Significance of blood neutrophil-to-lymphocyte ratio for prognostic stratification of patients with gastroesophageal junction adenocarcinoma in the era of the 8th edition of the American Joint Committee on Cancer (AJCC8) staging

Abstract

The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma depends mainly on the clinical staging, as described by the new AJCC8 (American Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in patients with upper gastrointestinal cancers. We examined the prognostic significance of NLR in the era of the new AJCC8 staging system. In this single-centre cohort study, retrospective data on patients with operable GOJ adenocarcinoma treated with perioperative chemotherapy were analysed. The prognostic significance of baseline NLR in combination with AJCC8 clinical staging and other patient characteristics was examined for both time-to-progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%) underwent radical surgery. Fifty-one patients (16.2%) developed unresectable disease due to early disease progression. NLR was the only baseline factor independently associated with the development of early disease progression. AJCC8 clinical staging was significantly associated with TTP and OS. In addition, NLR ≥ 3 was predictive of poorer TTP (p = 0.001) and OS (p = 0.002), confirmed in multivariate Cox-regression analysis. NLR ≥ 3 was prognostic, especially in patients with clinical stage III for TTP (p = 0.006) and OS (p = 0.025) and in patients with clinical stage IVA for OS (p = 0.017). NLR significantly improved the prognostic classification of patients by different AJCC8 clinical stages, with a c-index improved from 0.554 to 0.592 (p < 0.001). NLR was confirmed to be an independent prognostic factor in this cohort and could be used in combination with AJCC8 clinical staging to improve the baseline prognostic stratification of patients with newly diagnosed resectable GOJ adenocarcinoma.

Blood-based Markers in the Prognostic Prediction of Esophagogastric Junction Cancer

“…A larger study (611 EJA patients) performed by Zhang et al suggested that NLR was associated with CSS, but does not play a vital role in predicting CSS of Siewert type II/III EJA [27]. Among these studies, NLR was correlated with T and N stages [24] and patients with NLR higher than 3 had a short overall survival time in stages IIB and III [22]. Therefore, it is important to further explore the predictive value of the NLR for predicting prognosis of EJA in a large-sample and multi-center study.…”

“…As shown in Table 1, increased NLR is one of the most frequently observed markers in EJC [15][16][17][18]. With cutoff values varying from 1.84 -4.00, the NLR might act as a potential marker in predicting the survival rate of patients with EJC [19][20][21][22][23][24][25][26], especially for patients who have undergone surgery. The NLR has been found to be correlated to tumor size [21], age [22] and T stage [24].…”

“…With cutoff values varying from 1.84 -4.00, the NLR might act as a potential marker in predicting the survival rate of patients with EJC [19][20][21][22][23][24][25][26], especially for patients who have undergone surgery. The NLR has been found to be correlated to tumor size [21], age [22] and T stage [24]. Although most of these studies involved a small sample size of patients, Wang et al conducted a large-sample study (435 EJA patients in 1498 gastroesophageal adenocarcinoma patients) and showed that pretreatment NLR, as a continuous variable, can predict cancer-specific survival (CSS) independently in resectable EJA patients regardless of whether or not patients received neoadjuvant therapy [24].…”

Baseline neutrophil–lymphocyte ratio holds no prognostic value for esophageal and junctional adenocarcinoma in patients treated with neoadjuvant chemotherapy

“…Interestingly, their median baseline NLR of 3.7 was considerably higher than found in the present study and other comparable literature which did not include metastasized tumors, indirectly suggesting that NLR may reflect the extent of dissemination. 30,31 A retrospective analysis of 117 patients with adenocarcinoma supports this theory by confirming that the NLR was an independent predictor of the discovery of peritoneal and/or metastatic disease. 32 Moreover, Conway et al recently reported an NLR ≥3 to be independently associated with early disease progression resulting in unresectable disease in patients receiving nCT for gastroesophageal junction adenocarcinoma.…”

“…32 Moreover, Conway et al recently reported an NLR ≥3 to be independently associated with early disease progression resulting in unresectable disease in patients receiving nCT for gastroesophageal junction adenocarcinoma. 30 The abovementioned findings, in addition to adequate staging and patient selection, might have played a role in our negative results as no patients with stage IV disease were included.…”