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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5370-5) contains supplementary material, which is available to authorized users.

The Effect of Diabetes Mellitus on Prognosis of Patients with Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…Four studies were from Asia [17][18][19][20] and 13 were from western countries. [21][22][23][24][25][26][27][28][29][30][31][32][33] Most studies were published within the last 10 years and the sample sizes ranged from 146 to 10378. Seven of the studies 17,19,24,25,27,29,31) investigated the outcomes of patients undergoing surgical treatment, while six studies 18,21,23,26,30,33) focused on those receiving non-surgical treatments like chemotherapy or radiotherapy and three studies 20,22,32) recruited patients receiving both of them.…”

“…All but one study were retrospective cohort studies while the only exception was designed as a prospective cohort. 31) In all, 13 of the studies [17][18][19][20][24][25][26][27][29][30][31][32][33] ascertained the diagnosis of preexisting DM in reference to medical records or documented use of anti-diabetic drugs, three retrieved the diagnostic information from local registry system. 21,22,28) In total, 13 studies adopted multivariate regression models to calculate HR while four studies chose univariate models.…”

“…21,22,28) In total, 13 studies adopted multivariate regression models to calculate HR while four studies chose univariate models. 17,23,27,33) There were 13 studies that adjusted for age when reporting the HR for OR, which was considered as the most important factor to assure the comparability of cohorts during the process of quality assessment. 17,18,20,22,[24][25][26][27][28][29][30]32,33) And 11 of the 13 controlled for age and stage, 17,18,20,22,25,26,[28][29][30]32,33) while other potential confounders including gender, smoking, histology type, comorbidities, adjuvant therapy varied across the studies.…”

“…23,[28][29][30]33) Inal et al found that DM at the time of diagnosis was associated with negative prognostic importance for PFS in advanced stage NSCLC patients receiving first-line platinum-based doublets chemotherapy (HR: 1.83, 95% CI: 1.20-2.79, p = 0.005), 30) and similar result was also reported by Bergamino et al (HR: 1.68, 95% CI: 1.14-2.47, p = 0.003. 33) In contrast, in the study by Medairos, it was revealed that diabetic NSCLC patients with metformin exposure might be associated with improved PFS compared with those non-diabetic NSCLC patients (HR: 0.415, 95% CI: 0.201-0.887, p = 0.017). 29) The results from Ahmed et al 23) and Hershman et al 28) were statistically insignificant, making it difficult to come to a confirmed conclusion with the existence of such a controversy.…”

Poor glycemic control might compromise the efficacy of chemotherapy in non‐small cell lung cancer patients with diabetes mellitus

“…The coexistence of T2DM in NSCLC patients has become more common, with an estimated proportion of 8%‐18% . Hyperinsulinemia, hyperglycemia and chronic inflammation in patients with T2DM may influence the progression and outcome of lung cancer . However, a large number of studies have been concerned with the prognostic significance of preexisting diabetes mellitus (DM) or the fasting blood glucose (FBG) level in patients with NSCLC, not the glycemic control conditions .…”