Fasting plasma glucose is an independent predictor of survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

Abstract

Background: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy.

Methods: One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and Cox proportional models and log-rank test were used.

Results: With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07-1.19, p < 0.001) and 31 months (HR 1.09; 95% CI 1.04-1.15; p < 0.001) respectively, for patients with FPG < 7 mmol/L. In the multivariate analysis of the entire cohort adjusted by platinum compound and comorbidities, high levels of FPG as a continuous variable (HR 1.14; 95% CI 1.07-1.21; p < 0.001), the presence of comorbidity (HR 1.72; 95% CI 1.12-2.63; p = 0.012), and treatment with carboplatin (HR 1.95; 95% CI 1.26-2.99; p = 0.002) were independent predictors for shorter OS. In additional multivariate models considering non-diabetic patients as a reference group, diabetic patients with poor metabolic control (HbA1c > 8.5%) (HR 4.53; 95% CI 2.21-9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90-5.46 p < 0.001) had significantly independent worse OS.

Conclusion: Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association.

Keywords: Comorbidities; Concurrent chemoradiotherapy; Hyperglycemia; Locally advanced unresectable non-small cell lung cancer; Type 2 diabetes mellitus.

Fig. 1

Kaplan Meier curves for overall survival (a) and progression-free survival (b) according to pre-treatment Fasting plasma glucose (FPG) in the whole cohort (n = 170). Patients with FPG ≥7 mmol/L had significantly shorter median OS and PFS compared with patients with FPG < 7 mmol/L. Abbreviations: Overall Survival (OS), Progression Free Survival (PFS)

Fig. 2

Kaplan Meier curves for overall survival (a) and progression-free survival (b) according to diagnosis of type 2 diabetes mellitus (T2DM) in the whole cohort (n = 170). Patients with T2DM diagnosis had significantly shorter median OS and PFS compared with patients without T2DM history. Abbreviations: Overall Survival (OS), Progression Free Survival (PFS)

Fig. 3

Kaplan Meier curves for OS in type 2 T2DM and non-diabetic patients according to metabolic control based on HbA1 (a) and type of anti-diabetic treatment (b). Patients with poor metabolic control (HbA1c > 8.5%) had shorter median OS as compared with the rest of diabetic patients and nondiabetic patients. Patient receiving insulin had also worse OS compared with the rest of diabetic patients. Abbreviations: Type 2 Diabetes Mellitus (T2DM), Overall survival (OS), Glycated Haemoglobin (HbA1c)