martes, 19 de abril de 2016

Imaging for the Pretreatment Staging of Small Cell Lung Cancer - Executive Summary | AHRQ Effective Health Care Program

Imaging for the Pretreatment Staging of Small Cell Lung Cancer - Executive Summary | AHRQ Effective Health Care Program

AHRQ--Agency for Healthcare Research and Quality: Advancing Excellence in Health Care

Executive Summary – Apr. 14, 2016

Imaging for the Pretreatment Staging of Small Cell Lung Cancer


Table of Contents


Lung cancer is the leading cause of cancer-related mortality, estimated to account for about 27 percent of cancer deaths in the United States in 2015.1 Small cell lung cancer (SCLC) is an aggressive subset of lung cancer characterized by rapid doubling time, high growth fraction, and early development of metastatic disease. This histologic subset of lung cancer is primarily seen in smokers2 and comprises approximately 15 percent of all lung cancers.3 Despite advances in diagnosis, treatment, and management of lung cancer, the 5-year survival rate for SCLC remains dismal at about 6 percent.1
Staging involves determining the extent of disease and guides the choice of treatment. SCLC is often staged using the Veterans Administration Lung Study Group (VALSG) system,4 which classifies SCLC as either "limited stage" or "extensive stage" disease with the following definitions:
  • Limited stage disease (LD): Cancer is confined to one hemithorax and may be present in the regional lymph nodes or in ipsilateral supraclavicular nodes, all of which can be encompassed in a safe radiotherapy field.
  • Extensive stage disease (ED): Cancer that cannot be classified as LD, such as when contralateral hilar or supraclavicular nodes, malignant pericardial or pleural effusions, or distant metastatic disease are present.
The revised AJCC TNM system5 can also be used; however, it is used less commonly for SCLC than in non-small cell lung cancer. Lung cancers are classified based on the size of the main tumor, whether it has locally invaded other organs/tissues, spread to lymph nodes, and metastasized to other parts of the body. This information is used to assign a stage between I and IV. A higher stage represents more extensive spread.
The National Cancer Institute reported that from 1975–2008, about 70 percent of SCLC cases presented with extensive stage disease, another 21 percent had regional spread such as mediastinal nodal involvement, and only 5 percent were localized (the other 4 percent were unstaged).6 The most common sites of metastases for SCLC are the liver, adrenal glands, bone, bone marrow, and brain.7
Patients with SCLC who have extensive disease at diagnosis have an estimated 5-year survival of only 1 percent.8 Chemotherapy has been shown to extend overall survival and improve quality of life. Patients with LD are treated more aggressively with concurrent chemotherapy and radiation with curative intent. After completion of first-line therapy, even without evidence of metastases in the brain, prophylactic cranial irradiation has been demonstrated to prolong survival in both LD and ED.
"Standard" staging of SCLC is not a precisely defined term, but may involve numerous investigations including history, physical exam, chest x-ray, chest CT, bone scan, bone marrow aspiration, and/or MRI or CT of the brain. Accurate staging of patients is essential to select the optimal treatment plan that will maximize a patient's chances of survival. On the one hand, overstaging of SCLC risks denies the patient potentially life-saving treatment, while understaging risks subjects the patient to the unnecessary risk of complications from more aggressive treatment. Given the rapid progression of SCLC, timely diagnosis and staging is important; performing potentially unnecessary tests during the diagnostic and staging process could delay treatment initiation, compromising treatment efficacy.
Multidetector computed tomography (MDCT) of the chest is typically the first test performed to diagnose lung cancer. For staging SCLC, additional MDCT images are taken of the abdomen, pelvis, or head to detect distant metastases. MDCT has general strengths of widespread availability, high spatial resolution, and high speed and is particularly useful for evaluating the lungs, airways, bowel, and cortical bone. However, because it is a structural imaging modality, it may not detect early metastatic disease involving sites such as the bone marrow or lymph nodes and is not always able to characterize lesions as benign or malignant based on their morphologic properties. In addition, some patients cannot receive iodinated contrast material due to allergy or renal insufficiency, limiting evaluation for presence of hilar lymphadenopathy, vascular abnormalities, and lesion characterization; for these patients, the sensitivity of CT may be lower.
Positron emission tomography (PET) is an imaging modality that localizes the uptake of a positron-emitting radioisotope in the body. [18F]-fluorodeoxyglucose (FDG) is the most commonly used PET radiotracer. Because FDG-PET identifies anatomic sites that harbor metabolically active malignant areas, FDG-PET helps distinguish malignant tumors from benign nodules or masses. FDG-PET can also uniquely detect metabolically active metastases that have not caused anatomic changes. Because PET images lack anatomic detail, combined PET/CT scanners have been developed so the molecular information from PET can be anatomically localized with CT. As of 2014, PET without a concurrent CT is no longer the state of the art. Even though they are widely used, PET/CT scans are not perfect, and are associated with false negative and false positive results. False negative scans usually result from non-metabolically active sites of tumor or from suboptimal quality studies. False positives scans can occur due to sites of metabolically active infection or inflammation.
Magnetic resonance imaging (MRI) is a structural and functional imaging technique that measures the biophysical properties of tissue. MRI has widespread availability, high spatial resolution, and high soft-tissue contrast resolution; this imaging modality is particularly useful for detection and characterization of lesions within tissues even when subcentimeter in size, as well as for evaluation of the internal architecture of organs/tissues such as the brain, spinal cord, breasts, bone marrow, muscles, tendons, ligaments, cartilage, and other solid organs. Also, functional imaging capabilities such as diffusion-weighted imaging and magnetic resonance spectroscopy may be used to improve diagnostic accuracy. MRI examinations take longer to perform and generally cost more than MDCT, patients with certain types of implanted electronic or metallic devices cannot undergo MRI. Newer devices, including some pacemakers, are increasingly MRI-compatible. Some patients with claustrophobia may have difficulty tolerating an MRI examination. Combined PET and MRI scanners are a recent technical development; they promise the sensitivity of PET combined with the anatomic detail of MRI.
Endobronchial ultrasound (EBUS) is a bronchoscopic technique utilizing ultrasonography to visualize structures within and adjacent to the airway wall, whereas endoscopic ultrasound (EUS) is an endoscopic technique that uses ultrasonography to visualize structures within and adjacent to the esophageal wall. These techniques are minimally invasive and can be performed on an outpatient basis. EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is generally performed if suspected lymph nodes are in the anterior or superior mediastinum and appear to be accessible based on prior cross-sectional imaging, whereas EUS-guided fine needle aspiration (EUS-FNA) may initially be used for nodes that are paraesophageal or subaortic in location or located in the posterior or inferior mediastinum. EBUS-TBNA can also be used to sample hilar lymph nodes. A typical EBUS procedure for lung cancer staging involves standardized sampling of multiple nodal stations that have >5 mm lymph nodes that are detectable and accessible via the EBUS scope.
Bone scintigraphy is a planar molecular imaging technique with widespread availability, high contrast resolution, and relatively low cost compared with FDG-PET/CT. However, false-negative results can occur since bone scintigraphy only indirectly detects the effects of metastatic lesions upon bone turnover. False-positive results can also occur due to visualization of increased bone turnover caused by non-neoplastic etiologies such as fractures and osteomyelitis.
Regarding patient subgroups, performance of various imaging modalities may be affected by comorbidities such renal insufficiency, which potentially limits use of contrast for MDCT or MRI. Generally, body habitus may limit the diagnostic quality and accuracy for any imaging modality. Many scanners are unable to safely accommodate patients above a particular weight or girth. Tumor characteristics may be associated with comparative accuracy and/or effectiveness.
A 2013 guideline from the American College of Chest Physicians recommended that patients with either proven or suspected SCLC undergo CT of the chest and abdomen or CT of the chest extending through the liver and adrenal glands, as well as MRI of the brain and bone scintigraphy.9 In patients with limited stage SCLC, PET was also suggested. In 2014, the American College of Radiology (ACR) appropriateness criteria review gave the highest rating of "usually appropriate" (with regard to staging SCLC) to the following specific modalities: CT of the chest and abdomen with contrast, MRI of the head with and without contrast, and FDG-PET/CT from skull base to mid-thigh.10 Bone scintigraphy was rated as "may be appropriate" and considered unnecessary if PET/CT had been performed.

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