Seeking a home for a PET, part 1: Defining the appropriate place for positron emission tomography imaging in the diagnosis of pulmonary nodules or masses

There is a growing experience with positron emission tomography (PET) in patients with pulmonary nodules or masses. As PET imaging becomes more widely available, it is important to thoughtfully define when application of this technology is warranted. Review of the literature to date suggests that PET imaging for diagnosis of pulmonary lesions is most useful in patients who have a low or intermediate risk of lung cancer as determined by an evaluation of symptoms, risk factors, and radiographic appearance. There is little role for PET in diagnosis in patients with a very low or a high risk of lung cancer, and there is little role in patients with lesions < 1 cm in diameter, or lesions suspected to be an infection, a bronchioloalveolar carcinoma, or a typical carcinoid tumor.     

Seeking a home for a PET, part 3: Emerging applications of positron emission tomography imaging in the management of patients with lung cancer

Positron emission tomography (PET) imaging is an important tool to refine the diagnosis and staging approach in patients with a possible lung cancer. In addition, other applications of PET imaging are being explored. Data consistently show that the intensity of uptake on a PET scan correlates with the biological aggressiveness of a tumor. PET imaging for restaging after induction therapy does not appear to be accurate enough to guide management. The results of PET imaging late after completion of treatment are highly predictive of future survival, and changes in PET images after only one cycle of chemotherapy are predictive of how a patient will respond to that planned treatment. PET imaging may allow radiotherapy treatment fields to be planned with greater accuracy, although data on how this affects patient outcomes are not yet available. Further technologic improvements in PET scanners are likely to bring further benefits to the management of patients with lung cancer in the future.     

Mediastinal lymph node sampling following positron emission tomography with fluorodeoxyglucose imaging in lung cancer staging

OBJECTIVES: To evaluate the predictive accuracy as well as the rates of false-positive and false-negative results of CT and positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging in detecting the metastatic intrathoracic lymph nodes in patients with suspected or proven non-small cell lung cancer (NSCLC). Our other objective was to determine the need for routine invasive sampling procedure in confirming PET/CT staging results. METHODS: The results of CT and PET-FDG scanning in 77 patients with suspected or proven NSCLC were correlated with the histologic findings of hilar/mediastinal lymph node sampling using mediastinoscopy, open biopsy, thoracotomy, or thoracotomy with resection. Patients were then classified into resectable and unresectable groups based initially on PET results and compared to histologic findings. RESULTS: The sensitivity, specificity, and accuracy of CT and PET for detecting metastatic lymphadenopathy were 68%, 61%, 63%, and 87%, 91%, and 82%, respectively. A change of management with routine sampling following PET was seen in five of six patients (83%) with false-positive findings (13%) but in none of four patients (9%) with false-negative findings. CONCLUSION: The false-positive findings of PET-FDG imaging affected selection of treatment in 83% of patients. However, false-negative results did not change management in any patient. This could potentially prevent unnecessary invasive thoracotomy, mediastinoscopy, or other sampling procedures in patients with negative PET results.     

正电子发射体层成像在肺癌诊断和分期中的价值

目的了解正电子发射体层成像(PET)在肺癌诊断和分期中的价值。方法收集1998年9月至2003年4月间行PET和CT检查,且诊断明确的肺部疾病患者的临床资料,对PET和CT检查结果与病理检查结果进行对比分析。结果在此期间共收集104例患者,其中肺癌64例(60%),肺部良性疾病40例(40%)。肺癌患者PET的标准摄取比值(SUV值)中位值为4.5(1.2～11.7),明显高于良性患者的1.0(0～7.7);且肺癌患者的SUV值与肺癌组织学类型、分化程度、临床分期和病灶大小均无关(P>0.05)。PET诊断肺癌的敏感性、特异性和准确性分别为88%、85%和87%;CT的敏感性、特异性和准确性分别为73%、28%、57%,PET的特异性和准确性显著高于CT(P<0.05)。对于胸腔淋巴结转移诊断的敏感性、特异性和准确性CT:N1期分别为33%、73%、59%,N2期分别为80%、79%、79%,N3期特异性及准确性均为97%;PET:N1期分别为33%、82%、65%,N2期分别为60%、83%、85%,N3期特异性及准确性均为85%;两者差异无统计学意义(P>0.05)。结论PET在鉴别肺内病灶良恶性质上有优势,对胸腔内淋巴结转移的诊断要结合CT结果综合判断。     

Endoscopic ultrasound and positron emission tomography for lung cancer staging.

BACKGROUND AND AIMS: Accurate assessment of mediastinal lymph nodes is vital for optimum treatment allocation in lung cancer patients. Currently available strategies fail to identify many patients with advanced mediastinal disease, resulting in unnecessary surgery. We prospectively compared 2 promising new modalities, positron emission tomography (PET) and endoscopic ultrasound (EUS), for staging mediastinal lymph nodes. METHODS: Consenting patients with lung cancer who also were suitable candidates for surgery were enrolled in the study. Patients underwent both PET and EUS. Outcomes were analyzed by surgery results or follow-up with serial imaging. RESULTS: Seventy-two eligible patients were enrolled, and adequate data were available for 65 patients. The final diagnosis was based on tissue analysis in 59 patients and 1-year radiologic follow-up evaluation in 6 patients. PET correctly diagnosed mediastinal lymph node status in 77% of patients, and EUS fine-needle aspiration was correct in 94% of patients (P = .012). The overall sensitivity, specificity, and accuracy of PET were 61%, 91%, and 77% compared with 87%, 100%, and 94% for EUS. We estimated that EUS obviated a surgical procedure in 55% (95% confidence interval, 40%-69%) of patients with radiologic evidence of mediastinal metastasis, and in 22% (95% confidence interval, 10%-41%) of patients without radiologic evidence of mediastinal metastasis. CONCLUSIONS: EUS fine-needle aspiration was more accurate than PET in staging mediastinal lymph nodes in lung cancer patients, and resulted in a substantial reduction in mediastinoscopy and thoracotomy.     

The future in diagnosis and staging of lung cancer: positron emission tomography

Since its introduction in 1974, positron emission tomography (PET) has gained widespread use, especially in diagnosis and staging of lung cancer. In this respect, (18)F-fluorodeoxyglucose (FDG) is by far the most used PET tracer exploiting the increased glucose uptake and metabolism in malignant cells. A large number of studies have suggested that addition of FDG-PET to conventional workup can improve diagnosis and staging in patients with non-small cell lung cancer (NSCLC). In meta-analysis, the sensitivity and specificity of PET in diagnosing single pulmonary nodules and masses is found to be 96 and 78%, respectively. In mediastinal staging, the sensitivity and specificity of PET is estimated to be 83 and 92%. In order to achieve high diagnostic values from PET, it is necessary to pay attention to a number of pitfalls, e.g., the uptake of FDG by inflammatory cells causing false-positive results, as well as size and histology of the tumour in order to avoid false-negative results. In 2001, the first integrated PET/computed tomography (CT) was installed, and since then, the use of this modality has expanded steadily, thereby decreasing examination time and overcoming the lack of anatomical details on PET. Recently, PET and PET/CT have become increasingly integrated in therapy planning and evaluation: response evaluation during and after chemotherapy, restaging after neoadjuvant therapy, planning of radiotherapy and detection of recurrent disease are all examples of emerging indications for PET and PET/CT in managing patients with lung cancer.     

The role of positron emission tomography (PET) in mediastinal staging of non-small cell lung cancer

Mediastinal lymph node metastasis (MLNM) is the most important prognostic factor and guide to the treatment in non-small cell lung cancer (NSCLC) patients with no distant metastasis. As a non invasive method, using of positron emission tomography (PET) to evaluate NSCLC is increasing. We aimed to compare results of PET and mediastinoscopy to reveal effectiveness of PET in the mediastinal staging of NSCLC patients. PET was performed to 100 operable NSCLC patients between 2004 and 2006. Later, standard cervical mediastinoscopy was performed to all of the patients. Twenty-six patients who detected MLNM at mediastinoscopy were referred to oncology clinic for neoadjuvant or definitive chemo-radiotherapy. Other 74 patients underwent thoracotomy and performed lung resection and mediastinal lymphatic dissection. Sensitivity and specificity rates for detecting mediastinal lymphatic metastasis of PET and mediastinoscopy were compared. There were 89 male and 11 female with mean age of 59 years. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates were calculated as 74%, 76%, 59%, 86% and 76% respectively for PET and 83%, 100%, 100%, 93% and 95% respectively for mediastinoscopy. Accuracy rate of PET is not sufficient and mediastinoscopy is still the gold standard to evaluate mediastinal staging of NSCLC, at present.     

Clinical role of F-18 fluorodeoxyglucose positron emission tomography imaging in patients with lung cancer and suspected malignant pleural effusion

STUDY OBJECTIVES: The goals of this study were to determine the sensitivity, specificity, and predictive accuracy of F-18 fluorodeoxyglucose positron emission tomography (PET-FDG) imaging in detecting metastatic disease involvement of pleura and/or presence of malignant pleural effusion in patients with proven lung cancer. We wanted to compare efficacy of PET-FDG imaging to CT scanning in differentiating benign pleural effusion from malignant effusion and/or pleural involvement in patients with lung cancer. METHODS: We studied 35 patients with biopsy-proven lung cancer and abnormal findings on CT scanning for presence of pleural effusion (n = 34) and/or pleural thickening or nodular involvement (n = 4). The results of positron emission tomography and CT scanning were compared to pleural cytology (n = 31), histologic findings of pleural biopsy (n = 3), and/or clinical follow-up (n = 3) for at least 1 year for presence or absence of malignant pleural effusion. RESULTS: PET-FDG imaging correctly detected the presence of malignant pleural effusion and malignant pleural involvement in 16 of 18 patients and excluded malignant effusion or pleural metastatic involvement in 16 of 17 patients (sensitivity, specificity, and accuracy of 88.8%, 94.1%, and 91.4% respectively). CONCLUSION: PET-FDG imaging is a highly accurate and reliable noninvasive test to differentiate malignant from benign pleural effusion and/or pleural involvement in patients with lung cancer and findings of suspected malignant pleural effusion on CT scanning.     

Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion

PURPOSES: To compare the diagnostic accuracy of positron emission tomography (PET) and integrated PET/CT and to evaluate the performance of software fusion for staging of non-small cell lung cancer (NSCLC). METHODS: Thirty-six patients (17 men and 19 women) with NSCLC underwent staging with integrated PET/CT followed by mediastinal lymph node dissection and tumor resection. Twenty-five of the 36 patients (69%) underwent separate CT studies for software fusion of images. Two blinded reviewers analyzed in consensus all PET images, and an experienced radiologist was added to assess integrated and software-fused PET/CT images. Histopathologic findings served as "gold standard" for determining the diagnostic accuracy of all modalities. RESULTS: Reviewers examining PET and integrated PET/CT classified T stage accurately in 67% (20 of 30 patients) and 97% (29 of 30 patients), respectively (p < 0.05). Overall, interpretations based on PET staged 57% (17 of 30 patients) correctly, over-staged 6 patients (20%), and under-staged 7 patients (23%). Interpretations based on integrated PET/CT correctly staged 83% (25 of 30 patients), over-staged 3 patients (10%), and under-staged 2 patients (7%). The overall staging accuracy of integrated PET/CT was significantly higher than that of PET (p < 0.05). Automatic software fusion of separately obtained PET and CT studies was successful in 68% of the patients but failed in 32%. In successful software fusion cases, the results of software fusion with regards to T stage and N stage were not different from integrated PET/CT. CONCLUSIONS: Integrated PET/CT compared with PET alone was associated with 26% points-greater overall diagnostic accuracy (p = 0.01). The software fusion method failed to provide acceptable co-registration in > 30% of the patients.     

Improvement of non-small-cell lung cancer staging by means of positron emission tomography

BACKGROUND: Exact staging of ipsi- and contralateral mediastinal lymph-node metastases (N 1/2 vs. N3) is essential for the therapeutic strategy in non-small-cell lung cancer (NSCLC). CT and mediastinoscopy are the standards of reference for N staging. However, even with these combined measures the extent of invasion of mediastinal lymph nodes can remain vague. 18FDG Positron Emission Tomography (18FDG-PET) has recently been shown to detect invaded nodes with high accuracy. The purpose of this study was to evaluate 18FDG-PET as an aid in N staging. METHODS: 27 patients with suspected NSCLC were clinically staged by means of CT, bronchoscopy, mediastinoscopy, and bone scintigraphy. Additionally, 18FDG-PET was performed preoperatively for analysis of topography of invaded lymph nodes. CT and 18FDG-PET were evaluated in a blinded fashion. Surgical therapy was performed with radical lymphadenectomy. CT N staging as well as PET N staging results were compared with the pathological diagnoses (pTN). Specificity, sensitivity, and accuracy of CT and PET in N staging were calculated. RESULTS: 14 squamous-cell carcinomas, 10 adenocarcinomas, and 3 non-malignant tumors were found. In 8 patients no invasion was found (N0), in 13 patients an ipsilateral invasion (N1/2), and in 3 patients a contralateral invasion (N3). In the correct detection of N1/2 the sensitivity of CT and of PET was 0.77, the specificity of CT and of PET was 0.79. The accuracy of CT was 0.74 and of PET 0.78. By combining CT and PET accuracy was 0.85. CONCLUSIONS: Adequate preoperative LN staging is possible with both CT and 18FDG-PET. The accuracy, however, can be improved by a combination of CT and 18FDG-PET.     

The utility of 99mTc depreotide compared with F-18 fluorodeoxyglucose positron emission tomography and surgical staging in patients with suspected non-small cell lung cancer

STUDY OBJECTIVES: The findings from conventional imaging modalities, such as chest CT, are frequently unreliable in patients with lung cancer. This study was designed to compare the relative diagnostic accuracies and utility of the two most widely used functional imaging examinations, F-18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and (99m)Tc depreotide scintigraphy, for the diagnosis and staging of lung cancer. DESIGN: Prospective, experimental investigation. SETTING: Academic medical center. PATIENTS: One hundred sixty-six subjects with suspected lung cancer were enrolled in the study. INTERVENTIONS: Whole-body and single-photon emission CT imaging of the chest was performed after IV administration of (99m)Tc depreotide. Attenuation-corrected FDG PET imaging was performed after IV administration of FDG. Image findings were compared with the biopsy results or clinical follow-up. Measurements and results: In 157 subjects with evaluable lung lesions, the sensitivities and specificities for detecting malignant disease (95% confidence intervals) of FDG PET are 96% (90 to 98%) and 71% (54 to 85%), and of (99m)Tc depreotide are 94% (88 to 98%) and 51% (34 to 68%). In the 139 subjects with available complete staging data, FDG PET correctly staged 76 of 139 patients (55%), and (99m)Tc depreotide correctly staged 63 of 139 patients (45%). CONCLUSIONS: The sensitivity for detection of lung cancer in the primary lesion is equally high for FDG PET and (99m)Tc depreotide. The specificity is superior for FDG PET. The staging accuracy of FDG PET and (99m)Tc depreotide is similar, but when read with the chest CT neither scintigraphic examination is sufficiently accurate to stage patients with non-small cell lung cancer.     

Positron emission tomography and computed tomography versus positron emission tomography computed tomography: tools for imaging the lung

This article reviews the potential use of positron emission tomography (PET), alone and in combination with computed tomography, for evaluating the severity of disease in cystic fibrosis. PET scanning using injected 18F-fluorodeoxyglucose provides visual and quantitative information for the rate at which glucose is taken up by the lung, a process that should relate to the presence of inflammation and reflect the extent of the disease. The computed tomography scan gives highly accurate density and anatomic information to locate areas of inflammation seen on the PET scan, increasing the accuracy of the interpretation. Until recently, the scanners have been single systems, often located in separate hospital departments. Combined systems are now commercially available, with major advantages for patients and in the quality of analytical information obtained for interpretation by the physician. The use of 18F-fluorodeoxyglucose uptake and PET scanning has been suggested as a biomarker of progressive pulmonary inflammation in cystic fibrosis. Although promising, the data so far are limited. Further studies will be needed to validate this measurement for this purpose.     

Usefulness of positron emission tomography imaging in the management of lung cancer.

Positron emission tomography imaging is useful for the characterization of the solitary pulmonary nodule and mediastinal staging. Potential future applications include extrathoracic staging to help to determine the ideal site for possible tissue diagnosis, to guide treatment plans, and to monitor the response to therapy and recurrence. Positron emission tomography may also predict prognosis. This review discusses the uses of positron emission tomography, the current literature, and the clinical guidelines for positron emission tomography imaging.     

Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer

STUDY OBJECTIVES: To perform a prospective comparison of direct real-time endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), positron emission tomography (PET), and thoracic CT for detection of mediastinal and hilar lymph node metastasis in patients with lung cancer considered for surgical resection. DESIGN: Prospective patient enrollment. SETTING: University teaching hospital. PATIENTS: One hundred two potentially operable patients with proven (n = 96) or radiologically suspected (n = 6) lung cancer were included in the study. INTERVENTIONS: CT, PET, and EBUS-TBNA were performed prior to surgery for the evaluation of mediastinal and hilar lymph node metastasis. The convex probe EBUS, which is integrated with a convex scanning probe on its tip, was used for EBUS-TBNA. Surgical histology was used as the "gold standard" to confirm lymph node metastasis unless patients were found inoperable for N3 or extensive N2 disease proven by EBUS-TBNA. Main results: EBUS-TBNA was successfully performed in all 102 patients (mean age, 67.8 years) from 147 mediastinal and 53 hilar lymph nodes. EBUS-TBNA proved malignancy in 37 lymph node stations in 24 patients. CT identified 92 positive lymph nodes, and PET identified 89 positive lymph nodes (4 supraclavicular, 63 mediastinal, 22 hilar). The sensitivities of CT, PET, and EBUS-TBNA for the correct diagnosis of mediastinal and hilar lymph node staging were 76.9%, 80.0%, and 92.3%, respectively; specificities were 55.3%, 70.1%, and 100%, and diagnostic accuracies were 60.8%, 72.5%, and 98.0%. EBUS-TBNA was uneventful, and there were no complications. CONCLUSION: Compared to CT and PET, EBUS-TBNA has a high sensitivity as well as specificity for mediastinal and hilar lymph node staging in patients with lung cancer. EBUS-TBNA should be considered for evaluation of the mediastinum early in the staging process of lung cancer.     

Endoscopic ultrasound,positron emission tomography,and computerized tomography for lung cancer

Staging of patients with lung cancer to determine operability is intended to efficiently limit futile thoracotomies without denying possibly curative surgery. Currently available staging tests are imperfect alone and in combination. Imaged suspected metastases often require tissue confirmation before surgery can be denied. Endoscopic ultrasound (EUS) may help identify inoperable patients by providing tissue proof of inoperability in a single staging test, with similar sensitivity for identifying inoperable patients as other staging tests. Therefore, we compared computed tomography, positron emission tomography (PET), and EUS with fine-needle aspiration under conscious sedation, each test interpreted blinded with respect to the other tests, for identifying inoperable patients in a consecutive cohort of 79 potentially operable patients with suspected or proven lung cancer. An economic analysis was also performed. Thirty-nine patients were found inoperable (a 40th patient's inoperability was missed by all preoperative staging tests). The sensitivity of computerized tomography was 43%. PET and EUS each had similar sensitivities (68 and 63%, respectively) and similar negative predictive values (64 and 68%, respectively), but EUS's superior specificity (100 vs. 72% for PET) and considerably lower expense means it may be preferred to PET early in staging to identify inoperable patients.     

Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.