ABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0252537.].
ABSTRACT
OBJECTIVE: We prospectively recorded clinical and laboratory parameters from patients with metastatic non-small cell lung cancer (NSCLC) treated with 2nd line PD-1/PD-L1 inhibitors in order to address their effect on treatment outcomes. MATERIALS AND METHODS: Clinicopathological information (age, performance status, smoking, body mass index, histology, organs with metastases), use and duration of proton pump inhibitors, steroids and antibiotics (ATB) and laboratory values [neutrophil/lymphocyte ratio, LDH, albumin] were prospectively collected. Steroid administration was defined as the use of > 10 mg prednisone equivalent for ≥ 10 days. Prolonged ATB administration was defined as ATB ≥ 14 days 30 days before or within the first 3 months of treatment. JADBio, a machine learning pipeline was applied for further multivariate analysis. RESULTS: Data from 66 pts with non-oncogenic driven metastatic NSCLC were analyzed; 15.2% experienced partial response (PR), 34.8% stable disease (SD) and 50% progressive disease (PD). Median overall survival (OS) was 6.77 months. ATB administration did not affect patient OS [HR = 1.35 (CI: 0.761-2.406, p = 0.304)], however, prolonged ATBs [HR = 2.95 (CI: 1.62-5.36, p = 0.0001)] and the presence of bone metastases [HR = 1.89 (CI: 1.02-3.51, p = 0.049)] independently predicted for shorter survival. Prolonged ATB administration, bone metastases, liver metastases and BMI < 25 kg/m2 were selected by JADbio as the important features that were associated with increased probability of developing disease progression as response to treatment. The resulting algorithm that was created was able to predict the probability of disease stabilization (PR or SD) in a single individual with an AUC = 0.806 [95% CI:0.714-0.889]. CONCLUSIONS: Our results demonstrate an adverse effect of prolonged ATBs on response and survival and underscore their importance along with the presence of bone metastases, liver metastases and low BMI in the individual prediction of outcomes in patients treated with immunotherapy.
Subject(s)
Anti-Bacterial Agents/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Bone Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/administration & dosage , Immunotherapy/methods , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Machine Learning , Male , Middle Aged , Prognosis , Progression-Free Survival , Prospective StudiesABSTRACT
Flow and mass cytometry technologies can probe proteins as biological markers in thousands of individual cells simultaneously, providing unprecedented opportunities for reconstructing networks of protein interactions through machine learning algorithms. The network reconstruction (NR) problem has been well-studied by the machine learning community. However, the potentials of available methods remain largely unknown to the cytometry community, mainly due to their intrinsic complexity and the lack of comprehensive, powerful and easy-to-use NR software implementations specific for cytometry data. To bridge this gap, we present Single CEll NEtwork Reconstruction sYstem (SCENERY), a web server featuring several standard and advanced cytometry data analysis methods coupled with NR algorithms in a user-friendly, on-line environment. In SCENERY, users may upload their data and set their own study design. The server offers several data analysis options categorized into three classes of methods: data (pre)processing, statistical analysis and NR. The server also provides interactive visualization and download of results as ready-to-publish images or multimedia reports. Its core is modular and based on the widely-used and robust R platform allowing power users to extend its functionalities by submitting their own NR methods. SCENERY is available at scenery.csd.uoc.gr or http://mensxmachina.org/en/software/.