Positron Emission Tomography 18F-Fluorodeoxyglucose Uptake and Prognosis in Patients with Surgically Treated, Stage I Non-small Cell Lung Cancer: A Systematic Review

Background18F-fluorodeoxyglucose (FDG) uptake holds potential as a noninvasive biomarker in patients with non-small cell lung cancer (NSCLC). We aimed to investigate the association between tumor FDG uptake and survival in patients with surgically resected, stage I NSCLC.MethodsWe used systematic methods to identify studies for inclusion, assess methodological quality, and abstract relevant data about study design and results.ResultsOur literature search identified 1578 citations, of which nine retrospective, cross-sectional studies met eligibility criteria. In all studies, higher degrees of FDG uptake in the primary tumor were associated with worse overall or disease free survival after 2 to 5 years of follow-up, but these differences were statistically significant in only five studies. Across studies, the median overall or disease free survival was 70% for patients with higher FDG uptake compared with 88% for patients with lower FDG uptake. In three studies that performed multivariable analysis, the adjusted hazard of death or recurrence was 1.9 to 8.6 times greater in patients with higher FDG uptake.ConclusionCurrent evidence suggests that increasing tumor FDG uptake is associated with worse survival in patients with stage I NSCLC. FDG uptake has the potential to be used as a biomarker for identifying stage I patients who are at increased risk of death or recurrence and therefore could identify candidates for participation in future trials of adjuvant therapy

A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer.

Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk.

BackgroundTumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway.ResultTo develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior.ConclusionThese results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance

A Rapid Segmentation-Insensitive “Digital Biopsy” Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non–Small Cell Lung Cancer

Quantitative imaging approaches compute features within images\u27 regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called “digital biopsy,” that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non–small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of 0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer.

Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required

[18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non–Small Cell Lung Cancer

We identified computational imaging features on 18F-fluorodeoxyglucose positron emission tomography (PET) that predict recurrence/progression in non–small cell lung cancer (NSCLC). We retrospectively identified 291 patients with NSCLC from 2 prospectively acquired cohorts (training, n = 145; validation, n = 146). We contoured the metabolic tumor volume (MTV) on all pretreatment PET images and added a 3-dimensional penumbra region that extended outward 1 cm from the tumor surface. We generated 512 radiomics features, selected 435 features based on robustness to contour variations, and then applied randomized sparse regression (LASSO) to identify features that predicted time to recurrence in the training cohort. We built Cox proportional hazards models in the training cohort and independently evaluated the models in the validation cohort. Two features including stage and a MTV plus penumbra texture feature were selected by LASSO. Both features were significant univariate predictors, with stage being the best predictor (hazard ratio [HR] = 2.15 [95% confidence interval (CI): 1.56–2.95], p < 0.001). However, adding the MTV plus penumbra texture feature to stage significantly improved prediction (p = 0.006). This multivariate model was a significant predictor of time to recurrence in the training cohort (concordance = 0.74 [95% CI: 0.66–0.81], p < 0.001) that was validated in a separate validation cohort (concordance = 0.74 [95% CI: 0.67–0.81], p < 0.001). A combined radiomics and clinical model improved NSCLC recurrence prediction. FDG PET radiomic features may be useful biomarkers for lung cancer prognosis and add clinical utility for risk stratification

Multigene profiling of single circulating tumor cells

Numerous techniques for isolating circulating tumor cells (CTCs) have been developed. Concurrently, single-cell techniques that can reveal molecular components of CTCs have become widely available. We discuss how the combination of isolation and multigene profiling of single CTCs in our platform can facilitate eventual translation to the clinic