Patricia M. de Groot

Lung Cancer Epidemiology, Risk Factors, and Prevention

The greatest risk by far for developing lung cancer is cigarette smoking, but age, radon exposure, environmental pollution, occupational exposures, gender, race, and pre-existing lung disease also are important contributors. However, not all people with these risk factors develop lung cancer, and some without any known risk factor do, indicating the importance of genetic influences. Future advances in understanding and treating lung cancer will be based on genetic analysis. The most effective preventive measure is to never start or to stop cigarette smoking.

Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells

Purpose: Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab. Experimental Design: SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver. MTD was determined with a 3 + 3 dose de-escalation design. Immune marker expression was assessed by flow cytometry. Results: Among 35 patients who initiated ipilimumab, 2 experienced dose-limiting toxicity and 12 (34%) grade 3 toxicity. Response outside the radiation field was assessable in 31 patients. Three patients (10%) exhibited partial response and 7 (23%) experienced clinical benefit (defined as partial response or stable disease lasting ≥6 months). Clinical benefit was associated with increases in peripheral CD8+ T cells, CD8+/CD4+ T-cell ratio, and proportion of CD8+ T cells expressing 4-1BB and PD1. Liver (vs. lung) irradiation produced greater T-cell activation, reflected as increases in the proportions of peripheral T cells expressing ICOS, GITR, and 4-1BB. Conclusions: Combining SABR and ipilimumab was safe with signs of efficacy, peripheral T-cell markers may predict clinical benefit, and systemic immune activation was greater after liver irradiation. Clin Cancer Res; 23(6); 1388–96. ©2016 AACR.

Benefit of computer-aided detection analysis for the detection of subsolid and solid lung nodules on thin- and thick-section CT

OBJECTIVE The objective of our study was to evaluate the impact of computer-aided detection (CAD) on the identification of subsolid and solid lung nodules on thin- and thick-section CT. MATERIALS AND METHODS For 46 chest CT examinations with ground-glass opacity (GGO) nodules, CAD marks computed using thin data were evaluated in two phases. First, four chest radiologists reviewed thin sections (reader(thin)) for nodules and subsequently CAD marks (reader(thin) + CAD(thin)). After 4 months, the same cases were reviewed on thick sections (reader(thick)) and subsequently with CAD marks (reader(thick) + CAD(thick)). Sensitivities were evaluated. Additionally, reader(thick) sensitivity with assessment of CAD marks on thin sections was estimated (reader(thick) + CAD(thin)). RESULTS For 155 nodules (mean, 5.5 mm; range, 4.0-27.5 mm)-74 solid nodules, 22 part-solid (part-solid nodules), and 59 GGO nodules-CAD stand-alone sensitivity was 80%, 95%, and 71%, respectively, with three false-positives on average (0-12) per CT study. Reader(thin) + CAD(thin) sensitivities were higher than reader(thin) for solid nodules (82% vs 57%, p < 0.001), part-solid nodules (97% vs 81%, p = 0.0027), and GGO nodules (82% vs 69%, p < 0.001) for all readers (p < 0.001). Respective sensitivities for reader(thick), reader(thick) + CAD(thick), reader(thick) + CAD(thin) were 40%, 58% (p < 0.001), and 77% (p < 0.001) for solid nodules; 72%, 73% (p = 0.322), and 94% (p < 0.001) for part-solid nodules; and 53%, 58% (p = 0.008), and 79% (p < 0.001) for GGO nodules. For reader(thin), false-positives increased from 0.64 per case to 0.90 with CAD(thin) (p < 0.001) but not for reader(thick); false-positive rates were 1.17, 1.19, and 1.26 per case for reader(thick), reader(thick) + CAD(thick), and reader(thick) + CAD(thin), respectively. CONCLUSION Detection of GGO nodules and solid nodules is significantly improved with CAD. When interpretation is performed on thick sections, the benefit is greater when CAD marks are reviewed on thin rather than thick sections.

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.

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.

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.

Staging of Lung Cancer

Primary lung cancer is the leading cause of cancer mortality in the world. Thorough clinical staging of patients with lung cancer is important, because therapeutic options and management are to a considerable degree dependent on stage at presentation. Radiologic imaging is an essential component of clinical staging, including chest radiography in some cases, computed tomography, MRI, and PET. Multiplanar imaging modalities allow assessment of features that are important for surgical, oncologic, and radiation therapy planning, including size of the primary tumor, location and relationship to normal anatomic structures in the thorax, and existence of nodal and/or metastatic disease.

Multimodality imaging of cardiothoracic lymphoma

Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and (18)F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

Immunotherapy in Non-Small Cell Lung Cancer Treatment: Current Status and the Role of Imaging

Lung cancer remains the leading cause of cancer-related mortality and is responsible for more deaths than breast, prostate, and colon cancer combined. Most patients are diagnosed with advanced disease at the time of presentation, and treatment options have traditionally included surgery, chemotherapy, and/or radiation. However, significant advances in the molecular characterization of lung cancer have led to the creation of effective immunotherapies that assist in the recognition of cancer as foreign by the host immune system, stimulate the immune system, and relieve the inhibition that allows tumor growth and spread. Extensive experience with the immunomodulatory monoclonal antibody ipilimumab has demonstrated that unique responses may be seen with immunotherapies that are not adequately captured by traditional response criteria such as the World Health Organization criteria and Response Evaluation Criteria in Solid Tumors (RECIST). Consequently, several modified criteria have been developed to evaluate patients treated with immunotherapy, including immune-related response criteria, immune-related RECIST, and immune RECIST. Finally, patients undergoing immunotherapy may develop a wide variety of immune-related adverse events with which the radiologist must be familiar. In this article, we present the fundamental concepts behind immunotherapy, specific agents currently approved for the treatment of lung cancer, and immune-related adverse events. The role of imaging in the evaluation of these patients will also be discussed, including the general principles of treatment response evaluation, specific response criteria adopted with these agents, including immune-related response criteria, immune-related RECIST, and immune RECIST, and the imaging of immune-related adverse events.