Integrated Biomarkers for the Management of Indeterminate Pulmonary Nodules.

Rationale: Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model that combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods: In this prospectively collected, retrospective blinded evaluation study, probability of cancer was calculated for 456 patient nodules using the Mayo Clinic model, and patients were categorized into low-, intermediate-, and high-risk groups. A combined biomarker model (CBM) including clinical variables, serum high sensitivity CYFRA 21-1 level, and a radiomic signature was trained in cohort 1 (n = 170) and validated in cohorts 2-4 (total n = 286). All patients were pooled to recalibrate the model for clinical implementation. The clinical utility of the CBM compared with current clinical care was evaluated in 2 cohorts. Measurements and Main Results: The CBM provided improved diagnostic accuracy over the Mayo Clinic model with an improvement in area under the curve of 0.124 (95% bootstrap confidence interval, 0.091-0.156; P < 2 × 10-16). Applying 10% and 70% risk thresholds resulted in a bias-corrected clinical reclassification index for cases and control subjects of 0.15 and 0.12, respectively. A clinical utility analysis of patient medical records estimated that a CBM-guided strategy would have reduced invasive procedures from 62.9% to 50.6% in the intermediate-risk benign population and shortened the median time to diagnosis of cancer from 60 to 21 days in intermediate-risk cancers. Conclusions: Integration of clinical, blood, and image biomarkers improves noninvasive diagnosis of patients with IPNs, potentially reducing the rate of unnecessary invasive procedures while shortening the time to diagnosis.

Quantitative Measures of Background Parenchymal Enhancement Predict Breast Cancer Risk.

BACKGROUND. Higher categories of background parenchymal enhancement (BPE) increase breast cancer risk. However, current clinical BPE categorization is subjective. OBJECTIVE. Using a semiautomated segmentation algorithm, we calculated quantitative BPE measures and investigated the utility of individual features and feature pairs in significantly predicting subsequent breast cancer risk compared with radiologist-assigned BPE category. METHODS. In this retrospective case-control study, we identified 95 women at high risk of breast cancer but without a personal history of breast cancer who underwent breast MRI. Of these women, 19 subsequently developed breast cancer and were included as cases. Each case was age matched to four control patients (76 control patients total). Sociodemographic characteristics were compared between the cases and matched control patients using the Mann-Whitney U test. From each dynamic contrast-enhanced MRI examination, quantitative fibroglandular tissue and BPE measures were computed by averaging enhancing voxels above enhancement ratio thresholds (0-100%), totaling the enhancing volume above thresholds (BPE volume in cm3), and estimating the percentage of enhancing tissue above thresholds relative to total breast volume (BPE%) on each gadolinium-enhanced phase. For the 91 imaging features generated, we compared predictive performance using conditional logistic regression with 80:20 hold-out cross validation and ROC curve analysis. ROC AUC was the figure of merit. Sensitivity, specificity, PPV, and NPV were also computed. All feature pairs were exhaustively searched to identify those with the highest AUC and Youden index. A DeLong test was used to compare predictive performance (AUCs). RESULTS. Women subsequently diagnosed with breast cancer were more likely to have mild, moderate, or marked BPE (odds ratio, 3.0; 95% CI, 0.9-10.0; p = .07). According to ROC curve analysis, a BPE category threshold greater than minimal resulted in a maximized AUC (0.62) in distinguishing cases from control patients. Compared with BPE category, the first gadolinium-enhanced (phase 1) BPE% at the 30% and 40% enhancement ratio thresholds yielded significantly higher AUC values of 0.85 (p = .0007) and 0.84 (p = .0004), respectively. Feature combinations showed similar AUC values with improved sensitivity. CONCLUSION. Preliminary data indicate that quantitative BPE measures may outperform radiologist-assigned category in breast cancer risk prediction. CLINICAL IMPACT. Future risk prediction models that incorporate quantitative measures warrant additional investigation.

Correction: Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer.

BACKGROUND: Tumours rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads to extracellular acidification. We hypothesise that acidity, independent from lactate, can augment the pro-tumour phenotype of macrophages. METHODS: We analysed publicly available data of human prostate cancer for linear correlation between macrophage markers and glycolysis genes. We used zwitterionic buffers to adjust the pH in series of in vitro experiments. We then utilised subcutaneous and transgenic tumour models developed in C57BL/6 mice as well as computer simulations to correlate tumour progression with macrophage infiltration and to delineate role of acidity. RESULTS: Activating macrophages at pH 6.8 in vitro enhanced an IL-4-driven phenotype as measured by gene expression, cytokine profiling, and functional assays. These results were recapitulated in vivo wherein neutralising intratumoural acidity reduced the pro-tumour phenotype of macrophages, while also decreasing tumour incidence and invasion in the TRAMP model of prostate cancer. These results were recapitulated using an in silico mathematical model that simulate macrophage responses to environmental signals. By turning off acid-induced cellular responses, our in silico mathematical modelling shows that acid-resistant macrophages can limit tumour progression. CONCLUSIONS: This study suggests that tumour acidity contributes to prostate carcinogenesis by altering the state of macrophage activation.

Semiautomated Measure of Abdominal Adiposity Using Computed Tomography Scan Analysis.

BACKGROUND: The obesity epidemic has prompted the need to better understand the impact of adipose tissue on human pathophysiology. However, accurate, efficient, and replicable models of quantifying adiposity have yet to be developed and clinically implemented. We propose a novel semiautomated radiologic method of measuring the visceral fat area (VFA) using computed tomography scan analysis. MATERIALS AND METHODS: We obtained a cohort of 100 patients with rectal adenocarcinoma, with a median age of 60.9 y (age range: 35-87 y) and an average body mass index of 28.8 kg/m2 ± 6.56 kg/m2. The semiautomated quantification method of adiposity was developed using a commercial imaging suite. The method was compared to two manual delineations performed using two different picture archiving communication systems. We quantified VFA, subcutaneous fat area (SFA), total fat area (TFA), and visceral-to-subcutaneous fat ratio (V/S ratio) on computed tomography axial slices that were at the L4-L5 intervertebral level. RESULTS: The semiautomated method was comparable to manual measurements for TFA, VFA, and SFA with intraclass correlation (ICC) of 0.99, 0.97, and 0.96, respectively. However, the ICC for the V/S ratio was only 0.44, which led to the identification of technical outliers that were identified using robust regression. After removal of these outliers, the ICC improved to 0.99 for TFA, VFA, and SFA and 0.97 for the V/S ratio. Measurements from the manual methodology highly correlated between the two picture archiving communication system platforms, with ICC of 0.98 for TFA, 0.98 for VFA, 0.96 for SFA, and 0.95 for the V/S ratio. CONCLUSIONS: This semiautomated method is able to generate precise and reproducible results. In the future, this method may be applied on a larger scale to facilitate risk stratification of patients using measures of abdominal adiposity.

Radiologic Features of Small Pulmonary Nodules and Lung Cancer Risk in the National Lung Screening Trial: A Nested Case-Control Study.

Purpose To extract radiologic features from small pulmonary nodules (SPNs) that did not meet the original criteria for a positive screening test and identify features associated with lung cancer risk by using data and images from the National Lung Screening Trial (NLST). Materials and Methods Radiologic features in SPNs in baseline low-dose computed tomography (CT) screening studies that did not meet NLST criteria to be considered a positive screening examination were extracted. SPNs were identified for 73 incident case patients who were given a diagnosis of lung cancer at either the first or second follow-up screening study and for 157 control subjects who had undergone three consecutive negative screening studies. Multivariable logistic regression was used to assess the association between radiologic features and lung cancer risk. All statistical tests were two sided. Results Nine features were significantly different between case patients and control subjects. Backward elimination followed by bootstrap resampling identified a reduced model of highly informative radiologic features with an area under the receiver operating characteristic curve of 0.932 (95% confidence interval [CI]: 0.88, 0.96), a specificity of 92.38% (95% CI: 52.22%, 84.91%), and a sensitivity of 76.55% (95% CI: 87.50%, 95.35%) that included total emphysema score (odds ratio [OR] = 1.71; 95% CI: 1.39, 2.01), attachment to vessel (OR = 2.41; 95% CI: 0.99, 5.81), nodule location (OR = 3.25; 95% CI: 1.09, 8.55), border definition (OR = 7.56; 95% CI: 1.89, 30.8), and concavity (OR = 2.58; 95% CI: 0.89, 5.64). Conclusion A set of clinically relevant radiologic features were identified that that can be easily scored in the clinical setting and may be of use to determine lung cancer risk among participants with SPNs. © RSNA, 2017 Online supplemental material is available for this article.

CT Features Associated with Epidermal Growth Factor Receptor Mutation Status in Patients with Lung Adenocarcinoma.

Purpose To retrospectively identify the relationship between epidermal growth factor receptor (EGFR) mutation status, predominant histologic subtype, and computed tomographic (CT) characteristics in surgically resected lung adenocarcinomas in a cohort of Asian patients. materials and Methods This study was approved by the institutional review board, with waiver of informed consent. Preoperative chest CT findings were retrospectively evaluated in 385 surgically resected lung adenocarcinomas. A total of 30 CT descriptors were assessed. EGFR mutations at exons 18-21 were determined by using the amplification refractory mutation system. Multiple logistic regression analyses were performed to identify independent factors of harboring EGFR mutation status. The final model was selected by using the backward elimination method, and two areas under the receiver operating characteristic curve (ROC) were compared with the nonparametric approach of DeLong, DeLong, and Clarke-Pearson. Results EGFR mutations were found in 168 (43.6%) of 385 patients. Mutations were found more frequently in (a) female patients (P < .001); (b)those who had never smoked (P < .001); (c)those with lepidic predominant adenocarcinomas (P = .001) or intermediate pathologic grade (P < .001); (e) smaller tumors (P < .001); (f)tumors with spiculation (P = .019), ground-glass opacity (GGO) or mixed GGO (P < .001), air bronchogram (P = .006), bubblelike lucency (P < .001), vascular convergence (P = .024), thickened adjacent bronchovascular bundles (P = .027), or pleural retraction (P < .001); and (g) tumors without pleural attachment (P = .004), a well-defined margin (P = .010), marked heterogeneous enhancement (P = .001), severe peripheral emphysema (P = .002), severe peripheral fibrosis (P = .013), or lymphadenopathy (P = .028). The most important and significantly independent prognostic factors of harboring EGFR-activating mutation for the model with both clinical variables and CT features were those who had never smoked and those with smaller tumors, bubblelike lucency, homogeneous enhancement, or pleural retraction when adjusting for histologic subtype, pathologic grade, or thickened adjacent bronchovascular bundles. ROC curve analysis showed that use of clinical variables combined with CT features (area under the ROC curve = 0.778) was superior to use of clinical variables alone (area under the ROC curve = 0.690). Conclusion CT imaging features of lung adenocarcinomas in combination with clinical variables can be used to prognosticate EGFR mutation status better than use of clinical variables alone. (©) RSNA, 2016 Online supplemental material is available for this article.

Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time.

In laboratory studies, acquired resistance to long-term antihormonal therapy in breast cancer evolves through two phases over 5 y. Phase I develops within 1 y, and tumor growth occurs with either 17ß-estradiol (E(2)) or tamoxifen. Phase II resistance develops after 5 y of therapy, and tamoxifen still stimulates growth; however, E(2) paradoxically induces apoptosis. This finding is the basis for the clinical use of estrogen to treat advanced antihormone-resistant breast cancer. We interrogated E(2)-induced apoptosis by analysis of gene expression across time (2-96 h) in MCF-7 cell variants that were estrogen-dependent (WS8) or resistant to estrogen deprivation and refractory (2A) or sensitive (5C) to E(2)-induced apoptosis. We developed a method termed differential area under the curve analysis that identified genes uniquely regulated by E(2) in 5C cells compared with both WS8 and 2A cells and hence, were associated with E(2)-induced apoptosis. Estrogen signaling, endoplasmic reticulum stress (ERS), and inflammatory response genes were overrepresented among the 5C-specific genes. The identified ERS genes indicated that E(2) inhibited protein folding, translation, and fatty acid synthesis. Meanwhile, the ERS-associated apoptotic genes Bcl-2 interacting mediator of cell death (BIM; BCL2L11) and caspase-4 (CASP4), among others, were induced. Evaluation of a caspase peptide inhibitor panel showed that the CASP4 inhibitor z-LEVD-fmk was the most active at blocking E(2)-induced apoptosis. Furthermore, z-LEVD-fmk completely prevented poly (ADP-ribose) polymerase (PARP) cleavage, E(2)-inhibited growth, and apoptotic morphology. The up-regulated proinflammatory genes included IL, IFN, and arachidonic acid-related genes. Functional testing showed that arachidonic acid and E(2) interacted to superadditively induce apoptosis. Therefore, these data indicate that E(2) induced apoptosis through ERS and inflammatory responses in advanced antihormone-resistant breast cancer.

Test-retest reproducibility analysis of lung CT image features.

Quantitative size, shape, and texture features derived from computed tomographic (CT) images may be useful as predictive, prognostic, or response biomarkers in non-small cell lung cancer (NSCLC). However, to be useful, such features must be reproducible, non-redundant, and have a large dynamic range. We developed a set of quantitative three-dimensional (3D) features to describe segmented tumors and evaluated their reproducibility to select features with high potential to have prognostic utility. Thirty-two patients with NSCLC were subjected to unenhanced thoracic CT scans acquired within 15 min of each other under an approved protocol. Primary lung cancer lesions were segmented using semi-automatic 3D region growing algorithms. Following segmentation, 219 quantitative 3D features were extracted from each lesion, corresponding to size, shape, and texture, including features in transformed spaces (laws, wavelets). The most informative features were selected using the concordance correlation coefficient across test-retest, the biological range and a feature independence measure. There were 66 (30.14%) features with concordance correlation coefficient ≥ 0.90 across test-retest and acceptable dynamic range. Of these, 42 features were non-redundant after grouping features with R (2) Bet ≥ 0.95. These reproducible features were found to be predictive of radiological prognosis. The area under the curve (AUC) was 91% for a size-based feature and 92% for the texture features (runlength, laws). We tested the ability of image features to predict a radiological prognostic score on an independent NSCLC (39 adenocarcinoma) samples, the AUC for texture features (runlength emphasis, energy) was 0.84 while the conventional size-based features (volume, longest diameter) was 0.80. Test-retest and correlation analyses have identified non-redundant CT image features with both high intra-patient reproducibility and inter-patient biological range. Thus making the case that quantitative image features are informative and prognostic biomarkers for NSCLC.

Classifying Malignancy in Prostate Glandular Structures from Biopsy Scans with Deep Learning.

Histopathological classification in prostate cancer remains a challenge with high dependence on the expert practitioner. We develop a deep learning (DL) model to identify the most prominent Gleason pattern in a highly curated data cohort and validate it on an independent dataset. The histology images are partitioned in tiles (14,509) and are curated by an expert to identify individual glandular structures with assigned primary Gleason pattern grades. We use transfer learning and fine-tuning approaches to compare several deep neural network architectures that are trained on a corpus of camera images (ImageNet) and tuned with histology examples to be context appropriate for histopathological discrimination with small samples. In our study, the best DL network is able to discriminate cancer grade (GS3/4) from benign with an accuracy of 91%, F1-score of 0.91 and AUC 0.96 in a baseline test (52 patients), while the cancer grade discrimination of the GS3 from GS4 had an accuracy of 68% and AUC of 0.71 (40 patients).

Overview of approaches to estimate real-world disease progression in lung cancer.

BACKGROUND: Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study. METHODS: A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable). RESULTS: A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics-based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96). CONCLUSIONS: Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data.

Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers.

The Metabolic Tumor Volume (MTV) and Tumor Lesion Glycolysis (TLG) has been shown to be independent prognostic predictors for clinical outcome in Diffuse Large B-cell Lymphoma (DLBCL). However, definitions of these measurements have not been standardized, leading to many sources of variation, operator evaluation continues to be one major source. In this study, we propose a reader reproducibility study to evaluate computation of TMV (& TLG) metrics based on differences in lesion delineation. In the first approach, reader manually corrected regional boundaries after automated detection performed across the lesions in a body scan (Reader M using a manual process, or manual). The other reader used a semi-automated method of lesion identification, without any boundary modification (Reader A using a semi- automated process, or auto). Parameters for active lesion were kept the same, derived from standard uptake values (SUVs) over a 41% threshold. We systematically contrasted MTV & TLG differences between expert readers (Reader M & A). We find that MTVs computed by Readers M and A were both concordant between them (concordant correlation coefficient of 0.96) and independently prognostic with a P-value of 0.0001 and 0.0002 respectively for overall survival after treatment. Additionally, we find TLG for these reader approaches showed concordance (CCC of 0.96) and was prognostic for over -all survival (p ≤ 0.0001 for both). In conclusion, the semi-automated approach (Reader A) provides acceptable quantification & prognosis of tumor burden (MTV) and TLG in comparison to expert reader assisted measurement (Reader M) on PET/CT scans.

In Vivo Imaging of Rat Vascularity with FDG-Labeled Erythrocytes.

Microvascular disease is frequently found in major pathologies affecting vital organs, such as the brain, heart, and kidneys. While imaging modalities, such as ultrasound, computed tomography, single photon emission computed tomography, and magnetic resonance imaging, are widely used to visualize vascular abnormalities, the ability to non-invasively assess an organ's total vasculature, including microvasculature, is often limited or cumbersome. Previously, we have demonstrated proof of concept that non-invasive imaging of the total mouse vasculature can be achieved with 18F-fluorodeoxyglucose (18F-FDG)-labeled human erythrocytes and positron emission tomography/computerized tomography (PET/CT). In this work, we demonstrate that changes in the total vascular volume of the brain and left ventricular myocardium of normal rats can be seen after pharmacological vasodilation using 18F-FDG-labeled rat red blood cells (FDG RBCs) and microPET/CT imaging. FDG RBC PET imaging was also used to approximate the location of myocardial injury in a surgical myocardial infarction rat model. Finally, we show that FDG RBC PET imaging can detect relative differences in the degree of drug-induced intra-myocardial vasodilation between diabetic rats and normal controls. This FDG-labeled RBC PET imaging technique may thus be useful for assessing microvascular disease pathologies and characterizing pharmacological responses in the vascular bed of interest.

Volume doubling time and radiomic features predict tumor behavior of screen-detected lung cancers.

BACKGROUND: Image-based biomarkers could have translational implications by characterizing tumor behavior of lung cancers diagnosed during lung cancer screening. In this study, peritumoral and intratumoral radiomics and volume doubling time (VDT) were used to identify high-risk subsets of lung patients diagnosed in lung cancer screening that are associated with poor survival outcomes. METHODS: Data and images were acquired from the National Lung Screening Trial. VDT was calculated between two consequent screening intervals approximately 1 year apart; peritumoral and intratumoral radiomics were extracted from the baseline screen. Overall survival (OS) was the main endpoint. Classification and Regression Tree analyses identified the most predictive covariates to classify patient outcomes. RESULTS: Decision tree analysis stratified patients into three risk-groups (low, intermediate, and high) based on VDT and one radiomic feature (compactness). High-risk patients had extremely poor survival outcomes (hazard ratio [HR] = 8.15; 25% 5-year OS) versus low-risk patients (HR = 1.00; 83.3% 5-year OS). Among early-stage lung cancers, high-risk patients had poor survival outcomes (HR = 9.07; 44.4% 5-year OS) versus the low-risk group (HR = 1.00; 90.9% 5-year OS). For VDT, the decision tree analysis identified a novel cut-point of 279 days and using this cut-point VDT alone discriminated between aggressive (HR = 4.18; 45% 5-year OS) versus indolent/low-risk cancers (HR = 1.00; 82.8% 5-year OS). CONCLUSION: We utilized peritumoral and intratumoral radiomic features and VDT to generate a model that identify a high-risk group of screen-detected lung cancers associated with poor survival outcomes. These vulnerable subset of screen-detected lung cancers may be candidates for more aggressive surveillance/follow-up and treatment, such as adjuvant therapy.

Noise-Based Image Harmonization Significantly Increases Repeatability and Reproducibility of Radiomics Features in PET Images: A Phantom Study.

For multicenter clinical studies, characterizing the robustness of image-derived radiomics features is essential. Features calculated on PET images have been shown to be very sensitive to image noise. The purpose of this work was to investigate the efficacy of a relatively simple harmonization strategy on feature robustness and agreement. A purpose-built texture pattern phantom was scanned on 10 different PET scanners in 7 institutions with various different image acquisition and reconstruction protocols. An image harmonization technique based on equalizing a contrast-to-noise ratio was employed to generate a "harmonized" alongside a "standard" dataset for a reproducibility study. In addition, a repeatability study was performed with images from a single PET scanner of variable image noise, varying the binning time of the reconstruction. Feature agreement was measured using the intraclass correlation coefficient (ICC). In the repeatability study, 81/93 features had a lower ICC on the images with the highest image noise as compared to the images with the lowest image noise. Using the harmonized dataset significantly improved the feature agreement for five of the six investigated feature classes over the standard dataset. For three feature classes, high feature agreement corresponded with higher sensitivity to the different patterns, suggesting a way to select suitable features for predictive models.

Requirements and reliability of AI in the medical context.

The digital information age has been a catalyst in creating a renewed interest in Artificial Intelligence (AI) approaches, especially the subclass of computer algorithms that are popularly grouped into Machine Learning (ML). These methods have allowed one to go beyond limited human cognitive ability into understanding the complexity in the high dimensional data. Medical sciences have seen a steady use of these methods but have been slow in adoption to improve patient care. There are some significant impediments that have diluted this effort, which include availability of curated diverse data sets for model building, reliable human-level interpretation of these models, and reliable reproducibility of these methods for routine clinical use. Each of these aspects has several limiting conditions that need to be balanced out, considering the data/model building efforts, clinical implementation, integration cost to translational effort with minimal patient level harm, which may directly impact future clinical adoption. In this review paper, we will assess each aspect of the problem in the context of reliable use of the ML methods in oncology, as a representative study case, with the goal to safeguard utility and improve patient care in medicine in general.

Correction: Quantitative Computed Tomographic Descriptors Associate Tumor Shape Complexity and Intratumor Heterogeneity with Prognosis in Lung Adenocarcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0118261.].

Lung Nodule Malignancy Prediction in Sequential CT Scans: Summary of ISBI 2018 Challenge.

Lung cancer is by far the leading cause of cancer death in the US. Recent studies have demonstrated the effectiveness of screening using low dose CT (LDCT) in reducing lung cancer related mortality. While lung nodules are detected with a high rate of sensitivity, this exam has a low specificity rate and it is still difficult to separate benign and malignant lesions. The ISBI 2018 Lung Nodule Malignancy Prediction Challenge, developed by a team from the Quantitative Imaging Network of the National Cancer Institute, was focused on the prediction of lung nodule malignancy from two sequential LDCT screening exams using automated (non-manual) algorithms. We curated a cohort of 100 subjects who participated in the National Lung Screening Trial and had established pathological diagnoses. Data from 30 subjects were randomly selected for training and the remaining was used for testing. Participants were evaluated based on the area under the receiver operating characteristic curve (AUC) of nodule-wise malignancy scores generated by their algorithms on the test set. The challenge had 17 participants, with 11 teams submitting reports with method description, mandated by the challenge rules. Participants used quantitative methods, resulting in a reporting test AUC ranging from 0.698 to 0.913. The top five contestants used deep learning approaches, reporting an AUC between 0.87 - 0.91. The team's predictor did not achieve significant differences from each other nor from a volume change estimate (p =.05 with Bonferroni-Holm's correction).

18F-FDG PET/CT Habitat Radiomics Predicts Outcome of Patients with Cervical Cancer Treated with Chemoradiotherapy.

PURPOSE: To determine if quantitative features extracted from pretherapy fluorine 18 fluorodeoxyglucose (18F-FDG) PET/CT estimate prognosis in patients with locally advanced cervical cancer treated with chemoradiotherapy. MATERIALS AND METHODS: In this retrospective study, PET/CT images and outcomes were curated from 154 patients with locally advanced cervical cancer, who underwent chemoradiotherapy from two institutions between March 2008 and June 2016, separated into independent training (n = 78; mean age, 51 years ± 13 [standard deviation]) and testing (n = 76; mean age, 50 years ± 10) cohorts. Radiomic features were extracted from PET, CT, and habitat (subregions with different metabolic characteristics) images that were derived by fusing PET and CT images. Parsimonious sets of these features were identified by the least absolute shrinkage and selection operator analysis and used to generate predictive radiomics signatures for progression-free survival (PFS) and overall survival (OS) estimation. Prognostic validation of the radiomic signatures as independent prognostic markers was performed using multivariable Cox regression, which was expressed as nomograms, together with other clinical risk factors. RESULTS: The radiomics nomograms constructed with T stage, lymph node status, and radiomics signatures resulted in significantly better performance for the estimation of PFS (Harrell concordance index [C-index], 0.85 for training and 0.82 for test) and OS (C-index, 0.86 for training and 0.82 for test) compared with International Federation of Gynecology and Obstetrics staging system (C-index for PFS, 0.70 for training [P = .001] and 0.70 for test [P = .002]; C-index for OS, 0.73 for training [P < .001] and 0.70 for test [P < .001]), respectively. CONCLUSION: Prognostic models were generated and validated from quantitative analysis of 18F-FDG PET/CT habitat images and clinical data, and may have the potential to identify the patients who need more aggressive treatment in clinical practice, pending further validation with larger prospective cohorts.Supplemental material is available for this article.© RSNA, 2020.