Computed Tomography Texture Analysis for Predicting Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors.

BACKGROUND: The treatment responses of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) vary, requiring reliable prognostic biomarkers. We assessed the prognostic ability of computed tomography (CT) texture analysis in patients with mRCC treated with programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors. MATERIALS AND METHODS: Sixty-eight patients with mRCC treated with PD-1/PD-L1 inhibitors between 2012 and 2019 were revaluated. Using baseline and first follow-up CT, baseline and follow-up texture models were developed to predict overall survival (OS) and progression-free survival (PFS) using least absolute shrinkage and selection operator Cox-proportional hazards analysis. Patients were divided into high-risk or low-risk group, and the survival difference was assessed using Kaplan-Meier and log-rank test. Multivariable Cox models were constructed by including only the clinical variables (clinical models) and by combining the clinical variables and the texture models (combined clinical-texture models), and their predictive performance was evaluated using Harrell's C-index. RESULTS: The baseline texture models distinguished longer- and shorter-term survivors for both OS (median, 60.1 vs. 17.0 months; P = .048) and PFS (5.2 vs. 2.8 months; P = .003). The follow-up texture models distinguished longer- and shorter-term overall survivors (40.3 vs. 15.2 months; P = .008) but not for PFS (5.0 vs. 3.6 months; P = .25). The combined clinical-texture model outperformed the clinical model in both predicting the OS (C-index, 0.70 vs. 0.63; P = .03) and PFS (C-index, 0.63 vs. 0.55; P = .04). CONCLUSION: CT texture analysis performed at baseline and early after starting PD-1/PD-L1 inhibitors is associated with clinical outcomes of patients with mRCC.

Subcutaneous metastasis from an atypical pulmonary carcinoid tumor.

Pulmonary carcinoid tumors are uncommon neuroendocrine tumors that rarely metastasize to the skin. We report the case of a 71-year-old woman with a longstanding history of primary atypical pulmonary carcinoid tumor who presented with a new tender cutaneous nodule. Immunostaining of the nodule was consistent with metastatic atypical carcinoid tumor of the skin including positive staining for neuroendocrine markers chromogranin and synaptophysin. Dermatologists should consider cutaneous neuroendocrine metastasis when evaluating new nodules in patients with stable pulmonary carcinoid tumors or in those with concomitant concerning respiratory symptoms.

A cost-effectiveness analysis of the diagnostic strategies for differentiating focal nodular hyperplasia from hepatocellular adenoma.

OBJECTIVES: We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). METHODS: A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. RESULTS: In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. KEY POINTS: • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.

Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine.

For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC. State-of-the-art knowledge of the molecular basis of RCC and its treatment and imaging will help ensure that the radiology community remains relevant and central in the care of patients with advanced RCC. This article will review developments in management of advanced RCC from a radiologist's perspective to highlight our clinical role. It will describe how the underlying molecular mechanisms of RCC provide specific targets for novel anticancer agents. The relationship between the mechanisms of action of these novel anticancer agents and the imaging appearance of tumor response will be discussed, along with the available tumor response criteria and their strengths and weaknesses, thus assisting radiologists in response assessment in the setting of clinical trials or routine practice. The class- and drug-specific toxicities and complications associated with the novel anticancer agents will be summarized, since these are frequently missed or misinterpreted and require the radiologist's input in prompt detection and management. The potential role of radiogenomics and texture analysis in the management of advanced RCC will also be discussed. © RSNA, 2017.

Novel imaging in renal cell carcinoma.

PURPOSE OF REVIEW: Renal cell carcinoma is a heterogeneous disease with a spectrum of subtypes and clinical behavior. Quantitative and qualitative imaging biomarkers are sought to correlate with genetic and histologic features and complement pathologic analysis. RECENT FINDINGS: Texture analysis, radiogenomics, and modality-specific advancements have yielded an array of renal cell carcinoma imaging biomarkers in the research domain. Although many techniques are promising, standardization and validation of these procedures are needed prior to implementation into clinical practice. SUMMARY: We introduce novel imaging techniques and analytic methods which have been shown to contribute to characterization of renal cell carcinoma and its subtypes, aggressiveness, and responsiveness to therapy, including associated advantages and limitations.

A New Look at Toxicity in the Era of Precision Oncology: Imaging Findings, Their Relationship With Tumor Response, and Effect on Metastasectomy.

OBJECTIVE: As cancer care becomes increasingly personalized and patients with metastatic disease live longer, oncologists' approach to drug toxicity is also evolving. CONCLUSION: This article aims to broaden the radiologist's understanding of imaging-evident toxicity by describing how oncologists grade toxicity, exploring toxicity as a biomarker of treatment response, discussing the effect of toxicity in patients who are candidates for metastasectomy, and illustrating how combining drugs of varying classes amplifies toxicity.

Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for Radiologists.

Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer. Surgery is the mainstay of treatment, with radioactive iodine (RAI) therapy reserved for differentiated subtypes. Posttreatment surveillance of thyroid cancer is done with US of the thyroid bed as well as monitoring of tumor markers such as serum thyroglobulin and serum calcitonin. Computed tomography (CT), magnetic resonance imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography/CT are used in the follow-up of patients with negative iodine 131 imaging and elevated tumor markers. Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance. Treatment options for metastatic RAI-refractory thyroid cancer are limited. Currently, Food and Drug Administration-approved molecularly targeted therapies for metastatic RAI-refractory thyroid cancer, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target the vascular endothelial growth factor receptor and RET kinases. Imaging plays an important role in assessment of response to these therapies, which can be atypical owing to antiangiogenic effects. A wide spectrum of toxic effects is associated with the molecularly targeted therapies used in thyroid cancer and can be detected at restaging scans. (©)RSNA, 2016.

Role of Imaging in Management of Desmoid-type Fibromatosis: A Primer for Radiologists.

Desmoid-type fibromatosis (DF) is a locally aggressive fibroblastic neoplasm that has variable clinical and biologic behaviors ranging from indolent tumors that can undergo spontaneous regression to aggressive tumors with a tendency toward local invasion and recurrence. The management of DF has evolved considerably in the last decade from aggressive first-line surgery and radiation therapy to systemic treatment (chemotherapy, hormonal therapy, and targeted therapy) and symptomatic local control (surgery and radiation therapy). Imaging plays an important role in each of these treatment settings. In surgical candidates, computed tomography (CT) and magnetic resonance (MR) imaging are the modalities of choice for assessing resectability and surgical planning. For evaluating recurrence, MR imaging is the modality of choice for extra-abdominal recurrence, whereas CT is the preferred modality for intra-abdominal recurrence. Signal intensity changes at MR imaging can be used to monitor the biologic behavior of certain DFs chosen for expectant management. Response to systemic treatment with anti-inflammatory agents, hormonal therapy (eg, tamoxifen), cytotoxic chemotherapy (eg, doxorubicin, vinblastine, methotrexate), and targeted therapy (eg, sorafenib), as well as to radiation therapy, can be assessed at CT by monitoring size and attenuation changes or at MR imaging by monitoring size, T2 signal intensity, and degree of enhancement. Several patterns of response can be seen at imaging. Imaging also helps in detecting complications associated with systemic therapy and radiation therapy. (©)RSNA, 2016.

RECIST 1.1 compared with RECIST 1.0 in patients with advanced renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy.

OBJECTIVE. Response Evaluation Criteria in Solid Tumors (RECIST) is the most widely accepted method to objectively assess response to therapy in renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. Both RECIST 1.0 and 1.1 have been used to assess response to VEGF-targeted therapies; however, systematic comparisons are lacking. MATERIALS AND METHODS. Sixty-two patients with metastatic RCC treated with VEGF-targeted therapies were retrospectively studied. Tumor measurements and response assessment according to RECIST 1.1 and RECIST 1.0 were compared, including the number of target lesions, baseline measurements, response at each follow-up, best overall response, and time to progression (TTP). Morphologic changes and new enhancement were also assessed over the course of treatment, and TTP was evaluated using morphologic change criteria in combination with RECIST 1.1. RESULTS. The number of target lesions according to RECIST 1.1 was significantly fewer than by RECIST 1.0 (median, 2 vs 4; p < 0.0001). At first imaging follow-up, the percentage change of the sums of the diameter measurements by RECIST 1.1 and RECIST 1.0 were highly concordant (R = 0.857; mean shrinkage, 12.1% by RECIST 1.1 vs 10.8% by RECIST 1.0). Best response assessment was highly concordant between the two criteria (weighted κ = 0.819). There was no evidence of a difference in TTP by the two criteria, with a median TTP of 8.9 months (95% CI for the median, 5.5-13.9) by RECIST 1.1 and 8.9 months (95% CI for the median, 5.8-13.6) by RECIST 1.0. The median TTP by RECIST 1.1 alone was 8.9 months compared with 5.6 months for RECIST 1.1 and morphologic changes combined. CONCLUSION. RECIST 1.1 and RECIST 1.0 response assessments were overall highly concordant in patients with RCC treated with VEGF-targeted therapy, with fewer target lesions according to RECIST 1.1 but no difference in TTP.

Imaging of Nervous System Involvement in Hematologic Malignancies: What Radiologists Need to Know.

OBJECTIVE: The purpose of this article is to provide a comprehensive review of the imaging features of neurologic involvement in hematologic malignancies. CONCLUSION: Neurologic involvement can be seen in lymphoma, leukemia, post-transplant lymphoproliferative disorder (PTLD), plasma cell neoplasms, and histiocytic and dendritic neoplasms. Imaging, MRI in particular, plays an important role in the workup of these patients. Familiarity with the imaging features of nervous system involvement in hematologic malignancies can help radiologists suggest the diagnosis and guide management.

Beyond the vascular endothelial growth factor axis: update on role of imaging in nonantiangiogenic molecular targeted therapies in oncology.

OBJECTIVE: This article provides a comprehensive review of molecular targeted therapies that do not act directly through vascular endothelial growth factor pathways, highlighting the role of imaging in assessment of treatment response and drug toxicities. CONCLUSION: A substantial number of molecular targeted therapies act on nonantiangiogenic pathways. Familiarity with these drugs, their personalized tumor response criteria, and class- and drug-specific toxicities will help radiologists to be an integral part of the multi-disciplinary oncology team.

Imaging of Fluid in Cancer Patients Treated With Systemic Therapy: Chemotherapy, Molecular Targeted Therapy, and Hematopoietic Stem Cell Transplantation.

OBJECTIVE: The purpose of this article is to provide a comprehensive review of the imaging features of various systemic treatment-related causes of fluid accumulation in cancer patients. CONCLUSION: Systemic treatment-related fluid accumulation can occur with chemotherapy, molecular targeted therapy, or hematopoietic stem cell transplantation. Imaging findings such as new ascites, pleural and pericardial effusions, and subcutaneous edema should be interpreted with caution on restaging studies.

Hormonal therapy in oncology: a primer for the radiologist.

OBJECTIVE: The purpose of this article is to provide a comprehensive imaging review of the common hormonal therapies used in oncology and the side effects associated with them. CONCLUSION: Commonly used hormones in oncology include corticosteroids, somatostatin analogues, progestins, gonadotropin-releasing hormone agonists and antagonists, antiandrogens, aromatase inhibitors, and selective estrogen receptor modulators. Familiarity with these hormones and their side effects can help radiologists to be vigilant for the side effects and complications of these agents.

Anti-VEGF molecular targeted therapies in common solid malignancies: comprehensive update for radiologists.

Angiogenesis is an essential component of the growth and dissemination of solid malignancies and is mediated by several proangiogenic factors. The most widely studied proangiogenic factor is vascular endothelial growth factor (VEGF). A major class of molecular targeted therapies (MTTs) inhibit the VEGF axis and are referred to as antiangiogenic MTTs. There are two main types of anti-VEGF MTTs: drugs targeting circulating VEGF and drugs interfering with the activity of the VEGF receptors. The cancers against which antiangiogenic MTTs have had the greatest effect are gliomas, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumor. These cancers respond to antiangiogenic MTTs in a different way than they respond to conventional chemotherapy. Instead of the traditional Response Evaluation Criteria in Solid Tumors (RECIST), each of these cancers therefore requires its own individualized treatment response criteria (TRC). Examples of individualized TRC include the Response Assessment in Neuro-oncology (RANO) criteria for gliomas, modified RECIST for hepatocellular carcinoma, and Morphology, Attenuation, Size, and Structure (MASS) criteria for renal cell carcinoma. Furthermore, antiangiogenic MTTs have a unique spectrum of class-specific and drug-specific toxic effects, some of which can be detected at imaging. Increasing use of antiangiogenic MTTs in clinical practice necessitates that radiologists be aware of these drugs, their response patterns, and TRC as well as their toxic effect profiles.

Multimodality Imaging of Tumour Thrombus.

Vascular thrombosis occurs commonly in cancer patients. Once the diagnosis of thrombosis is established, it is important to characterize the nature of thrombus, tumoural versus bland, as each have a different prognosis, clinical significance, and management. This review paper discusses the imaging spectrum of tumour thrombus and its clinical significance emphasizing the role of imaging in differentiating tumour from bland thrombus.

Esophageal Carcinoma: Current Concepts in the Role of Imaging in Staging and Management.

Over the past few decades, the survival of esophageal cancer patients has improved owing to early detection and advances in multimodality treatment strategies. Imaging plays an important role in every step in the management of esophageal cancer, including diagnosis, staging, assessment of treatment response, and post-treatment surveillance. In this article, we provide a comprehensive review of the role of imaging in these various time points of esophageal cancer management.

Intraobserver and interobserver variability in computed tomography size and attenuation measurements in patients with renal cell carcinoma receiving antiangiogenic therapy: implications for alternative response criteria.

BACKGROUND: Alternative response criteria have been proposed in patients with metastatic renal cell carcinoma (mRCC) who are receiving vascular endothelial growth factor (VEGF)-targeted therapy, including 10% tumor shrinkage as an indicator of response/outcome. However, to the authors' knowledge, intraobserver and interobserver measurement variability have not been defined in this setting. The objective of the current study was to determine intraobserver and interobserver agreement of computed tomography (CT) size and attenuation measurements to establish reproducible response indicators. METHODS: Seventy-one patients with mRCC with 179 target lesions were enrolled in phase 2 and phase 3 trials of VEGF-targeted therapies and retrospectively studied with Institutional Review Board approval. Two radiologists independently measured the long axis diameter and mean attenuation of target lesions at baseline and on follow-up CT. Concordance correlation coefficients and Bland-Altman plots were used to assess intraobserver and interobserver agreement. RESULTS: High concordance correlation coefficients (range, 0.8602-0.9984) were observed in all types of measurements. The 95% limits of agreement for the percentage change of the sum longest diameter was -7.30% to 7.86% for intraobserver variability, indicating that 10% tumor shrinkage represents a true change in tumor size when measured by a single observer. The 95% limits of interobserver variability were -16.3% to 15.4%. On multivariate analysis, the location of the lesion was found to significantly contribute to interobserver variability (P = .048). The 95% limits of intraobserver agreement for the percentage change in CT attenuation were -18.34% to 16.7%. CONCLUSIONS: In patients with mRCC who are treated with VEGF inhibitors, 10% tumor shrinkage is a reproducible radiologic response indicator when baseline and follow-up studies are measured by a single radiologist. Lesion location contributes significantly to measurement variability and should be considered when selecting target lesions.

Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis.

OBJECTIVE: To systematically determine the imaging findings for distinguishing malignant and benign branch-duct type intraductal papillary mucinous neoplasms (BD-IPMNs), including mixed type, and their diagnostic value through meta-analysis of published studies. BACKGROUND: Management of BD-IPMNs, including mixed type, largely relies on imaging findings. The current knowledge on imaging findings to distinguish malignant and benign BD-IPMNs has weak evidence and is mostly from scattered individual retrospective studies. METHODS: Thorough literature search in Ovid-MEDLINE and EMBASE databases was conducted to identify studies where findings of computed tomography, magnetic resonance imaging, and endoscopic ultrasonography of BD-IPMNs with or without main pancreatic duct (MPD) dilatation were correlated with surgical/pathological findings. Review of 1128 article candidates, including full-text review of 102 articles, identified 23 eligible articles with a total of 1373 patients for meta-analysis. Dichotomous data regarding distinction between malignant and benign BD-IPMNs were pooled using random effects model to obtain the diagnostic odds ratios (DORs) and their 95% confidence intervals (CIs) of various individual imaging findings for diagnosing malignant BD-IPMN. RESULTS: Presence of mural nodules revealed the highest pooled DOR (95% CI) of 6.0 (4.1-8.8) followed by MPD dilatation [3.4 (2.3-5.2)], thick septum/wall [unadjusted, 3.3 (1.5-6.9); publication bias-adjusted, 2.3 (0.9-5.5)], and cyst size greater than 3 cm [2.3 (1.5-3.5)]. Multilocularity and multiplicity of the cystic lesions did not reveal statistically significant association with malignancy. CONCLUSIONS: Presence of mural nodules should be regarded highly suspicious for malignancy warranting a surgical excision whereas cyst size greater than 3 cm, MPD dilatation (5-9 mm), or thick septum/wall may better be managed by careful observation and/or further evaluation.

10% Tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study.

Vascular endothelial growth factor (VEGF)-targeted agents are standard therapies for metastatic renal cell carcinoma (mRCC), associated with variable tumor shrinkage. Response Evaluation Criteria in Solid Tumors (RECIST) is of limited utility in this setting, and other imaging changes are sought to reliably predict outcome early. We aim to validate 10% tumor shrinkage as the best early indicator of outcome. Methods. In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, 66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted agents underwent thoracic and abdominal computed tomography at baseline and at first follow-up after therapy. Measurements were performed according to RECIST and tumor shrinkage of ≥10% decrease in sum of the longest diameter (-10%SLD). Correlation with time-to-treatment failure (TTF) and overall survival (OS) were compared and stratified by response to the radiologic criteria. Receiver-operating characteristics (ROC) analysis yielded the optimal threshold change in SLD, defining patients with prolonged survival. Results. More than -10%SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial response by RECIST did not (median TTF 6.9 vs. 5.5 months in responders vs. nonresponders, p = .34). -10%SLD was also significantly predictive of OS (median OS 35.1 vs. 15.0 months in responders vs. nonresponders, p = .003). ROC curve analysis yielded -9.3% in SLD as the optimal threshold for response/no response. Conclusion. Ten percent tumor shrinkage is validated as a reliable early predictor of outcome in mRCC patients receiving VEGF-targeted therapies and may provide a practical measure to guide therapeutic decisions.

Vascular toxicity associated with chemotherapy and molecular targeted therapy: what should a radiologist know?

OBJECTIVE: Venous and arterial thromboembolic events and rarely hemorrhage are complications of chemotherapy and, more recently, of molecular targeted therapy in patients with solid and hematologic malignancies. This article will use a drug-based approach to illustrate, with examples, vessel damage and end-organ damage induced by molecular targeted therapy and chemotherapy in cancer patients and will provide a clinical perspective. CONCLUSION: Imaging plays a key role in the detection of complications of cancer therapies. A high index of suspicion and an awareness of modern-day drug toxicities are key to the early diagnosis and management of these complications.