Non-invasive CT radiomic biomarkers predict microsatellite stability status in colorectal cancer: a multicenter validation study.

BACKGROUND: Microsatellite instability (MSI) status is a strong predictor of response to immunotherapy of colorectal cancer. Radiogenomic approaches promise the ability to gain insight into the underlying tumor biology using non-invasive routine clinical images. This study investigates the association between tumor morphology and the status of MSI versus microsatellite stability (MSS), validating a novel radiomic signature on an external multicenter cohort. METHODS: Preoperative computed tomography scans with matched MSI status were retrospectively collected for 243 colorectal cancer patients from three hospitals: Seoul National University Hospital (SNUH); Netherlands Cancer Institute (NKI); and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy (INT). Radiologists delineated primary tumors in each scan, from which radiomic features were extracted. Machine learning models trained on SNUH data to identify MSI tumors underwent external validation using NKI and INT images. Performances were compared in terms of area under the receiving operating curve (AUROC). RESULTS: We identified a radiomic signature comprising seven radiomic features that were predictive of tumors with MSS or MSI (AUROC 0.69, 95% confidence interval [CI] 0.54-0.84, p = 0.018). Integrating radiomic and clinical data into an algorithm improved predictive performance to an AUROC of 0.78 (95% CI 0.60-0.91, p = 0.002) and enhanced the reliability of the predictions. CONCLUSION: Differences in the radiomic morphological phenotype between tumors MSS or MSI could be detected using radiogenomic approaches. Future research involving large-scale multicenter prospective studies that combine various diagnostic data is necessary to refine and validate more robust, potentially tumor-agnostic MSI radiogenomic models. RELEVANCE STATEMENT: Noninvasive radiomic signatures derived from computed tomography scans can predict MSI in colorectal cancer, potentially augmenting traditional biopsy-based methods and enhancing personalized treatment strategies. KEY POINTS: Noninvasive CT-based radiomics predicted MSI in colorectal cancer, enhancing stratification. A seven-feature radiomic signature differentiated tumors with MSI from those with MSS in multicenter cohorts. Integrating radiomic and clinical data improved the algorithm's predictive performance.

Response Evaluation Criteria in Gastrointestinal and Abdominal Cancers: Which to Use and How to Measure.

As the management of gastrointestinal malignancy has evolved, tumor response assessment has expanded from size-based assessments to those that include tumor enhancement, in addition to functional data such as those derived from PET and diffusion-weighted imaging. Accurate interpretation of tumor response therefore requires knowledge of imaging modalities used in gastrointestinal malignancy, anticancer therapies, and tumor biology. Targeted therapies such as immunotherapy pose additional considerations due to unique imaging response patterns and drug toxicity; as a consequence, immunotherapy response criteria have been developed. Some gastrointestinal malignancies require assessment with tumor-specific criteria when assessing response, often to guide clinical management (such as watchful waiting in rectal cancer or suitability for surgery in pancreatic cancer). Moreover, anatomic measurements can underestimate therapeutic response when applied to molecular-targeted therapies or locoregional therapies in hypervascular malignancies such as hepatocellular carcinoma. In these cases, responding tumors may exhibit morphologic changes including cystic degeneration, necrosis, and hemorrhage, often without significant reduction in size. Awareness of pitfalls when interpreting gastrointestinal tumor response is required to correctly interpret response assessment imaging and guide appropriate oncologic management. Data-driven image analyses such as radiomics have been investigated in a variety of gastrointestinal tumors, such as identifying those more likely to respond to therapy or recur, with the aim of delivering precision medicine. Multimedia-enhanced radiology reports can facilitate communication of gastrointestinal tumor response by automatically embedding response categories, key data, and representative images. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Overcoming data scarcity in radiomics/radiogenomics using synthetic radiomic features.

PURPOSE: To evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models. METHODS: This study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on "real-world" radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with "real-world" radiomic training data to evaluate their impact on the predictive model's performance. RESULTS: A prediction model was generated using only "real-world" radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to "real-world" data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so. CONCLUSION: Synthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity.

Intra-patient and inter-observer image quality analysis in liver MRI study with gadoxetic acid using two different multi-arterial phase techniques.

PURPOSE: To evaluate intra-patient and interobserver agreement in patients who underwent liver MRI with gadoxetic acid using two different multi-arterial phase (AP) techniques. METHODS: A total of 154 prospectively enrolled patients underwent clinical gadoxetic acid-enhanced liver MRI twice within 12 months, using two different multi-arterial algorithms: CAIPIRINHA-VIBE and TWIST-VIBE. For every patient, breath-holding time, body mass index, sex, age were recorded. The phase without contrast media and the APs were independently evaluated by two radiologists who quantified Gibbs artefacts, noise, respiratory motion artefacts, and general image quality. Presence or absence of Gibbs artefacts and noise was compared by the McNemar's test. Respiratory motion artefacts and image quality scores were compared using Wilcoxon signed rank test. Interobserver agreement was assessed by Cohen kappa statistics. RESULTS: Compared with TWIST-VIBE, CAIPIRINHA-VIBE images had better scores for every parameter except higher noise score. Triple APs were always acquired with TWIST-VIBE but failed in 37% using CAIPIRINHA-VIBE: 11% have only one AP, 26% have two. Breath-holding time was the only parameter that influenced the success of multi-arterial techniques. TWIST-VIBE images had worst score for Gibbs and respiratory motion artefacts but lower noise score. CONCLUSION: CAIPIRINHA-VIBE images were always diagnostic, but with a failure of triple-AP in 37%. TWIST-VIBE was successful in obtaining three APs in all patients. Breath-holding time is the only parameter which can influence the preliminary choice between CAIPIRINHA-VIBE and TWIST-VIBE algorithm. ADVANCES IN KNOWLEDGE: If the patient is expected to perform good breath-holds, TWIST-VIBE is preferable; otherwise, CAIPIRINHA-VIBE is more appropriate.

Evaluation of simultaneous multi-slice acquisition with advanced processing for free-breathing diffusion-weighted imaging in patients with liver metastasis.

OBJECTIVES: Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) acquisition and advanced processing can accelerate acquisition time and improve MR image quality. This study evaluated the image quality and apparent diffusion coefficient (ADC) measurements of free-breathing DWI acquired from patients with liver metastases using a prototype SMS-DWI acquisition (with/without an advanced processing option) and conventional DWI. METHODS: Four DWI schemes were compared in a pilot 5-patient cohort; three DWI schemes were further assessed in a 24-patient cohort. Two readers scored image quality of all b-value images and ADC maps across the three methods. ADC measurements were performed, for all three methods, in left and right liver parenchyma, spleen, and liver metastases. The Friedman non-parametric test (post-hoc Wilcoxon test with Bonferroni correction) was used to compare image quality scoring; t-test was used for ADC comparisons. RESULTS: SMS-DWI was faster (by 24%) than conventional DWI. Both readers scored the SMS-DWI with advanced processing as having the best image quality for highest b-value images (b750) and ADC maps; Cohen's kappa inter-reader agreement was 0.6 for b750 image and 0.56 for ADC maps. The prototype SMS-DWI sequence with advanced processing allowed a better visualization of the left lobe of the liver. ADC measured in liver parenchyma, spleen, and liver metastases using the SMS-DWI with advanced processing option showed lower values than those derived from the SMS-DWI method alone (t-test, p < 0.0001; p < 0.0001; p = 0.002). CONCLUSIONS: Free-breathing SMS-DWI with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients. CLINICAL RELEVANCE STATEMENT: Free-breathing simultaneous multi-slice- diffusion-weighted imaging (DWI) with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients. KEY POINTS: • Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) can accelerate acquisition time and improve image quality. • Apparent diffusion coefficients (ADC) measured in liver parenchyma, spleen, and liver metastases using the simultaneous multi-slice DWI with advanced processing were significantly lower than those derived from the simultaneous multi-slice DWI method alone. • Simultaneous multi-slice DWI sequence with inline advanced processing was faster and demonstrated better image quality in liver patients.

Artificial Intelligence-based Quantification of Pleural Plaque Volume and Association With Lung Function in Asbestos-exposed Patients.

PURPOSE: Pleural plaques (PPs) are morphologic manifestations of long-term asbestos exposure. The relationship between PP and lung function is not well understood, whereas the time-consuming nature of PP delineation to obtain volume impedes research. To automate the laborious task of delineation, we aimed to develop automatic artificial intelligence (AI)-driven segmentation of PP. Moreover, we aimed to explore the relationship between pleural plaque volume (PPV) and pulmonary function tests. MATERIALS AND METHODS: Radiologists manually delineated PPs retrospectively in computed tomography (CT) images of patients with occupational exposure to asbestos (May 2014 to November 2019). We trained an AI model with a no-new-UNet architecture. The Dice Similarity Coefficient quantified the overlap between AI and radiologists. The Spearman correlation coefficient ( r ) was used for the correlation between PPV and pulmonary function test metrics. When recorded, these were vital capacity (VC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO). RESULTS: We trained the AI system on 422 CT scans in 5 folds, each time with a different fold (n = 84 to 85) as a test set. On these independent test sets combined, the correlation between the predicted volumes and the ground truth was r = 0.90, and the median overlap was 0.71 Dice Similarity Coefficient. We found weak to moderate correlations with PPV for VC (n = 80, r = -0.40) and FVC (n = 82, r = -0.38), but no correlation for DLCO (n = 84, r = -0.09). When the cohort was split on the median PPV, we observed statistically significantly lower VC ( P = 0.001) and FVC ( P = 0.04) values for the higher PPV patients, but not for DLCO ( P = 0.19). CONCLUSION: We successfully developed an AI algorithm to automatically segment PP in CT images to enable fast volume extraction. Moreover, we have observed that PPV is associated with loss in VC and FVC.

Relative fat fraction of malignant bone lesions from breast cancer, prostate cancer and myeloma are significantly lower than normal bone marrow and shows excellent interobserver agreement.

OBJECTIVES: To compare relative fat fraction (rFF) of active bone lesions from breast, prostate and myeloma malignancies and normal bone marrow; to assess its inter-reader agreement. METHODS: Patients with breast (n = 26), myeloma (n = 32) and prostate cancer (n = 52) were retrospectively evaluated. 110 baseline rFF maps from whole-body MRI were reviewed by two radiologists. Regions of interest for up to four focal active lesions in each patient were drawn on rFF maps, one each at the cervicothoracic spine, lumbosacral spine, pelvis and extremity. The mean and standard deviation of rFF were recorded. The rFF of normal marrow was measured in the pelvis for patients without diffuse bone disease (n = 88). We compared the rFF of malignant bone lesions and normal marrow using Mann-Whitney test. Interobserver agreement was assessed by interclass correlation coefficient. RESULTS: Malignant bone lesions showed significantly lower median rFF (13.87%) compared with normal marrow (89.76%) with little overlap (p < 0.0001). There was no significant difference in the median rFF of malignant lesions from breast (14.46%), myeloma (13.12%) and prostate cancer (13.67%) (p > 0.017, Bonferroni correction) and in the median rFF of bone disease according to their anatomical locations (p > 0.008, Bonferroni correction). There was excellent interobserver agreement (0.95). CONCLUSION: The low rFF of active bone lesions in breast, prostate and myeloma malignancies provides high image contrast relative to normal marrow that may be used to detect bone metastases. ADVANCES IN KNOWLEDGE: This study shows the importance of rFF towards detecting bone metastases.

Colon cancer CT staging according to mismatch repair status: Comparison and suggestion of imaging features for high-risk colon cancer.

BACKGROUND: Neoadjuvant treatment with either chemotherapy or immunotherapy is gaining momentum in colon cancers (CC). To reduce over-treatment, increasing staging accuracy using computed tomography (CT) is of high importance. PURPOSE: To assess and compare CT imaging features of CC between mismatch repair-proficient (pMMR) and MMR-deficient (dMMR) tumours and identify CT features that can distinguish high-risk (pT3-4, N+) CC according to MMR status. METHODS: Primary staging CTs of 266 patients who underwent primary surgical resection of a colon tumour were retrospectively and independently evaluated by two radiologists. Logistic regression analysis was performed to identify significant associations between imaging features and positive lymph node status. Receiver operating characteristic (ROC) curves of significantly associated features were assessed and validated in an external cohort of 104 patients. RESULTS: Among pT3 tumours only, dMMR CC were significantly larger than pMMR CC in both length and thickness (length 59.39 ± 26.28 mm versus 48.70 ± 23.72, respectively, p = 0.031; thickness 20.54 mm ± 11.17 versus 16.34 ± 8.73, respectively, p = 0.027). For pMMR tumours, nodal internal heterogeneity on CT was significantly associated with a positive lymph node status (odds ratio (OR) = 2.66, p = 0.027), while for dMMR tumours, the largest short diameter of the nodes was associated with lymph node status (OR = 2.01, p = 0.049). The best cut-off value of the largest short diameter of involved nodes was 10.4 mm for dMMR and 7.95 mm for pMMR. In the external validation cohort, AUCs for predicting involved nodes based on the largest short diameter was 0.764 for dMMR tumours using 10 mm size cut-off and 0.624 for pMMR tumours using 7 mm cut-off. CONCLUSION: These data show that CT imaging features of primary CC differ between dMMR and pMMR tumours, suggesting that the assessment of CT-based CC staging should take MMR status into consideration, especially for lymph node status, and thus may help in selecting patients for neoadjuvant treatment.

Splenic volume as a predictor of treatment response in patients with non-small cell lung cancer receiving immunotherapy.

INTRODUCTION: The spleen is a lymphoid organ and we hypothesize that clinical benefit to immunotherapy may present with an increase in splenic volume during treatment. The purpose of this study was to investigate whether changes in splenic volume could be observed in those showing clinical benefit versus those not showing clinical benefit to pembrolizumab treatment in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this study, 70 patients with locally advanced or metastatic NSCLC treated with pembrolizumab; and who underwent baseline CT scan within 2 weeks before treatment and follow-up CT within 3 months after commencing immunotherapy were retrospectively evaluated. The splenic volume on each CT was segmented manually by outlining the splenic contour on every image and the total volume summated. We compared the splenic volume in those achieving a clinical benefit and those not achieving clinical benefit, using non-parametric Wilcoxon signed-rank test. Clinical benefit was defined as stable disease or partial response lasting for greater than 24 weeks. A p-value of <0.05 was considered statistically significant. RESULTS: There were 23 responders and 47 non-responders based on iRECIST criteria and 35 patients with clinical benefit and 35 without clinical benefit. There was no significant difference in the median pre-treatment volume (175 vs 187 cm3, p = 0.34), post-treatment volume (168 vs 167 cm3, p = 0.39) or change in splenic volume (-0.002 vs 0.0002 cm3, p = 0.97) between the two groups. No significant differences were also found between the splenic volume of patients with partial response, stable disease or progressive disease (p>0.017). Moreover, there was no statistically significant difference between progression-free survival and time to disease progression when the splenic volume was categorized as smaller or larger than the median pre-treatment or post-treatment volume (p>0.05). CONCLUSION: No significant differences were observed in the splenic volume of those showing clinical benefit versus those without clinical benefit to pembrolizumab treatment in NSCLC patients. CT splenic volume cannot be used as a potentially simple biomarker of response to immunotherapy.

Sources of variation in multicenter rectal MRI data and their effect on radiomics feature reproducibility.

OBJECTIVES: To investigate sources of variation in a multicenter rectal cancer MRI dataset focusing on hardware and image acquisition, segmentation methodology, and radiomics feature extraction software. METHODS: T2W and DWI/ADC MRIs from 649 rectal cancer patients were retrospectively acquired in 9 centers. Fifty-two imaging features (14 first-order/6 shape/32 higher-order) were extracted from each scan using whole-volume (expert/non-expert) and single-slice segmentations using two different software packages (PyRadiomics/CapTk). Influence of hardware, acquisition, and patient-intrinsic factors (age/gender/cTN-stage) on ADC was assessed using linear regression. Feature reproducibility was assessed between segmentation methods and software packages using the intraclass correlation coefficient. RESULTS: Image features differed significantly (p < 0.001) between centers with more substantial variations in ADC compared to T2W-MRI. In total, 64.3% of the variation in mean ADC was explained by differences in hardware and acquisition, compared to 0.4% by patient-intrinsic factors. Feature reproducibility between expert and non-expert segmentations was good to excellent (median ICC 0.89-0.90). Reproducibility for single-slice versus whole-volume segmentations was substantially poorer (median ICC 0.40-0.58). Between software packages, reproducibility was good to excellent (median ICC 0.99) for most features (first-order/shape/GLCM/GLRLM) but poor for higher-order (GLSZM/NGTDM) features (median ICC 0.00-0.41). CONCLUSIONS: Significant variations are present in multicenter MRI data, particularly related to differences in hardware and acquisition, which will likely negatively influence subsequent analysis if not corrected for. Segmentation variations had a minor impact when using whole volume segmentations. Between software packages, higher-order features were less reproducible and caution is warranted when implementing these in prediction models. KEY POINTS: • Features derived from T2W-MRI and in particular ADC differ significantly between centers when performing multicenter data analysis. • Variations in ADC are mainly (> 60%) caused by hardware and image acquisition differences and less so (< 1%) by patient- or tumor-intrinsic variations. • Features derived using different image segmentations (expert/non-expert) were reproducible, provided that whole-volume segmentations were used. When using different feature extraction software packages with similar settings, higher-order features were less reproducible.

A decade of multi-modality PET and MR imaging in abdominal oncology.

OBJECTIVES: To investigate trends observed in a decade of published research on multimodality PET(/CT)+MR imaging in abdominal oncology, and to explore how these trends are reflected by the use of multimodality imaging performed at our institution. METHODS: First, we performed a literature search (2009-2018) including all papers published on the multimodality combination of PET(/CT) and MRI in abdominal oncology. Retrieved papers were categorized according to a structured labelling system, including study design and outcome, cancer and lesion type under investigation and PET-tracer type. Results were analysed using descriptive statistics and evolutions over time were plotted graphically. Second, we performed a descriptive analysis of the numbers of MRI, PET/CT and multimodality PET/CT+MRI combinations (performed within a ≤14 days interval) performed during a similar time span at our institution. RESULTS: Published research papers involving multimodality PET(/CT)+MRI combinations showed an impressive increase in numbers, both for retrospective combinations of PET/CT and MRI, as well as hybrid PET/MRI. Main areas of research included new PET-tracers, visual PET(/CT)+MRI assessment for staging, and (semi-)quantitative analysis of PET-parameters compared to or combined with MRI-parameters as predictive biomarkers. In line with literature, we also observed a vast increase in numbers of multimodality PET/CT+MRI imaging in our institutional data. CONCLUSIONS: The tremendous increase in published literature on multimodality imaging, reflected by our institutional data, shows the continuously growing interest in comprehensive multivariable imaging evaluations to guide oncological practice. ADVANCES IN KNOWLEDGE: The role of multimodality imaging in oncology is rapidly evolving. This paper summarizes the main applications and recent developments in multimodality imaging, with a specific focus on the combination of PET+MRI in abdominal oncology.

CT for lymph node staging of Colon cancer: not only size but also location and number of lymph node count.

PURPOSE: To evaluate the diagnostic accuracy of imaging features to predict lymph node status of colon cancer using CT. METHODS: This was a retrospective study from 2 tertiary hospitals in South Korea and Netherlands. 317 Colon cancer patients who underwent primary surgical treatment were included. Number of lymph nodes according to the anatomical location, size, cluster, degree of attenuation, shape, presence of internal heterogeneity and ill-defined margin of the lymph node were assessed and compared according to histological lymph node status. RESULTS: The largest short diameter of lymph node and presence of internal heterogeneity of lymph node showed significant association with malignant lymph node status (P < 0.001 and P = 0.041, respectively). The ROC curve analysis revealed AUC of 0.703 for the largest short diameter of lymph node (P < 0.001), and AUC of the presence of internal heterogeneity was 0.630 (P < 0.001). In addition, our study showed that a total number of lymph nodes, regardless of size, (P = 0.022) and number of lymph nodes in peritumoral area (P < 0.001) and along the mesenteric vessels (P < 0.001) on CT demonstrated significant association with malignant status of lymph nodes in colon cancer. CONCLUSIONS: There were significant associations between lymph node status and imaging features of lymph nodes on CT in colon cancer patients. The largest short diameter of lymph node and presence of internal heterogeneity can be used to predict the malignant status of lymph node in colon cancer patients. Also, the number of lymph nodes near the colonic tumor should be considered in assessment of colon cancer lymph node involvement on CT.

Locoregional CT staging of colon cancer: does a learning curve exist?

PURPOSE: To evaluate the learning curve for locoreginal staging of colon cancer in radiologist trainees. METHODS: Eighty-eight cases of colon cancer CT were included in this retrospective study. Four senior radiology residents staged the CTs according to TNM classification. Two out of four radiologists received feedback after reading every 20 cases. Radiologic staging was compared with pathologic staging and the learning curve, diagnostic performance, reader confidence and reading time were evaluated and compared between the two groups (feedback vs. no feedback). Generalized estimating equations logistic regression, QICu statistic, ANOVA and t test/Mann-Whitney test were utilized. RESULTS: Radiologists demonstrated a significant increase in their performance to distinguish between ≤ T2 and ≥ T3 and reached an inflection point at 38 cases, with a significant association with increased number of cases reviewed (P < 0.001). Sensitivity (P < 0.001), specificity (P = 0.030) and NPV (P = 0.002) demonstrated significant associations with increased experience. The overall reader's confidence was significantly higher in the group which received feedback (P < 0.001). There was no significant improvement in performance nor in reader's confidence for N staging (N0 vs. ≥ N1) for all readers. Reading time decreased with experience and showed a significant negative association with experience (P < 0.001). CONCLUSION: Diagnostic performance of senior radiology trainees in differentiating between T2 and T3 colon cancer on CTs improved with increased experience. In contrast, evaluation of lymph node involvement did not improve with more experience. Feedback had no significant effect on improvement of diagnostic performances.