Pet and Lung Cancer

SYMPOSIA
Positron Emission Tomography/Computed Tomography in Lung Cancer Staging, Prognosis, and Assessment of Therapeutic Response
Mylene T. Truong, MD, Chitra Viswanathan, MD, and Jeremy J. Erasmus, MD
Abstract: Positron emission tomography (PET)/computed tomographic scanning, using 18F-2-deoxy-D-glucose, complements conventional imaging evaluation of patients with lung cancer. The strength of PET scanning lies in the detection of nodal and extrathoracic metastases. PET scanning is also currently being studied in the assessment of prognosis and therapeutic response and has the potential to alter management of oncologic patients. This review will discuss the role of PET/computed tomographic scanning in the diagnosis, staging, and evaluation of prognosis and treatment response in patients with lung cancer. Key Words: lung cancer, staging, positron emission tomography/ computed tomography
(J Thorac Imaging 2011;26:132146)
ung cancer is a common malignancy. The American Cancer Society estimated that 219,440 new cases were diagnosed in the United States in 2009 (www.cancer.org) and that lung cancer accounted for 28% of all cancer deaths in 2009. Imaging plays an integral role in the detection, diagnosis, and staging of the disease, as well as in the assessment of treatment response and in the surveillance for tumor recurrence after therapy. Typically, imaging with computed tomographic (CT) scanning is used to assess the anatomic extent of the disease and to determine appropriate treatment. Positron emission tomography (PET) using the radiopharmaceutical 18F-2deoxy-D-glucose (FDG), a D-glucose analog labeled with uorine-18, complements conventional radiologic assessment in the evaluation of patients with lung cancer and improves the detection of nodal and extrathoracic metastatic disease. Metabolism of glucose is typically increased in malignancies due to an overexpression of glucose transporter receptors on the surface of tumor cells and an upregulation of hexokinase (a phosphorylating enzyme). Due to a downregulation of phosphatase, FDG is unable to enter intracellular glycolytic pathways and is sequestered in tumor cells. The most common semiquantitative method of evaluating malignancies using PET is FDG standardized uptake value (SUV) calculated as a ratio of tissue radiotracer concentration (mCi/mL) and injected dose (mCi) at the time of injection divided by body weight (in grams). Most factors that change SUV measurements aect the
From the Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX. Reprints: Mylene T. Truong, MD, M.D. Anderson Cancer Center, Division of Diagnostic Imaging Unit 1478, 1515 Holcombe boulevard, Houston, TX 77030 (e-mail: mtruong@mdanderson.org). Copyright r 2011 by Lippincott Williams & Wilkins
measurement of the radioactivity concentration. Biological factors, such as patient blood glucose level, uptake time of the tracer, and respiratory motion, can impact SUV measurements. Technologic factors, such as variability among dierent scanners, image acquisition and reconstruction parameters, and interobserver variability, can impact SUV measurements as well.1 Thus, it is important to keep as many of these factors as possible the same between baseline and follow-up studies of a patient. An SUV threshold of 2.5 has been used to dierentiate benign from malignant nodules.2 In the staging of lung cancer, imaging has evolved from an anatomic basis with CT scanning alone to a combination of anatomic and functional data with the introduction of PET scanning. Initially, PET scanning was performed separately from CT scanning, and the 2 studies were viewed side by side with visual correlation. This was succeeded by various software-based algorithms to fuse CT and PET scanning data once the studies had been acquired separately.3 Finally, integrated whole-body PET/CT imaging has enabled the acquisition of coregistered, spatially matched functional data of PET scanning and anatomic data of CT scanning in a single examination. This review will discuss the current applications of PET/CT scanning in the diagnosis, staging, and assessment of prognosis, treatment response, and tumor recurrence in patients with lung cancer.
BACKGROUND
A typical whole-body PET scan is performed 60 minutes after the intravenous administration of FDG. With an acquisition time of 4 to 6 minutes per bed position, the total imaging time is 30 to 40 minutes. When quantitative assessment of FDG metabolism is needed, for example, for the evaluation of the therapeutic response, correction for soft tissue attenuation is important. To use CT scanning for attenuation correction, the attenuation values of lowdose CT energies must be scaled to high-dose (511 keV) PET energies using scaling algorithms. CT-based attenuation correction in integrated PET/CT scanning results in a lower noise emission scan and faster acquisition times, and, thus, fewer motion artifacts and a higher throughput. With integrated PET/CT scanners, the use of CT scanning for attenuation correction of the PET images has introduced artifacts and quantitative errors that can aect the emission image and lead to misinterpretation.4 These artifacts relate to patient respiration, the use of intravenous and oral CT contrast media, and the presence of catheters and other metal objects in the patients.5 For example, imaging during dierent stages of the patients respiratory cycle may introduce a mismatch between the CT scan attenuation data obtained during breathhold and the PET emission J Thorac Imaging

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PET/CT in Evaluation of Lung Cancer
data obtained during quiet tidal breathing.6,7 In addition to localization errors, this misregistration may also result in incorrect attenuation coecients applied to the PET data that can aect the SUV, the most widely used parameter to quantify FDG uptake.6,8 Misregistration may lead to SUV being lower than expected and can potentially result in a false-negative study. Strategies to reduce the respiratory mismatch between the CT and PET images include performing the CT scanning at end expiration, which most closely approximates the lung volumes during PET data acquisition at quiet tidal breathing. However, CT scans of the lungs at end expiration compromise anatomic detail and small nodules may be obscured. A more recent approach suggests the use of respiratory-averaged CT scanning (CT cine images obtained over dierent portions of the respiratory cycle using 4-dimensional CT scanning techniques) to improve SUV quantication.9 Respiratory-averaged CT scanning used for attenuation correction of a PET scan has shown SUV dierences of more than 50% in some lesions, compared with the standard method of CT attenuation using data obtained in the mid-expiratory phase.9,10
DIAGNOSIS
As many patients with early-stage lung cancer can present with a solitary pulmonary nodule (SPN), an important imaging goal is to accurately dierentiate malignant from benign lesions. The use of PET/CT scanning is established in the evaluation of SPNs. In a meta-analysis of 40 studies, PET scanning was found to operate at a point on the summary receiver operating characteristic curve corresponding to a sensitivity of 96.8% and a specicity of 78% for the detection of malignancy in nodules of 10 mm or greater in diameter.11 Using a threshold SUV of 2.5 and comparing with background activity in the mediastinum, Rohren and Lowe12 reported a sensitivity of 95% and a specicity of 81% for malignancy by compiling data from 7 studies evaluating PET scans and pulmonary nodules. In a study comparing integrated PET/CT scans and helical dynamic CT scans in the evaluation of SPNs, PET/CT scanning was more sensitive (96% vs. 81%) and accurate (93% vs. 85%) than helical dynamic CT scanning.13 A recent prospective integrated PET/CT scanning study evaluating 585 patients (496 malignant and 89 benign nodules) showed that although a nodule with high SUV (>4.1) was associated with a 96% likelihood of malignancy, a nodule with low SUV (<2.5) was also associated with a 25% likelihood of malignancy.14 This underscores the importance of accurate SUV measurements in PET/CT scan interpretation. It is important to note that the high sensitivity and specicity of PET scanning in the evaluation of SPNs pertain to solid nodules of 10 mm or greater in diameter. In contrast, FDG uptake in malignant ground-glass and partially solid nodules is variable and cannot be used reliably to distinguish benign from malignant lesions (Fig. 1). In a recent study, 9 of 10 well-dierentiated adenocarcinomas presenting as ground-glass nodular opacities were falsely negative on PET scanning, whereas 4 of 5 benign ground-glass nodular opacities were falsely positive.15 The sensitivity (10%) and specicity (20%) for ground-glass opacities in this study were signicantly lower than those for solid nodules (90% and 71%, respectively). Limitations in spatial resolution can also result in false-negative studies when lesions <10 mm in diameter are evaluated.15,16 With
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advances in PET technology, the evaluation of nodules of approximately 7 mm is possible.17 Thus, PET scanning is not recommended in the routine evaluation of small lung nodules. Otherwise, false-negative PET scanning results are uncommon, but may occur with carcinoid tumors, bronchioloalveolar carcinomas, and early-stage disease.1821 The lower positive predictive value (PPV) relates to the falsepositive lesions due to infection and inammation. Falsepositive lesions have been reported to include pulmonary hamartoma, pneumonia, caseating granulomas, sarcoidosis, amyloidosis, talc pleurodesis, rounded atelectasis, pleural brosis, and atherosclerosis.22 The usefulness of PET scanning in the evaluation of SPNs takes into consideration clinical risk factors such as patient age, smoking history and history of malignancy, as well as imaging characteristics, to determine patient management. For instance, in a patient with a low pretest likelihood of malignancy (20%) being considered for serial imaging reassessment, a negative PET scan will reduce the likelihood of malignancy to 1% and would support conservative management.11,23 However, in a patient with a high pretest likelihood of malignancy (80%), a negative PET scan will only reduce the likelihood of malignancy to 14%.23,24 Accordingly, obtaining tissue for diagnosis with biopsy or resection is recommended. Although the additional benet of PET scanning as a function of clinical pretest risk assessment for malignancy has not been clearly established, a recent cost-eectiveness analysis supports this diagnostic strategy.25
STAGING
In patients with non-small cell lung cancer (NSCLC), staging, the assessment of the anatomic extent of disease at presentation determines treatment and prognosis. Patients are typically staged according to the TNM (Tumor, Node, Metastasis) classication system. In 2009, the seventh edition of the TNM staging system for lung cancer was published by the International Union Against Cancer and the American Joint Committee on Cancer, based on proposals from the International Staging Project of the International Association for the Study of Lung Cancer, which will be reviewed in depth in another section in this symposium. In terms of the T, N, and M descriptors, staging evaluation is usually aimed at distinguishing resectable from unresectable disease (T4 or N3 or M1). The dierentiation of T1 to T3 from T4 lung cancer and the detection of contralateral nodal (N3) and/or metastases (M1) are important, as these descriptors typically preclude surgical resection or require additional chemotherapy or radiotherapy. Recently, the American Society of Clinical Oncology (ASCO) published evidence-based guidelines for the diagnostic evaluation of patients with NSCLC.26 As stated in these guidelines, chest radiography and contrastenhanced chest CT scanning, which includes the liver and adrenals, are performed in the initial staging of lung cancer. Whole-body PET scanning is an integral component of NSCLC staging, as it improves the detection of nodal and distant metastases and frequently changes patient management.2732 PET scanning complements radiologic ndings, and the ASCO recommendations are that PET scanning should be performed when there is no evidence of distant metastatic disease on CT scan.26 Integrated PET/ CT scanning, with coregistration of PET and CT images, www.thoracicimaging.com |
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FIGURE 1. A 62-year-old woman with chest and shoulder pain. CT scan (A) shows a 2.5 cm right upper lobe lesion with mixed attenuation associated with an air bronchogram. Note the spiculated solid component (arrow) and the ground-glass component (arrowheads). PET/CT scan (B) and PET scan (C) show low-grade FDG uptake in the lung lesion (SUV, 1.6). Resection revealed adenocarcinoma with bronchioloalveolar features. False-negative PET scan may be due to slow cell proliferation or poor cellularity.
overcomes the limitations inherent in both modalities when used separately. In fact, staging of NSCLC has been reported to be more accurate with integrated PET/CT scanning than when using visual correlation of PET and CT images taken separately.28,33
T Descriptor
In the evaluation of the primary tumor (T descriptor), the anatomic information provided by CT scanning compensates for the relatively poor spatial resolution of the PET scan. The CT scan is used to determine the characteristics of the primary tumor, including size, location, and anatomic relationship to adjacent structures such as the pleura, mediastinum, and bones, as well as for the detection of small nodules in the same lobe (T3), same lung (T4), or contralateral lung (M1a). PET/CT scanning has no real advantage over CT scanning for assessing chest wall or mediastinal invasion. However, for central tumors causing collapse of a lobe or a lung, PET/CT scanning can dierentiate tumor from adjacent lung atelectasis (Fig. 2). This aids in radiation therapy (RT) planning and reduces toxicity to the normal tissues.34 In a recent study, PET/CT scanning was found to be superior to CT scanning alone and PET scanning alone in T staging accuracy (82% vs. 68% vs. 55%).5
N Descriptor
The most important prognostic factor in patients with localized and resectable NSCLC is nodal disease
(N descriptor).35 Accurate lymph node staging is essential, and CT scanning is generally used to evaluate hilar and mediastinal lymph nodes. Size is typically the only criterion used for dierentiating normal from abnormal nodes with a threshold of 1 cm for the short-axis diameter. However, node size has not been shown to be a reliable parameter for the evaluation of nodal metastatic disease in patients with NSCLC.3638 Prenzel et al36 reported that in 2891 resected hilar and mediastinal nodes in 256 patients with NSCLC, 77% of the 139 patients with no nodal metastases had at least 1 node >1 cm in diameter. With regard to the lymph nodes with histologic signs of metastases (405), 44% (180 lymph nodes) were <1 cm.36 Furthermore, 12% of the 127 patients with nodal metastases had no nodes >1 cm. A recent meta-analysis of 20 studies (3438 patients) evaluating CT scanning accuracy for staging the mediastinum yielded a pooled sensitivity of 57% and a specicity of 82%.39 Interestingly, PET/CT scanning enhanced accuracy of nodal staging in patients with NSCLC and underlying pulmonary brosis. Patients with pulmonary brosis have a 5-fold to 14-fold increased risk of developing lung cancer and frequently have reactive mediastinal lymph node enlargement (55% to 93% of cases). PET/CT scanning in patients with pulmonary brosis had similar sensitivity (60% vs. 60%), better specicity (91% vs. 47%) and better accuracy (83% vs. 50%) than CT scanning alone. This was compared with sensitivity (63% vs. 40%), specicity (96% vs. 84%), and accuracy (88% vs. 73%) in patients without pulmonary brosis.40
FIGURE 2. A 48-year-old man with hemoptysis and left upper lobe collapse due to central obstructing tumor. On contrast-enhanced CT scan (A), it is difficult to differentiate the tumor from the adjacent atelectatic lung. PET/CT scan (B) shows the FDG-avid 3 cm central tumor (SUV, 11.8) within the nonhypermetabolic collapsed lung parenchyma. Delineation of the primary tumor is important for radiation treatment planning.
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As the treatment decisions concerning surgery and potential use of adjuvant therapy are dependent on patients N descriptor, improvement in the accuracy of detection of nodal metastases is needed. PET scanning complements CT ndings and provides information on locoregional nodal staging that can impact management.30,41,42 In a recent meta-analysis of 17 studies (833 patients), PET scanning was superior to CT scanning in the detection of nodal metastatic disease, with sensitivities of 83% versus 59% and specicities of 92% versus 78%.41 Recently, signicant improvements in the accuracy of overall staging have been reported when using integrated PET/CT scanning compared with CT and PET scanning when interpreted separately.33 In many institutions, mediastinoscopy and, more recently, endoscopic ultrasound-guided and endobronchial ultrasound-guided biopsy of nodes are performed to accurately determine the presence and location of nodal metastases in patients with NSCLC.30,43 The precise role of PET scanning with regard to invasive nodal staging is unclear, but should be considered an adjunct rather than an alternative.26,30 In an attempt to determine the need for mediastinoscopy after PET and CT imaging, a metaanalysis evaluated the association between the size of mediastinal lymph nodes and the probability of malignancy.44 In patients with a negative PET scan and lymph nodes of 10 to 15 mm in size on CT scanning, the posttest probability for N2 disease was only 5%. Consequently, the researchers suggest that these patients should proceed directly to thoracotomy. In patients with a negative PET scan and lymph nodes of >16 mm on CT scanning, the posttest probability for N2 disease was 21%, and the researchers suggest that these patients should have mediastinoscopy prior to thoracotomy (Fig. 3). In patients with T1 lung cancer and good performance status, the nding of PET-negative nodes of <10 mm in size on CT scanning would favor surgical resection without preoperative invasive nodal sampling due to the high negative predictive value (NPV) of a PET scan. In patients with poor performance status, the treatment is stereotactic or intensity-modulated RT without pretreatment invasive nodal sampling. Although PET scanning for nodal staging is costeective and can reduce the likelihood that a patient with N3 disease would undergo attempted resection, decision analyses show that the number of false-positive results due to infectious or inammatory etiologies is too high to preclude mediastinoscopy.45,46 Consequently, invasive
sampling of FDG-avid nodes is recommended to conrm nodal metastatic disease in patients in whom accurate N staging may impact management. For example, if the ipsilateral mediastinal nodes (N2 disease) are histologically positive for malignancy by invasive sampling, patients are treated with chemotherapy and then possibly surgery. If the contralateral nodes (N3 disease) are positive for malignancy, patients would receive chemotherapy and RT. In the latter scenario, PET/CT scanning aids in the delineation of the radiation treatment planning for the primary tumor and the nodal metastases.
M Descriptor
Distant metastases (M1) occur in 21% of patients with NSCLC.47 Common sites of metastases are the adrenal glands, liver, brain, bones, and abdominal lymph nodes.47 Imaging evaluation for metastatic disease is often determined by clinical history and physical examination. Wholebody PET scanning is increasingly being used to improve the accuracy of staging due to its strength in the detection of metastases, some of which may be clinically occult. PET scanning has a higher sensitivity and specicity than CT scanning in detecting metastases to the adrenals, bones, and extrathoracic lymph nodes. The American College of Surgeons Oncology Trial reports a sensitivity, specicity, PPV, and NPV of 83%, 90%, 36%, and 99%, respectively, for M1 disease.30 Whole-body PET imaging stages intrathoracic and extrathoracic disease in a single examination, detects occult extrathoracic metastases in up to 24% of patients selected for curative resection, and has been shown to be costeective.27,30,32,48,49 Schrevens et al50 reported that after a negative conventional staging, occult metastases were found on PET scans in 5% to 29% of the patients. MacManus et al49 reported that the incidence of occult metastases increases with the increase in T and N staging, that is, 7.5% in early-stage disease compared with 24% in advanced disease. A recent randomized controlled trial evaluating the role of PET scanning in early-stage lung cancer (>90% T1-2N0) showed that distant metastases were rarely detected (<5%), and the researchers concluded that PET scanning improves the accuracy of staging and leads to more stage-specic therapy.51 In addition, 2 studies with a higher proportion of more advanced lung cancers, considered resectable by conventional staging, showed that the addition of PET scanning prevented futile surgery in 1 in 5 patients.30,48
FIGURE 3. A 61-year-old man with a 4-month history of cough. CT scan (A) shows a left upper lobe mass and right paratracheal adenopathy (asterisk) measuring 2 cm in short-axis diameter. PET/CT scan (B) shows FDG-avidity in the primary tumor (SUV, 15) and left hilar adenopathy. However, the right paratracheal adenopathy (asterisk) has FDG uptake similar to that of the mediastinal blood pool. Mediastinoscopy confirmed N3 (contralateral nodal) disease from the primary lung cancer and the patient was treated palliatively. A negative PET scan does not preclude biopsy of enlarged mediastinal lymph nodes.
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FIGURE 4. A 62-year-old man with malaise and weight loss. Chest radiograph (A) shows left upper lobe cancer (arrow) and mediastinal and bilateral hilar adenopathy. PET/CT scan (B) shows FDG-avid nasopharyngeal mass (SUV, 35.2) and left retropharyngeal lymph node (SUV, 15.4). Biopsy of the nasopharyngeal mass revealed poorly differentiated invasive squamous cell carcinoma. Note whole-body PET/CT scanning is useful in detecting disease unrelated to the primary NSCLC.
Although whole-body PET imaging improves the accuracy of staging and, consequently, impacts treatment strategy, incidental ndings of FDG-avid lesions unrelated to the NSCLC can mimic distant metastases and lead to misinterpretation. Accordingly, tissue histopathologic diagnosis should be obtained in any FDG-avid lesions that may alter patient management. The rationale for this management strategy is supported by the results of a recent prospective study performed to assess the incidence and diagnosis of a single site of extrapulmonary accumulation of FDG in patients with newly diagnosed NSCLC.52 Of the 72 patients (21% of the study population) who had solitary FDG-avid lesions, 69 patients were biopsied. Thirty-seven (54%) of these patients had a solitary metastasis, whereas 32 (46%) had lesions unrelated to the NSCLC [benign tumor or inammatory lesion (n=26), clinically unsuspected second malignancy or recurrence of a previously diagnosed carcinoma (n=6)] (Fig. 4).52 Metastases to the adrenal glands are common and are detected in up to 20% of patients with NSCLC at presentation.53 A decision analysis model to determine the most cost-eective way to evaluate an adrenal mass in patients with newly diagnosed NSCLC showed that unenhanced CT scanning using a threshold of 10 Hounseld units, followed by magnetic resonance (MR) imaging,
if needed, was the most cost-eective strategy.54 However, PET scanning was not included in this analysis. In fact, PET scanning is useful in distinguishing benign from malignant adrenal masses detected on CT scanning (Fig. 5), particularly when the adrenal lesion is small. Two series have shown a sensitivity of 100% and specicities of 80% to 90% of PET scanning in identifying adrenal metastases.55,56 PET/CT scanning demonstrated sensitivity, specicity, PPV, NPV, and accuracy of 100%, 93.8%, 81.8%, 100%, and 95.1%, respectively, in the detection of malignant adrenal lesions.57 The malignant adrenal lesions demonstrated increased FDG activity relative to that of the liver. Blake et al57 reported that 67% of adrenal metastases had an adrenal/liver activity ratio of >2.0 and that 33% had a ratio of 1.5 to 2.0. No benign lesions had an adrenalto-liver activity ratio of >1.47. Metser et al58 found that when malignant lesions were compared with adenomas, PET data alone using an SUV cuto of 3.1 yielded a sensitivity, specicity, PPV, and NPV of 98.5%, 92%, 89.3%, 98.9%, respectively. Consequently, if FDG uptake by an adrenal mass is normal in a patient with potentially resectable NSCLC, curative resection should be considered without further evaluation. Patients with NSCLC and an isolated adrenal mass with increased FDG uptake should have the adrenal lesion biopsied before surgery is precluded.
FIGURE 5. A 58-year-old man with NSCLC. Staging revealed a 2.5-cm right adrenal (arrow) low-attenuation lesion with -19 Hounsfield units on noncontrast enhanced CT scanning (A) and was negative on PET/CT scanning (B) consistent with an adenoma. However, follow-up PET/CT scanning (C) 8 months later shows new focal FDG uptake in the right adrenal (SUV, 7.3) consistent with interval development of metastatic disease (arrow). PET scanning is useful in differentiating benign from malignant adrenal lesions and in detecting metastatic disease.
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FIGURE 6. A 52-year-old man with dizziness and confusion. Chest radiograph (A) shows a right upper lobe mass and biopsy revealed squamous cell carcinoma. PET/CT scanning (B) shows a focus of FDG uptake in the right iliac bone with SUV of 9.3. Contrast-enhanced T1-weighted MR imaging (C) shows an enhancing lesion in the right iliac bone consistent with metastatic disease (arrow). Note detection of clinically occult bone metastasis precluded the patient from curative resection.
Metastases to the brain are present in up to 18% of patients with NSCLC at presentation. As approximately one third of patients with oligometastatic disease to the brain will have potentially resectable disease, it has been suggested that routine CT scanning of the brain should be performed in the initial staging evaluation of patients with NSCLC.59 However, a recent meta-analysis in patients with no neurologic abnormality on clinical examination calculated the NPV in this setting as 95%.60,61 According to the 2003 ASCO recommendations, asymptomatic patients with stage III disease being considered for aggressive local therapy should have CT or MR imaging performed.26 As the brain routinely shows increased metabolic activity on FDG-PET imaging, there is no support for the routine use of PET to detect brain metastases. Metastases to the bones are detected in >10% of patients with NSCLC at initial presentation.47 Patients with skeletal metastases are usually symptomatic or have laboratory abnormalities suggestive of bone metastases.62 Due to the high false-positive rate of radionuclide Technetium-99 methylene diphosphonate (99Tc-MDP) bone scanning in the detection of occult skeletal metastases, it is recommended that bone scintigraphy should not be routinely performed in asymptomatic patients.6264 PET scanning is a potential alternative to 99Tc-MDP bone scanning in the detection of skeletal metastases (Fig. 6). PET scanning is more sensitive and accurate than bone scanning for the detection of skeletal metastases (91% and 94% vs. 75% and 85%, respectively), with a high PPV of 98% if the ndings on PET/CT scanning are concordant, but decreases to 61% if the CT scan is negative.65 Metastases to the pleura resulting in a malignant eusion are detected in up to 15% of patients with NSCLC at presentation.66 PET scanning has been shown to have sensitivities of 92% to 100% and specicities of 67% to 71%, NPV of 100%, and PPV of 63% to 79%.67,68 Falsepositive pleural FDG uptake can be seen in infectious and inammatory conditions, including after talc pleurodesis. However, a negative PET scan, together with thoracentesis results showing no malignant cells, is useful to conrm the absence of pleural metastasis. Finally, PET/CT scanning also plays a role in the detection of lymphangitic carcinomatosis, with a sensitivity and specicity of 100% and 86%, respectively.69 The mean SUV was 1.37 in the region of lymphangitic spread of tumor, signicantly greater than in the normal lung.69
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SUMMARY OF EVALUATION OF PATIENTS WITH NSCLC

1. A chest x-ray and contrast-enhanced CT scanning including the adrenals are performed to stage locoregional disease. In the absence of distant metastases on CT scan, PET/CT scanning is performed. 2. PET/CT scanning is performed in all patients with clinically resectable disease to direct nodal sampling, as well as to detect distant occult metastasis. In the absence of distant metastasis, FDG-avid mediastinal nodes are biopsied to conrm nodal mediastinal disease. According to the American College of Chest Physicians Guidelines for invasive mediastinal staging of lung cancer, patients with central tumors require invasive sampling of mediastinal nodes, whereas patients with small peripheral tumors with PET-negative nodes do not.70 Patients undergoing a localized surgical procedure (lobectomy or segmentectomy) with normal PET scanning of the mediastinum and normal-sized nodes on CT scanning may proceed to surgical resection without preoperative mediastinoscopy. However, if the surgical procedure is extensive (pneumonectomy) and carries higher risk of complications, invasive staging
FIGURE 7. A 53-year-old man with a 3-month history of cough and shortness of breath. PET/CT scan shows markedly FDG-avid right upper lobe mass (SUV, 29.8) and right paratracheal adenopathy (SUV, 20.7). Lung biopsy revealed adenocarcinoma. While on chemotherapy, patient developed hepatic metastases and died 6 months later. Note high SUV of the primary tumor may be an indicator of poor prognosis.
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with endobronchial ultrasound, endoscopic ultrasound, or mediastinoscopy is performed regardless of the size of mediastinal nodes or the degree of nodal FDG uptake. 3. All extrathoracic FDG-avid lesions suspicious for metastases in patients being considered for surgical resection should be biopsied to obtain a histopathologic diagnosis if conrmation of metastatic disease alters patient management. If biopsy is not feasible, the lesion should be further evaluated with additional imaging studies (CT and/or MR imaging). 4. Brain CT or MR imaging is performed in patients with signs or symptoms of central nervous system disease, as well as in asymptomatic patients with stage III disease being considered for aggressive local therapy (surgery or chemoradiation therapy).
PROGNOSIS
Multiple studies have observed that patients with lung cancers that are highly metabolic as measured by the degree of FDG uptake tend to have a more aggressive clinical course than those with a low metabolic rate.7178 This nding has been reported across the various stages of lung cancer, from early-stage disease amenable to curative resection to advanced inoperable disease. A recent metaanalysis performed by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project concluded that metabolic activity of the primary tumor as determined by the SUV on PET imaging is a prognostic indicator in patients with NSCLC.79 Berghmans et al79 identied a high SUV as a poor prognostic factor for survival (Fig. 7) and recommended a formal analysis of SUV with respect to stage and performance status to determine the prognostic value of PET imaging. Several studies have evaluated the potential role of PET scanning as a prognostic indicator using the degree of increased FDG uptake in the primary tumor at diagnosis to predict survival.71,72,7678,8083 The threshold SUV used for univariate analysis in these studies ranged from 3.3 to 20. A review of the results of these studies will be presented organized according to disease stage. For stage I disease, FDG uptake of the primary tumor at diagnosis was found to be predictive of disease-free survival.71,72 In a retrospective study of 136 patients with stage I NSCLC treated with curative surgical resection by Goodgame et al,72 an SUV threshold of 5.5 was used to assess prognostic signicance. Thirty-two of 136 patients developed recurrence of malignancy after a mean postresection interval of 46 months. Patients with a primary tumor with high SUV (>5.5) were approximately 3 times more likely to have relapse.72 The 5-year estimates of recurrence rates for patients with high and low SUV were 37% and 14%, respectively (P=0.002), with 5-year overall survivals of 53% and 74%, respectively (P=0.006). In multivariate analyses based on SUV, T descriptor, age, and histology, there were signicant correlations between high SUV and recurrence (P=0.002) and high SUV and mortality (P=0.041).72 Similar results were reported by Hanin et al71 in a retrospective study evaluating the prognostic value of FDG uptake (using an SUV threshold of 7.8) in 96 patients with stage I and II tumors that were completely resected. The median survival of stage I patients with low-SUV tumors was signicantly longer than those with high-SUV tumors
(127 mo vs. 69 mo, P=0.001). Although there was no statistical dierence seen in patients with stage II tumors (72 mo vs. 40 mo), there was a trend toward reduced survival for high-SUV (>7.8) tumors. Disease-free survival for all patients with low-SUV tumors was longer than those with high-SUV tumors (96.1 mo vs. 87.7 mo, P=0.01). The researchers of these 2 studies hypothesized that PET imaging may be of potential use in selecting patients for postoperative adjuvant chemotherapy.71,72 The use of adjuvant chemotherapy in patients with stage I NSCLC is not currently supported by evidence from clinical trials. However, there may be a subset of patients with highly metabolic tumors with high risk for relapse who may have a survival benet from postoperative adjuvant chemotherapy. In the study by Ohtsuka et al77 using an SUV threshold of 3.3 to evaluate the prognostic value of FDG uptake in patients with pathologic stage I adenocarcinomas who underwent curative resection, patients with high-SUV stage IA and IB disease had shorter disease-free intervals, suggesting that these patients could be candidates for adjuvant chemotherapy. Furthermore, none of the patients with low-SUV stage IB disease developed recurrence of malignancy, suggesting that these patients may not benet from adjuvant therapy. In contrast, in a retrospective study by Cerfolio et al84 of 315 patients with complete resection for NSCLC, patients in the same stage with high-SUV tumors were more likely to have tumor recurrence (signicant for stages IB and II) and shorter survival (signicant for stage IB, II, and IIIA disease), compared with those with low-SUV tumors. Patients with stage IB and stage II disease with an SUV of greater than the median for their respective stages had a lower disease-free survival at 4 years. The dierences in disease-free survival between groups with low-SUV tumors versus high-SUV tumors were signicant in patients with stage IB (92% vs. 51%) and stage II (64% vs. 47%) disease. Stratied by stage, the 4-year survival for patients with low-SUV tumors versus high-SUV tumors was 80% versus 66% for stage IB, 64% versus 32% for stage II, and 64% versus 16% for stage IIIA. Results show that SUV was an independent predictor of the likelihood of nodal involvement and distant metastases, that is, patients with a high SUV (>10) were more likely to have advanced stage. In fact, SUV was found to be the best predictor of diseasefree survival and overall survival. In inoperable stage III patients, a phase II study was performed in 31 patients using PET before and after 3 cycles of neoadjuvant chemotherapy followed by consolidation RT.85 All the tumors had a marked increase in FDG uptake (median SUV, 11.3) at baseline. After 3 cycles of neoadjuvant chemotherapy, 10 patients with complete metabolic response dened as an SUV of <2.5 showed benet compared with the patients with a posttherapy SUV of >2.5 (19.9 mo vs. 9.8 mo for time to progression and 49 mo vs. 14.4 mo for overall survival).85 In addition, in a prospective study of the prognostic value of PET scanning after the completion of denitive radiotherapy (n=10) or chemoradiotherapy (n=63) in patients of various stages (13 patients with stage I, 14 patients with stage II, and 46 patients with stage III), MacManus et al86 reported a signicant correlation between the decrease in FDG uptake within the primary tumor and mediastinal lymph nodes, and patient outcome. Furthermore, the study is also in agreement with previous reports of the superior prognostic value of PET scanning
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compared with CT scanning after therapy.86 In fact, a single early posttreatment PET scan was found to be a better predictor of survival than CT scanning response, stage, or pretreatment performance status. In contrast, data from a retrospective study of 214 patients with advanced-stage NSCLC (stages IIIA, IIIB, and IV) using a median SUV threshold of 11.1 at the time of diagnosis did not show a survival benet for patients with low-SUV tumors (median survival of 16 mo vs. 12 mo).87 Seventy-four percent of the 214 patients died, and 56 patients were alive at 27 months (range, 3 to 140 mo) after the diagnosis of NSCLC. A possible explanation is that the short survival time and high mortality rate in patients with advanced-stage NSCLC may account for the lack of correlation between survival and FDG uptake in the primary tumor. In summary, although PET imaging shows promise as a prognostic indicator in patients with lung cancer, particularly in early-stage disease, multiinstitutional prospective randomized trials are necessary to fully elucidate the role of PET scanning in patient treatment algorithms.
RADIATION THERAPY PLANNING

Radiation therapy plays a central role in the management of NSCLC, either alone or in combination with surgery and/or chemotherapy. In curative RT, the target volume of tissue irradiated with a high dose must encompass the entire tumor and any microscopic extensions of disease. However, the target volume should be kept as small as possible to minimize damage to adjacent normal tissues. Advances in computer-assisted 3-dimensional planning, such as 3-dimensional conformal radiotherapy, intensity-modulated RT, and image-guided RT, enable delivery of higher radiation doses to the tumor and improve normal tissue sparing. Thus, accurate target delineation is essential. The gross tumor volume indicates palpable or visible disease, which may be the primary tumor, metastatic lymph nodes, or other metastases. The clinical target volume (CTV) is dened as the gross tumor volume with the addition of sucient margins to account for subclinical disease extension. The planning target volume derives from the CTV and is a geometrical parameter that is obtained by adding adequate margins around the CTV to account for set-up errors and organ motion. With image-guided RT, treatment plans can be adjusted as needed on the basis of information from imaging modalities including therapyinduced tumor changes. This is the basis for adaptive RT.88 Due to its remarkable accuracy in staging and the demonstration of a powerful eect on treatment volumes, there is a strong case for the routine use of PET/CT scanning in RT planning for NSCLC.89 Inclusion of PET scanning in staging evaluation has proven to be more accurate than conventional staging for NSCLCs, and when available, PET scanning should be used to select patients with NSCLC for treatment with denitive RT. PET scanning detects unsuspected distant metastasis (>20% of pre-PET stage III) and identies patients with very advanced locoregional disease not suitable for radical RT.90 Inclusion of PET scanning in the staging workup improves the apparent survival of patients treated with RT or chemoradiation therapy by excluding incurable patients.91 In a large prospective study, 30% of patients who were candidates for high-dose RT on the basis of conventional staging received only palliative
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therapy after PET scanning, because of unexpected distant metastasis (20%) or very extensive intrathoracic disease (10%).92 In a prospective study, knowledge of preradiotherapy PET data caused treatment to be canceled or modied from curative to palliative in 15 patients (11%).93 Of the 119 patients in whom radical radiotherapy was conrmed, the treatment plan was modied in 37 patients (31%).93 PET/CT scanning should be used for RT planning in NSCLC because it more accurately images tumor extent than CT scanning alone.94 This has been proven by the extensive surgical literature on the accuracy of PET scanning in the lymph node staging of NSCLC. Despite its higher accuracy, the limitations of PET scanning should be remembered. The rate of false-negative lymph node station assessment (posttest probability) in NSCLC RT candidates is 5% to 10%.95 The 2 most important and consistent reasons cited in the literature96 for signicant changes in target volumes in NSCLC with PET scanning were: 1. FDG-PET scanning signicantly changed lymph node staging in the thorax, usually by showing more positive nodes than CT scanning. 2. In cases with atelectasis, PET scanning helped to delineate the border between the tumor and the collapsed lung, allowing a smaller volume of the lung to be treated.97
THERAPEUTIC RESPONSE
NSCLC commonly presents at an advanced stage of disease, and chemotherapy plays a vital role in the treatment of these patients. With initiation of chemotherapy, progression of disease may occur in up to one third of patients.98 Early recognition of therapeutic failure is important in patient management because it can lead to cessation of ineective treatment and institution of an alternative regimen. Anatomic imaging alone using standard World Health Organization or Response Evaluation Criteria in Solid Tumors is widely applied, but has limitations in response assessment, as size measurements may not correlate with pathologic response or tumor viability. Furthermore, with the development of treatment alternatives targeting tumor biology, such as tumor cell proliferation and invasion, angiogenesis, and metastasis, the eect in many of these novel regimens is cytostatic, not cytotoxic, and may not lead to regression in tumor size. In contradistinction, metabolic imaging with PET scanning may allow an early and sensitive indication of the eectiveness of chemotherapy, as FDG uptake is not only a function of proliferative activity, but is also related to viable tumor cell number.99102 Multiple studies have examined the role of PET scanning in assessing treatment response in patients with locally advanced (stages IIIA and IIIB) NSCLC who have completed neoadjuvant therapy and are being considered for curative surgical resection.103109 Because metabolic response to therapy may occur earlier and may be more accurate than anatomic response, PET imaging has the potential to improve the assessment of residual tumor and could be useful in selecting patients for resection. Although not used in the routine evaluation of tumor response in patients with NSCLC after neoadjuvant treatment, small studies suggest a promising role for PET scanning. In a study by Eschmann et al109 of 70 patients with advanced NSCLC (stage III) who had neoadjuvant chemoradiotherapy, the dierence between initial FDG www.thoracicimaging.com |
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FIGURE 8. A 74-year-old man with shoulder pain and left apical lesion. PET/CT scan (A) shows FDG-avid lesion in the left apex (SUV, 10.8) and biopsy confirmed adenocarcinoma. PET/CT scanning (B) after 2 cycles of carboplatin and pemetrexed showed complete metabolic response. Note there is generally a significant association between marked decrease in FDG uptake within the tumor and patient outcome.
uptake and uptake after induction chemotherapy was predictive of long-term survival. Patients with normal FDG uptake or an 80% or more decrease in tumor SUV after therapy had a signicantly longer survival than those below this threshold (Fig. 8). Of note, the few patients with PET ndings of progressive disease who underwent surgical resection had only slightly longer survival than patients who did not undergo surgery.109 In a prospective trial of 93 patients with NSCLC and biopsy-proven stage IIIA N2 disease, the patients were staged with mediastinoscopy, integrated PET/CT scanning, and CT scanning. Repeat evaluation was performed 4 to 12 weeks after neoadjuvant chemoradiation therapy.107 PET/CT scanning was superior to CT scanning in assessing these patients after neoadjuvant chemoradiation therapy. Receiver Operating Characteristic curve analysis showed that a decrease of 75% or more in the SUV of the primary tumor indicated a high likelihood of a complete response, and a decrease by more than 50% in the SUV of the N2 node indicated a high likelihood of no residual disease. The study reported that the median decrease in SUV in patients with N2 disease and complete response was 87%, compared with 52% in patients with residual N2 disease.107 However, if the N2 nodes had a persistently high SUV, pathologic conrmation of metastatic disease was recommended, as increased FDG uptake did not reliably indicate residual disease. This strategy is supported by the results of a small study by Ohtsuka et al,110 which used PET scanning to assess pathologic tumor response and lymph node staging after neoadjuvant therapy in patients with NSCLC, and in whom the sensitivity (0.61), specicity (0.69), PPV (0.36), NPV (0.86), and accuracy (0.67) for lymph node staging were suboptimal. The interpretation of SUV measurements after neoadjuvant therapy (especially when radiotherapy has been administered) is problematic because of confounding factors including tumor cell dierentiation and macrophage inltration. Animal studies have shown that up to 30% of the FDG uptake in a tumor may be caused by the macrophage/monocyte system and that some tumors may retain high SUV measurements at the end of therapy even with histopathologic complete remission at the time of resection.110113 Accordingly, PET scanning should not be the sole determinant of eligibility for surgical resection or dose-escalated radiotherapy after neoadjuvant treatment of NSCLC. This recommendation is supported by the results of a study by Poettgen et al,111 which correlated PET/CT scanning and histopathology after neoadjuvant therapy in
NSCLC. Forty-six patients with stage IIIA and IIIB disease who received neoadjuvant therapy underwent surgical resection. Of the 19 patients with complete pathologic response of the primary tumor, 44% had a postinduction SUV of >2.5, suggesting residual viable tumor. There have been relatively few studies assessing the value of early PET scanning in assessing tumor response while patients are still receiving therapy.104,114 A decline in tumor SUV after 1 cycle of chemotherapy may predict outcome, with survival benet directly related to the magnitude of the decline. In a recent prospective study of 57 patients with stage IIIB or IV unresectable NSCLC who underwent restaging PET scanning after only 1 cycle of platinum-based chemotherapy, a decline in SUV of 20% or greater in the primary tumor was an independent predictor of long-term survival.114 This metabolic response correlated highly with the best response to therapy according to the Response Evaluation Criteria in Solid Tumors as determined on serial CT scans and was associated with a higher overall survival than in nonresponders (median survival of 252 d vs. 151 d). Furthermore, in a prospective study of 47 patients with locally advanced but potentially resectable stage IIIA N2 NSCLC who were receiving neoadjuvant chemotherapy, a reevaluation PET scan performed after 1 cycle of induction chemotherapy showed that a decrease in FDG uptake of 35% or greater correlated with improved survival (P=0.03).104 In this study, PET scanning was superior to CT scanning in monitoring response and also enabled an early prediction of survival during the initiation of therapy. A problematic issue in implementing the wide use of PET scanning in the assessment of early therapeutic response in patients with NSCLC is that there is no consensus on the timing of performance of PET imaging or the most appropriate criteria for assessment. Furthermore, for SUV measurements to be comparable and reproducible, standardization of scanning methods, including time to imaging after FDG administration, is required. To address the issue of reproducibility of data, the European Organization for Research and Treatment of Cancer PET Study Group and the Cancer Imaging Program of the National Cancer Institute have issued guidelines for the use of PET scanning in the assessment of prognosis and response to therapy in oncologic studies.100,115 The use of PET scanning to determine selection of appropriate therapy and as a marker of therapeutic ecacy in patients with NSCLC requires that the recommendations pertaining to the standardization of patient preparation, image acquisition
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and reconstruction, and PET timing relative to therapy be implemented.115 In addition, an agreement on the optimal threshold levels for the determination of response is required for PET scanning to be comparable and widely applicable clinically. In this regard, a new framework for PET Response Criteria in Solid Tumors has been proposed. This framework recommends assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol and a xed small region of interest, about 1 cm3 in volume (1.2 cm diameter), in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, and requiring a 30% decline in SUV for response. This framework should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are performed.116
RECURRENT LUNG CANCER

Early detection of local tumor recurrence is important as patients can be treated with repeat surgery, salvage chemotherapy, or radiotherapy.117120 Symptoms of local recurrence of lung cancer may not manifest until later, and this can lead to delays in diagnosis and can limit retreatment options. Findings on CT scanning or MR imaging are unreliable in distinguishing tumor from necrosis, posttherapy scarring, or brosis.121 PET scanning can detect local recurrence of tumor after denitive treatment with surgery, chemotherapy, or radiotherapy earlier than conventional imaging and has been reported to have a sensitivity of 98% to 100% and specicity of 62% to 92% (Fig. 9).122125 In a recent prospective study of 62 patients who had undergone surgical resection of NSCLC, PET scanning was able to detect tumor recurrence (sensitivity 93%, specicity 89%, and accuracy 92%) and predict which patients would benet most from surgical retreatment.126 Similarly, Keidar et al127 used PET/CT scanning to evaluate 42 patients with NSCLC at least 6 months after initial therapy (surgery, n=25; surgery and radiotherapy or chemotherapy, n=15; radiotherapy and chemotherapy, n=2) who had an uncertain diagnosis of recurrent disease or its extent after routine clinical and CT evaluation. Twenty-ve patients had recurrence of NSCLC, and the sensitivity, specicity, PPV, and NPV of PET/CT scanning for diagnosis of recurrence were 96%, 82%, 89%, and 93%, respectively. Hicks et al124 also evaluated patients with suspected relapse of more than 6 months after
denitive curative treatment (surgery, n=18; surgery and chemoradiotherapy, n=12; radical radiotherapy with or without concurrent chemotherapy, n=33). Forty-two of the 63 patients had tumor relapse. PET scanning was positive in 41 patients (sensitivity 98%), whereas CT scanning indicated recurrence in all 42 patients. Seventeen of the 63 patients (27%) had no evidence of relapse, and PET scanning was negative in 14 of these patients (specicity 82%). In contradistinction, CT scanning indicated recurrence of malignancy in 15 of the 17 patients. Of note, PET scanning resulted in a signicant change in the management of 40 patients (63%), including a change from curative to palliative therapy in 6 patients and from palliative to curative therapy in 3 patients. The high sensitivity and specicity of PET scanning for the detection of recurrent malignancy may be related to the timing of imaging. In Hicks study,124 PET scanning was performed more than 6 months after therapy, thus limiting the confounding eect of increased FDG uptake due to therapy-induced inammation and/or macrophage inltration that may occur when PET scanning is performed soon after completion of radiotherapy. In a recent study of 73 patients with NSCLC, it was reported that the ability of PET scanning performed a median of 70 days (range, 39 to 123 d in 90% of patients) after the completion of radical radiotherapy to assess therapeutic response was not confounded by radiation-induced inammation.128 Furthermore, PET scanning not only improves the detection of recurrent disease, but also provides prognostic information useful in selecting patients for repeat surgical resection. In a study by Hellwig et al,126 patients who had tumor recurrence with SUV of <11 had a longer median survival (46 mo) compared with those patients with a higher SUV (3 mo).
SMALL CELL LUNG CANCER

In contrast to the numerous studies evaluating PET scanning in NSCLC, there are far fewer studies on its utility in small cell lung cancer (SCLC). SCLC accounts for 15% to 20% of all lung cancers, and staging is based on dierentiating patients with limited disease from those with extensive disease. Limited disease is conned to the hemithorax of origin, including contralateral hilar and supraclavicular nodes, which can be encompassed within a tolerable RT portal, and patients are candidates for radical concurrent chemoradiotherapy (Fig. 10). Extensive disease has spread beyond the supraclavicular region or to distant organs, and patients receive palliative chemotherapy alone.
FIGURE 9. A 51-year-old woman with a right upper lobe lung cancer treated with RT. Ten years later, contrast-enhanced CT scan (A) shows increased soft tissue within the area of radiation fibrosis (arrow). PET/CT scan (B) reveals intense focal FDG uptake with SUV of 10.4 suspicious for local recurrence of malignancy (arrow) and was useful in directing needle biopsy.
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FIGURE 10. A 68-year-old man with a 6-month history of shortness of breath. PET/CT scanning shows FDG-avid mediastinal adenopathy in the aortopulmonary window (APW) and contralateral paratracheal region. Biopsy of the APW mediastinal lymph nodes revealed small cell carcinoma. Note PET scanning is useful in assessing extent of disease; patients with limited disease (confined to 1 hemithorax and contralateral mediastinal nodes) are treated with definitive chemoradiation therapy.
Patients with malignant pleural eusions have an intermediate prognosis between limited and extensive disease. In a prospective study of 24 patients with SCLC considered to have limited disease based on conventional workup, PET scanning correctly upstaged 8.3% of patients with sensitivity of 100% and specicity of 95.5% for detecting metastatic disease.129 Furthermore, PET scanning can lead to a change in the radiation treatment plan in 25% of patients by detecting unsuspected locoregional nodal disease.129 Brink et al130 reported that PET scanning caused a stage migration in 14 of 120 patients (including upstaging 10 patients to extensive disease and downstaging 3 patients by not conrming metastases of the adrenals suspected on CT scanning). PET scanning was superior to CT scanning in the detection of extrathoracic nodal disease, with a sensitivity of 100% versus 70% and a specicity of 98% versus 94%, respectively. Furthermore, PET scanning
showed superiority compared with CT scanning in the detection of distant metastases (excluding the brain), with a sensitivity of 98% versus 83% and a specicity of 92% versus 79%, respectively.
CONCLUSION
Integrated PET/CT scanning complements conventional imaging assessment in the staging of patients with lung cancer by improving the detection of nodal and extrathoracic metastases. PET/CT scanning is also used for RT planning in NSCLC because it more accurately images tumor extent than CT scanning alone. PET/CT scanning is currently being studied in the evaluation of prognosis and therapeutic response and has the potential to provide more appropriate selection of patients for surgical resection and neoadjuvant and adjuvant therapy. Furthermore, this imaging modality
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may impact patient management by allowing an earlier assessment of tumor response to chemotherapeutic regimens. Multi-institutional, prospective randomized controlled trials and standardization of PET imaging protocols to accurately measure the degree of FDG uptake are needed to fully elucidate the clinical applications of PET scanning in the management of patients with lung cancer. REFERENCES
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Volume 26, Number 2, May 2011

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PET/CT in Evaluation of Lung Cancer

2011 Lippincott Williams & Wilkins

Volume 26, Number 2, May 2011

2011 Lippincott Williams & Wilkins

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PET/CT in Evaluation of Lung Cancer

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SUMMARY OF EVALUATION OF PATIENTS WITH NSCLC

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RADIATION THERAPY PLANNING

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RECURRENT LUNG CANCER

SMALL CELL LUNG CANCER

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