Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer.

Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component and the tumor microenvironment, which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intratumoral heterogeneity in PDAC. In this study, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest across 9 patients, capturing more than 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a proangiogenic gene signature. Taken together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche. Significance: Imaging mass cytometry revealed that pancreatic ductal cancers are composed of 10 distinct cellular neighborhoods, including a vascular niche enriched for macrophages expressing high levels of CD44 and a proangiogenic gene signature.

Use of Response Permutation to Measure an Imaging Dataset's Susceptibility to Overfitting by Selected Standard Analysis Pipelines.

RATIONALE AND OBJECTIVES: This study demonstrates a method for quantifying the impact of overfitting on the receiving operator characteristic curve (AUC) when using standard analysis pipelines to develop imaging biomarkers. We illustrate the approach using two publicly available repositories of radiology and pathology images for breast cancer diagnosis. MATERIALS AND METHODS: For each dataset, we permuted the outcome (cancer diagnosis) values to eliminate any true association between imaging features and outcome. Seven types of classification models (logistic regression, linear discriminant analysis, Naïve Bayes, linear support vector machines, nonlinear support vector machine, random forest, and multi-layer perceptron) were fitted to each scrambled dataset and evaluated by each of four techniques (all data, hold-out, 10-fold cross-validation, and bootstrapping). After repeating this process for a total of 50 outcome permutations, we averaged the resulting AUCs. Any increase over a null AUC of 0.5 can be attributed to overfitting. RESULTS: Applying this approach and varying sample size and the number of imaging features, we found that failing to control for overfitting could result in near-perfect prediction (AUC near 1.0). Cross-validation offered greater protection against overfitting than the other evaluation techniques, and for most classification algorithms a sample size of at least 200 was required to assess as few as 10 features with less than 0.05 AUC inflation attributable to overfitting. CONCLUSION: This approach could be applied to any curated dataset to suggest the number of features and analysis approaches to limit overfitting.

Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.

PURPOSE: The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. METHODS: Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. RESULTS: Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. CONCLUSIONS: Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.

Preoperative CT and survival data for patients undergoing resection of colorectal liver metastases.

The liver is a common site for the development of metastases in colorectal cancer. Treatment selection for patients with colorectal liver metastases (CRLM) is difficult; although hepatic resection will cure a minority of CRLM patients, recurrence is common. Reliable preoperative prediction of recurrence could therefore be a valuable tool for physicians in selecting the best candidates for hepatic resection in the treatment of CRLM. It has been hypothesized that evidence for recurrence could be found via quantitative image analysis on preoperative CT imaging of the future liver remnant before resection. To investigate this hypothesis, we have collected preoperative hepatic CT scans, clinicopathologic data, and recurrence/survival data, from a large, single-institution series of patients (n = 197) who underwent hepatic resection of CRLM. For each patient, we also created segmentations of the liver, vessels, tumors, and future liver remnant. The largest of its kind, this dataset is a resource that may aid in the development of quantitative imaging biomarkers and machine learning models for the prediction of post-resection hepatic recurrence of CRLM.

Medical image synthesis via conditional GANs: Application to segmenting brain tumours.

Accurate brain tumour segmentation is critical for tasks such as surgical planning, diagnosis, and analysis, with magnetic resonance imaging (MRI) being the preferred modality due to its excellent visualisation of brain tissues. However, the wide intensity range of voxel values in MR scans often results in significant overlap between the density distributions of different tumour tissues, leading to reduced contrast and segmentation accuracy. This paper introduces a novel framework based on conditional generative adversarial networks (cGANs) aimed at enhancing the contrast of tumour subregions for both voxel-wise and region-wise segmentation approaches. We present two models: Enhancement and Segmentation GAN (ESGAN), which combines classifier loss with adversarial loss to predict central labels of input patches, and Enhancement GAN (EnhGAN), which generates high-contrast synthetic images with reduced inter-class overlap. These synthetic images are then fused with corresponding modalities to emphasise meaningful tissues while suppressing weaker ones. We also introduce a novel generator that adaptively calibrates voxel values within input patches, leveraging fully convolutional networks. Both models employ a multi-scale Markovian network as a GAN discriminator to capture local patch statistics and estimate the distribution of MR images in complex contexts. Experimental results on publicly available MR brain tumour datasets demonstrate the competitive accuracy of our models compared to current brain tumour segmentation techniques.

Applying Natural Language Processing to Single-Report Prediction of Metastatic Disease Response Using the OR-RADS Lexicon.

Generating Real World Evidence (RWE) on disease responses from radiological reports is important for understanding cancer treatment effectiveness and developing personalized treatment. A lack of standardization in reporting among radiologists impacts the feasibility of large-scale interpretation of disease response. This study examines the utility of applying natural language processing (NLP) to the large-scale interpretation of disease responses using a standardized oncologic response lexicon (OR-RADS) to facilitate RWE collection. Radiologists annotated 3503 retrospectively collected clinical impressions from radiological reports across several cancer types with one of seven OR-RADS categories. A Bidirectional Encoder Representations from Transformers (BERT) model was trained on this dataset with an 80-20% train/test split to perform multiclass and single-class classification tasks using the OR-RADS. Radiologists also performed the classification to compare human and model performance. The model achieved accuracies from 95 to 99% across all classification tasks, performing better in single-class tasks compared to the multiclass task and producing minimal misclassifications, which pertained mostly to overpredicting the equivocal and mixed OR-RADS labels. Human accuracy ranged from 74 to 93% across all classification tasks, performing better on single-class tasks. This study demonstrates the feasibility of the BERT NLP model in predicting disease response in cancer patients, exceeding human performance, and encourages the use of the standardized OR-RADS lexicon to improve large-scale prediction accuracy.

The RSNA Cervical Spine Fracture CT Dataset.

This dataset is composed of cervical spine CT images with annotations related to fractures; it is available at https://www.kaggle.com/competitions/rsna-2022-cervical-spine-fracture-detection/.

Computerized Diagnosis of Liver Tumors From CT Scans Using a Deep Neural Network Approach.

The liver is a frequent site of benign and malignant, primary and metastatic tumors. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers, and colorectal liver metastasis (CRLM) is the most common secondary liver cancer. Although the imaging characteristic of these tumors is central to optimal clinical management, it relies on imaging features that are often non-specific, overlap, and are subject to inter-observer variability. Thus, in this study, we aimed to categorize liver tumors automatically from CT scans using a deep learning approach that objectively extracts discriminating features not visible to the naked eye. Specifically, we used a modified Inception v3 network-based classification model to classify HCC, ICC, CRLM, and benign tumors from pretreatment portal venous phase computed tomography (CT) scans. Using a multi-institutional dataset of 814 patients, this method achieved an overall accuracy rate of 96%, with sensitivity rates of 96%, 94%, 99%, and 86% for HCC, ICC, CRLM, and benign tumors, respectively, using an independent dataset. These results demonstrate the feasibility of the proposed computer-assisted system as a novel non-invasive diagnostic tool to classify the most common liver tumors objectively.

Radiomics artificial intelligence modelling for prediction of local control for colorectal liver metastases treated with radiotherapy.

Background and Purpose: Prognostic assessment of local therapies for colorectal liver metastases (CLM) is essential for guiding management in radiation oncology. Computed tomography (CT) contains liver texture information which may be predictive of metastatic environments. To investigate the feasibility of analyzing CT texture, we sought to build an automated model to predict progression-free survival using CT radiomics and artificial intelligence (AI). Materials and Methods: Liver CT scans and outcomes for N = 97 CLM patients treated with radiotherapy were retrospectively obtained. A survival model was built by extracting 108 radiomic features from liver and tumor CT volumes for a random survival forest (RSF) to predict local progression. Accuracies were measured by concordance indices (C-index) and integrated Brier scores (IBS) with 4-fold cross-validation. This was repeated with different liver segmentations and radiotherapy clinical variables as inputs to the RSF. Predictive features were identified by perturbation importances. Results: The AI radiomics model achieved a C-index of 0.68 (CI: 0.62-0.74) and IBS below 0.25 and the most predictive radiomic feature was gray tone difference matrix strength (importance: 1.90 CI: 0.93-2.86) and most predictive treatment feature was maximum dose (importance: 3.83, CI: 1.05-6.62). The clinical data only model achieved a similar C-index of 0.62 (CI: 0.56-0.69), suggesting that predictive signals exist in radiomics and clinical data. Conclusions: The AI model achieved good prediction accuracy for progression-free survival of CLM, providing support that radiomics or clinical data combined with machine learning may aid prognostic assessment and management.

Natural Language Processing of Computed Tomography Reports to Label Metastatic Phenotypes With Prognostic Significance in Patients With Colorectal Cancer.

PURPOSE: Natural language processing (NLP) applied to radiology reports can help identify clinically relevant M1 subcategories of patients with colorectal cancer (CRC). The primary purpose was to compare the overall survival (OS) of CRC according to American Joint Committee on Cancer TNM staging and explore an alternative classification. The secondary objective was to estimate the frequency of metastasis for each organ. METHODS: Retrospective study of CRC who underwent computed tomography (CT) chest, abdomen, and pelvis between July 1, 2009, and March 26, 2019, at a tertiary cancer center, previously labeled for the presence or absence of metastasis by an NLP prediction model. Patients were classified in M0, M1a, M1b, and M1c (American Joint Committee on Cancer), or an alternative classification on the basis of the metastasis organ number: M1, single; M2, two; M3, three or more organs. Cox regression models were used to estimate hazard ratios; Kaplan-Meier curves were used to visualize survival curves using the two M1 subclassifications. RESULTS: Nine thousand nine hundred twenty-eight patients with a total of 48,408 CT chest, abdomen, and pelvis reports were included. On the basis of NLP prediction, the median OS of M1a, M1b, and M1c was 4.47, 1.72, and 1.52 years, respectively. The median OS of M1, M2, and M3 was 4.24, 2.05, and 1.04 years, respectively. Metastases occurred most often in liver (35.8%), abdominopelvic lymph nodes (32.9%), lungs (29.3%), peritoneum (22.0%), thoracic nodes (19.9%), bones (9.2%), and pelvic organs (7.5%). Spleen and adrenal metastases occurred in < 5%. CONCLUSION: NLP applied to a large radiology report database can identify clinically relevant metastatic phenotypes and be used to investigate new M1 substaging for CRC. Patients with three or more metastatic disease organs have the worst prognosis, with an OS of 1 year.

Radiomic Analysis: Study Design, Statistical Analysis, and Other Bias Mitigation Strategies.

Rapid advances in automated methods for extracting large numbers of quantitative features from medical images have led to tremendous growth of publications reporting on radiomic analyses. Translation of these research studies into clinical practice can be hindered by biases introduced during the design, analysis, or reporting of the studies. Herein, the authors review biases, sources of variability, and pitfalls that frequently arise in radiomic research, with an emphasis on study design and statistical analysis considerations. Drawing on existing work in the statistical, radiologic, and machine learning literature, approaches for avoiding these pitfalls are described.

Recurrence After Resection of Pancreatic Cancer: Can Radiomics Predict Patients at Greatest Risk of Liver Metastasis?

BACKGROUND: Liver metastasis (LM) after pancreatic ductal adenocarcinoma (PDAC) resection is common but difficult to predict and has grave prognosis. We combined preoperative clinicopathological variables and quantitative analysis of computed tomography (CT) imaging to predict early LM. METHODS: We retrospectively evaluated patients with PDAC submitted to resection between 2005 and 2014 and identified clinicopathological variables associated with early LM. We performed liver radiomic analysis on preoperative contrast-enhanced CT scans and developed a logistic regression classifier to predict early LM (< 6 months). RESULTS: In 688 resected PDAC patients, there were 516 recurrences (75%). The cumulative incidence of LM at 5 years was 41%, and patients who developed LM first (n = 194) had the lowest 1-year overall survival (OS) (34%), compared with 322 patients who developed extrahepatic recurrence first (61%). Independent predictors of time to LM included poor tumor differentiation (hazard ratio (HR) = 2.30; P < 0.001), large tumor size (HR = 1.17 per 2-cm increase; P = 0.048), lymphovascular invasion (HR = 1.50; P = 0.015), and liver Fibrosis-4 score (HR = 0.89 per 1-unit increase; P = 0.029) on multivariate analysis. A model using radiomic variables that reflect hepatic parenchymal heterogeneity identified patients at risk for early LM with an area under the receiver operating characteristic curve (AUC) of 0.71; the performance of the model was improved by incorporating preoperative clinicopathological variables (tumor size and differentiation status; AUC = 0.74, negative predictive value (NPV) = 0.86). CONCLUSIONS: We confirm the adverse survival impact of early LM after resection of PDAC. We further show that a model using radiomic data from preoperative imaging combined with tumor-related variables has great potential for identifying patients at high risk for LM and may help guide treatment selection.

Developing a Cancer Digital Twin: Supervised Metastases Detection From Consecutive Structured Radiology Reports.

The development of digital cancer twins relies on the capture of high-resolution representations of individual cancer patients throughout the course of their treatment. Our research aims to improve the detection of metastatic disease over time from structured radiology reports by exposing prediction models to historical information. We demonstrate that Natural language processing (NLP) can generate better weak labels for semi-supervised classification of computed tomography (CT) reports when it is exposed to consecutive reports through a patient's treatment history. Around 714,454 structured radiology reports from Memorial Sloan Kettering Cancer Center adhering to a standardized departmental structured template were used for model development with a subset of the reports included for validation. To develop the models, a subset of the reports was curated for ground-truth: 7,732 total reports in the lung metastases dataset from 867 individual patients; 2,777 reports in the liver metastases dataset from 315 patients; and 4,107 reports in the adrenal metastases dataset from 404 patients. We use NLP to extract and encode important features from the structured text reports, which are then used to develop, train, and validate models. Three models-a simple convolutional neural network (CNN), a CNN augmented with an attention layer, and a recurrent neural network (RNN)-were developed to classify the type of metastatic disease and validated against the ground truth labels. The models use features from consecutive structured text radiology reports of a patient to predict the presence of metastatic disease in the reports. A single-report model, previously developed to analyze one report instead of multiple past reports, is included and the results from all four models are compared based on accuracy, precision, recall, and F1-score. The best model is used to label all 714,454 reports to generate metastases maps. Our results suggest that NLP models can extract cancer progression patterns from multiple consecutive reports and predict the presence of metastatic disease in multiple organs with higher performance when compared with a single-report-based prediction. It demonstrates a promising automated approach to label large numbers of radiology reports without involving human experts in a time- and cost-effective manner and enables tracking of cancer progression over time.

A primer on texture analysis in abdominal radiology.

The number of publications on texture analysis (TA), radiomics, and radiogenomics has been growing exponentially, with abdominal radiologists aiming to build new prognostic or predictive biomarkers for a wide range of clinical applications including the use of oncological imaging to advance the field of precision medicine. TA is specifically concerned with the study of the variation of pixel intensity values in radiological images. Radiologists aim to capture pixel variation in radiological images to deliver new insights into tumor biology that cannot be derived from visual inspection alone. TA remains an active area of investigation and requires further standardization prior to its clinical acceptance and applicability. This review is for radiologists interested in this rapidly evolving field, who are thinking of performing research or want to better interpret results in this arena. We will review the main concepts in TA, workflow processes, and existing challenges and steps to overcome them, as well as look at publications in body imaging with external validation.

Radiomics in surgical oncology: applications and challenges.

Surgery is a curative treatment option for many patients with malignant tumors. Increased attention has focused on the combination of surgery with chemotherapy, as multimodality treatment has been associated with promising results in certain cancer types. Despite these data, there remains clinical equipoise on optimal timing and patient selection for neoadjuvant or adjuvant strategies. Radiomics, an emerging field involving the extraction of advanced features from radiographic images, has the potential to revolutionize oncologic treatment and contribute to the advance of personalized therapy by helping predict tumor behavior and response to therapy. This review analyzes and summarizes studies that use radiomics with machine learning in patients who have received neoadjuvant and/or adjuvant chemotherapy to predict prognosis, recurrence, survival, and therapeutic response for various cancer types. While studies in both neoadjuvant and adjuvant settings demonstrate above average performance on ability to predict progression-free and overall survival, there remain many challenges and limitations to widespread implementation of this technology. The lack of standardization of common practices to analyze radiomics, limited data sharing, and absence of auto-segmentation have hindered the inclusion and rapid adoption of radiomics in prospective, clinical studies.

Interactive Machine Learning-Based Multi-Label Segmentation of Solid Tumors and Organs.

We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% on average. We found significant (p < 0.001) overlap difference for spleen (DiceIML/DiceManual = 0.91/0.87), breast tumors (DiceIML/DiceManual = 0.84/0.82), and lung nodules (DiceIML/DiceManual = 0.78/0.83). For intra-rater consistency, a significant (p = 0.003) difference was found for spleen (DiceIML/DiceManual = 0.91/0.89). For inter-rater consistency, significant (p < 0.045) differences were found for spleen (DiceIML/DiceManual = 0.91/0.87), breast (DiceIML/DiceManual = 0.86/0.81), lung (DiceIML/DiceManual = 0.85/0.89), the non-enhancing (DiceIML/DiceManual = 0.79/0.67) and the enhancing (DiceIML/DiceManual = 0.79/0.84) brain tumor sub-regions, which, in aggregation, favored our method. Quantitative evaluation for speed, spatial overlap, and consistency, reveals the benefits of our proposed method when compared with manual annotation, for several clinically relevant problems. We publicly release our implementation through CaPTk (Cancer Imaging Phenomics Toolkit) and as an MITK plugin.

Quantitative Computed Tomography Image Analysis to Predict Pancreatic Neuroendocrine Tumor Grade.

PURPOSE: The therapeutic management of pancreatic neuroendocrine tumors (PanNETs) is based on pathological tumor grade assessment. A noninvasive imaging method to grade tumors would facilitate treatment selection. This study evaluated the ability of quantitative image analysis derived from computed tomography (CT) images to predict PanNET grade. METHODS: Institutional database was queried for resected PanNET (2000-2017) with a preoperative arterial phase CT scan. Radiomic features were extracted from the primary tumor on the CT scan using quantitative image analysis, and qualitative radiographic descriptors were assessed by two radiologists. Significant features were identified by univariable analysis and used to build multivariable models to predict PanNET grade. RESULTS: Overall, 150 patients were included. The performance of models based on qualitative radiographic descriptors varied between the two radiologists (reader 1: sensitivity, 33%; specificity, 66%; negative predictive value [NPV], 63%; and positive predictive value [PPV], 37%; reader 2: sensitivity, 45%; specificity, 70%; NPV, 72%; and PPV, 47%). The model based on radiomics had a better performance predicting the tumor grade with a sensitivity of 54%, a specificity of 80%, an NPV of 81%, and a PPV of 54%. The inclusion of radiomics in the radiographic descriptor models improved both the radiologists' performance. CONCLUSION: CT quantitative image analysis of PanNETs helps predict tumor grade from routinely acquired scans and should be investigated in future prospective studies.

Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma.

BACKGROUND AND AIM: Genetic alterations in intrahepatic cholangiocarcinoma (iCCA) are increasingly well characterized, but their impact on outcome and prognosis remains unknown. APPROACH AND RESULTS: This bi-institutional study of patients with confirmed iCCA (n = 412) used targeted next-generation sequencing of primary tumors to define associations among genetic alterations, clinicopathological variables, and outcome. The most common oncogenic alterations were isocitrate dehydrogenase 1 (IDH1; 20%), AT-rich interactive domain-containing protein 1A (20%), tumor protein P53 (TP53; 17%), cyclin-dependent kinase inhibitor 2A (CDKN2A; 15%), breast cancer 1-associated protein 1 (15%), FGFR2 (15%), polybromo 1 (12%), and KRAS (10%). IDH1/2 mutations (mut) were mutually exclusive with FGFR2 fusions, but neither was associated with outcome. For all patients, TP53 (P < 0.0001), KRAS (P = 0.0001), and CDKN2A (P < 0.0001) alterations predicted worse overall survival (OS). These high-risk alterations were enriched in advanced disease but adversely impacted survival across all stages, even when controlling for known correlates of outcome (multifocal disease, lymph node involvement, bile duct type, periductal infiltration). In resected patients (n = 209), TP53mut (HR, 1.82; 95% CI, 1.08-3.06; P = 0.03) and CDKN2A deletions (del; HR, 3.40; 95% CI, 1.95-5.94; P < 0.001) independently predicted shorter OS, as did high-risk clinical variables (multifocal liver disease [P < 0.001]; regional lymph node metastases [P < 0.001]), whereas KRASmut (HR, 1.69; 95% CI, 0.97-2.93; P = 0.06) trended toward statistical significance. The presence of both or neither high-risk clinical or genetic factors represented outcome extremes (median OS, 18.3 vs. 74.2 months; P < 0.001), with high-risk genetic alterations alone (median OS, 38.6 months; 95% CI, 28.8-73.5) or high-risk clinical variables alone (median OS, 37.0 months; 95% CI, 27.6-not available) associated with intermediate outcome. TP53mut, KRASmut, and CDKN2Adel similarly predicted worse outcome in patients with unresectable iCCA. CDKN2Adel tumors with high-risk clinical features were notable for limited survival and no benefit of resection over chemotherapy. CONCLUSIONS: TP53, KRAS, and CDKN2A alterations were independent prognostic factors in iCCA when controlling for clinical and pathologic variables, disease stage, and treatment. Because genetic profiling can be integrated into pretreatment therapeutic decision-making, combining clinical variables with targeted tumor sequencing may identify patient subgroups with poor outcome irrespective of treatment strategy.

Differences in Liver Parenchyma are Measurable with CT Radiomics at Initial Colon Resection in Patients that Develop Hepatic Metastases from Stage II/III Colon Cancer.

BACKGROUND: Currently, there are no methods to identify patients with an increased risk of liver metastases to guide patient selection for liver-directed therapies. We tried to determine whether quantitative image features (radiomics) of the liver obtained from preoperative staging CT scans at the time of initial colon resection differ in patients that subsequently develop liver metastases, extrahepatic metastases, or demonstrate prolonged disease-free survival. METHODS: Patients who underwent resection of stage II/III colon cancer from 2004 to 2012 with available preoperative CT scans were included in this single-institution, retrospective case-control study. Patients were grouped by initial recurrence patterns: liver recurrence, extrahepatic recurrence, or no evidence of disease at 5 years. Radiomic features of the liver parenchyma extracted from CT images were compared across groups. RESULTS: The cohort consisted of 120 patients divided evenly between three recurrence groups, with an equal number of stage II and III patients in each group. After adjusting for multiple comparisons, 44 of 254 (17%) imaging features displayed different distributions across the three patient groups (p < 0.05), with the clearest distinction between those with liver recurrence and no evidence of disease. Increased heterogeneity in the liver parenchyma by radiomic analysis was protective of liver metastases. CONCLUSIONS: CT radiomics is a promising tool to identify patients at high risk of developing liver metastases and is worthy of further investigation and validation.

Preoperative CT predictors of survival in patients with pancreatic ductal adenocarcinoma undergoing curative intent surgery.

PURPOSE: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective analysis included consecutive patients with PDAC who consented to genomic tumor testing and underwent preoperative imaging and curative intent surgical resection from December 2006 to July 2017. Two radiologists assessed preoperative CT imaging using the APA/SAR PDAC-reporting template. Univariable associations between overall survival and imaging variables were evaluated using Cox proportional hazards regression. RESULTS: The study included 168 patients (66 years ± 11; 91 women). 126/168 patients (75%) received upfront surgical resection whereas 42/168 (25%) received neoadjuvant therapy prior to surgical resection. In the entire cohort, features associated with decreased overall survival were tumor arterial contact of any kind (hazard ratio (HR) 1.89, 95% CI 1.13-3.14, p = 0.020), tumor contact with the common hepatic artery (HR 2.33, 95% CI 1.35-4.04, p = 0.009), and portal vein deformity (HR 3.22, 95% CI 1.63-6.37, p = 0.003). In the upfront surgical group, larger tumor size was associated with decreased overall survival (HR 2.30, 95% CI 1.19-4.42, p = 0.013). In the neoadjuvant therapy group, the presence of venous collaterals was the only feature associated with decreased overall survival (HR 2.28, 95% CI 1.04-4.99, p = 0.042). CONCLUSION: The application of the APA/SAR pancreatic adenocarcinoma reporting template may identify predictors of survival that can aid in preoperative stratification of patients.