Abstract

BackgroundThere is a lack of effective treatments for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Furthermore, the response rate of NPC patients to programmed death 1 (PD-1) inhibitors is approximately 20% to 30%. Thus, we aimed to explore reliable and minimally invasive prognostic indicators to predict the efficacy of PD-1 inhibitors combination therapy in RM-NPC.MethodsThe serum markers of 160 RM-NPC patients were measured before and three weeks after the first anti-PD-1 treatment. The least absolute shrinkage and selection operator (LASSO) logistic regression was carried out to select dynamic serum indicators and construct a prediction model. Furthermore, we carried out univariate, multivariate, nomogram and survival analyses to identify independent prognostic factors that were associated with 1-year progression-free survival (PFS).ResultsBased on two markers that were screened by Lasso logistic regression, we constructed a risk score prediction model for the prediction of anti-PD-1 efficacy at 8–12 weeks with an AUC of 0.737 in the training cohort and 0.723 in the validation cohort. Risk score and metastases were included in the nomogram, and the Kaplan–Meier survival curves demonstrated that the high-risk group has shorter PFS compared to the low-risk group. The concordance index (C-index) of the nomogram for PFS is higher than that of the TNM stage in the training and validation cohort.ConclusionWe proposed a strategy to monitor dynamic changes in the biochemistry markers and emphasized their importance as potential prognostic biomarkers for the treatment of advanced NPC treated with PD-1 inhibitors. Our risk score prediction model was based on the dynamic change of LDH and AST/ALT, which has predictive and prognostic value for NPC patients who were treated with PD-1 inhibitors.

Highlights

  • Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignant tumors in Southeast Asia, including southern China [1, 2]

  • All patients were in the advanced TNM stage when using programmed death 1 (PD-1) inhibitors and underwent recurrence or/and lymph node metastasis or/ and distant metastasis

  • The response to progressive disease (PD)-1 inhibitor treatment in NPC patients was initially evaluated at 8–12 weeks and updated continuously

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Summary

Introduction

Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignant tumors in Southeast Asia, including southern China [1, 2]. Further studies have demonstrated that EBV infection can be identified in high-grade precancerous lesions of NPC, while it is rarely detected in low-grade precancerous lesions [3, 4] Both the serum EBV antibody and plasma EBV DNA copy number are commonly used biomarkers for NPC diagnosis. By detecting two serum EBV antibodies, VCA-IgA and EA-IgA, and further examinations, the diagnosis rate was found to be significantly higher than that of the control group (79.0% vs 45.9%, P < 0.0001) after six years of follow-up [5] Another prospective study found that 78 patients (15.1%) out of 518 patients with non-metastatic NPC were plasma EBV DNA-negative (0–20 copies/ml), and 62 patients in this subset (12.0%) had 0 copy/ml [6]. We aimed to explore reliable and minimally invasive prognostic indicators to predict the efficacy of PD-1 inhibitors combination therapy in RM-NPC

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