86 to 5.04. The pooled analysis results are shown in Figure 3A.…”

“…The addition of other predictive markers, such as tumor mutational burden 5 and sarcopenia, 47 may further increase the predictive ability. Recent reports showed that post‐treatment NLR is indicative of progressive disease 18 and that NLR assessed 28 days after ICI initiation was better associated with survival than pretreatment NLR 19 . Further research is required to determine the optimal timing of NLR assessment and how NLR should be combined with other markers.…”

“…Moreover, meta‐analyses of the prognostic impact of NLR in patients treated with ICIs have been published for some types of cancers 9–12 . However, only small‐scale cohort studies with inconsistent results have reported the association between the NLR and ICIs in HNSCC 5,13–25 …”

METTL3 is a Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma

“…In the present study, KEGG pathway analysis indicated that METTL3-related differentially expressed genes were involved not only in common oncogenic pathways but also in immune pathways. Several studies have con rmed the characterization of the immune microenvironment involved in the occurrence and development of HNSCC [34][35][36][37]. Studies have shown that the risk score composed of the m 6 A gene is related to the in ltration of dendritic cells, neutrophils, CD4 + T cells, CD8 + T cells, and B cells, and upregulated m 6 A regulators are positively correlated with PD-L1 in the HNSCC tumor immune microenvironment [38].…”