ABSTRACT
Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance the efficiency of a lung cancer diagnosis. BALF analysis is a promising approach to evaluating the tumor progression microenvironment. BALF's cellular and non-cellular components dictate the inflammatory response in a cancer-proliferating microenvironment. Furthermore, it is an essential material for detecting clinically significant predictive and prognostic biomarkers that may aid in guiding treatment choices and evaluating therapy-induced toxicities in lung cancer. In the present article, we have reviewed recent literature about the utility of BALF analysis for detecting markers in different stages of tumor cell metabolism, employing either specific biomarker assays or broader omics approaches.
ABSTRACT
Systematic treatment of advanced non-small cell lung cancer (NSCLC) includes targeted treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The development of skin rash and its intensity have been associated with EGFR TKI's efficacy. The main purpose of this study was to further investigate the potential value of erlotinib-associated rash as a predictor of prognosis and treatment response in a real-world cohort of patients with advanced NSCLC. The medical records of all NSCLC patients treated with erlotinib at the Oncology Unit of GPP, Sotiria Athens General Hospital between January 1, 2014 and August 31, 2016 were retrospectively reviewed. Seventy-nine patient medical records fulfilled the criteria and were included in the study. Development of erlotinib-associated rash was correlated with clinicopathological characteristics of patients, treatment response, and overall survival (OS) using univariate and multivariate Cox regression analysis. The number of patients with rash was greater in the responders group (90% vs. 46.4%, p = 0.015). In univariate analysis, there was a statistically significant association between rash development and time to progression (TTP) [HR: 0.32 (0.17-0.57), p < 0.001]. With multivariate Cox regression analysis, it was found that PS ≥ 2 (HR: 2.01, 95% CI: 1.12-3.60, p = 0.018) and rash (HR: 0.34, 95% CI: 0.18-0.63, p = 0.001) were independently associated with TTP and also that the duration of treatment with erlotinib (HR: 0.58, 95% CI: 0.42-0.80, p = 0.001) and rash (HR: 0.10, 95% CI: 0.20-0.48, p = 0.004) was an independent predictor of survival. Our results suggest that erlotinib-associated rash may represent a clinically valuable biomarker for the prediction of treatment response and OS in patients with advanced NSCLC.
Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Eruptions , Erlotinib Hydrochloride/adverse effects , Lung Neoplasms/drug therapy , Adult , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
Immune checkpoint inhibitors (ICIs) are a newly developed component of cancer care that expands the treatment possibilities for patients. Their use has been associated with several immune-related adverse events, including ICI-induced sarcoidosis-like reactions. This article reviews the data concerning ICI-induced sarcoidosis-like reactions currently available in the medical literature. These reactions have been reported in three classes of ICIs: anti-cytotoxic T-lymphocyte associated protein 4 antibodies, programmed death 1 inhibitors and programmed death ligand 1 inhibitors. These reactions are indistinguishable from sarcoidosis with a similar histology, pattern of organ involvement, and pattern of clinical manifestations. The most common locations to observe granulomatous inflammation from these reactions is in intrathoracic locations (the lung and/or mediastinal lymph nodes) and the skin. The median time between initiation of an ICI and the development of a sarcoidosis-like reaction averaged 14 weeks. Clinicians have opted to use corticosteroids and/or discontinue the ICI, or take no action when these reactions have developed. Regardless of whether the clinician performed an intervention or not, these reactions have uniformly improved or resolved after ICI-treatment, which provides additional temporal evidence supporting the presence of a sarcoidosis-like reaction as opposed to sarcoidosis. There is even evidence that the development of an ICI-induced sarcoidosis-like reaction suggests that the ICI is effective as an anti-tumor agent and should be continued. As is the case for sarcoidosis, sarcoidosis-like reactions do not mandate antisarcoidosis therapy, especially if the condition is asymptomatic. When treatment of sarcoidosis-like reaction is required, it may be prudent to continue ICI therapy and add antisarcoidosis therapy because standard antisarcoidosis regimens seem to be effective. Further research into the mechanisms involved in the development of ICI-induced sarcoidosis-like reactions may give insights into the immunopathogenesis of sarcoidosis.