Rules-based Volumetric Segmentation of Multiparametric MRI for Response Assessment in Recurrent High-Grade Glioma.

We report domain knowledge-based rules for assigning voxels in brain multiparametric MRI (mpMRI) to distinct tissuetypes based on their appearance on Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced and contrast-enhanced, T2-weighted, and Fluid-Attenuated Inversion Recovery images. The development dataset comprised mpMRI of 18 participants with preoperative high-grade glioma (HGG), recurrent HGG (rHGG), and brain metastases. External validation was performed on mpMRI of 235 HGG participants in the BraTS 2020 training dataset. The treatment dataset comprised serial mpMRI of 32 participants (total 231 scan dates) in a clinical trial of immunoradiotherapy in rHGG (NCT02313272). Pixel intensity-based rules for segmenting contrast-enhancing tumor (CE), hemorrhage, Fluid, non-enhancing tumor (Edema1), and leukoaraiosis (Edema2) were identified on calibrated, co-registered mpMRI images in the development dataset. On validation, rule-based CE and High FLAIR (Edema1 + Edema2) volumes were significantly correlated with ground truth volumes of enhancing tumor (R = 0.85;p < 0.001) and peritumoral edema (R = 0.87;p < 0.001), respectively. In the treatment dataset, a model combining time-on-treatment and rule-based volumes of CE and intratumoral Fluid was 82.5% accurate for predicting progression within 30 days of the scan date. An explainable decision tree applied to brain mpMRI yields validated, consistent, intratumoral tissuetype volumes suitable for quantitative response assessment in clinical trials of rHGG.

Grading of lung adenocarcinomas with simultaneous segmentation by artificial intelligence (GLASS-AI).

Preclinical genetically engineered mouse models (GEMMs) of lung adenocarcinoma are invaluable for investigating molecular drivers of tumor formation, progression, and therapeutic resistance. However, histological analysis of these GEMMs requires significant time and training to ensure accuracy and consistency. To achieve a more objective and standardized analysis, we used machine learning to create GLASS-AI, a histological image analysis tool that the broader cancer research community can utilize to grade, segment, and analyze tumors in preclinical models of lung adenocarcinoma. GLASS-AI demonstrates strong agreement with expert human raters while uncovering a significant degree of unreported intratumor heterogeneity. Integrating immunohistochemical staining with high-resolution grade analysis by GLASS-AI identified dysregulation of Mapk/Erk signaling in high-grade lung adenocarcinomas and locally advanced tumor regions. Our work demonstrates the benefit of employing GLASS-AI in preclinical lung adenocarcinoma models and the power of integrating machine learning and molecular biology techniques for studying the molecular pathways that underlie cancer progression.

Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer.

While HDAC inhibitors have shown promise in hematologic cancers, their efficacy remains limited in solid cancers. In the present study, we evaluated the immunomodulatory properties of the HDAC6 inhibitor, Citarinostat (ACY241) on lung tumor immune compartment and its therapeutic potential in combination with Oxaliplatin. As a single agent, ACY241 treatment promoted increased infiltration, activation, proliferation, and effector function of T cells in the tumors of lung adenocarcinoma-bearing mice. Furthermore, tumor-associated macrophages exhibited downregulated expression of inhibitory ligands in favor of increased MHC and co-stimulatory molecules in addition to higher expression of CCL4 that favored increased T cell numbers in the tumors. RNA-sequencing of tumor-associated T cells and macrophages after ACY241 treatment revealed significant genomic changes that is consistent with improved T cell viability, reduced inhibitory molecular signature, and enhancement of macrophage capacity for improved T cell priming. Finally, coupling these ACY241-mediated effects with the chemotherapy drug Oxaliplatin led to significantly enhanced tumor-associated T cell effector functionality in lung cancer-bearing mice and in patient-derived tumors. Collectively, our studies highlight the molecular underpinnings of the expansive immunomodulatory activity of ACY241 and supports its suitability as a partner agent in combination with rationally selected chemotherapy agents for therapeutic intervention in NSCLC.

MRI Response to Pre-operative Stereotactic Ablative Body Radiotherapy (SABR) in Early Stage ER/PR+ HER2- Breast Cancer correlates with Surgical Pathology Tumor Bed Cellularity.

OBJECTIVE: This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation. METHODS: Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.5 Gy in 3 fractions), follow-up MRI 5 to 6 weeks post-SABR, and lumpectomy. Tumor size and BI-RADS descriptors on pre and post-SABR breast MRIs were compared to determine correlation with surgical specimen % tumor cellularity (%TC). Reported MRI tumor dimensions were used to calculate percent cubic volume remaining (%VR). Partial MRI response was defined as a BI-RADs descriptor change or %VR ≤ 70%, while partial pathologic response (pPR) was defined as %TC ≤ 70%. RESULTS: Nineteen patients completed the trial, and %TC ranged 10% to 80%. For BI-RADS descriptor analysis, 12 of 19 (63%) showed change in lesion or kinetic enhancement descriptors post-SABR. This was associated with lower %TC (29% vs. 47%, P = .042). BI-RADS descriptor change analysis also demonstrated high PPV (100%) and specificity (100%) for predicting pPR to treatment (sensitivity 71%, accuracy 74%), but low NPV (29%). MRI %VR demonstrated strong linear correlation with %TC (R = 0.70, P < .001, Pearson's Correlation) and high accuracy (89%) for predicting pPR (sensitivity 88%, specificity 100%, PPV 100%, and NPV 50%). CONCLUSION: Evaluating breast cancer response on MRI using %VR after pre-operative SABR treatment can help identify patients benefiting the most from neoadjuvant radiation treatment of their ER/PR+ HER2- tumors, a group in which pCR to neoadjuvant therapy is rare.

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR). Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1-4, L1-4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response. Results: Sixteen patients completed the trial. The %TC ranged 20%-80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7-0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to <0.00001). Post-SABR %HM of tumor habitat H4 demonstrated the largest change, increasing 13% (P = 0.039). Conversely, combined %HM for H1-3 decreased 17% (P = 0.006). This change correlated with %TC (P < 0.00001) and distinguished pathologic partial responders (≤70 %TC) from nonresponders with 94% accuracy, 93% sensitivity, 100% specificity, 100% positive predictive value, and 67% negative predictive value. Conclusion: In patients undergoing preoperative SABR treatment for ER/PR+ HER2- breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.

Identification of sarcomatoid differentiation in renal cell carcinoma by machine learning on multiparametric MRI.

Sarcomatoid differentiation in RCC (sRCC) is associated with a poor prognosis, necessitating more aggressive management than RCC without sarcomatoid components (nsRCC). Since suspected renal cell carcinoma (RCC) tumors are not routinely biopsied for histologic evaluation, there is a clinical need for a non-invasive method to detect sarcomatoid differentiation pre-operatively. We utilized unsupervised self-organizing map (SOM) and supervised Learning Vector Quantizer (LVQ) machine learning to classify RCC tumors on T2-weighted, non-contrast T1-weighted fat-saturated, contrast-enhanced arterial-phase T1-weighted fat-saturated, and contrast-enhanced venous-phase T1-weighted fat-saturated MRI images. The SOM was trained on 8 nsRCC and 8 sRCC tumors, and used to compute Activation Maps for each training, validation (3 nsRCC and 3 sRCC), and test (5 nsRCC and 5 sRCC) tumor. The LVQ classifier was trained and optimized on Activation Maps from the 22 training and validation cohort tumors, and tested on Activation Maps of the 10 unseen test tumors. In this preliminary study, the SOM-LVQ model achieved a hold-out testing accuracy of 70% in the task of identifying sarcomatoid differentiation in RCC on standard multiparameter MRI (mpMRI) images. We have demonstrated a combined SOM-LVQ machine learning approach that is suitable for analysis of limited mpMRI datasets for the task of differential 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.

Peritumoral and intratumoral radiomic features predict survival outcomes among patients diagnosed in lung cancer screening.

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose computed tomography (LDCT) is associated with a 20% reduction in lung cancer mortality. One potential limitation of LDCT screening is overdiagnosis of slow growing and indolent cancers. In this study, peritumoral and intratumoral radiomics was used to identify a vulnerable subset of lung patients associated with poor survival outcomes. Incident lung cancer patients from the NLST were split into training and test cohorts and an external cohort of non-screen detected adenocarcinomas was used for further validation. After removing redundant and non-reproducible radiomics features, backward elimination analyses identified a single model which was subjected to Classification and Regression Tree to stratify patients into three risk-groups based on two radiomics features (NGTDM Busyness and Statistical Root Mean Square [RMS]). The final model was validated in the test cohort and the cohort of non-screen detected adenocarcinomas. Using a radio-genomics dataset, Statistical RMS was significantly associated with FOXF2 gene by both correlation and two-group analyses. Our rigorous approach generated a novel radiomics model that identified a vulnerable high-risk group of early stage patients associated with poor outcomes. These patients may require aggressive follow-up and/or adjuvant therapy to mitigate their poor outcomes.

Multiparameter MRI Predictors of Long-Term Survival in Glioblastoma Multiforme.

Standard-of-care multiparameter magnetic resonance imaging (MRI) scans of the brain were used to objectively subdivide glioblastoma multiforme (GBM) tumors into regions that correspond to variations in blood flow, interstitial edema, and cellular density. We hypothesized that the distribution of these distinct tumor ecological "habitats" at the time of presentation will impact the course of the disease. We retrospectively analyzed initial MRI scans in 2 groups of patients diagnosed with GBM, a long-term survival group comprising subjects who survived >36 month postdiagnosis, and a short-term survival group comprising subjects who survived ≤19 month postdiagnosis. The single-institution discovery cohort contained 22 subjects in each group, while the multi-institution validation cohort contained 15 subjects per group. MRI voxel intensities were calibrated, and tumor voxels clustered on contrast-enhanced T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images into 6 distinct "habitats" based on low- to medium- to high-contrast enhancement and low-high signal on FLAIR scans. Habitat 6 (high signal on calibrated contrast-enhanced T1-weighted and FLAIR sequences) comprised a significantly higher volume fraction of tumors in the long-term survival group (discovery cohort, 35% ± 6.5%; validation cohort, 34% ± 4.8%) compared with tumors in the short-term survival group (discovery cohort, 17% ± 4.5%, P < .03; validation cohort, 16 ± 4.0%, P < .007). Of the 6 distinct MRI-defined habitats, the fractional tumor volume of habitat 6 at diagnosis was significantly predictive of long- or short-term survival. We discuss a possible mechanistic basis for this association and implications for habitat-driven adaptive therapy of GBM.

Prediction of pathological nodal involvement by CT-based Radiomic features of the primary tumor in patients with clinically node-negative peripheral lung adenocarcinomas.

PURPOSE: The purpose of this study was to investigate the potential of computed tomography (CT) based radiomic features of primary tumors to predict pathological nodal involvement in clinically node-negative (N0) peripheral lung adenocarcinomas. METHODS: A total of 187 patients with clinical N0 peripheral lung adenocarcinomas who underwent preoperative CT scan and subsequently received systematic lymph node dissection were retrospectively reviewed. 219 quantitative 3D radiomic features of primary lung tumor were extracted; meanwhile, nine radiological semantic features were evaluated. Univariate and multivariate logistic regression analysis were used to explore the role of these features in predicting pathological nodal involvement. The areas under the ROC curves (AUCs) were compared between multivariate logistic regression models. RESULTS: A total of 153 patients had pathological N0 status and 34 had pathological lymph node metastasis. On univariate analysis, fissure attachment and 17 radiomic features were significantly associated with pathological nodal involvement. Multivariate analysis revealed that semantic features of pleural retraction (P = 0.048) and fissure attachment (P = 0.023) were significant predictors of pathological nodal involvement (AUC = 0.659); and the radiomic feature F185 (Histogram SD Layer 1) (P = 0.0001) was an independent prognostic factor of pathological nodal involvement (AUC = 0.73). A logistic regression model produced from combining radiomic feature and semantic feature showed the highest AUC of 0.758 (95% CI: 0.685-0.831), and the AUC value computed by fivefold cross-validation method was 0.737 (95% CI: 0.73-0.744). CONCLUSIONS: Features derived on primary lung tumor described by semantic and radiomic could provide information of pathological nodal involvement in clinical N0 peripheral lung adenocarcinomas.

Radial gradient and radial deviation radiomic features from pre-surgical CT scans are associated with survival among lung adenocarcinoma patients.

The goal of this study was to extract features from radial deviation and radial gradient maps which were derived from thoracic CT scans of patients diagnosed with lung adenocarcinoma and assess whether these features are associated with overall survival. We used two independent cohorts from different institutions for training (n= 61) and test (n= 47) and focused our analyses on features that were non-redundant and highly reproducible. To reduce the number of features and covariates into a single parsimonious model, a backward elimination approach was applied. Out of 48 features that were extracted, 31 were eliminated because they were not reproducible or were redundant. We considered 17 features for statistical analysis and identified a final model containing the two most highly informative features that were associated with lung cancer survival. One of the two features, radial deviation outside-border separation standard deviation, was replicated in a test cohort exhibiting a statistically significant association with lung cancer survival (multivariable hazard ratio = 0.40; 95% confidence interval 0.17-0.97). Additionally, we explored the biological underpinnings of these features and found radial gradient and radial deviation image features were significantly associated with semantic radiological features.

Defining the biological basis of radiomic phenotypes in lung cancer.

Medical imaging can visualize characteristics of human cancer noninvasively. Radiomics is an emerging field that translates these medical images into quantitative data to enable phenotypic profiling of tumors. While radiomics has been associated with several clinical endpoints, the complex relationships of radiomics, clinical factors, and tumor biology are largely unknown. To this end, we analyzed two independent cohorts of respectively 262 North American and 89 European patients with lung cancer, and consistently identified previously undescribed associations between radiomic imaging features, molecular pathways, and clinical factors. In particular, we found a relationship between imaging features, immune response, inflammation, and survival, which was further validated by immunohistochemical staining. Moreover, a number of imaging features showed predictive value for specific pathways; for example, intra-tumor heterogeneity features predicted activity of RNA polymerase transcription (AUC = 0.62, p=0.03) and intensity dispersion was predictive of the autodegration pathway of a ubiquitin ligase (AUC = 0.69, p<10-4). Finally, we observed that prognostic biomarkers performed highest when combining radiomic, genetic, and clinical information (CI = 0.73, p<10-9) indicating complementary value of these data. In conclusion, we demonstrate that radiomic approaches permit noninvasive assessment of both molecular and clinical characteristics of tumors, and therefore have the potential to advance clinical decision-making by systematically analyzing standard-of-care medical images.

Somatic Mutations Drive Distinct Imaging Phenotypes in Lung Cancer.

Tumors are characterized by somatic mutations that drive biological processes ultimately reflected in tumor phenotype. With regard to radiographic phenotypes, generally unconnected through present understanding to the presence of specific mutations, artificial intelligence methods can automatically quantify phenotypic characters by using predefined, engineered algorithms or automatic deep-learning methods, a process also known as radiomics. Here we demonstrate how imaging phenotypes can be connected to somatic mutations through an integrated analysis of independent datasets of 763 lung adenocarcinoma patients with somatic mutation testing and engineered CT image analytics. We developed radiomic signatures capable of distinguishing between tumor genotypes in a discovery cohort (n = 353) and verified them in an independent validation cohort (n = 352). All radiomic signatures significantly outperformed conventional radiographic predictors (tumor volume and maximum diameter). We found a radiomic signature related to radiographic heterogeneity that successfully discriminated between EGFR+ and EGFR- cases (AUC = 0.69). Combining this signature with a clinical model of EGFR status (AUC = 0.70) significantly improved prediction accuracy (AUC = 0.75). The highest performing signature was capable of distinguishing between EGFR+ and KRAS+ tumors (AUC = 0.80) and, when combined with a clinical model (AUC = 0.81), substantially improved its performance (AUC = 0.86). A KRAS+/KRAS- radiomic signature also showed significant albeit lower performance (AUC = 0.63) and did not improve the accuracy of a clinical predictor of KRAS status. Our results argue that somatic mutations drive distinct radiographic phenotypes that can be predicted by radiomics. This work has implications for the use of imaging-based biomarkers in the clinic, as applied noninvasively, repeatedly, and at low cost. Cancer Res; 77(14); 3922-30. ©2017 AACR.

Imaging features from pretreatment CT scans are associated with clinical outcomes in nonsmall-cell lung cancer patients treated with stereotactic body radiotherapy.

PURPOSE: To investigate whether imaging features from pretreatment planning CT scans are associated with overall survival (OS), recurrence-free survival (RFS), and loco-regional recurrence-free survival (LR-RFS) after stereotactic body radiotherapy (SBRT) among nonsmall-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A total of 92 patients (median age: 73 yr) with stage I or IIA NSCLC were qualified for this study. A total dose of 50 Gy in five fractions was the standard treatment. Besides clinical characteristics, 24 "semantic" image features were manually scored based on a point scale (up to 5) and 219 computer-derived "radiomic" features were extracted based on whole tumor segmentation. Statistical analysis was performed using Cox proportional hazards model and Harrell's C-index, and the robustness of final prognostic model was assessed using tenfold cross validation by dichotomizing patients according to the survival or recurrence status at 24 months. RESULTS: Two-year OS, RFS and LR-RFS were 69.95%, 41.3%, and 51.85%, respectively. There was an improvement of Harrell's C-index when adding imaging features to a clinical model. The model for OS contained the Eastern Cooperative Oncology Group (ECOG) performance status [Hazard Ratio (HR) = 2.78, 95% Confidence Interval (CI): 1.37-5.65], pleural retraction (HR = 0.27, 95% CI: 0.08-0.92), F2 (short axis × longest diameter, HR = 1.72, 95% CI: 1.21-2.44) and F186 (Hist-Energy-L1, HR = 1.27, 95% CI: 1.00-1.61); The prognostic model for RFS contained vessel attachment (HR = 2.13, 95% CI: 1.24-3.64) and F2 (HR = 1.69, 95% CI: 1.33-2.15); and the model for LR-RFS contained the ECOG performance status (HR = 2.01, 95% CI: 1.12-3.60) and F2 (HR = 1.67, 95% CI: 1.29-2.18). CONCLUSIONS: Imaging features derived from planning CT demonstrate prognostic value for recurrence following SBRT treatment, and might be helpful in patient stratification.

Predicting Malignant Nodules from Screening CT Scans.

OBJECTIVES: The aim of this study was to determine whether quantitative analyses ("radiomics") of low-dose computed tomography lung cancer screening images at baseline can predict subsequent emergence of cancer. METHODS: Public data from the National Lung Screening Trial (ACRIN 6684) were assembled into two cohorts of 104 and 92 patients with screen-detected lung cancer and then matched with cohorts of 208 and 196 screening subjects with benign pulmonary nodules. Image features were extracted from each nodule and used to predict the subsequent emergence of cancer. RESULTS: The best models used 23 stable features in a random forests classifier and could predict nodules that would become cancerous 1 and 2 years hence with accuracies of 80% (area under the curve 0.83) and 79% (area under the curve 0.75), respectively. Radiomics outperformed the Lung Imaging Reporting and Data System and volume-only approaches. The performance of the McWilliams risk assessment model was commensurate. CONCLUSIONS: The radiomics of lung cancer screening computed tomography scans at baseline can be used to assess risk for development of cancer.

Radiomic Features Are Associated With EGFR Mutation Status in Lung Adenocarcinomas.

BACKGROUND: In this study we retrospectively evaluated the capability of computed tomography (CT)-based radiomic features to predict epidermal growth factor receptor (EGFR) mutation status in surgically-resected peripheral lung adenocarcinomas in an Asian cohort of patients. PATIENTS AND METHODS: Two hundred ninety-eight patients with surgically resected peripheral lung adenocarcinomas were investigated in this institutional review board-approved retrospective study with requirement waived to obtain informed consent. Two hundred nineteen quantitative 3-D features were extracted from segmented volumes of each tumor, and 59 of these, which were considered independent features, were included in the analysis. Clinical and pathological information was obtained from the institutional database. RESULTS: Mutant EGFR was significantly associated with female sex (P = .0005); never smoker status (P < .0001), lepidic predominant adenocarcinomas (P = .017), and low or intermediate pathologic grade (P = .0002). Statistically significant differences were found in 11 radiomic features between EGFR mutant and wild type groups in univariate analysis. Mutant EGFR status could be predicted by a set of 5 radiomic features that fell into 3 broad groups: CT attenuation energy, tumor main direction, and texture defined according to wavelets and Laws (area under the curve [AUC], 0.647). A multiple logistic regression model showed that adding radiomic features to a clinical model resulted in a significant improvement of predicting power, because the AUC increased from 0.667 to 0.709 (P < .0001). CONCLUSION: Computed tomography-based radiomic features of peripheral lung adenocarcinomas can capture useful information regarding tumor phenotype, and the model we built can be useful to predict the presence of EGFR mutations in peripheral lung adenocarcinoma in Asian patients when mutational profiling is not available or possible.

Association Between Computed Tomographic Features and Kirsten Rat Sarcoma Viral Oncogene Mutations in Patients With Stage I Lung Adenocarcinoma and Their Prognostic Value.

BACKGROUND: We investigated the association between computed tomographic (CT) features and Kirsten rat sarcoma viral oncogene (KRAS) mutations in patients with stage I lung adenocarcinoma and their prognostic value. PATIENTS AND METHODS: A total of 79 patients with pathologic stage I lung adenocarcinoma, available KRAS mutational status, preoperative CT images available, and survival data were included in the present study. Seven CT features, including spiculation, concavity, ground-glass opacity, bubble-like lucency, air bronchogram, pleural retraction, and pleural attachment, were evaluated. The association among the clinical characteristics, CT features, and mutational status was analyzed using Student's t test, the χ(2) test or Fisher's exact test, and logistic regression. The association among CT features, mutational status, and overall survival was analyzed using Kaplan-Meier survival curves with the log-rank test and Cox proportional hazard regression. RESULTS: The prevalence of KRAS mutations was 41.77%. Spiculation was significantly associated with the presence of KRAS mutations (odds ratio, 2.99; 95% confidence interval [CI], 1.16-7.68). Although KRAS mutational status was not significantly associated with overall survival, the presence of pleural attachment was associated with an increased risk of death (hazard ratio, 2.46; 95% CI, 1.09-5.53). When analyzing KRAS mutational status and pleural attachment combined, patients with wild-type KRAS and no pleural attachment had significantly better survival than did those with wild-type KRAS and pleural attachment (P = .014). CONCLUSION: These data suggest that spiculation is associated with KRAS mutations and pleural attachment is associated with overall survival in patients with stage I lung adenocarcinoma. Combining the analysis of KRAS mutational status and CT features could better predict survival.

Semiquantitative Computed Tomography Characteristics for Lung Adenocarcinoma and Their Association With Lung Cancer Survival.

UNLABELLED: In this study we developed 25 computed tomography descriptors among 117 patients with lung adenocarcinoma to semiquantitatively assess their association with overall survival. Pleural attachment was significantly associated with an increased risk of death and texture was most important for distinguishing histological subtypes. This approach has the potential to support automated analyses and develop decision-support clinical tools. BACKGROUND: Computed tomography (CT) characteristics derived from noninvasive images that represent the entire tumor might have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival. PATIENTS AND METHODS: An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n = 117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that might differentiate histological subtypes. RESULTS: Characteristics significantly associated with overall survival included pleural attachment (P < .001), air bronchogram (P = .03), and lymphadenopathy (P = .02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.53-6.70) and among patients with lepidic predominant adenocarcinomas (HR, 5.85; 95% CI, 1.75-19.59), and lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR, 3.07; 95% CI, 1.09-8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the 2 subtypes. CONCLUSION: A subset of the semiquantitative characteristics described herein has prognostic importance and provides the ability to distinguish between different histological subtypes of lung adenocarcinoma.