Prognostic value of pre-therapeutic nutritional risk factors in elderly patients with locally advanced esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or radiotherapy

Abstract

Background: The nutritional status of cancer patients is a crucial factor in determining their prognosis. The objective of this study was to investigate and compare the prognostic value of pretreatment nutrition-related indicators in elderly esophageal squamous cell carcinoma (ESCC). Risk stratification was performed according to independent risk factors and a new nutritional prognostic index was constructed.

Methods: We retrospectively reviewed 460 older locally advanced ESCC patients receiving definitive chemoradiotherapy (dCRT) or radiotherapy (dRT). This study included five pre- therapeutic nutrition-related indicators. The optimal cut-off values for these indices were calculated from the Receiver Operating Curve (ROC). Univariate and multivariate COX analyses were employed to determine the association between each indicator and clinical outcomes. The predictive ability of each independently nutrition-related prognostic indicator was assessed using the time-dependent ROC (time-ROC) and C-index.

Results: Multivariate analyses indicated that the geriatric nutrition risk index (GNRI), body mass index (BMI), the controlling nutritional status (CONUT) score, and platelet-albumin ratio (PAR) could independently predict overall survival (OS) and progression-free survival (PFS) in elderly patients with ESCC (all p < 0.05), except for prognostic nutritional index (PNI). Based on four independently nutrition-related prognostic indicators, we developed pre-therapeutic nutritional prognostic score (PTNPS) and new nutritional prognostic index (NNPI). No-risk (PTNPS = 0-1 point), moderate-risk (PTNPS = 2 points), and high-risk (PTNPS = 3-4 points) groups had 5-year OS rates of 42.3%, 22.9%, and 8.8%, respectively (p < 0.001), and 5-year PFS rates of 44.4%, 26.5%, and 11.3%, respectively (p < 0.001). The Kaplan-Meier curves showed that the mortality of elderly ESCC patients in the high-risk group was higher than that in the low-risk group according to the NNPI. Analysis of time-AUC and C-index revealed that the NNPI (C-index: 0.663) had the greatest predictive power on the prognosis in older ESCC patients.

Conclusions: In elderly ESCC patients, the GNRI, BMI, CONUT score, and PAR can be used as objective assessment measures for the risk of nutrition-related death. Compared to the other four indexes, the NNPI has the greatest prognostic value for prognosis, and elderly patients with a higher nutritional risk have a poor prognosis, which is helpful in guiding early clinical nutrition intervention.

Keywords: Elderly esophageal squamous cell carcinoma; Pre- therapeutic nutrition-related indicators; Risk stratification; Survival.

Fig. 1

Kaplan–Meier analysis of (A, C, E, G) OS and (B, D, F, H) PFS were grouped by pre-therapeutic nutritional-related prognostic indicators. OS, overall survival; PFS, progression-free survival; GNRI, geriatric nutrition risk index; BMI, body mass index; CONUT score, the controlling nutritional status score; PAR, platelet-albumin ratio

Fig. 2

The PTNPS and NNPI for OS and PFS were risk stratified by risk group. A, B Risk stratification for PTNPS on OS and PFS (p < 0.001); C, D Risk stratification for NNPI on OS and PFS. PTNPS, pre-therapeutic nutritional prognostic score; NNPI, novel nutritional prognostic index; OS, overall survival; PFS, progression-free survival

Fig. 3

The time-ROC of nutritional-related indicators in older locally advanced ESCC patients. A, B The time-ROC of GNRI on OS and PFS (3-year and 5-year); C, D The time-ROC of BMI on OS and PFS (3-year and 5-year); E, F The time-ROC of CONUT on OS and PFS (3-year and 5-year); G, H The time-ROC of PAR on OS and PFS (3-year and 5-year); I, J The time-ROC of NNPI on OS and PFS (3-year and 5-year). time-ROC, the time-dependent receiver operating curve; ESCC, esophageal squamous cell carcinoma; GNRI, geriatric nutrition risk index; OS, overall survival; PFS, progression-free survival; BMI, body mass index; CONUT score, the controlling nutritional status score; PAR, platelet-albumin ratio; NNPI, novel nutritional prognostic index

Fig. 4

The sub-group analysis of GNRI, BMI, CONUT, PAR, and NNPI in elderly locally advanced ESCC patients. The adjusted factors include age, sex, RT dose, chemotherapy, tumor location, tumor length, T stage, N stage, tumor stage, and PNI. HR, hazard ratio; 95% CI, 95% confidence interval; GNRI, geriatric nutrition risk index; BMI, body mass index; CONUT score, the controlling nutritional status score; PAR, platelet-albumin ratio; ESCC, esophageal squamous cell carcinoma; RT, radiotherapy; PNI, prognostic nutritional index

Fig. 5

Kaplan–Meier curves are according to age, sex, and tumor stage in different risk groups. A OS and PFS of patients with < 76; B OS and PFS of patients with ≥ 76; C OS and PFS of patients with males; D OS and PFS of patients with females; E OS and PFS of patients with stage II; F OS and PFS of patients with stage III; G OS and PFS of patients with stage IVA. OS, overall survival; PFS, progression-free survival

Fig. 6

The restricted cubic spline of pre-therapeutic nutritional-related prognostic indicators in elderly locally advanced ESCC patients. A, B GNRI on OS and PFS; C, D BMI on OS and PFS; E, F) CONUT on OS and PFS; G, H PAR on OS and PFS. HR, hazard ratio; GNRI, geriatric nutrition risk index; OS, overall survival; PFS, progression-free survival; BMI, body mass index; CONUT score, the controlling nutritional status score; PAR, platelet-albumin ratio