Tumour-infiltrating lymphocytes in the risk stratification of squamous cell carcinoma of the head and neck

Abstract Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.

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Early Response Prediction of Multiparametric Functional MRI and 18F-FDG-PET in Patients with Head and Neck Squamous Cell Carcinoma Treated with (Chemo)Radiation

Cancers ◽

10.3390/cancers14010216 ◽

2022 ◽

Vol 14 (1) ◽

pp. 216

Author(s):

Roland M. Martens ◽

Thomas Koopman ◽

Cristina Lavini ◽

Tim van de Brug ◽

Gerben J. C. Zwezerijnen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Risk Stratification ◽

Cell Carcinoma ◽

Head And Neck ◽

Functional Imaging ◽

Squamous Cell ◽

Fdg Pet ◽

Free Survival ◽

Imaging Parameters ◽

18F Fdg

Background: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Methods: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). Results: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). Conclusions: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.

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