*2.2.2. Metastases in regional lymph nodes: N*

**Study group** **Characteristics**

Metastatic advanced

268

3.0

GC treated by palliative

chemotherapy

Inoperable advanced

384

2.75

Median

OS

Multivariate

High NLR shows

[68]

significant association

with OS but is not an

independent factor

Low baseline NLR and

[57]

normalisation of NLR

were independent

predictors of better OS.

Normalisation of NLR

was an independent

predictor of better PFS.

[58]

and metastatic GC

patients receiving

palliative chemotherapy

Advanced GC

174

3

OS curve

OS

Multivariate

PFS

analysis

patients treated with

chemotherapy

Advanced GC treated

46

2.5

Ref. [40]

OS

Multivariate

PFS

Abbreviations: OS, overall survival; NLR, neutrophil to lymphocyte ratio; GC, gastric cancer; Ref., reference; N+, presence of metastases in regional lymph nodes; ROC,

receiver operating characteristic curve; N, regional lymph node status in respect to metastases by tumour-nodes-metastasis (TNM) classification; R0, resection line free of

tumour; PLR, platelet to lymphocyte ratio; AUC, area under the curve; T, local spread of primary gastric cancer by TNM classification; LN, lymph node; MTS, metastasis;

CSS, cancer-specific survival; CD, cluster of differentiation; Ly, lymphocyte; CFS, cancer-free survival; GPS, Glasgow prognostic score; TNM, tumour-nodes-metastasis

classification; G, grade; PFS, progression-free survival.

**Table 2.**

Cut-offs of NLR in gastric cancer studies.

by neoadjuvant

chemotherapy

**Size**

**Value**

**Approach**

Median

OS, PFS

Multivariate

Higher NLR is

[50]

an independent

risk factor for

worse response to

chemotherapy, OS

and PFS

Response to

chemotherapy

**Cut-off**

**Study target**

**Level of** 

**Main conclusions**

**References**

160 Gastric Cancer

**justification**

Metastatic involvement of regional lymph nodes is associated with worse prognosis, being especially important in the early stages of gastric cancer. Presence of lymph node metastases also limits and changes the treatment options as endoscopic resection is not feasible anymore but D2 lymphadenectomy becomes more appropriate than D1 lymphadenectomy. In addition, neoadjuvant treatment can be offered now to gastric cancer patients affected by lymph node metastases [55]. NLR can be used to predict lymph node metastasis. In a retrospective study of 230 surgically treated patients, affected by T2 gastric cancer, NLR exceeding the median value of 2.18 was associated with higher number of lymph node metastases and higher N characteristics. The findings were confirmed by multivariate analysis. The relative risk was as high as 4.15 and 7.09 in regard to high number of metastases and N stage, respectively [70]. NLR at the cut-off level 1.59 (detected by ROC) was an independent factor associated with lymph node metastasis; however, higher informativity reflected by higher AUC was achieved by complex score (see further) including NLR, PLR and tumour-related factors [55]. The conclusions are justified by other researchers reporting correlation between NLR and N parameter since the early reports [65] until recent studies [77]. Thus, high NLR (exceeding the ROC-set cut-off value of 1.59) was associated with high N [55] while low preoperative NLR level (less than 4.02) was associated with lower number of lymph node metastases [16]. The variability of applied cut-off values is evident.

Lymph node metastases were significantly more frequent in elderly patients having high NLR: 83.0% vs. 55.6% [23]. In a large cohort of 1030 patients with resectable gastric cancer, high ratio of metastatic to examined lymph nodes defined as exceeding 0.18 was more frequent in those who had high NLR (greater than 3.44). Interestingly, in the same study N distribution showed only a trend to differences [22]. Significant difference in N0 vs. N+ distribution was reported by Deng et al. In addition, the mean NLR was 4.81 in N0 patients and 6.41 in N+ cases [47]. Statistically significant correlation between presence of lymph node metastasis, high NLR was confirmed in a multicentre study [61]. In a prospective study of 1131 surgically treated cases, high NLR (exceeding the median 3.5) was associated with higher N. The mean NLR was 2.31 in N0; 2.32 in N1; 2.43 in N2 and 2.75 in N3 cases [54].

Negative findings have been published as well. Some of them could be easily explained by small group size, e.g. only 61 gastric cancer patients were enrolled in the study of Pietrzyk et al. [18]. No differences in N distribution by NLR were found by Kim et al. who analysed a large group of 601 patients [48] and Yu et al. who assessed another significant cohort of 291 patients. In the same study, association with T and TNM stage was significant [20]. There was no correlation between NLR and N in a reasonable group of 262 surgically treated patients affected by T2–T4 gastric cancer while correlation with T in the same study was meaningful. The cut-off in this study was detected by ROC and was 3.2 [73].

Some reports have re-evaluated the meaning of NLR in predicting N status, arriving to less positive conclusions. In early gastric cancer (T1a–T1b), NLR was significantly associated with presence of lymph node metastases. The mean NLR was 2.07 in N0 group while it increased to 2.60 in N+ group. However, by multivariate analysis NLR was not an independent prognostic factor. Complex score not including NLR was more informative for preoperative estimation of lymph node metastases [72].
