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.

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.

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.

Imaging Evaluation of Malignant Chest Wall Neoplasms.

Neoplasms of the chest wall are uncommon lesions that represent approximately 5% of all thoracic malignancies. These tumors comprise a heterogeneous group of neoplasms that may arise from osseous structures or soft tissues, and they may be malignant or benign. More than 50% of chest wall neoplasms are malignancies and include tumors that may arise as primary malignancies or secondarily involve the chest wall by way of direct invasion or metastasis from intrathoracic or extrathoracic neoplasms. Although 20% of chest wall tumors may be detected at chest radiography, chest wall malignancies are best evaluated with cross-sectional imaging, principally multidetector computed tomography (CT) and magnetic resonance (MR) imaging, each of which has distinct strengths and limitations. Multidetector CT is optimal for depicting bone, muscle, and vascular structures, whereas MR imaging renders superior soft-tissue contrast and spatial resolution and is better for delineating the full extent of disease. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is not routinely performed to evaluate chest wall malignancies. The primary functions of PET/CT in this setting include staging of disease, evaluation of treatment response, and detection of recurrent disease. Ultrasonography has a limited role in the evaluation and characterization of superficial chest wall lesions; however, it can be used to guide biopsy and has been shown to depict chest wall invasion by lung cancer more accurately than CT. It is important that radiologists be able to identify the key multidetector CT and MR imaging features that can be used to differentiate malignant from benign chest lesions, suggest specific histologic tumor types, and ultimately guide patient treatment. (©)RSNA, 2016.

Total artificial heart implantation: clinical indications, expected postoperative imaging findings, and recognition of complications.

OBJECTIVE: The purposes of this article are to review the treatment options for late-stage biventricular heart failure, discuss the clinical indications for total artificial heart (TAH) implantation, illustrate the expected imaging findings after uncomplicated TAH implantation, and highlight the radiologic findings of common and uncommon complications associated with TAH implantation through case examples. CONCLUSION: TAH implantation is an effective therapeutic option for the treatment of patients with end-stage biventricular heart failure. The duration of implantation varies depending on a particular patient's medical condition and the eventual availability of a human heart for orthotopic transplantation. TAH recipients often undergo imaging with conventional radiography, CT, or both for the assessment of device-related issues, many of which are life-threatening and require emergency management. As the clinical use of the TAH increases and becomes more commonplace, it is imperative that radiologists interpreting imaging studies recognize both the expected and the unexpected imaging findings that affect patient care.

Radiation dose reduction for CT lung cancer screening using ASIR and MBIR: a phantom study.

The purpose of this study was to reduce the radiation dosage associated with computed tomography (CT) lung cancer screening while maintaining overall diagnostic image quality and definition of ground-glass opacities (GGOs). A lung screening phantom and a multipurpose chest phantom were used to quantitatively assess the performance of two iterative image reconstruction algorithms (adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR)) used in conjunction with reduced tube currents relative to a standard clinical lung cancer screening protocol (51 effective mAs (3.9 mGy) and filtered back-projection (FBP) reconstruction). To further assess the algorithms' performances, qualitative image analysis was conducted (in the form of a reader study) using the multipurpose chest phantom, which was implanted with GGOs of two densities. Our quantitative image analysis indicated that tube current, and thus radiation dose, could be reduced by 40% or 80% from ASIR or MBIR, respectively, compared with conventional FBP, while maintaining similar image noise magnitude and contrast-to-noise ratio. The qualitative portion of our study, which assessed reader preference, yielded similar results, indicating that dose could be reduced by 60% (to 20 effective mAs (1.6 mGy)) with either ASIR or MBIR, while maintaining GGO definition. Additionally, the readers' preferences (as indicated by their ratings) regarding overall image quality were equal or better (for a given dose) when using ASIR or MBIR, compared with FBP. In conclusion, combining ASIR or MBIR with reduced tube current may allow for lower doses while maintaining overall diagnostic image quality, as well as GGO definition, during CT lung cancer screening.

Chest radiography in the ICU: Part 1, Evaluation of airway, enteric, and pleural tubes.

OBJECTIVE: In this pictorial essay, we discuss and illustrate normal and aberrant positioning of nonvascular support and monitoring devices frequently used in critically ill patients, including endotracheal and tracheostomy tubes, chest tubes, and nasogastric and nasoenteric tubes, as well as their inherent complications. CONCLUSION: The radiographic evaluation of the support and monitoring devices used in patients in the ICU is important because the potentially serious complications arising from their introduction and use are often not clinically apparent. Familiarity with normal and abnormal radiographic findings is critical for the detection of these complications.

Chest radiography in the ICU: Part 2, Evaluation of cardiovascular lines and other devices.

OBJECTIVE: In this pictorial essay, we discuss and illustrate normal and aberrant positioning of the cardiovascular support and monitoring devices frequently used in critically ill patients, including central venous catheters, pulmonary artery catheters, left atrial catheters, transvenous pacemakers, automatic implantable cardioverter defibrillators, intraaortic counterpulsation balloon pump, and ventricular assist devices, as well as their inherent complications. CONCLUSION: The radiographic evaluation of the support and monitoring devices used in patients in the ICU is important, because the potentially serious complications arising from their introduction and use are often not clinically apparent. Familiarity with normal and abnormal radiographic findings is critical for the detection of these complications.

Habitat Imaging Biomarkers for Diagnosis and Prognosis in Cancer Patients Infected with COVID-19.

OBJECTIVES: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population. METHODS: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and 420 CT scans from 414 cancer patients. In particular, the habitat imaging pipeline was developed to quantify the complex infection patterns by partitioning the whole lung regions into phenotypically different subregions. Subsequently, various machine learning models nested with feature selection were built for COVID-19 detection and severity prediction. RESULTS: These models showed almost perfect performance in COVID-19 infection diagnosis and predicting its severity during cross validation. Our analysis revealed that models built separately on the cancer population performed significantly better than those built on the general population and locked to test on the cancer population. This may be because of the significant difference among the habitat features across the two different cohorts. CONCLUSIONS: Taken together, our habitat imaging analysis as a proof-of-concept study has highlighted the unique radiologic features of cancer patients and demonstrated effectiveness of CT-based machine learning model in informing COVID-19 management in the cancer population.

Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: Radiotherapy might augment systemic antitumoral responses to immunotherapy. In the PEMBRO-RT (phase 2) and MDACC (phase 1/2) trials, patients with metastatic non-small-cell lung cancer were randomly allocated immunotherapy (pembrolizumab) with or without radiotherapy. When the trials were analysed individually, a potential benefit was noted in the combination treatment arm. However, owing to the small sample size of each trial, differences in response rates and outcomes were not statistically significant but remained clinically notable. We therefore did a pooled analysis to infer whether radiotherapy improves responses to immunotherapy in patients with metastatic non-small-cell lung cancer. METHODS: Inclusion criteria for the PEMBRO-RT and MDACC trials were patients (aged ≥18 years) with metastatic non-small-cell lung cancer and at least one unirradiated lesion to monitor for out-of-field response. In the PEMBRO-RT trial, patients had previously received chemotherapy, whereas in the MDACC trial, patients could be either previously treated or newly diagnosed. Patients in both trials were immunotherapy-naive. In the PEMBRO-RT trial, patients were randomly assigned (1:1) and stratified by smoking status (<10 vs ≥10 pack-years). In the MDACC trial, patients were entered into one of two cohorts based on radiotherapy schedule feasibility and randomly assigned (1:1). Because of the nature of the intervention in the combination treatment arm, blinding to radiotherapy was not feasible in either trial. Pembrolizumab was administered intravenously (200 mg every 3 weeks) with or without radiotherapy in both trials. In the PEMBRO-RT trial, the first dose of pembrolizumab was given sequentially less than 1 week after the last dose of radiotherapy (24 Gy in three fractions), whereas in the MDACC trial, pembrolizumab was given concurrently with the first dose of radiotherapy (50 Gy in four fractions or 45 Gy in 15 fractions). Only unirradiated lesions were measured for response. The endpoints for this pooled analysis were best out-of-field (abscopal) response rate (ARR), best abscopal disease control rate (ACR), ARR at 12 weeks, ACR at 12 weeks, progression-free survival, and overall survival. The intention-to-treat populations from both trials were included in analyses. The PEMBRO-RT trial (NCT02492568) and the MDACC trial (NCT02444741) are registered with ClinicalTrials.gov. FINDINGS: Overall, 148 patients were included in the pooled analysis, 76 of whom had been assigned pembrolizumab and 72 who had been assigned pembrolizumab plus radiotherapy. Median follow-up for all patients was 33 months (IQR 32·4-33·6). 124 (84%) of 148 patients had non-squamous histological features and 111 (75%) had previously received chemotherapy. Baseline variables did not differ between treatment groups, including PD-L1 status and metastatic disease volume. The most frequently irradiated sites were lung metastases (28 of 72 [39%]), intrathoracic lymph nodes (15 of 72 [21%]), and lung primary disease (12 of 72 [17%]). Best ARR was 19·7% (15 of 76) with pembrolizumab versus 41·7% (30 of 72) with pembrolizumab plus radiotherapy (odds ratio [OR] 2·96, 95% CI 1·42-6·20; p=0·0039), and best ACR was 43·4% (33 of 76) with pembrolizumab versus 65·3% (47 of 72) with pembrolizumab plus radiotherapy (2·51, 1·28-4·91; p=0·0071). Median progression-free survival was 4·4 months (IQR 2·9-5·9) with pembrolizumab alone versus 9·0 months (6·8-11·2) with pembrolizumab plus radiotherapy (hazard ratio [HR] 0·67, 95% CI 0·45-0·99; p=0·045), and median overall survival was 8·7 months (6·4-11·0) with pembrolizumab versus 19·2 months (14·6-23·8) with pembrolizumab plus radiotherapy (0·67, 0·54-0·84; p=0·0004). No new safety concerns were noted in the pooled analysis. INTERPRETATION: Adding radiotherapy to pembrolizumab immunotherapy significantly increased responses and outcomes in patients with metastatic non-small-cell lung cancer. These results warrant validation in a randomised phase 3 trial. FUNDING: Merck Sharp & Dohme.

ACR Appropriateness Criteria® Occupational Lung Diseases.

Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients.

The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Noninvasive Clinical Staging of Primary Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths in both men and women. The major risk factor for lung cancer is personal tobacco smoking, particularly for small-cell lung cancer (SCLC) and squamous cell lung cancers, but other significant risk factors include exposure to secondhand smoke, environmental radon, occupational exposures, and air pollution. Education and socioeconomic status affect both incidence and outcomes. Non-small-cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, comprises about 85% of lung cancers. SCLC accounts for approximately 13% to 15% of cases. Prognosis is directly related to stage at presentation. NSCLC is staged using the eighth edition of the tumor-node-metastasis (TNM) criteria of the American Joint Committee on Cancer. For SCLC the eighth edition of TNM staging is recommended to be used in conjunction with the modified Veterans Administration Lung Study Group classification system distinguishing limited stage from extensive stage SCLC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Postoperative Imaging and Complications in Resection of Lung Cancer.

Surgical resection offers the best hope of cure for patients with operable early-stage lung cancer. Wedge resection, segmentectomy, lobectomy, or pneumonectomy may be performed depending on the size and location of the tumor. Radiologists must be familiar with the types of surgical resection utilized in the treatment of lung carcinoma and with their normal and abnormal postsurgical appearance on imaging studies. Prompt identification of postoperative complications on imaging is essential to appropriate patient management and helps to determine when additional intervention is warranted.

The epidemiology of lung cancer.

The incidence and mortality from lung cancer is decreasing in the US due to decades of public education and tobacco control policies, but are increasing elsewhere in the world related to the commencement of the tobacco epidemic in various countries and populations in the developing world. Individual cigarette smoking is by far the most common risk factor for lung carcinoma; other risks include passive smoke inhalation, residential radon, occupational exposures, infection and genetic susceptibility. The predominant disease burden currently falls on minority populations and socioeconomically disadvantaged people. In the US, the recent legalization of marijuana for recreational use in many states and the rapid growth of commercially available electronic nicotine delivery systems (ENDS) present challenges to public health for which little short term and no long term safety data is available.

Missed Lung Cancer.

The chest radiograph is one of the most commonly used imaging studies and is the modality of choice for initial evaluation of many common clinical scenarios. Over the last two decades, chest computed tomography has been increasingly used for a wide variety of indications, including respiratory illnesses, trauma, oncologic staging, and more recently lung cancer screening. Diagnostic radiologists should be familiar with the common causes of missed lung cancers on imaging studies in order to avoid detection and interpretation errors. Failure to detect these lesions can potentially have serious implications for both patients as well as the interpreting radiologist.

Targeted Therapy and Immunotherapy in the Treatment of Non-Small Cell Lung Cancer.

The treatment strategy in advanced non-small cell lung cancer (NSCLC) has evolved from empirical chemotherapy to a personalized approach based on histology and molecular markers of primary tumors. Targeted therapies are directed at the products of oncogenic driver mutations. Immunotherapy facilitates the recognition of cancer as foreign by the host immune system, stimulates the immune system, and alleviates the inhibition that allows the growth and spread of cancer cells. The authors describes the role of targeted therapy and immunotherapy in the treatment of NSCLC, patterns of disease present on imaging studies, and immune-related adverse events encountered with immunotherapy.

Role of Dual-Energy Computed Tomography in Thoracic Oncology.

Dual-energy CT (DECT) is an emerging technology that has potential to enhance diagnostic performance and radiologists' confidence in the evaluation of thoracic malignancies. DECT clinical applications include characterization of solitary pulmonary nodule, lung masses and mediastinal tumors. DECT-derived iodine uptake quantification may assist in characterization of tumor differentiation and gene expression. The use DECT in oncology has potential to improve lung cancer staging, therapy planning, and assessment of response to therapy as well as detection of incidental pulmonary embolism.

Pulmonary Nodule Management in Lung Cancer Screening: A Pictorial Review of Lung-RADS Version 1.0.

The number of screening-detected lung nodules is expected to increase as low-dose computed tomography screening is implemented nationally. Standardized guidelines for image acquisition, interpretation, and screen-detected nodule workup are essential to ensure a high standard of medical care and that lung cancer screening is implemented safely and cost effectively. In this article, we review the current guidelines for pulmonary nodule management in the lung cancer screening setting.