Abstract
Background/Aim: A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg_/height2 (m2)], is a good predictor of postoperative complications and cancer survival. However, no study has used this index in patients with gastric cancer (GC). Therefore, we aimed to investigate the clinical significance of the preoperative mNRI values in patients with GC who underwent curative resection. Patients and Methods: We examined 449 patients who underwent curative resection for GC at Kanagawa Cancer Center between 2013 and 2017. The mNRI cutoff value obtained using a receiver operating characteristic analysis was 23.31. Patients were divided into high and low mNRI groups according to the cutoff value, and the clinicopathological characteristics and outcomes were compared between the two groups. Results: In terms of clinicopathological characteristics, the high mNRI group had a higher proportion of men, higher BMI, and a higher proportion of patients with American Society of Anesthesiologists physical status class 2/3 compared with the low mNRI group; the low mNRI group had significantly worse 5-year recurrence-free survival (RFS) and overall survival (OS) than the high mNRI group (OS, p=0.005) (OS, p=0.006; RFS, p=0.018) did. In the multivariate analysis, a low mNRI was an independent predictor of OS (p=0.006) and RFS (p=0.013). Conclusion: Preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection.
Gastric cancer (GC), including gastroesophageal junction cancer, is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide (1). For early-stage GC, endoscopic resection and/or conventional gastrectomy with D1+ lymphadenectomy is the current standard treatment (2-5). By contrast, for locally advanced GC, radical gastrectomy with D2 lymphadenectomy following postoperative adjuvant chemotherapy is the current standard treatment, based on the findings of the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer and Japan Clinical Cancer Research Organization Gastric Cancer-07 studies (6-8). However, despite receiving the current standard treatment, the prognosis of most patients with GC remains poor (6). Thus, the search for predictive biomarkers for patients with GC may help improve their outcomes and further increase the chance of their survival.
To date, various preoperative nutritional indices, calculated using peripheral blood data, have been reported as prognostic factors and evaluated by several studies (9-18). However, efforts to search for a simpler and more composite index for the assessment of nutritional status in patients with GC remain inadequate. In 2021, a new modified nutritional risk index (mNRI), conveniently calculated as serum albumin (g/l)+body mass index (BMI) [weight (kg)/height2 (m2)], was reported to be relevant to the survival of patients with esophageal cancer (19). However, whether preoperative mNRI is useful as a survival factor for patients with GC undergoing curative resection remains unclear. In this study, we investigated the usefulness of the mNRI as a survival factor in patients with GC who underwent curative resection.
Patients and Methods
Ethical approval. This study was approved by the Institutional Review Board of Kanagawa Cancer Center (approval number: 25Research-20). The study was conducted in accordance with the principles of the Declaration of Helsinki. All participants signed a consent form.
Patients. Consecutive patients with GC who underwent curative gastrectomy between December 2013 and November 2017 at the Kanagawa Cancer Center were considered eligible for the study. Patients with 1) a history of primary gastric or gastroesophageal junction cancer, 2) a history of curative resection (R0) with radical lymph node dissection, 3) age >20 years, and 4) an Eastern Cooperative Oncology Group performance status score of 0-2 were included in the study. In contrast, patients with a history of 1) disqualification or withdrawal of consent, 2) receiving neoadjuvant chemotherapy, 3) undergoing unresectable or incomplete resection, 4) being diagnosed with pathological stage IV gastric or gastroesophageal junction cancer, 5) being diagnosed with non-adenocarcinoma, and 6) undergoing proximal or pylorus-preserving gastrectomy were excluded.
Definition of modified nutrition. mNRI was calculated as serum albumin (g/l)+body mass index [weight (kg)/height (m2)] based on the preoperative blood test data. Receiver operating characteristic analyses of the mNRI were performed to identify an appropriate cutoff value for recurrence or death. Figure 1 shows the receiver operating characteristic curve. The appropriate cutoff value for the mNRI was determined as 23.3. The patients were divided into a low mNRI group (≤23.3) and a high mNRI group (>23.3) according to the mNRI levels.
Receiver operating characteristic curve. The area under the curve is 0.53. The appropriate cutoff value for the modified nutritional risk index was determined as 23.3.
Data collection. All clinicopathological and laboratory data were retrospectively obtained from the patients’ medical records, including sex, age, BMI, American Society of Anesthesiologists physical status (ASA-PS) score, main tumor location, tumor size, histological type, type of surgery performed, pathological factors, lymphatic or venous invasion status, postoperative complications (PCs), and adjuvant chemotherapy used. PCs that occurred during hospitalization or within 30 days of surgery were retrospectively identified from the patients’ records and assessed using the Clavien-Dindo classification (20).
Statistical analyses. The patients’ characteristics were compared using Fisher’s exact and chi-square tests. The Kaplan-Meier method was used to calculate the overall survival (OS) and recurrence-free survival (RFS) rates, and the log-rank test was performed to compare the differences in survival rates. OS was defined as the period between the date of surgery and death from any cause or the last follow-up. RFS was defined as the period between surgery and the date of either recurrence, death, or last follow-up, whichever occurred first. The data of patients who did not experience an event were censored at the date of their last follow-up visit. Univariate and multivariate analyses were performed to determine the hazard ratios (HRs) and explore the prognostic factors for OS and RFS using a Cox proportional hazards regression model. A p-value of <0.05 was considered significant. The EZR version 1.37 program (Jichi University, Tochigi, Japan) was used to perform all statistical analyses (21).
Results
Patient characteristics. In total, 540 patients were included in the database. The Consort diagram of patient selection is shown in Figure 2. Of the 540 patients, 20 who underwent proximal or pylorus-reserving gastrectomy, 19 pathologically diagnosed with non-adenocarcinoma, 18 diagnosed with pathological stage IV disease, 17 who received neoadjuvant chemotherapy, 12 who were disqualified or withdrew the consent, and 5 who underwent unresectable or incomplete resection were excluded. Ultimately, 449 patients were eligible for inclusion, of whom 377 comprised the high mNRI group and 72 comprised the low mNRI group (Table I). Table I summarizes the relationship between mNRI and the clinical characteristics. The high mNRI group had a significantly higher proportion of men (71.9% vs. 51.4%, p<0.01), higher BMI (23.2kg/m2 vs. 18.3 kg/m2, p<0.01), and a higher incidence of ASA-PS class 2/3 (78.8% vs. 63.9%, p=0.01) compared with the low mNRI group.
Consort diagram. In total, 540 patients were included in the database. Of these, 12 who were disqualified or withdrew the consent, 17 who received neoadjuvant chemotherapy, 5 who underwent unresectable or incomplete resection, 20 who underwent proximal or pylorus-reserving gastrectomy, 8 diagnosed with pathological stage IV disease and 19 pathologically diagnosed with non-adenocarcinoma were excluded. Hence, only data from 449 patients were analyzed.
Association between blood transfusion and clinicopathological features.
Five-year OS and RFS rates according to the mNRI values. The 5-year OS rate was significantly lower in the low mNRI group than in the high mNRI group (74.6% vs. 87.9%, p=0.006; Figure 3). The 5-year RFS rate was significantly lower in the low mNRI group than in the high mNRI group (75.1% vs. 85.8%, p=0.018; Figure 4).
Comparison of the 5-year overall survival (OS) between the high and low modified nutritional risk index (mNRI) groups. The 5-year OS rate of the low mNRI group was significantly poorer than that of the high mNRI group (74.6% vs. 87.9%, p=0.006).
Comparison of the 5-year recurrence-free survival (RFS) between the high and low modified nutritional risk index (mNRI) groups. The 5-year RFS rate of the low mNRI group was poorer than that of the high mNRI group (75.1% vs. 85.8%, p=0.018).
Univariate and multivariate analyses. The univariate analysis demonstrated that age [hazard ratio (HR)=2.22, 95% confidence interval (CI)=1.11-4.46, p=0.02], tumor size (HR=2.28, 95%CI=1.27-4.12, p=0.01), type of surgery (HR=2.13, 95%CI=1.272-4.12, p=0.01), pathological stage (HR=4.56, 95%CI=2.65-7.87, p<0.01), lymphatic invasion status (HR=3.53, 95%CI=2.08-5.99, p<0.01), venous invasion status (HR=4.91, 95%CI=2.68-8.98, p<0.01), and mNRI (HR=2.20, 95%CI=1.24-3.92, p=0.01) were significantly associated with poor OS (Table II). The multivariate analysis demonstrated that pathological stage (HR=2.22, 95%CI=1.11-4.46, p=0.02), venous invasion status (HR=2.49, 95%CI=1.22-5.07, p=0.01), and mNRI (HR=2.29, 95%CI=1.27-4.12, p=0.01) were significant independent prognostic factors of OS (Table II). Additionally, the univariate analysis demonstrated that the tumor size (HR=2.09, 95%CI=1.23-3.56, p=0.01), type of surgery (HR=1.86, 95%CI=1.13-3.05, p=0.01), pathological stage (HR=4.01, 95%CI=2.45-6.55, p<0.01), lymphatic invasion status (HR=3.93, 95%CI=2.40-6.42, p<0.01), venous invasion status (HR=4.01, 95%CI=2.36-6.83, p<0.01), and mNRI (HR=1.92, 95%CI=1.11-3.34, p=0.02) were significantly associated with poor RFS (Table II). The multivariate analysis demonstrated that pathological stage (HR=1.90, 95%CI=1.00-3.59, p=0.05), lymphatic invasion status (HR=2.11, 95%CI=1.20-3.74, p=0.01), venous invasion status (HR=2.01, 95%CI=1.06-3.79, p=0.03), and mNRI (HR=2.03, 95%CI=1.16-3.54, p=0.01) were significant independent prognostic factors for the RFS (Table III).
Univariate and multivariate analyses of the clinicopathological features for overall survival.
Univariate and multivariate analyses of the clinicopathological features for recurrence-free survival.
Discussion
In this study, we calculated the preoperative mNRI value, which is a new nutritional parameter obtained by adding the BMI and serum albumin levels of patients with GC (19, 22), and investigated its clinical significance after radical resection. We divided the patients into high and low mNRI groups based on the cutoff values obtained using a receiver operating characteristic analysis and examined the survival outcomes of the two groups. In the multivariate analysis, a low mNRI was an independent predictor of both RFS and OS.
mNRI is a new nutritional parameter that can be obtained inexpensively by adding BMI and albumin levels, as reported by Chen et al. in 2021. Chen et al. evaluated the serum albumin level, BMI, geriatric nutritional risk index, prognostic nutritional index, and mNRI in 620 patients with esophageal squamous cell carcinoma who underwent esophagectomy. They were divided into high and low groups based on the cutoff values calculated from the receiver operating characteristic curves, and the stratification of survival in the two groups was compared. They reported that only low mNRI was an independent poor survival factor in the multivariate analysis and that mNRI was a potentially useful prognostic factor (19). Furthermore, Moore et al. reported that a low mNRI is a significant risk factor for postoperative complications in patients with head and neck cancer (22).
Thus, the mNRI is a simple new index for evaluating the nutritional status of patients; however, only a few studies have examined its usefulness, and none have been conducted in patients with GC. Therefore, we investigated the clinical significance of the preoperative mNRI in patients with GC who underwent radical resection.
A decreased mNRI in patients with cancer indicates malnutrition due to the carcinomatous state, which may decrease tolerance to treatment, increase the risk of surgical complications, and decrease the long-term survival rate. Therefore, early measurement of the mNRI and appropriate perioperative nutritional management as early as possible when a decline is observed may improve patient survival and lower the postoperative complication rate.
Although the mNRI uses inexpensive and simple parameters, such as BMI and plasma albumin level, our study on patients with GC as well as that reported by Chen et al. in patients with esophageal cancer suggested that the mNRI is a useful prognostic factor (16). Therefore, the reasons supporting the clinical usefulness of mNRI were analyzed. First, the BMI can be used to evaluate body shape as it is calculated based on weight and height. Nutritional assessment using BMI allows the evaluation of nutritional status based on body shape and not just weight change and provides some insight into the balance between muscle and fat mass (23-25). Therefore, one advantage of including BMI in the calculation of mNRI is that it may allow for a more comprehensive assessment of nutritional risks. Furthermore, a detailed nutritional assessment is possible, making it easier to plan appropriate nutritional support and interventions. Next, albumin is the major plasma protein in the body and has traditionally been considered an important indicator of nutritional status in the body; a low preoperative albumin level is often associated with postoperative complications and decreased long-term survival (26). Therefore, the use of mNRI, which is calculated by adding the albumin levels to the BMI, allows for a more specific assessment of nutritional status in patients with cancer and may improve the accuracy of predicting postoperative complication risk and survival. In addition, lower albumin levels may indicate the need for nutritional supplementation or other treatment strategies, and the inclusion of albumin values in the calculation of mNRI allows the formulation of personalized treatment plans. Monitoring the mNRI helps detect early changes in a patients’ nutritional status. This allows for appropriately timed nutritional support intervention and monitoring, thereby preventing postoperative complications and improving the prognosis. However, as albumin is susceptible to disturbance in various fluids and inflammation, albumin levels and BMI are complementary to each other, and their combination as mNRI could also take into account the differences in nutritional status due to the variations in individual body size.
Malnutrition increases the risk of developing surgical complications and worsens the long-term survival of patients with GC. Therefore, appropriate nutritional care and monitoring are necessary. The mNRI can provide an objective and accurate assessment of the nutritional status of patients with cancer. It can be used to identify patients with cancer who need nutritional support prior to surgery and may be used to plan the appropriate nutritional support during the perioperative period for these patients. Good nutritional status may improve a patient’s ability to tolerate surgery, reduce the risk of complications, accelerate recovery, and improve long-term outcomes (27). However, when using mNRI, an appropriate method should be used for assessing the individual patient’s situation. Nutritional assessment should be multifaceted; an overall clinical evaluation and assessment of GC progression should be performed without relying solely on mNRI.
Study limitations. This was a retrospective single-center cohort study. Hence, a multicenter, prospective, large-cohort study is required to validate the association between preoperative mNRI and long-term survival.
Conclusion
In conclusion, preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection. In cases of low preoperative mNRI, aggressive perioperative nutritional therapy may improve postoperative recurrence and survival.
Acknowledgements
The Authors would like to thank the patients, their families, and the staff at Kanagawa Cancer Center for participating in this study.
Footnotes
Authors’ Contributions
HW and IH designed this study. Data collection and literature searches were performed by HW, IH, and TO. HW, IH, and TO performed the data analysis and interpretation. All researchers interpreted the data. HW, IH, and TO drafted the manuscript and figures. Finally, the paper was revised and approved by all Authors.
Conflicts of Interest
The Authors declare that they have no conflicts of interest or financial ties in relation to this study.
- Received September 3, 2023.
- Revision received September 21, 2023.
- Accepted September 25, 2023.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
