Imaging in Lung Cancer Staging.

Lung cancer remains one of the leading causes of mortality worldwide, as well as in the United States. Clinical staging, primarily with imaging, is integral to stratify patients into groups that determine treatment options and predict survival. The eighth edition of the tumor, node, metastasis (TNM-8) staging system proposed in 2016 by the International Association for the Study of Lung Cancer remains the current standard for lung cancer staging. The system is used for all subtypes of lung cancer, including non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumors.

Thymic Imaging Pitfalls and Strategies for Optimized Diagnosis.

Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Lung Cancer Staging: Imaging and Potential Pitfalls.

Lung cancer is the leading cause of cancer deaths in men and women in the United States. Accurate staging is needed to determine prognosis and devise effective treatment plans. The International Association for the Study of Lung Cancer (IASLC) has made multiple revisions to the tumor, node, metastasis (TNM) staging system used by the Union for International Cancer Control and the American Joint Committee on Cancer to stage lung cancer. The eighth edition of this staging system includes modifications to the T classification with cut points of 1 cm increments in tumor size, grouping of lung cancers associated with partial or complete lung atelectasis or pneumonitis, grouping of tumors with involvement of a main bronchus regardless of distance from the carina, and upstaging of diaphragmatic invasion to T4. The N classification describes the spread to regional lymph nodes and no changes were proposed for TNM-8. In the M classification, metastatic disease is divided into intra- versus extrathoracic metastasis, and single versus multiple metastases. In order to optimize patient outcomes, it is important to understand the nuances of the TNM staging system, the strengths and weaknesses of various imaging modalities used in lung cancer staging, and potential pitfalls in image interpretation.

Approach to Imaging of Mediastinal Masses.

Mediastinal masses present a diagnostic challenge due to their diverse etiologies. Accurate localization and internal characteristics of the mass are the two most important factors to narrow the differential diagnosis or provide a specific diagnosis. The International Thymic Malignancy Interest Group (ITMIG) classification is the standard classification system used to localize mediastinal masses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two most commonly used imaging modalities for characterization of the mediastinal masses.

Spectrum of Imaging Patterns of Lung Cancer following Radiation Therapy.

Radiation therapy using conventional or newer high-precision dose techniques, including three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, four-dimensional conformational radiotherapy, and proton therapy, is an important component of treating patients with lung cancer. Knowledge of the radiation technique used and the expected temporal evolution of radiation-induced lung injury, as well as patient-specific parameters such as previous radiotherapy, concurrent chemoradiotherapy, or immunotherapy, is important in image interpretation. This review discusses factors that affect the development and severity of radiation-induced lung injury and its radiological manifestations, as well as the differences between conventional and high-precision dose radiotherapy techniques.

Imaging evaluation of thymic tumors.

An integral part of managing patients with thymoma and thymic carcinoma is imaging. At diagnosis and staging, imaging helps demonstrate the extent of local invasion and distant metastases which allows the proper stratification of patients for therapy. For decades, the predominant staging system for thymic tumors was the Masaoka-Koga staging system. More recently, however, the International Association for the Study of Lung Cancer, the International Thymic Malignancies Interest Group (ITMIG), the European Society of Thoracic Surgeons, the Chinese Alliance for Research on Thymomas, and the Japanese Association of Research on Thymus partnered together to develop a tumor-node-metastasis (TNM) staging system specifically for thymic tumors based on a retrospective database of nearly 10,000 patients. The TNM 8th edition defines specific criteria for thymic tumors. Imaging also serves to assess treatment response and detect recurrent disease after various treatment modalities. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is currently used to assess response to treatment. ITMIG recommends certain modifications to RECIST version 1.1, however, in thymic tumors due to unique patterns of spread. While there is often overlap, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) characteristics can help differentiate thymoma and thymic carcinoma, with newer CT and MRI techniques under evaluation showing encouraging potential.

Multimodality imaging of mediastinal masses and mimics.

A wide variety of neoplastic and nonneoplastic conditions occur in the mediastinum. Imaging plays a central role in the evaluation of mediastinal pathologies and their mimics. Localization of a mediastinal lesion to a compartment and characterization of morphology, density/signal intensity, enhancement, and mass effect on neighboring structures can help narrow the differentials. The International Thymic Malignancy Interest Group (ITMIG) established a cross-sectional imaging-derived and anatomy-based classification system for mediastinal compartments, comprising the prevascular (anterior), visceral (middle), and paravertebral (posterior) compartments. Cross-sectional imaging is integral in the evaluation of mediastinal lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to characterize mediastinal lesions detected on radiography. Advantages of CT include its widespread availability, fast acquisition time, relatively low cost, and ability to detect calcium. Advantages of MRI include the lack of radiation exposure, superior soft tissue contrast resolution to detect invasion of the mass across tissue planes, including the chest wall and diaphragm, involvement of neurovascular structures, and the potential for dynamic sequences during free-breathing or cinematic cardiac gating to assess motion of the mass relative to adjacent structures. MRI is superior to CT in the differentiation of cystic from solid lesions and in the detection of fat to differentiate thymic hyperplasia from thymic malignancy.

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.

Imaging of Immune Checkpoint Inhibitor Immunotherapy for Non-Small Cell Lung Cancer.

The normal immune system identifies and eliminates precancerous and cancerous cells. However, tumors can develop immune resistance mechanisms, one of which involves the exploitation of pathways, termed immune checkpoints, that normally suppress T-cell function. The goal of immune checkpoint inhibitor (ICI) immunotherapy is to boost T-cell-mediated immunity to mount a more effective attack on cancer cells. ICIs have changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and numerous ICIs have now been approved as first-line treatments for NSCLC by the U.S. Food and Drug Administration. ICIs can cause atypical response patterns such as pseudoprogression, whereby the tumor burden initially increases but then decreases. Therefore, response criteria have been developed specifically for patients receiving immunotherapy. Because ICIs activate the immune system, they can lead to inflammatory side effects, termed immune-related adverse events (irAEs). Usually occurring within weeks to months after the start of therapy, irAEs range from asymptomatic abnormal laboratory results to life-threatening conditions such as encephalitis, pneumonitis, myocarditis, hepatitis, and colitis. It is important to be aware of the imaging appearances of the various irAEs to avoid misinterpreting them as metastatic disease, progressive disease, or infection. The basic principles of ICI therapy; indications for ICI therapy in the setting of NSCLC; response assessment and atypical response patterns of ICI therapy, as compared with conventional chemotherapy; and the spectrum of irAEs seen at imaging are reviewed. An invited commentary by Nishino is available online. ©RSNA, 2022.

Pitfalls in Oncologic Imaging of the Pericardium on CT and PET/CT.

In the oncologic setting, misinterpretation of fluid in pericardial recesses as mediastinal adenopathy or benign pericardial findings as malignant can lead to inaccurate staging and inappropriate management. Knowledge of normal pericardial anatomy, imaging features to differentiate fluid in pericardial sinuses and recesses from mediastinal adenopathy and potential pitfalls in imaging of the pericardium on CT and PET/CT is important to avoid misinterpretation.

Pitfalls in the imaging of pulmonary embolism.

Pulmonary embolism (PE) can present with a wide spectrum of clinical symptoms that can overlap considerably with other cardiovascular diseases. To avoid PE related morbidity and mortality, it is vital to identify this disease accurately and in a timely fashion. Several clinical criteria have been developed to standardize the diagnostic approach for patients with suspected PE. Computed tomographic pulmonary angiogram has significantly improved the detection of pulmonary embolism and is considered the imaging modality of choice to diagnose this disease. However, there are several potential pitfalls associated with this modality which can make diagnosis of PE challenging. In this review, we will discuss various pitfalls routinely encountered in the diagnostic work up of patients with suspected PE, approaches to mitigate these pitfalls and incidental pulmonary embolism.

Pearls and Pitfalls in Lung Cancer CT Screening.

Annual LDCT lung cancer screening is recommended by the United States Preventive Services Task Force (USPSTF) for high-risk population based on the results from the National Lung Cancer Screening Trial (NLST) that showed a significant (20%) reduction in lung cancer-specific mortality rate with the use of annual low-dose computed tomography (LDCT) screening. More recently, the benefits of lung cancer screening were confirmed by the Dutch- Belgian NELSON trial in Europe. With the implementation of lung screening in large scale, knowledge of the limitations related to false positive, false negative and other potential pitfalls is essential to avoid misdiagnosis. This review outlines the most common potential pitfalls in the characterization of screen-detected lung nodules that include artifacts in LDCT, benign nodules that mimic lung cancer, and causes of false negative evaluations of lung cancer with LDCT and PET/CT studies. Awareness of the spectrum of potential pitfalls in pulmonary nodule detection and characterization, including equivocal or atypical presentations, is important for avoiding misinterpretation that can alter patient management.

Pearls and pitfalls in imaging of mediastinal masses.

In imaging of the mediastinum, advances in computed tomography (CT), and magnetic resonance imaging (MRI) technology enable improved characterization of mediastinal masses. Knowledge of the boundaries of the mediastinal compartments is key to accurate localization. Awareness of distinguishing imaging characteristics allows radiologists to suggest a specific diagnosis or narrow the differential. In certain situations, MRI adds value to further characterize mediastinal lesions.

Thymic Carcinomas-A Concise Multidisciplinary Update on Recent Developments From the Thymic Carcinoma Working Group of the International Thymic Malignancy Interest Group.

Thymic carcinomas are rare malignancies that in general arise in the prevascular (anterior) mediastinum. These tumors are usually invasive, often present at advanced stages, and typically behave aggressively. Studies are hampered by the paucity of these tumors, the large variety of carcinoma subtypes, and the lack of unique morphologic and immunophenotypic features. Despite these challenges, advances in diagnostic imaging, surgical approaches, systemic therapies, and radiation therapy techniques have been made. The WHO classification of thymic epithelial tumors has been updated in 2021, and the eighth tumor nodal metastasis staging by the American Joint Committee on Cancer/Union for International Cancer Control included thymic carcinomas in 2017. Molecular alterations that provide more insight into the pathogenesis of these tumors and that potentially permit use of novel targeted therapies are increasingly being identified. New approaches to radiation therapy, chemotherapy, and immunotherapy are under evaluation. International societies, including the International Thymic Malignancy Interest Group, European Society of Thoracic Surgeons, and Japanese, Chinese, and Korean thymic associations, have been critical in organizing and conducting multi-institutional clinical studies. Herein, we review contemporary multidisciplinary perspectives in diagnosis and management of thymic carcinoma.

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists.

Chimeric antigen receptor (CAR) T-cell therapy is a recently approved breakthrough treatment that has become a new paradigm in treatment of recurrent or refractory B-cell lymphomas and pediatric or adult acute lymphoid leukemia. CAR T cells are a type of cellular immunotherapy that artificially enhances T cells to boost eradication of malignancy through activation of the native immune system. The CAR construct is a synthetically created functional cell receptor grafted onto previously harvested patient T cells, which bind to preselected tumor-associated antigens and thereby activate host immune signaling cascades to attack tumor cells. Advantages include a single treatment episode of 2-3 weeks and durable disease elimination, with remission rates of over 80%. Responses to therapy are more rapid than with conventional chemotherapy or immunotherapy, with intervening short-interval edema. CAR T-cell administration is associated with therapy-related toxic effects in a large percentage of patients, notably cytokine release syndrome, immune effect cell-associated neurotoxicity syndrome, and infections related to immunosuppression. Knowledge of the expected evolution of therapy response and potential adverse events in CAR T-cell therapy and correlation with the timeline of treatment are important to optimize patient care. Some toxic effects are radiologically evident, and familiarity with their imaging spectrum is key to avoiding misinterpretation. Other clinical toxic effects may be occult at imaging and are diagnosed on the basis of clinical assessment. Future directions for CAR T-cell therapy include new indications and expanded tumor targets, along with novel ways to capture T-cell activation with imaging. An invited commentary by Ramaiya and Smith is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Preoperative Maximum Standardized Uptake Value Associated With Recurrence Risk in Early Lung Cancer.

BACKGROUND: This study aimed to investigate the maximum standardized uptake value (SUVmax) as a predictor of recurrence and timing of recurrence after resection of early-stage non-small cell lung cancer. METHODS: The study retrospectively reviewed patients from a single institution who underwent lobectomy for stage I to IIa non-small cell lung cancer from 2013 to 2018. Exclusion criteria included preoperative therapy and neuroendocrine histologic type. The study investigators collected recurrence and follow-up data, as well as preoperative SUVmax. A receiver operating characteristic curve was used to identify the optimal SUVmax for predicting recurrence. Kaplan-Meier curves and Cox regression analyses were used to identify predictors of freedom from recurrence (FFR). RESULTS: The study included 238 patients, 30 (12.6%) of whom had disease recurrence. The receiver operating characteristic curve had an area under the curve of 0.671 and identified 4.93 as the optimal SUVmax cutoff. Patients were stratified into groups on the basis of this value; each group included 119 patients. High SUVmax was associated with larger tumor size, poor differentiation, lymphovascular invasion, and shorter FFR. The proportion of patients without recurrence at 5 years in the low- and high-SUVmax groups were 92.4% and 73.4%, respectively (P < .001). On univariate analysis, poor differentiation (hazard ratio [HR],2.35; 95% confidence interval [CI], 1.04 to 5.31; P = .04), lymphovascular invasion (HR, 3.19; 95% CI, 1.37 to 7.44; P = .007), visceral pleural invasion (HR, 2.33; 95% CI, 1.05 to 5.20; P = .04), and SUVmax 4.93 or greater (HR, 4.51; 95% CI, 1.84 to 11.03; P = .001) predicted FFR. On multivariable analysis, only SUVmax 4.93 or greater remained significant (HR, 5.36; 95% CI, 1.50 to 19.17; P = .01). CONCLUSIONS: SUVmax is independently associated with a risk of recurrence after resection of early-stage lung cancer. SUVmax may be a valuable tool for stratifying patients with early-stage lung cancer for adjuvant therapy and surveillance frequency.

Imaging of the mediastinum: Mimics of malignancy.

In the imaging of the mediastinum, benign lesions mimicking malignancy constitute potential pitfalls in interpretation. Localization and characteristic imaging features are key to narrow the differential diagnosis and avoid potential pitfalls in interpretation. Based on certain anatomic landmarks, the mediastinal compartment model enables accurate localization. Depending on the anatomic origin, mediastinal lesions can have various etiologies. The anatomic location and structures contained within each mediastinal compartment are helpful in generating the differential diagnoses. These structures include thyroid, thymus, parathyroid, lymph nodes, pericardium, embryogenic remnants, and parts of the enteric tracts, vessels, and nerves. Imaging characteristics on computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT), including attenuation (fluid, fat, calcification), contrast enhancement, and metabolic activity, aid in narrowing the differential diagnoses. Understanding the roles and limitations of various imaging modalities is helpful in the evaluation of mediastinal masses. In this review, we present potential pitfalls in the imaging of mediastinal lesions with emphasis on the mimics of malignancy.

Pearls and Pitfalls in the Imaging of Targeted Therapy and Immunotherapy in Lung Cancer.

Most lung cancers are diagnosed at advanced stage when the cancer has metastasized outside the lung. These patients are not eligible for curative surgery or radiation therapy and treated with systemic therapy. Advances in the understanding of the biology of lung cancer has resulted in the development of targeted therapy aimed at specific genetic mutations identified with non-small cell lung cancer and immunotherapy that helps the immune system recognize tumors as foreign, stimulates the immune system, and removes the inhibition that allows growth and spread of cancer cells. Tumors treated with targeted or immunotherapies respond differently when compared with traditional chemotherapy and not captured by conventional response criteria such as the World Health Organization criteria and Response Evaluation Criteria in Solid Tumors. Therefore, several modified criteria have been developed to appropriately address the treatment response when using these novel agents. Numerous treatment-related side effects have been described that are important to recognize to avoid misinterpretation as worsening tumor and to ensure appropriate management.

Imaging of Malignant Pleural Mesothelioma: Pearls and Pitfalls.

Malignant pleural mesothelioma is a rare tumor arising from the pleural mesothelial cells. Imaging plays a crucial role in the diagnosis, staging, and management of patients with mesothelioma. Accurate staging to stratify patients into homogeneous groups is required to evaluate the effectiveness of multimodality therapeutic regimens. CT and PET/CT are recommended for the initial staging of MPM. MRI adds value to further assess invasion of the tumor into the diaphragm, chest wall, and mediastinum. This review will discuss pearls and pitfalls in the imaging of mesothelioma with emphasis on the roles of CT, MRI, and PET/CT.

Pearls and Pitfalls in Postsurgical Imaging of the Chest.

A variety of surgical procedures are utilized to treat a spectrum of cardiopulmonary diseases. In the imaging of patients in the post-operative period, it is important to have an understanding of surgical techniques including invasive and minimally invasive procedures and the expected postsurgical findings. Knowledge of certain patient risk factors, various complications associated with specific surgical procedures, and a keen attention to detail are essential to avoid misinterpretation and delay diagnosis. Prompt detection of potential complications allows timely intervention, thereby, optimizing patient outcomes in the post-operative period.