Association of Systemic Inflammation and Malnutrition With Survival in Nasopharyngeal Carcinoma Undergoing Chemoradiotherapy: Results From a Multicenter Cohort Study

Xin Wang; Ming Yang; Yizhong Ge; Meng Tang; Benqiang Rao; Yongbing Chen; Hongxia Xu; Minghua Cong; Zengqing Guo; Hanping Shi

doi:10.3389/fonc.2021.766398

Association of Systemic Inflammation and Malnutrition With Survival in Nasopharyngeal Carcinoma Undergoing Chemoradiotherapy: Results From a Multicenter Cohort Study

Front Oncol. 2021 Oct 26:11:766398. doi: 10.3389/fonc.2021.766398. eCollection 2021.

Authors

Xin Wang^{1

2}, Ming Yang^{1

2}, Yizhong Ge^{1

2}, Meng Tang^{1

2}, Benqiang Rao^{1

2}, Yongbing Chen^{1

2}, Hongxia Xu³, Minghua Cong⁴, Zengqing Guo⁵, Hanping Shi^{1

2}

Affiliations

¹ Departments of Gastrointestinal Surgery and Clinical Nutrition, Beijing Shijitan Hospital, Beijing, China.
² Department of Oncology, Capital Medical University/Ninth Clinical Medical College, Peking University, Beijing, China.
³ Department of Clinical Nutrition, Daping Hospital, Army Medical University, Chongqing, China.
⁴ Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.

Abstract

Background: Malnutrition and systemic inflammation are common in patients with nasopharyngeal carcinoma (NPC). The Patient-Generated Subjective Global Assessment (PG-SGA) score and neutrophil-to-lymphocyte ratio (NLR) reflect the integrated nutritional status and inflammatory level of patients with NPC, respectively. We performed this study to identify whether NLR and PG-SGA score are associated with outcome and survival time for patients with NPC undergoing chemoradiotherapy.

Methods: The multicenter cohort study included 1,102 patients with NPC between June 2012 and December 2019. The associations of all-cause mortality with NLR and PG-SGA score were calculated using the Kaplan-Meier method and the log-rank test. We also did a multivariate-adjusted Cox regression analysis to identify the independent significance of different parameters. Restricted cubic spline regression was carried out to evaluate the association between NLR and overall survival (OS). A nomogram was established using the independent prognostic variables. Interaction terms were used to investigate whether there was an interactive association between NLR and PG-SGA.

Results: A total of 923 patients with NPC undergoing chemoradiotherapy were included in this study: 672 (72.8%) were males and 251 (27.2%) were females, with a mean age of 49.3 ± 11.5 years. The Kaplan-Meier curves revealed that patients with malnutrition (PG-SGA score >3) had worse survival than patients who were in the well-nourished group (PG-SGA score ≤3) (p < 0.0001). In addition, patients in the high NLR group (NLR ≥ 3) had worse survival than those in the low NLR group (NLR < 3) (p < 0.0001). Patients with high PG-SGA and high NLR had the worst survival (p < 0.0001). An increase in NLR had an inverted L-shaped dose-response association with all-cause mortality. A nomogram was developed by incorporating domains of NLR and PG-SGA score to accurately predict OS 12-60 months for patients [the C-index for OS prediction of nomogram was 0.75 (95% CI, 0.70-0.80)]. The interaction of PG-SGA with NLR was significant (p = 0.009). Patients with high PG-SGA and high NLR had a nearly 4.5-fold increased risk of death (HR = 4.43, 95% CI = 2.60-7.56) as compared with patients with low PG-SGA and low NLR.

Conclusions: Our study provided clear evidence that high PG-SGA score and high NLR adversely and interactively affects the OS of patients with NPC undergoing chemoradiotherapy.

Keywords: PG-SGA; chemoradiotherapy; malnutrition; nasopharyngeal carcinoma; neutrophil-to-lymphocyte ratio (NLR); systemic inflammation.