Imaging of Malignant Pleural, Pericardial, and Peritoneal Mesothelioma.

Malignant mesothelioma is a rare tumor arising from the mesothelial cells that line the pleura, pericardium, peritoneum, and tunica vaginalis. Imaging plays a primary role in the diagnosis, staging, and management of malignant mesothelioma. Multimodality imaging, including radiography, computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), is used in a variety of scenarios, including diagnosis, guidance for tissue sampling, staging, and reassessment of disease after therapy. CT is the primary imaging modality used in staging. MRI has superior contrast resolution compared with CT and can add value in terms of determining surgical resectability in equivocal cases. MRI can further assess the degree of local invasion, particularly into the mediastinum, chest wall, and diaphragm, for malignant pleural and pericardial mesotheliomas. FDG PET/CT plays a role in the diagnosis and staging of malignant pleural mesothelioma (MPM) and has been shown to be more accurate than CT, MRI, and PET alone in the staging of malignant pleural mesothelioma. PET/CT can also be used to target lesions for biopsy and to assess prognosis, treatment response, and tumor recurrence.

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study.

BACKGROUND: Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies. METHODS: This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible. RESULTS: Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks. CONCLUSION: The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information. CLINICALTRIALS: gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ).

Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study.

Background Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a "basket type" expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Patients with advanced or metastatic relapsed/refractory solid tumors following prior systemic therapy, or in whom the addition of selinexor to standard chemotherapy deemed appropriate, were eligible. Results Fourteen patients with the median age of 61 years (range, 22-68years) were treated, and the most common cancer types were gynecological cancers; ovarian (n = 5), endometrial (n = 2), and 1 each with fallopian tube and vaginal cancers. Of the 14 patients treated, 12 (86 %) had at least one treatment-related adverse event (TRAE). The most common TRAEs were anemia (71 %), thrombocytopenia (57 %), hyponatremia (57 %), vomiting (57 %), fatigue (50 %), nausea (50 %), and neutropenia (36 %). Two patients had dose limiting toxicities. One patient dosed at selinexor 80 mg had grade 3 nausea and vomiting and one patient dosed at selinexor 60 mg experienced grade 4 neutropenia and thrombocytopenia. Of the 13 efficacy evaluable patients, one (8 %) with endometrial cancer achieved unconfirmed partial response (uPR) and the time-to-treatment failure (TTF) was 48 weeks, whereas 6 of the 13 (46 %) patients had stable disease (SD) contributing to the clinical benefit rate of 46 %. The median TTF for all patients was 9 weeks (range, 2-48weeks). Conclusions Once weekly selinexor in combination with topotecan was viable and showed some preliminary tumor efficacy. The recommend phase 2 dose of selinexor was 60 mg once weekly in combination with IV topotecan.Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495.

Lymphatic Pathways of the Thorax: Predictable Patterns of Spread.

OBJECTIVE. This article reviews thoracic lymphatic pathways and tributaries, discusses lymphatic anatomic variants and their clinical implications, and emphasizes common patterns of thoracic lymphadenopathy from extrapulmonary malignancies. CONCLUSION. Recognition of common patterns and pathways of thoracic lymphatic drainage can help identify the site of tumor origin and allow a more focused examination of disease extent, both of which are important for disease prognosis and management.

18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer.

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor 18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) 18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each 18F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated 18F-FDG SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57+ cell density, and increased T cell exhaustion gene signature. Elevated SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.

Recognizing Radiation Therapy-related Complications in the Chest.

Radiation therapy is one of the cornerstones for the treatment of thoracic malignancies. Although advances in radiation therapy technology have improved the delivery of radiation considerably, adverse effects are still common. Postirradiation changes affect the organ or tissue treated and the neighboring structures. Advances in external-beam radiation delivery techniques and how these techniques affect the expected thoracic radiation-induced changes are described. In addition, how to distinguish these expected changes from complications such as infection and radiation-induced malignancy, and identify treatment failure, that is, local tumor recurrence, is reviewed. ©RSNA, 2019.

Leukemic Involvement in the Thorax.

Leukemias are malignancies in which abnormal white blood cells are produced in the bone marrow, resulting in compromise of normal bone marrow hematopoiesis and subsequent cytopenias. Leukemias are classified as myeloid or lymphoid depending on the type of abnormal cells produced and as acute or chronic according to cellular maturity. The four major types of leukemia are acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia. Clinical manifestations are due to either bone marrow suppression (anemia, thrombocytopenia, or neutropenia) or leukemic organ infiltration. Imaging manifestations of leukemia in the thorax are myriad. While lymphadenopathy is the most common manifestation of intrathoracic leukemia, leukemia may also involve the lungs, pleura, heart, and bones and soft tissues. Myeloid sarcomas occur in 5%-7% of patients with acute myeloid leukemia and represent masses of myeloid blast cells in an extramedullary location. ©RSNA, 2019.

Comparison of Abdominal Computed Tomographic Enhancement and Organ Lesion Depiction Between Weight-Based Scanner Software Contrast Dosing and a Fixed-Dose Protocol in a Tertiary Care Oncologic Center.

OBJECTIVE: This study aimed to evaluate the quality of enhancement and solid-organ lesion depiction using weight-based intravenous (IV) contrast dosing calculated by injector software versus fixed IV contrast dose in oncologic abdominal computed tomographic (CT) examinations. METHODS: This institutional review board-exempt retrospective cohort study included 134 patients who underwent single-phase abdominal CT before and after implementation of weight-based IV contrast injector software. Patient weight, height, body mass index, and body surface area were determined. Two radiologists qualitatively assessed examinations (4 indicating markedly superior to -4 indicating markedly inferior), and Hounsfield unit measurements were performed. RESULTS: Enhancement (estimated mean, -0.05; 95% confidence interval [CI], -0.19 to 0.09; P = 0.46) and lesion depiction (estimated mean, -0.01; 95% CI, -0.10 to 0.07; P = 0.79) scores did not differ between CT examinations using weight-based IV contrast versus fixed IV contrast dosing when a minimum of 38.5 g of iodine was used. However, the scores using weight-based IV contrast dosing were lower when the injector software calculated and delivered less than 38.5 g of iodine (estimated mean, -0.81; 95% CI, -1.06 to -0.56; P < 0.0001). There were no significant differences in measured Hounsfield units between the CT examinations using weight-based IV contrast dosing versus fixed IV contrast dosing. CONCLUSIONS: Oncologic CT image quality was maintained or improved with weight-based IV contrast dosing using injector software when using a minimum amount of 38.5 g of iodine.

Immunotherapy and the role of imaging.

Significant advances in the genetic and molecular characterization of cancer have led to the development of effective immunotherapies. These therapeutics help the host immune system recognize cancer as foreign, promote the immune system, and relieve the inhibition that allows growth and spread of tumors. Experience with various immunotherapies, particularly the immunomodulatory monoclonal antibody ipilimumab, has demonstrated that unique patterns of response may be encountered that cannot be adequately captured by traditional response criteria, such as the World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), which have been used primarily with cytotoxic chemotherapies. In response to these observations, several novel response criteria have been developed to evaluate patients who receive immunotherapy, including immune-related response criteria (irRC), immune-related RECIST (irRECIST), and immune RECIST (iRECIST). These criteria are typically used in conjunction with RECIST version 1.1 in the clinical trial setting, because approval of new therapeutics by the US Food and Drug Administration relies on the responses derived from RECIST version 1.1. Finally, a wide variety of immune-related adverse events may affect patients who receive immunotherapy, many of which can be identified on imaging studies such as computed tomography, magnetic resonance imaging, and 2-deoxy-2-(fluorine-18)fluoro-D-glucose-positron emission tomography/computed tomography. In this review, the authors present the role of imaging in the evaluation of patients treated with immunotherapy, including the background and application of irRC, irRECIST, and iRECIST; the imaging of immune-related adverse events; and future directions in advanced imaging of immunotherapy. Cancer 2018;124:2906-22. © 2018 American Cancer Society.

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma.

PURPOSE: To develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk. METHODS: In total, 568 consecutive patients with potentially resectable esophageal adenocarcinoma who underwent CRT were included for analysis, including 373 patients who underwent esophagectomy after CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality therapy). A nomogram for 1-year RFS was created using a Cox regression model. The upper tertile of the nomogram score was used to stratify patients in low-risk and high-risk groups for 1-year recurrence. The 5-year OS was compared between trimodality and bimodality therapy in low-risk and high-risk patients after propensity score matching, respectively. RESULTS: Median follow-up for the entire cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment groups was 56.3% (95% confidence interval [CI] 47.9-64.7) and 36.9% (95% CI 31.4-42.4), respectively. The final nomogram for the prediction of 1-year RFS included male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3, and baseline SUVmax, with accurate calibration and reasonable discrimination (C-statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in low-risk patients (p = 0.003), whereas it showed no significant survival benefit in high-risk patients (p = 0.302). CONCLUSIONS: The proposed nomogram estimates early recurrence risk. The addition of surgery to CRT provides a clear OS benefit in low-risk patients. The OS benefit of surgery in high-risk patients is less pronounced.

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT.

OBJECTIVE: During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients. METHODS: In total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis. RESULTS: Of 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3-83.4%) and 93.7% (95% CI: 91.6-95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration. CONCLUSIONS: 18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.

Screening for Lung Cancer: Lexicon for Communicating With Health Care Providers.

OBJECTIVE: The effectiveness of lung cancer screening with low-dose CT (LDCT) has been shown by multiple clinical trials, particularly the National Lung Screening Trial. Accurate communication of LDCT results to health care providers is critical to optimal patient care. CONCLUSION: The Lung CT Screening Reporting and Data System (Lung-RADS), a structured decision-oriented reporting system designed to minimize the rate of false-positive results and developed by the American College of Radiology, is recommended for use with all LDCT examinations.

Primary Lung Tumors in Children: Radiologic-Pathologic Correlation From the Radiologic Pathology Archives.

Primary lung tumors in children are rare, with a narrow range of diagnostic considerations. However, the overlapping imaging appearances of these tumors necessitate attention to key discriminating imaging and pathologic features. In the neonate and infant, the important considerations include pleuropulmonary blastoma (PPB), infantile fibrosarcoma, and fetal lung interstitial tumor. Among these tumors, imaging findings such as air-filled cysts in type 1 PPB and homogeneously low attenuation of fetal lung interstitial tumors are relatively specific. Key pathologic and genetic discriminators among this group of tumors include the DICER1 germline mutation found in PPB and the t(12,15)(p13;q25) translocation and ETV6-NTRK3 fusion gene seen in infantile fibrosarcoma. Primary lung tumors in older children include inflammatory myofibroblastic tumors (IMTs), carcinoid salivary gland-type tumors of the lung, recurrent respiratory papillomatosis, and other rare entities. IMT, a spindle-cell proliferation with inflammatory elements, is the most common lung tumor in children. Anaplastic lymphoma kinase, a receptor-type protein tyrosine kinase, is present in 50% of these tumors, and this finding may support an imaging diagnosis of IMT. Carcinoid tumors account for a substantial portion of childhood lung tumors, and their characteristic avid enhancement on images corresponds to the compressed fibrovascular stroma histologically. Furthermore, novel imaging agents used with somatostatin receptor analogs have an emerging role in the evaluation of carcinoid tumors. Although less common than mucoepidermoid carcinoma, adenoid cystic carcinoma tends to recur given the perineural spread seen histologically. Integrating radiologic and pathologic knowledge is critical to accurate diagnosis, treatment planning, and surveillance of primary lung tumors in children.

Revisions to the TNM Staging of Lung Cancer: Rationale, Significance, and Clinical Application.

Lung cancer remains the leading cause of cancer-related mortality worldwide. To formulate effective treatment strategies and optimize patient outcomes, accurate staging is essential. Lung cancer staging has traditionally relied on a TNM staging system, for which the International Association for the Study of Lung Cancer (IASLC) has recently proposed changes. The revised classification for this eighth edition of the TNM staging system (TNM-8) is based on detailed analysis of a new large international database of lung cancer cases assembled by the IASLC for the purposes of this project. Fundamental changes incorporated into TNM-8 include (a) modifications to the T classification on the basis of 1-cm increments in tumor size; (b) grouping of lung cancers that result in partial or complete lung atelectasis or pneumonitis; (c) grouping of tumors with involvement of a main bronchus irrespective of distance from the carina; (d) reassignment of diaphragmatic invasion in terms of T classification; (e) elimination of mediastinal pleural invasion from the T classification; and (f) subdivision of the M classification into different descriptors on the basis of the number and site of extrathoracic metastases. In response to these revisions, established stage groups have been modified, and others have been created. In addition, recommendations for classifying patterns of disease that result in multiple sites of pulmonary involvement, including multiple primary lung cancers, lung cancers with separate tumor nodules, multiple ground-glass/lepidic lesions, and consolidation, as well as recommendations for lesion measurement, are addressed. Understanding the key revisions introduced in TNM-8 allows radiologists to accurately stage patients with lung cancer and optimize therapy. ©RSNA, 2018.

The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma.

PURPOSE: The purpose of our study was to determine the value of 18F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). METHODS: In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. RESULTS: A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). CONCLUSIONS: 18F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

ITMIG Classification of Mediastinal Compartments and Multidisciplinary Approach to Mediastinal Masses.

Division of the mediastinum into specific compartments is beneficial for a number of reasons, including generation of a focused differential diagnosis for mediastinal masses identified on imaging examinations, assistance in planning for biopsies and surgical procedures, and facilitation of communication between clinicians in a multidisciplinary setting. Several classification schemes for the mediastinum have been created and used to varying degrees in clinical practice. Most radiology classifications have been based on arbitrary landmarks outlined on the lateral chest radiograph. A new scheme based on cross-sectional imaging, principally multidetector computed tomography (CT), has been developed by the International Thymic Malignancy Interest Group (ITMIG) and accepted as a new standard. This clinical division scheme defines unique prevascular, visceral, and paravertebral compartments based on boundaries delineated by specific anatomic structures at multidetector CT. This new definition plays an important role in identification and characterization of mediastinal abnormalities, which, although uncommon and encompassing a wide variety of entities, can often be diagnosed with confidence based on location and imaging features alone. In other scenarios, a diagnosis may be suggested when radiologic features are combined with specific clinical information. In this article, the authors present the new multidetector CT-based classification of mediastinal compartments introduced by ITMIG and a structured approach to imaging evaluation of mediastinal abnormalities. ©RSNA, 2017.

IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms.

Thymic epithelial neoplasms are rare malignancies that arise from the thymus and include thymoma, thymic carcinoma, and thymic neuroendocrine tumors. At least 15 different stage classifications have been proposed for thymic epithelial neoplasms and used to varying degrees in clinical practice, many of which have been constructed from small groups of patients. Traditionally, the Masaoka and Masaoka-Koga staging systems have been the schemes most commonly employed, and the latter has been recommended for use by the International Thymic Malignancy Interest Group (ITMIG). An official, consistent stage classification system has recently been recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC), which are responsible for defining stage classifications for neoplasms. To establish this stage classification system, the International Association for the Study of Lung Cancer (IASLC) and ITMIG amassed a large retrospective database and evaluated this group of cases to develop proposals for the eighth edition of the stage classification manuals. For this endeavor, IASLC provided funding and statistical analysis and ITMIG provided the involvement of the clinicians and researchers actively participating in the study of thymic epithelial neoplasms. To accomplish this, a Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) was established to formulate the rationale, methodology, and definitions of this tumor-node-metastasis (TNM) staging system, which is presented in this article. © RSNA, 2017.

Metastasis to the Heart: A Radiologic Approach to Diagnosis With Pathologic Correlation.

OBJECTIVE: Evaluating metastatic disease to the heart and pericardium, from detection to diagnosis, often requires a multimodality imaging approach. A radiologist's ability to evaluate cardiac metastases hinges on an understanding of the epidemiology, anatomy, and imaging features of this disease process. CONCLUSION: On surveillance imaging of patients with cancer or when metastatic disease is suspected, detection of metastatic disease may be greatly enhanced by an understanding of which primary tumors metastasize to the heart and the most common routes of spread.