Indeterminate Solitary Pulmonary Nodules Research Articles

Economic evaluation studies in nuclear medicine: the need for standardization.

The guidelines for publishing economic evaluations require a statement of the economic importance of the analysis and the viewpoint from which it has been carried out, as well as specification of at least two alternative programmes or interventions, the form of economic evaluation, the outcome measure, the method of costing, the time horizon and adjustment for timing of costs and benefits (e.g. by a discount factor), and the allowance for uncertainties (e.g. by implementation of a sensitivity analysis). The decision analysis can be based on clinical trial data, on retrospective or administrative databases, or on modelling. The choice of outcome measures is the key issue in an economic evaluation. In cost-effectiveness analysis, benefits are usually measured in natural units. This is the form of economic evaluation most frequently used in nuclear medicine. Endpoints of effectiveness applied in studies in this field have been procedures avoided, procedures initiated, cardiac events, survival probability, morbidity, quality of life and protracted or failed surgical procedures. In other instances, surrogate endpoints have been used such as metastases detected, staging, viability or tumour response. This, however, limits comparability of cost-effectiveness considerably, as proof of a change in the health outcome cannot be obtained. Measures of utility such as QALYs (quality-adjusted life years) have so far only been applied for decision tree analysis. Useful examples of economic evaluation studies in nuclear medicine are presented here for fluorodeoxyglucose positron emission tomography (FDG-PET) in the preoperative staging of non-small cell lung cancer, for FDG-PET in differentiating indeterminate solitary pulmonary nodules, for somatostatin receptor scintigraphy in detecting metastases of carcinoid tumours, for routine preoperative scintigraphy with sestamibi in patients with parathyroid adenoma, for periodic measurement of thyroid-stimulating hormone in detecting mild thyroid failure, for diagnostic algorithms including a lung scan in patients with suspected pulmonary embolism, for myocardial perfusion imaging as an incremental prognostic factor in patients with coronary artery disease, and for the use of radioiodine as first-line therapy of Graves' hyperthyroidism and of toxic nodular goitres. Further evaluations of effectiveness or utility should be carried out within a multidisciplinary framework to ensure that nuclear medical procedures are included in the general management guidelines.

Solitary Pulmonary Nodules: Clinical Prediction Model Versus Physicians

To determine whether a clinical prediction model developed to identify malignant lung nodules based on clinical data and radiologic lung nodule characteristics could predict a malignant lung nodule diagnosis with higher accuracy than physicians. One hundred cases were obtained by using a stratified random sample from a retrospective cohort of 629 patients with newly discovered 4- to 30-mm radiologically indeterminate solitary pulmonary nodules (SPNs) on chest radiography. A chest radiologist, pulmonologist, thoracic surgeon, and general internist made predictions of a malignant lesion and recommendations for management (thoracotomy, transthoracic needle aspiration biopsy, or observation) on the basis of radiologic and clinical data used to develop the clinical prediction rule. The predictions of a malignant lung nodule were compared with the probability of malignant involvement from a previously validated clinical prediction model to identify malignant nodules on the basis of three clinical characteristics (age, smoking status, and history of cancer greater than or equal to 5 years previously) and three radiologic characteristics (nodule diameter, spiculation, and upper lobe location). Receiver operating characteristic analysis showed no significant difference between the logistic model and the physicians' predictions. Calibration curves revealed that physicians overestimated the probability of a malignant lesion in patients with low risk of malignant disease by the prediction rule; this finding suggests a potential for the decision rule to improve the management of patients with SPNs that are likely to be benign. The prediction model was not better than physicians' predictions of malignant SPNs. The prediction rule may have potential to improve the management of patients with SPNs that are likely to be benign.

The Utility of a Somatostatin-Type Receptor Binding Peptide Radiopharmaceutical (P829) in the Evaluation of Solitary Pulmonary Nodules

Many neoplasms including small cell cancers more densely express somatostatin-type receptors or more avidly bind somatostatin than granulomatous and other nonmalignant processes. While non-small cell neoplasms of the lung have not yet been shown to demonstrate this receptor expression, previous studies have documented non-small cell lung cancer detection with somatostatin analog scintigraphy. This phenomenon can be conceivably exploited utilizing technetium Tc-99m P829 (P829), a unique low molecular weight somatostatin-type receptor binding polypeptide radiopharmaceutical. The objective of this study was to determine the ability of P829 scintigraphy to noninvasively differentiate malignant and nonmalignant solitary pulmonary nodules (SPNs). The radiopharmaceutical technetium 99mTc-P829 was utilized for scintigraphy including single photon emission computed tomography. Thirty individuals with indeterminate SPNs of > or = 1 cm and significant risk factors for primary lung cancer were identified and underwent P829 scintigraphy. Tissue diagnosis was then established by transthoracic needle biopsy specimens. Fourteen subjects demonstrated abnormal P829 scans in the region of the radiographic abnormality. Twelve of this group had biopsy specimens revealing neoplasia. Two subjects with necrotizing granuloma on biopsy specimen had abnormal P829 scans in the region of the nodule. Sixteen subjects had no abnormal P829 tracer uptake in the region of the nodule. Fourteen subjects had benign diagnoses on biopsy specimens. One member of this group with a non-diagnostic biopsy specimen refused thoracotomy and remains radiographically stable at 24 months of follow-up. One subject with a squamous cell carcinoma demonstrated no P829 activity in the region of the nodule. The specificity of P829 scintigraphy based on transthoracic needle biopsy specimen was 88%. The sensitivity was 93%. P829 scintigraphy correctly identified or excluded malignancy in 27 of 30 subjects. P829 scintigraphy reliably identified or excluded malignancy in radiographically indeterminate solitary pulmonary nodules. The sensitivity and specificity compared favorably with the reported results of F-18 fluorodeoxyglucose positron emission tomographic imaging.

Analytical decision model for the cost-effective management of solitary pulmonary nodules.

Multiple strategies are currently being used to manage patients who present with indeterminate solitary pulmonary nodules (SPN). We have used decision-analysis models to assess the cost-effectiveness of various strategies for the diagnosis and management of SPN. Four decision strategies were compared: a wait and watch strategy, a surgery strategy, a computed tomography (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy. An incremental cost-effectiveness ratio (ICER) was used to compare all strategies to the wait and watch strategy. A CT-plus-PET strategy was the most cost-effective over a large pretest likelihood (probability of having a malignant nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range, the potential cost savings of using the CT-plus-PET strategy over the CT strategy ranged from $91 to $2,200 per patient. This translates to a yearly national savings of approximately $62.7 million. Decision-analysis modeling indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can be used to model various features of the management of SPN, including modeling the cost-effectiveness of other newly emerging technologies.

422 The diagnosis with video-assisted thoracoscopy toward the indeterminate solitary pulmonary nodule

422 The diagnosis with video-assisted thoracoscopy toward the indeterminate solitary pulmonary nodule

CT-Guided Fine-Needle Aspiration Cytology of Solitary Pulmonary Nodules*: A Prospective, Randomized Study of Immediate Cytologic Evaluation

To evaluate the immediate cytologic assessment during CT-guided fine-needle aspiration cytology (FNAC) in the diagnosis of operable indeterminate solitary pulmonary nodules (SPNs). Prospective randomized study. Two hundred twenty patients with SPN undergoing CT-guided FNAC were divided into two groups. In the first one (group A, 110 patients), a cytologist assessed the adequacy of the sample obtained immediately, and when the sample was considered inadequate, fine-needle aspiration (FNA) was repeated. In the second group (B, 110 patients), an immediate cytologic examination was not performed, but only a gross assessment by the surgeon. Histologic study of the SPN was possible in 217 cases, whereas three patients were followed up radiologically. Adequate samples were obtained in 100% of group A and 88% of group B (p<0.001). The diagnostic accuracy was 99% in group A and 81% in group B (p<0.001). Group A required a mean of 1.22 FNAs compared with 1.10 in group B (p=0.015). The rate of pneumothorax in the whole series was 24%, and statistically significant differences between the two groups were not detected. Immediate cytologic study significantly increased the adequacy and diagnostic accuracy of CT-guided FNAC of indeterminate SPNs without causing a significant increase of complications.

The Probability of Malignancy in Solitary Pulmonary Nodules

A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a random sample of patients (n = 419) and tested on data from a separate group of patients (n = 210). To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules (SPNs) in a clinically relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter. A retrospective cohort study at a multispecialty group practice included 629 patients (320 men, 309 women) with newly discovered (between January 1, 1984, and May 1, 1986) 4- to 30-mm radiologically indeterminate SPNs on chest radiography. Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded. Clinical data included age, sex, cigarette-smoking status, and history of extrathoracic malignant neoplasm, asbestos exposure, and chronic interstitial or obstructive lung disease; chest radiological data included the diameter, location, edge characteristics (eg, lobulation, spiculation, and shagginess), and other characteristics (eg, cavitation) of the SPNs. Predictors were identified in a random sample of two thirds of the patients and tested in the remaining one third. Sixty-five percent of the nodules were benign, 23% were malignant, and 12% were indeterminate. Three clinical characteristics (age, cigarette-smoking status, and history of cancer [diagnosis, > or = 5 years ago]) and 3 radiological characteristics (diameter, spiculation, and upper lobe location of the SPNs) were independent predictors of malignancy. The area (+/-SE) under the evaluated receiver operating characteristic curve was 0.8328 +/- 0.0226. Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs.

Invited commentary to: “Video assisted thoracic surgery of indeterminate solitary pulmonary nodules—Wedge resection and requirement of thoracotomy”

Invited commentary to: “Video assisted thoracic surgery of indeterminate solitary pulmonary nodules—Wedge resection and requirement of thoracotomy”

Video assisted thoracic surgery of indeterminate solitary pulmonary nodules—Wedge resection and requirement of thoracotomy

Background Wedge resection for undefined pulmonary nodules can not always be performed with only minimally invasive technique. Preoperative knowledge about the exclusive videoendoscopic resectability would save operating time.

Staging Bronchoscopy in the Preoperative Assessment of a Solitary Nodule

In the July 1993 issue of Chest, Dr. Goldberg et al1 recommended that based on the investigation of 33 patients who presented with an indeterminate solitary pulmonary nodule (SPN) on chest x-ray film to abandon staging bronchoscopy in the diagnostic management of such cases. They found an unfavorable cost-effectiveness ratio for bronchoscopy in this specific setting because of the cost of the procedure and its low rate of positive findings.

Diagnostic Efficacy of PET-FDG Imaging in Solitary Pulmonary Nodules: Potential Role in Evaluation and Management

Background Positron emission tomography (PET), a new noninvasive imaging modality, utilizing 2-[F-18]-fluoro-2-deoxy-D-glucose (FDC), has demonstrated increased FDC uptake in lung tumors. Objective To determine the diagnostic efficacy of PET-FDG imaging in differentiating benign from malignant solitary pulmonary nodules. Patient selection A prospective study of 30 patients who presented with indeterminate solitary pulmonary nodules less than 3 cm in size based on chest radiograph and computed tomographic (CT) scan. Setting Two tertiary care medical centers in Omaha, Neb: Creighton University Medical Center and the Omaha Veterans Administration Medical Center. Measurements Positron emission tomographic imaging of the lung was performed 1 h after intravenous injection of 10 mCi of F-18-FDG. Qualitative analysis of the images was performed independently by two observers by visual identification of the areas of increased FDC uptake in the lung nodules. Semiquantitative analysis was performed using computation of differential uptake ratio (DUR). Histologic specimens were obtained in 29 patients (thoracotomy 20, transthoracic needle aspiration biopsy 8, bronchoscopy1). Results Positron emission tomographic imaging correctly identified 27 of 30 pulmonary nodules. Diagnostic accuracy was high with sensitivity of 95 percent and specificity of 80 percent. The positive and negative predictive value of PET imaging for solitary pulmonary nodules was 90 percent and 89 percent, respectively. The DUR values were significantly higher for malignant nodules (mean± SD, 5.55 ±2.79) than benign nodules (mean±SD, 0.95 ±0.99) (p<0.001). There was one false-negative result in a patient with a 1-cm nodule identified as a scar adenocarcinoma. There were two false-positive cases and both had caseating granulomas with active inflammation and Histoplasma organisms. Conclusion PET-FDC imaging of the lung, a new noninvasive diagnostic test, has a high degree of accuracy in differentiating benign from malignant pulmonary nodules. PET-FDC imaging could complement CT scanning in the evaluation and treatment of patients with solitary pulmonary nodules. Positron emission tomography (PET), a new noninvasive imaging modality, utilizing 2-[F-18]-fluoro-2-deoxy-D-glucose (FDC), has demonstrated increased FDC uptake in lung tumors. To determine the diagnostic efficacy of PET-FDG imaging in differentiating benign from malignant solitary pulmonary nodules. A prospective study of 30 patients who presented with indeterminate solitary pulmonary nodules less than 3 cm in size based on chest radiograph and computed tomographic (CT) scan. Two tertiary care medical centers in Omaha, Neb: Creighton University Medical Center and the Omaha Veterans Administration Medical Center. Positron emission tomographic imaging of the lung was performed 1 h after intravenous injection of 10 mCi of F-18-FDG. Qualitative analysis of the images was performed independently by two observers by visual identification of the areas of increased FDC uptake in the lung nodules. Semiquantitative analysis was performed using computation of differential uptake ratio (DUR). Histologic specimens were obtained in 29 patients (thoracotomy 20, transthoracic needle aspiration biopsy 8, bronchoscopy1). Positron emission tomographic imaging correctly identified 27 of 30 pulmonary nodules. Diagnostic accuracy was high with sensitivity of 95 percent and specificity of 80 percent. The positive and negative predictive value of PET imaging for solitary pulmonary nodules was 90 percent and 89 percent, respectively. The DUR values were significantly higher for malignant nodules (mean± SD, 5.55 ±2.79) than benign nodules (mean±SD, 0.95 ±0.99) (p<0.001). There was one false-negative result in a patient with a 1-cm nodule identified as a scar adenocarcinoma. There were two false-positive cases and both had caseating granulomas with active inflammation and Histoplasma organisms. PET-FDC imaging of the lung, a new noninvasive diagnostic test, has a high degree of accuracy in differentiating benign from malignant pulmonary nodules. PET-FDC imaging could complement CT scanning in the evaluation and treatment of patients with solitary pulmonary nodules.

Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule

Traditional nonoperative diagnostic approaches to the indeterminate solitary pulmonary nodule include bronchoscopy and percutaneous needle biopsy. Although both methods are minimally invasive, the diagnosis of the small, peripheral nodule may remain elusive. Open thoracotomy is often required when these methods fail to obtain a diagnosis. Between January 1991 and June 1992, 242 patients with indeterminate solitary lung nodules underwent thoracoscopic excisional biopsy as the primary diagnostic method. Wedge excisions of the nodules were all performed by thoracoscopic techniques using an endoscopie stapler alone (72%), neodymium:yttriumaluminum garnet laser (18%), or both (10%). A definite diagnosis was obtained in all patients. Two patients required conversion to thoracotomy to locate the nodule (both malignant). A benign diagnosis was obtained in 127 patients (52%) and a malignant diagnosis in 115 (48%). Of the malignant nodules, 51 (44%) were primary lung cancer and 64 (56%) were métastases. All patients diagnosed with primary lung cancer having adequate pulmonary reserve (n = 29) underwent formal open lung resection during the same procedure. There was no mortality, and significant morbidity was limited to atelectasis in 3 patients (1.2%), pneumonia in 2 patients (0.8%), and prolonged air leak more than 7 days in 4 patients (1.6%). Average hospital stay for patients having thoracoscopy only (n = 213) was 2.4 days (range, 1 to 12 days). Thoracoscopy offers a minimally invasive approach for the diagnosis of the indeterminate solitary nodule. It has advantages over traditional diagnostic methods of being virtually 100% sensitive and 100% specific with no mortality and minimal morbidity. Based on these results, as well as the benefits of cost and time effectiveness, we anticipate a larger role for thoracoscopy in the diagnostic management of the indeterminate solitary pulmonary nodule.

Management of the indeterminate solitary pulmonary nodule: A pulmonologist's view

Management of indeterminate solitary pulmonary nodules includes clinical assessment, radiographic examination, and bronchoscopic or transthoracic biopsy. Despite these management techniques, definitive diagnosis often remains elusive. Thoracoscopy offers another diagnostic modality to the algorithm for management of indeterminate nodules.

The Role of Staging Bronchoscopy in the Preoperative Assessment of a Solitary Pulmonary Nodule

In order to assess the role of a staging fiberoptic bronchoscopy in the preoperative assessment of an indeterminate solitary pulmonary nodule (SPN), we reviewed our experience in 33 SPNs identified among 1,269 bronchoscopies performed at the Albert Einstein Medical Center between 1985 and 1989. All lesions were less than 4 cm in greatest diameter and were not associated with symptoms of weight loss, chest pain, hemoptysis, localized wheezing, or hoarseness. A tissue diagnosis was established in 25 patients, 23 of whom had a malignant SPN. This study failed to detect a single case in which a fiberoptic bronchoscopic examination of the airway discovered a lesion that would preclude surgery and potentially curative resection. We recommend the abandonment of a staging bronchoscopy in the evaluation of a patient with an indeterminant SPN in whom history, physical examination, laboratory, and imaging studies fail to document contraindications to surgery. No additional useful information is derived and a substantial cost savings to the patient can be realized if the procedure is eliminated.

Solitary pulmonary nodules: detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose.

It is estimated that nearly one-third of solitary pulmonary nodules (SPNs) may represent bronchogenic carcinoma. The noninvasive imaging methods used currently (ie, plain radiography, computed tomography) are not reliable for accurate detection of malignancy in most SPNs. The authors prospectively evaluated use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) for identification of malignancy in 20 patients with noncalcific, radiographically indeterminate SPNs. PET-FDG imaging demonstrated focal hypermetabolism in 13 biopsy-proved malignant nodules, whereas no increased FDG uptake was seen in the seven benign SPNs. Semiquantitative analysis with computation of differential uptake ratios also helped clearly differentiate benign nodules (mean +/- standard deviation, 0.56 +/- 0.27) from malignant nodules (mean +/- standard deviation, 5.63 +/- 2.38) (P less than .001). Thus, PET-FDG imaging may be a potentially useful noninvasive technique for accurate differentiation of benign and malignant SPNs that are radiographically indeterminate.

Video-Assisted Thoracic Surgical Procedure: Management of a Solitary Pulmonary Nodule

Solitary pulmonary nodules continue to challenge all diagnostic skills. Herein we describe video-assisted thoracic surgical intervention, a new, minimally invasive technique that aids physicians in obtaining a definitive histologic diagnosis in a select group of patients with an indeterminate solitary pulmonary nodule.