Mediastinal staging of non-small cell lung carcinoma using computed and positron-emission tomography.
Background. We evaluated the accuracy of computed tomography Computed tomography (CT scan)
X rays are aimed at slices of the body (by rotating equipment) and results are assembled with a computer to give a three-dimensional picture of a structure. (CT) and positron-emission tomography (PET) in the mediastinal mediastinal /me·di·as·ti·nal/ (-as-ti´n'l) of or pertaining to the mediastinum.
of or pertaining to the mediastinum. staging of non-small cell lung cancer Lung Cancer, Non-Small Cell Definition
Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
There are two kinds of lung cancers, primary and secondary. .
Methods. Between May 14, 1999, and November 28, 2000, computerized tomography computerized tomography
n. Abbr. CT
Computerized axial tomography.
Noun 1. computerized tomography - a method of examining body organs by scanning them with X rays and using a computer to construct a series of (CT) and positron-emission tomography (PET) were used to clinically stage 94 consecutive patients with non-small cell carcinoma of the lung (NSCCL NSCCL Non-Small Cell Carcinoma of the Lung
NSCCL NSE National Securities Clearing Corporation Limited ). All patients underwent subsequent surgical staging with mediastinoscopy, anterior mediastinotomy, and/or thoracotomy thoracotomy /tho·ra·cot·o·my/ (-kot´ah-me) pleurotomy; incision of the chest wall.
Incision into the chest wall. Also called pleurotomy. with mediastinal lymphadenectomy.
Results. Overall accuracy was the same for both procedures. False-negative results occurred 3 times more often with CT; false-positive results occurred twice as often with PET. Sensitivity and specificity were 64% and 94%, respectively, for CT, versus 88% and 86%, respectively, for PET. Positive and negative predictive values were 80% and 88%, respectively, for CT, versus 71% and 95%, respectively, for PET.
Conclusion. In addition to routine use of CT, PET seems to achieve high negative predictive value in the evaluation of mediastinal disease; PET seems particularly helpful in assessing absence of tumor in bulky nodes after neoadjuvant chemotherapy Neoadjuvant chemotherapy
Treatment of the tumor with drugs before surgery to reduce the size of the tumor.
Mentioned in: Neuroblastoma
neoadjuvant chemotherapy and/or radiotherapy.
IT HAS BEEN STATED, (1,2) "The tumor-node-metastasis system (of staging) has proved to be the best method ... to determine treatment strategies and ultimate prognosis ... (and) the involvement of local (intrapulmonary) or regional (extrapulmonary) lymph nodes Lymph nodes
Small, bean-shaped masses of tissue scattered along the lymphatic system that act as filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph system. remains the most important predictor of outcome after resection of lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. ."
Regional, extrapleural, and distant metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.
Mentioned in: Coagulation Disorders
pertaining to or of the nature of a metastasis. disease so adversely affect the prognosis of patients with non-small cell carcinoma of the lung (NSCCL) that surgical resection is not an appropriate option for treatment in most patients with stage III and IV disease (ie, patients with regional mediastinal or distant spread of disease, respectively), at least not until they have received preoperative pre·op·er·a·tive
Preceding a surgical operation.
preceding an operation.
the preparation of a patient before operation. therapy.
Computed tomography (CT) has supplanted simple chest roentgenograms, planigrams, fluoroscopy fluoroscopy /flu·o·ros·co·py/ (fldbobr-ros´kah-pe) examination by means of the fluoroscope.
Examination by means of a fluoroscope. Also called radioscopy. , and radionuclide radionuclide /ra·dio·nu·clide/ (-noo´klid) a nuclide that disintegrates with the emission of corpuscular or electromagnetic radiations.
n. bone scanning for routine clinical staging purposes. Now the emergence of positron-emission tomography (PET) allows a marriage of metabolic imaging (PET) to complement the anatomic imaging of CT, hopefully to more appropriately guide therapy.
Positron-emission tomography is a relatively noninvasive nuclear technique that delivers high resolution images using positron-emitting radiotracers, most commonly 2-(F-18)-fluoro-2-dioxy-D-glucose (FDG FDG Fluorodeoxyglucose
FDG Fundação de Desenvolvimento Gerencial
FDG Franchise Development Group
FDG Function Dependence Graph
FDG Fraud Detection Group
FDG Functional Dependency Gate
FDG Front des Gaulois
FDG Falling Down Giggling ). Because malignant cells typically exhibit accelerated glycolysis glycolysis (glīkŏl`ĭsĭs), term given to the metabolic pathway utilized by most microorganisms (yeast and bacteria) and by all "higher" animals (including humans) for the degradation of glucose. , FDG is rapidly concentrated and well imaged, with a high tumor-to-background ratio. There is also concentration in the brain, urinary tract, and areas of inflammation.
Positron-emission tomography may be used as a diagnostic aid in evaluating pulmonary nodules/masses, extrathoracic staging, and monitoring therapy, as well as for mediastinal staging, which is the subject of this study.
MATERIALS AND METHODS
Between May 14, 1999, and November 28, 2000, all 104 patients evaluated for surgical resection for non-small cell carcinoma of the lung (NSCCL) were evaluated with CT and PET. Computed tomography scans Computed Tomography Scans Definition
Computed tomography (CT) scans are completed with the use of a 360-degree x-ray beam and computer production of images. These scans allow for cross-sectional views of body organs and tissues. varied by manufacturer, model, institution, and slice thickness (5 to 10 mm); all were conducted with intravenous contrast. Whole body PET scans were all done with an ECAT ECAT Escambia County Area Transit
ECAT Emergency Committee for American Trade
ECAT Electronic Commerce Action Team (New Zealand)
Ecat equilibrium catalyst
ECAT electronic card assembly and test
ECAT Electronic Commerce Acquisition Team model 951/31 Siemens-CTI (Siemens AG Siemens AG
German electrical-equipment manufacturer. The first Siemens company, Siemens & Halske, was founded in Berlin in 1847 to build telegraph installations. , Munich, Germany) with an axial field view of 10.8 cm and a full-width at half-maximal resolution of 6 mm.
Computed tomography scans were interpreted by the radiologist of record, the attending pulmonary medicine specialist, and the surgeon involved. If any of these 3 principals deemed the mediastinum mediastinum /me·di·as·ti·num/ (me?de-ah-sti´num) pl. mediasti´na [L.]
1. a median septum or partition.
2. positive or worrisome (or in doubt) for lymphadenopathy lymphadenopathy /lym·phad·e·nop·a·thy/ (-op´ah-the) disease of the lymph nodes.
angioimmunoblastic lymphadenopathy , angioimmunoblastic lymphadenopathy with dysproteinemia , the CT scan CT scan: see CAT scan.
See CAT scan. was classified as clinically positive (or indeterminate) for mediastinal spread of disease. Lymphadenopathy of the mediastinum was not solely defined by short-axis length / width of nodes. Rather, the whole image on the CT, including the primary tumor primary tumor A neoplasm which, in clinical parlance, is regarded as malignant, arising in one site and capable of giving rise to metastatic or secondary tumors. See Metastasis. Cf Tumor of unknown origin. , its size and location, and the appearance of the mediastinum, as well as the clinicians' impressions of the appearance and performance status of the patient, were considered in declaring the likely presence of mediastinal disease (positive for N2 disease). Disease spread to the mediastinum was to be either positive or negative according to clinical suspicion clinical suspicion A working hypothesis about a Pt's diagnosis, which is then tested with appropriately targeted tests to arrive at a definitive diagnosis; a CS is based on a constellation of findings in a Pt that suggests to the physician a limited palette of (preoperative) or pathologic fact (postoperative).
All patients had surgical excision of their lung tumor if it was benign. If it was malignant, they had surgical staging by mediastinoscopy, anterior mediastinotomy, and/or thoracotomy for primary lung resection and thorough mediastinal lymphadenectomy. All surgery was done by one surgeon. The Figure illustrates the definitions and calculations used to compare results of CT and PET. We use this experience to examine the utility of CT and PET in the staging of N2 disease in patients with NSCCL.
Of the 104 patients, 10 were found to have benign disease: 3 granulomas, 2 subpleural lymph nodes, and 1 patient each with hamartoma, abscess abscess, localized inflamation associated with tissue necrosis. Abscesses are characterized by inflamation, which is due to the accumulation of pus in the local tissues, and often painful swelling. , typical carcinoid carcinoid /car·ci·noid/ (kahr´si-noid) a yellow circumscribed tumor arising from enterochromaffin cells, usually in the gastrointestinal tract; the term is sometimes used to refer specifically to the gastrointestinal tumor , Schwannoma, and localized bronchiolitis obliterans with organizing pneumonia (BOOP BOOP Bronchiolitis obliterans organizing pneumonia A disease once considered a form of interstitial pneumonia Etiology Obscure; ? associated with toxic fumes, infection, connective tissue disease Clinical Cough, dyspnea, 'flu' symptoms, 50% recovery, 12% BOOPs ). Computed tomography did not delineate mediastinal metastases Metastasis (plural, metastases)
A tumor growth or deposit that has spread via lymph or blood to an area of the body remote from the primary tumor.
Mentioned in: Malignant Melanoma in any of these 10 cases, while PET erroneously indicated positive results in 1 case that was found to have no mediastinal metastases on pathologic examination.
Of the 94 patients with NSCCL, the primary tumors were worrisome for malignancy or indeterminate by CT in all cases. Positron-emission tomography was misleading in 4 cases, denoting benign disease, yet pathologically all 4 were adenocarcinomas with predominant bronchoalveolar features. Of 4 other patients with multicentric tumors, CT accurately predicted the number of separate malignancies in 2 (50%), PET in none.
This group of 94 patients with NSCCL forms the cohort of our study in examining the utility of CT and PET in preoperative recognition of mediastinal (N2) spread of disease. The presence or absence of likely mediastinal disease could not be characterized in 2 patients evaluated by CT and 6 patients evaluated by PET (Table 1). The most likely explanations for this were either the paratracheal and/or hilar hi·lar
Of or relating to a hilum. locations of their primary tumors (CT) or misinterpretation of whether hilar or mediastinal lymph nodes were imaged (PET). Of the remaining patients, the sensitivity in detecting N2 disease was 64% for CT and 88% for PET. The specificity in detecting the absence of N2 disease in these patients was 94% for CT, whereas for PET it was 86%. The positive and negative predictive values for CT were 80% and 88%, respectively, while for PET they were 71% and 95%, respectively. The overall accuracy of both modalities was 86%, excluding those cases judged to be indeterminate (Table 1).
Table 2 depicts the utility of CT and PET in delineating the presence or absence of mediastinal spread of disease in 8 patients treated with preoperative (neoadjuvant) chemotherapy and/or radiation therapy. For these patients, the sensitivity of both techniques was equal and marginal (50%), but PET had higher specificity, positive and negative predictive values, and overall accuracy.
Computed tomography resulted in 3 times as many false-negative results as PET regarding mediastinal status, whereas PET resulted in about twice as many false-positive results as CT (Table 1). While PET and CT were equally accurate (86%) in assessing untreated disease, PET outperformed CT in our small sample of patients treated neoadjuvantly (Table 2).
Comparing our results to 3 reports in the literature reveals a good amount of variability, with the exception of the negative predictive value of PET (Table 3). (3-5) The negative predictive value of PET consistently ranged from 93% to 95% among the 3 studies cited, which is reassuring when using PET to help select patients for resection.
It is difficult to know why the sensitivity of CT was so low in the experiences of Saunders et al. (3) Perhaps they narrowly assessed mediastinal adenopathy, without context of primary tumor size and/or location relative to the mediastinum. The experience of Pieterman et al (4) with PET in the Netherlands closely matches our own results.
The European experience (5) with minimal staging is cited in Table 3. Despite their results, mediastinoscopy/mediastinotomy does not assess subcarinal anatomy. The subcarinal area is precisely where noninvasive testing with methods such as CT and PET has great theoretical advantage. The advantage of combining an anatomic diagnostic test (CT) with PET, which depicts metabolically active nodules Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.
Mentioned in: Leprosy , seems to be borne out by others, (3,4,6) as well as our own results in which PET reduced the CT rate of false-negative results by two thirds.
We do not recommend using CT and/or PET in lieu of mediastinoscopy and/or anterior mediastinotomy in all cases. Similarly, we have not yet concluded that both CT and PET should routinely be used in all cases of suspected NSCCL. We are comfortable, when progressing directly to thoracotomy after negative CT and PET, performing thorough mediastinal lymphadenopathy at the time of resection of the primary tumor. We further recognize that others have shown that the routine use of PET after negative CT may be financially efficacious as well. (6)
For N2 disease in patients with NSCCL, directly proceeding to resection after negative CT and PET seems appropriate. Clinical appearance of disease may be misleading, however. (7) Watanabe (8) noted his institution's "true-positive rate of (N2 disease) was only 57% in patients pathologically evaluated post-resection following preoperative 'positive' CT scanning CT scanning
Computer tomography scanning is a diagnostic imaging tool that uses x rays sent through the body at different angles.
Mentioned in: Apraxia over the years 1980-1990." That same study noted that if all patients with the suggestion of N2 disease on CT were excluded from surgery, 39% of the ultimately resectable re·sect·a·ble
Suitable for resection. pathologic stage N0 and N1 patients would have been denied surgery. We agree with the opinion that "one does not cure NSCCL by unnecessarily excluding patients from surgery." (9)
Further, in our experience (10) and that of others, (11,12) minimal N2 disease has clearly been shown not to be associated with the devastating dev·as·tate
tr.v. dev·as·tat·ed, dev·as·tat·ing, dev·as·tates
1. To lay waste; destroy.
2. To overwhelm; confound; stun: was devastated by the rude remark. prognosis of bulky N2 disease. The 5-year survival rate of 42% in our patients with occult N2 disease (10) is matched by results reported from Memorial Sloan-Kettering (11) and Tufts, (12) in contradistinction con·tra·dis·tinc·tion
Distinction by contrasting or opposing qualities.
contra·dis·tinc to the vast majority of patients with stage N2 disease (90%) who have bulky disease bulky disease Oncology A term for a CA with a considerable tumor burden–'bulk'; BD generally has a poorer prognosis independent of the histologic grade; a major priority in oncology is to debulk a tumor to optimize chemo- or RT. See Debulking operation. , in whom the 3-year survival rate may be less than 10%. (11)
Non-small cell carcinoma of the lung is the leading cause of death from cancer. Refinements are being made in diagnostic tests in an attempt to reliably sort out patients with local, resectable disease from those with regional and distant metastatic disease, where optimum treatments may be neoadjuvant therapy Neoadjuvant therapy
Radiation therapy or chemotherapy used to shrink a tumor before surgical removal of the tumor.
Mentioned in: Thymoma
neoadjuvant therapy 1 Neoadjuvant chemotherapy, see there 2. or chemotherapy and radiotherapy with curative intent, respectively.
Based on our results, as well as others cited, (3,4) we believe that the addition of PET scanning to routine use of CT is progress in the direction of less invasive and more efficacious diagnosis and therapy. In our experience and the experience of others, (3,4) PET scanning seems to achieve a high negative predictive value (93% to 95%) in the evaluation of mediastinal disease. Positron-emission tomography seems to be particularly helpful in evaluating patients whose bulky nodes may persist on CT after chemotherapy and/or radiotherapy. Metabolically sensitive PET seems to achieve higher overall accuracy (88% vs 63%) in determining the persistence/absence of viable cancer after such therapy.
Test Result Mediastinal Pathology Positive Negative Positive True positive A B False positive Negative False negative C D True negative Definitions and calculations used to compare results of CT and PET: Sensitivity = accuracy in detecting individuals with disease = A/(A+C). Specificity = accuracy in detecting individuals without disease = D/(B+D). Positive predictive value = probability that disease is present when test is positive = A/(A+B). Negative predictive value = probability that disease is absent when test is negative = D/(C+D). Overall accuracy = percent correct classification of all individuals = (A+D)/(A+B+C+D). Scientific assessment according to documented pathology. TABLE 1 Mediastinal Status in Non-Small Cell Carcinoma of the Lung Mediastinal Pathology Positive Negative Total CT Results Positive 16 4 20 Negative 9 63 72 Total * 25 67 92 PET Results Positive 22 9 31 Negative 3 54 57 Total + 25 63 88 Positive Negative P Predictive Predictive Modality Sensitivity Specificity Value Value Accuracy CT 64% 94% 80% 88% 86% PET 88% 86% 71% 95% 86% * cases had indeterminate status. + 6 cases had indeterminate status. CT = Computed tomography PET = positron-emission tomography. TABLE 2 Mediastinal Status in Non-Small Cell Carcinoma of the Lung After Neoadjuvant Therapy Mediastinal Pathology Positive Negative Total CT Results Positive 1 2 3 Negative 1 4 5 Total 2 6 8 PET Results Positive 1 0 1 Negative 1 6 7 Total 2 6 8 Positive Negative Predictive Predictive Modality Sensitivity Specificity Value Value Accuracy CT 50% 67% 33% 80% 63% PET 50% 100% 100% 86% 88% CT = Computed tomography, PET = positron-emission tomography. TABLE 3 Comparison of CT and PET in Assessing the Presence or Absence of Mediastinal Pathology in Several Studies Study Hospital Kiernan et al Saunders et al (3) Modality (N = 94) (N = 84) CT Sensitivity 64% 20% Specificity 94% 90% +PV 80% 30% -PV 88% 84% PET Sensitivity 88% 71% Specificity 86% 97% +PV 71% 86% -PV 95% 93% Study Pieternan et al (4) (N = 102) Dillemans et al (5) CT 75% 72% 66% 100% NA - NA - PET 91% 72% 86% 100% 74% - 95% - + PV = Positive predictive value, - PV = negative predictive value, NA = not applicable.
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positron emission tomography (PET)
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JWG GCOS/GOOS Joint Working Group (Australia)
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Squamous cell or oat cell carcinoma that develops in the mucosa of the large bronchi and produces a persistent productive cough or hemoptysis. . J Thorac Cardiovasc Surg 1988; 95:876-882
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IIIA Integrated Intelligence Information Application
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RELATED ARTICLE: KEY POINTS
* Overall accuracy for computed tomography (CT) and positron-emission tomography (PET) is approximately the same--in our experience, 86%.
* False-negatives occurred three times more commonly with CT; false-positives occurred two times more often with PET.
* Positron-emission tomography seems to achieve a high negative predictive value (93% to 95%) in the evaluation of mediastinal disease.
* Positron-emission tomography seems to be particularly helpful in evaluating patients with bulky nodes that may persist after chemotherapy and/or radiation therapy as delivered neoadjuvantly.
From the Sections of Thoracic Surgery Thoracic Surgery Definition
Thoracic surgery is the repair of organs located in the thorax, or chest. The thoracic cavity lies between the neck and the diaphragm, and contains the heart and lungs (cardiopulmonary system), the esophagus, trachea, pleura, and Pulmonary Medicine, and the Department of Medicine, Inova Fairfax and Inova Alexandria Hospitals, Fairfax and Alexandria, Va.
Reprint requests to Paul Kiernan, MD, 3301 Woodburn Rd. Suite 301, Annandale, VA 22003.