SCLC accounts for almost 15% of lung cancer cases in the United States. Nomogram prognostic models could greatly facilitate risk stratification and treatment planning, as well as more refined enrollment criteria for clinical trials. We developed and validated a new nomogram prognostic model for SCLC patients using a large SCLC patient cohort from the National Cancer Database (NCDB). Clinical data for 24,680 SCLC patients diagnosed from 2004 to 2011 were used to develop the nomogram prognostic model. The model was then validated using an independent cohort of 9700 SCLC patients diagnosed from 2012 to 2013. The prognostic performance was evaluated using p value, concordance index and integrated area under the (time-dependent receiver operating characteristic) curve (AUC). The following variables were contained in the final prognostic model: age, sex, race, ethnicity, Charlson/Deyo score, TNM stage (assigned according to the American Joint Committee on Cancer [AJCC] eighth edition), treatment type (combination of surgery, radiation therapy, and chemotherapy), and laterality. The model was validated in an independent testing group with a concordance index of 0.722 ± 0.004 and an integrated area under the curve of 0.79. The nomogram model has a significantly higher prognostic accuracy than previously developed models, including the AJCC eighth edition TNM-staging system. We implemented the proposed nomogram and four previously published nomograms in an online webserver. We developed a nomogram prognostic model for SCLC patients, and validated the model using an independent patient cohort. The nomogram performs better than earlier models, including models using AJCC staging.
Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer characterized by rapid tumor growth and early metastasis. Accurate prediction of prognosis and therapeutic response is crucial for optimizing treatment strategies and improving patient outcomes. In this study, we conducted a deep-learning analysis of Hematoxylin and Eosin (H&E) stained histopathological images using contrastive clustering and identified 50 intricate histomorphological phenotype clusters (HPCs) as pathomic features. We identified two of 50 HPCs with significant prognostic value and then integrated them into a pathomics signature (PathoSig) using the Cox regression model. PathoSig showed significant risk stratification for overall survival and disease-free survival and successfully identified patients who may benefit from postoperative or preoperative chemoradiotherapy. The predictive power of PathoSig was validated in independent multicenter cohorts. Furthermore, PathoSig can provide comprehensive prognostic information beyond the current TNM staging system and molecular subtyping. Overall, our study highlights the significant potential of utilizing histopathology images-based deep learning in improving prognostic predictions and evaluating therapeutic response in SCLC. PathoSig represents an effective tool that aids clinicians in making informed decisions and selecting personalized treatment strategies for SCLC patients.
We constructed a lung cancer-specific database housing expression data and clinical data from over 6700 patients in 56 studies. Expression data from 23 genome-wide platforms were carefully processed and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer database, we created an open access web resource—the Lung Cancer Explorer (LCE), which enables researchers and clinicians to explore these data and perform analyses. Users can perform meta-analyses on LCE to gain a quick overview of the results on tumor vs non-malignant tissue (normal) differential gene expression and expression-survival association. Individual dataset-based survival analysis, comparative analysis, and correlation analysis are also provided with flexible options to allow for customized analyses from the user.
Pathology images capture tumor histomorphological details in high resolution. However, manual detection and characterization of tumor regions in pathology images is labor intensive and subjective. Using a deep convolutional neural network (CNN), we developed an automated tumor region recognition system for lung cancer pathology images. From the identified tumor regions, we extracted 22 well-defined shape and boundary features and found that 15 of them were significantly associated with patient survival outcome in lung adenocarcinoma patients from the National Lung Screening Trial. A tumor region shape-based prognostic model was developed and validated in an independent patient cohort (n = 389). The predicted high-risk group had significantly worse survival than the low-risk group (p value = 0.0029). Predicted risk group serves as an independent prognostic factor (high-risk vs. low-risk, hazard ratio = 2.25, 95% CI 1.34–3.77, p value = 0.0022) after adjusting for age, gender, smoking status, and stage. This study provides new insights into the relationship between tumor shape and patient prognosis.