Modified Geriatric Nutrition Risk Index as a Prognostic Predictor for Unresectable/Recurrent Esophageal Cancer

Patients and Methods

Patients. This study was a retrospective single-center file review of a cohort of patients with unresectable/recurrent EC. All procedures of this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. The Institutional Review Board approved the study protocol of the National Defense Medical College (registration number: 4374).

Of the 632 patients who were diagnosed with EC at the National Defense Medical College (Saitama, Japan) between January 2009 and December 2020, 53 patients with unresectable EC because of distant metastasis and 90 patients with recurrent EC after radical esophagectomy (a total of 143 cases) were included in this study (Figure 1). Patients who met the following criteria were excluded: 1) aged <65 years, 2) unresectable locally advanced EC, 3) performance status score 2 or more at the time of diagnosis with unresectable or recurrent EC, 4) other malignant disease requiring any treatment or observation, 5) cardiac, liver, renal, or endocrine dysfunction, 6) missing data of body weight, serum CRP, and serum albumin at the time of diagnosis of unresectable or recurrent EC, and 7) suspected of active infectious disease at the time of blood test. Conversion surgery after CT (chemotherapy) or CRT (chemoradiotherapy) cases were included in patients with resectable EC. We retrospectively evaluated patients’ clinical data and pathological records of biopsy specimens. Hematological findings were based on the date of a patient’s first visit to our department. Sarcopenia was defined separately for each sex according to the psoas muscle index (the psoas muscle area at the level of the third lumbar vertebra and the square of height), calculated from computed tomography images at the time of diagnosis. Cutoff values of the psoas muscle index were set at the 25^th percentile (4.04 and 2.04 cm²/m² for males and females, respectively). The clinical stage of EC was classified by the findings of endoscopy, computed tomography, and positron emission tomography/computed tomography, and described according to the TNM staging system (8^th edition) of the Union for International Cancer Control (3). In patients with unresectable EC, overall survival (OS) time was measured from the date of the first visit to our hospital to the date of death due to any cause. In patients with recurrent EC, OS was measured from the date of diagnosis with recurrence to the date of death due to any cause.

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Figure 1.

Inclusion criteria for this study. EC: Esophageal cancer; CT: chemotherapy; CRT: chemoradiotherapy.

Systematic inflammation indices. The mGNRI was calculated as (1.489/CRP in mg/dl) + (41.7 × body mass index/22) (11). Given that a serum CRP level ≤0.3 mg/dl was considered within normal limits, serum CRP ≤0.3 mg/dl was considered as 0.3 mg/dl in this study. According to the Youden index, the optimal cutoff value for the mGNRI was 80, and the area under the curve was 0.657. Patients were divided into two groups: low-mGNRI with mGNRI <80 (90 patients, 62.9%) and high-mGNRI with mGNRI ≥80 (53 patients, 37.1%) (Table I).

The prognostic indices based on systematic inflammation examined in this study were as follows: CAR (CRP measured in mg/l and albumin measured in g/l); PNI (10 × albumin in g/dl + 0.005 × lymphocyte count/μl); and GNRI (1.489 × albumin in g/dl + 41.7 × body mass index/22). Data used for each calculation were based on a blood sample obtained during the patient’s first visit to our department.

Management of chemotherapy. Out of the 143 patients, 90 received CT/CRT, where 88 received the FP regimen and the rest received docetaxel therapy (chemotherapy alone) for first-line chemotherapy. Moreover, 53 patients only received best supportive care due to the patients’ own requests. Chemotherapy-related adverse events were evaluated based on Common Terminology Criteria for Adverse Events version 5.0 (12).

Statistical analysis. All statistical analyses were performed using JMP^® Pro software package version 15.2.0 (SAS Institute, Cary, NC, USA). Mann–Whitney U-tests and Pearson’s chi-square test were performed as appropriate. Survival rates were obtained using the Kaplan–Meier method, and the log-rank test determined statistical significance. Cox proportional hazards regression modeling was performed for univariate and multivariate analyses. To determine the most appropriate prognostic index, we compared indices using the Akaike information criterion (AIC) and Bayesian information criterion (BIC). A p-value of <0.05 was considered statistically significant.