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Purpose: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. Methods: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. Results: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057–9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023–0.290) and 0.474 (0.213–1.109) μg/mL, P = 0.001]. Conclusion: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia. [ABSTRACT FROM AUTHOR]

Objectives: Chemotherapy-related acute exacerbation (AE) of interstitial lung disease (ILD) is observed in certain patients with non-small cell lung cancer (NSCLC) who have ILD. Although the prognosis of AE-ILD is extremely poor, there are no established risk factors for its occurrence. Therefore, we retrospectively investigated whether high-resolution computed tomography (HRCT) findings could identify risk factors for AE-ILD.Materials and Methods: Between January 2005 and December 2016, 35 patients with NSCLC who received chemotherapy at Hiroshima University Hospital and were diagnosed with ILD on HRCT were enrolled. The extent of ground-glass attenuation (GGA), reticulation, honeycomb appearance, and emphysema, as well as the presence of micronodules, traction bronchiectasis, and consolidation were evaluated in five levels of the lung bilaterally. The HRCT scores of GGA, reticulation, honeycomb appearance, and emphysema were determined by the following formula: 100 × sum of the extent of the HRCT findings/lung area.Results: Thirty-five patients underwent various first- to fifth-line chemotherapy regimens. Nine patients (25.7%) developed AE-ILD. The median HRCT scores of GGA and reticulation were significantly higher in patients with AE-ILD than in those without. On univariate analysis, a GGA area score ≥ 24.8, reticulation area score ≥ 19.5, and KL-6 level ≥ 946 U/mL were significant risk factors. Multivariate logistic analysis revealed that only a GGA area score ≥ 24.8 was an independent risk factor of AE-ILD.Conclusions: The GGA area on HRCT is a risk factor for chemotherapy-related AE-ILD. Therefore, this parameter can be used to predict the risk of AE-ILD before administering chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: We have treated patients with non-small-cell lung cancer (NSCLC) who developed leptomeningeal metastases (LM) during gefitinib therapy, and then found symptomatic improvement following treatment change to erlotinib. Based on this experience, we wondered whether erlotinib could be detected in cerebrospinal fluid (CSF) when it was used for NSCLC patients with LM. This study was conducted to determine erlotinib concentrations in CSF and assess responses to erlotinib in patients with NSCLC developing LM during gefitinib therapy. Methods: Three advanced NSCLC patients with LM that developed during gefitinib therapy were treated with erlotinib. On day 28 after the initiation of erlotinib treatment, plasma and CSF were obtained and the concentrations of erlotinib in these samples were measured. Eastern Cooperative Oncology Group (ECOG) performance status (PS) and neurologic symptoms were determined. Results: Erlotinib CSF penetration was 6.3% ± 6.1% (mean ± SD). In cases 1 and 2, we observed improvements in ECOG PS and neurologic symptoms. In case 3, cytological improvement was seen in the CSF. In each patient, deletion of exon 19 or exon 21 L858R mutation of the epidermal growth factor receptor ( EGFR) gene was detected in carcinoma cells from the CSF. Conclusions: We report on 3 patients with NSCLC who had developed LM during gefitinib treatment and showed clinical improvements following change to erlotinib therapy. In all cases, small but measurable penetration of erlotinib into CSF was observed. Because EGFR mutations were detected in all cases, we suggest that erlotinib is a therapeutic option for LM carcinoma cells with EGFR mutations. [ABSTRACT FROM AUTHOR]