Purpose: Hepatic injury is a common side effect following tyrosine kinase inhibitor (TKI) therapy and our understanding usually comes from clinical trials. In this retrospective study, we aimed to investigate the characteristics, risk factors and regimen-related differences of epidermal growth factor receptor (EGFR)-TKI-related hepatic toxicity in patients with advanced lung adenocarcinoma (LAD). Patients and Methods: Liver function tests were documented in 424 patients admitted into the Shanghai Chest Hospital between January 2014 and December 2016 with advanced (IIIB/IV) LAD who received first-line gefitinib, erlotinib or icotinib. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. The clinical spectrum and onset time of hepatic injury were evaluated. The risk factors of hepatic dysfunction were determined using a logistic regression analysis. Results: A total of 87 (20.5%) patients experienced hepatotoxicity and 5.7% were of grade 3/4 liver dysfunction. The median onset time of hepatotoxicity was 7 weeks. Presence of hepatitis virus (HR: 2.593, 95% CI: 1.090– 6.170, P=0.031) and pretreatment liver impairment (HR: 3.460, 95% CI: 1.746– 6.855, P< 0.001) were risk factors associated with increased risk of hepatotoxicity. Gefitinib (HR: 1.872, 95% CI: 1.028– 3.412, P=0.040) and erlotinib (HR: 3.578, 95% CI: 1.683– 7.609, P=0.001) had increased risk of hepatotoxicity compared to icotinib. Conclusion: The different toxic profile of EGFR-TKIs should be taken into account in the choice of treatment based on the patients’ comorbidity.

Background: Diabetes mellitus (DM) is a frequent comorbidity in patients with cancer. This study aimed to evaluate the prognosis of advanced non-small cell lung cancer (NSCLC) patients with DM and to assess whether an optimal glycemic control improves overall survival (OS).Methods: A total of 1279 advanced NSCLC patients including 300 (23.5%) with preexisting DM were retrospectively reviewed. The continuous relationship between glycated hemoglobin A1C (HbA1c) level and OS was analyzed by restricted cubic spline (RCS) function. Optimal HbA1c cut-off point was determined using X-tile analysis. Survival was analyzed with the Kaplan–Meier method and compared among groups stratified by diabetes status and HbA1c. Multivariable Cox proportional hazards regression analysis was employed to identify prognostic factors for OS after adjusting for baseline characteristics.Results: DM and non-DM patients had similar OS (median (95% CI): 22.85 (20.05-26.73) vs. 22.22 (20.35-24.76) months, P=0.950). The multivariate Cox regression analyses showed that DM status was not a prognostic factor for OS (HR: 0.952, 95% CI: 0.808-1.122, P=0.559). However, there existed a non-linear but generally positive relationship between the elevated HbA1c level and increased risk of overall mortality. HbA1c > 6.6% was a negative prognostic factor for OS (HR: 1.593, 95% CI: 1.113-2.280, P=0.011). The median OS (95% CI) for nondiabetic patients, DM patients with HbA1c ≤6.6% and those with HbA1c > 6.6% was 22.22 (20.01-24.43), 25.28 (21.79-28.77) and 15.45 (7.57-23.33) months, respectively. Well-controlled DM patients had a comparable crude OS (HR (95% CI): 0.90 (0.76-1.08), P=0.273] compared to nondiabetic patients while patients with HbA1c>6.6% had a worse crude OS than patients without DM (HR (95% CI): 1.70 (1.24-2.34), P=0.001]. The survival benefit of good HbA1c control was prominent in all subgroups.Conclusion: Impaired glycemic level negatively affects survival for patients with advanced NSCLC while proper glycemic control with HbA1c ≤6.6% improves the OS.

Background: Lung cancer (LC) is the most common solid tumor type in the intensive care unit (ICU). This study investigated the characteristics of LC patients admitted to the ICU, the major reasons for their admission, short-term mortality, and associated risk factors. Methods: Patients with LC were retrospectively identified in the publicly available, large-scale, single-center database Medical Information Mart for Intensive Care (MIMIC) III. Demographic and clinical characteristics, including age, sex, smoking history, comorbidities, type of admission to ICU, major diagnoses, illness severity score as assessed by the Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA), ICU length of stay (LOS), use of mechanic ventilation (MV) or vasopressors, the existence of do-not-resuscitate (DNR) orders, and metastatic status were collected. The major reasons for ICU admission were analyzed in subgroups. The multivariate logistic regression analysis was used to determine the factors associated with the 28-day and 6-month mortality. Results: A total of 1242 ICU admissions were included. Diseases of respiratory (42.7%), nervous (14.3%), and cardiovascular (11.9%) systems accounted for the top reasons for admission. Pneumonia/pneumonitis, respiratory failure, and sepsis were the primary reasons for ICU admission. The median survival was 2.93 (95% CI: 2.42–3.43) months. The 28-day inhospital and the 6-month mortality were 30.6% and 68.2%, respectively. Sepsis (63.9%), respiratory failure (47.0%), and pleural effusion (40.9%) accounted for the top three highest 28-day ICU mortality in all causes. An age ≥ 65 years, a SAPS II ≥ 37, a SOFA ≥ 3, metastasis, and MV use were independent risk factors for an inferior 28-day survival rate, while only metastatic status and SOFA score were associated with the 6-month mortality. SAPS II was accepatable and better than SOFA in predicting 28-day ICU [area under the curve (AUC): 0.714 and 0.658, respectively] or 28-day inhospital mortality (AUC: 0.717 and 0.660, respectively). Conclusion: The 6-month prognosis for LC patients admitted to ICU was dismal. Multidisciplinary collaboration between intensivists and oncologists to identify high-risk patients and to determine a risk-benefit ratio of ICU treatment may improve survival prospects.