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Study Objectives: We have longstanding experience with tissue polypeptide antigen (TPA), a tumor marker of the cytokeratin (CK) family. In the mid-1990s, a new CK marker, CK 19 fragments (CYFRA 21-1), became popular and widely accepted. This is the first study specifically designed to compare the two markers.Design: Analysis of a single institution database over a 3-year period (ie, 1998 to 2000).Setting: Community-based hospital and second referral level institution for a province of 500,000 people.Patients: The study included 180 new consecutive patients (143 men) with pathologically documented non-small cell lung cancer (NSCLC), who were observed during and after treatment, and eventually were assessed for status.Interventions: Anthropometric, clinical, and laboratory data, including TPA and CYFRA 21-1 serum levels, were recorded prospectively. Standard nonparametric tests, Kaplan-Meyer survival analyses, Cox proportional hazards models, receiver-operating characteristic (ROC) curves, and estimates were used for statistical analysis.Measurements and Results: A total of 1,299 twin TPA and CYFRA 21-1 serum assays (180 performed at diagnosis and 1,119 performed during or after treatment) were obtained. Intermarker correlation tests revealed incredibly high Spearman rho indexes, ranging from 0.935 at diagnosis to 0.813 to 0.921 at the different follow-up times. The substantial equivalence of the two tests explained all the other results, as follows: their similar profile of correlation with the other variables (objective treatment response: TPA rho, 0.456; CYFRA 21-1 rho, 0.463; follow-up performance status: rho range, 0.424 to 0.435); their superimposable capability to predict important clinical situations (eg, recognizing a metastatic disease at diagnosis with areas under the ROC curve of 0.742 and 0.706, respectively); their nearly identical prognostic significance (the D statistic of the goodness-of-fit of a multivariate survival model: TPA, 851.0; CYFRA 21-1, 851.6).Conclusions: In most of their traditional clinical applications the two serum tests are equivalent because of their virtual identity. We strongly recommend using a CK test in the evaluation of each NSCLC patient. The choice between TPA and CYFRA 21-1 can be based on nonclinical factors, such as the laboratory experience or preference, and the cost of the two kits. [ABSTRACT FROM AUTHOR]

Study Objectives: The International Staging System for Lung Cancer (ISSLC) was revised in 1997. Validation studies are numerous but include only selected surgical patients. This study aims to verify the following: (1) the reliability of the ISSLC in an unselected lung cancer population; (2) the likely improvement in prognostic capability of the new classification; and (3) the possibilities for further improvements., Design: Analysis of a single institution database over a 16-year period from 1983 to 1998., Setting: Community-based hospital and second referral level institution for a province of 500,000 people., Patients: The study included 1,296 consecutive patients (1,117 men), with pathologically documented lung cancer (46% with squamous cell cancer), staged both clinically (77%) and pathologically (23%), and treated, for the most part, with chemotherapy (52%)., Interventions: Anthropometric, clinical, and laboratory data were recorded prospectively. Survival analysis was performed by the Kaplan-Meier method and Cox multivariate regression analysis., Measurement and Results: The 1997 revised ISSLC classification fit well with the cohort studied. Each stage and substage significantly differed from each other, except for stage IIA. In this stratum, there were only 13 patients. Comparing the 1986 and the 1997 classifications, no substantial differences were observed (log-rank statistics, 295 vs 293, respectively; p < 0.0001). Independent of the classification used, the Cox models were always highly predictive of the outcome. The only way to increase their efficiency was to replace the variable stage with the original TNM descriptors., Conclusions: Since grouping different TNM subsets into one stage is not really helpful, we might choose to use TNM descriptors in clinical practice and in research.

Tissue polypeptide antigen (TPA) is a protein produced and released by proliferating cells that has been shown to possess several characteristics for an ideal tumor marker. Our purpose was to determine the yield of TPA in the pretreatment assessment of non-small cell lung cancer (NSCLC), in comparison with a baseline clinical evaluation and multiorgan computed tomography (CT) assumed to be the gold standard for presurgical staging. One hundred four patients with NSCLC underwent thoracotomy, mediastinoscopy, or biopsy of suspected metastatic deposits, in addition to an extensive noninvasive evaluation of their stage of disease. We restaged retrospectively (UICC 1987 classification) these patients, on the basis of the following: (1) clinical history and physical examination, routine laboratory tests, bronchoscopy, chest radiographs, and any other examination as indicated by the prior baseline evaluation (BE stage); (2) the serum level of TPA (TPA stage); (3) the reading of a CT scan of brain, thorax, and abdomen obtained with no limitation to clinical information (CT stage); and (4) pathologic findings (RE stage). The TPA stage was calculated using 20 threshold values ranging from 45 U/L to 450 U/L. On the basis of the RE stage, sensitivity, specificity, accuracy, and predictive capabilities of BE, CT, and TPA were determined for stage I and II (full operability, FO), stage IIIa (possible operability, PO), and stage IIIb and IV (full inoperability, FI). The TPA thresholds were 110 U/L for detecting FO with the highest rate of success, and 160 U/L for detecting FI. Using these thresholds BE, CT, and TPA showed a diagnostic accuracy of, respectively, 75%, 79%, and 68% for FO; 87%, 69%, and 77% for PO; 87%, 77%, and 76% for FI. The accuracy of BE, CT, and TPA for both FO and FI was, respectively, 85%, 69%, and 69%. Of 74 patients classified operable by BE, 6 had a serum concentration of TPA less than 50 U/L and all 6 were confirmed in stage I or II at the subsequent thoracotomy; 15 others, out of 26 patients judged to have inoperable conditions by BE, had a TPA test result above 135 U/L and all 15 were pathologically classified in stage IIIb or IV. Using appropriate threshold values of TPA, it should be possible to predict NSCLC resectability with a diagnostic accuracy similar to that routinely achieved by CT.

With the possible exception of chemotherapy for the small-cell type, a complete surgical excision is still the only effective treatment of lung cancer. Routine brain computed tomography (CT) for staging purposes has been both advocated and opposed. In this retrospective study, we aimed to assess the clinical yield of the technique. We saw 184 consecutive patients with a new histologically proven non-small-cell lung cancer. Using as reference criteria clinical judgment supported by a strict follow-up evaluation, we counted 1 false- and 23 true-positive brain CT results, plus 2 false- and 158 true-negative findings. These figures allow for sensitivity, specificity, and accuracy of 92 percent, 99 percent, and 98 percent. The frequency of brain metastases did not correlate with the various histologic types, even though adenocarcinoma was the most common cause of cerebral metastases. The absence of neurologic symptoms did not exclude cerebral involvement: in our experience, 16 of 25 patients with positive brain CT scans were asymptomatic (64 percent). Three of 31 subjects (10 percent) with an otherwise operable carcinoma were found to have metastases after brain CT. We conclude that routine cranial CT is useful in the staging evaluation of the patient with non-small-cell lung cancer (NSCLC) and that it should be performed in any candidate prior to surgical resection.

While a clinical, plain radiographic, and bronchoscopic assessment yields most of the essential information needed in lung cancer, computed tomography (CT) of the thorax provides diagnostic information previously unobtainable, potentially capable of reducing the number of explorative thoracotomies. In a few recent studies, immunoscintigraphy with anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies (MA) has shown remarkable staging potential. To compare the diagnostic accuracy of the two techniques, we photoscanned with indium-111 (111In)-labeled-F(ab')2 fragments of the murine anti-CEA MA FO23C5 45 patients, who were pathologically assessed for possible loco-regional extension of lung cancer. Both planar and single photo emission computed tomography (SPECT) images were obtained. Additionally, CT of the thorax (contiguous CT slices, 10 mm thick, from the lung apices to the upper abdomen), and other routine tests of preoperative evaluation were obtained. On the basis of 37 (N1, T3, and T4), 38 (N2), and 12 (N3) pathologically documented sites, an accuracy of 65, 76, 92, 78, and 86 percent (SPECT images), and 62, 68, 42, 78, and 84 percent (CT images) was calculated (figures are relevant to N1, N2, N3, T3, and T4 disease, respectively). Thus, both techniques shared a significant margin of error in almost all the categories of evaluation; however, immunoscintigraphy showed equivalent, and, in the lymph node assessment, superior results to CT. A marginal improvement of diagnostic accuracy was recorded combining the three techniques in one case (SPECT plus planar immunoscintigraphic images), while there was no benefit in any possible integration of CT and immunoscintigraphic images. In patients with peripheral nonsquamous cell cancers, the accuracy of anti-CEA immunoscintigraphy was of 90 percent or higher. Variations in the modality of performing immunoscintigraphy, such as changes in the dose of antibody fragments to be injected, in the percentage of radiolabeling, or in the time of imaging, affected the quality of immunoscintigraphic series, and the consequent interpretation of findings. At the present time, there are very few reliable tests capable of selecting patients to proceed directly to thoracotomy or to receive some intermediate surgical test, such as a prior mediastinoscopy. Traditionally, CT has been this type of "filter-test." If current findings will be confirmed in future studies, anti-CEA immunoscintigraphy might replace CT in the evaluation of particular subgroups of patients, such as patients with peripheral nonsquamous cell bronchogenic carcinoma.

The prognostic impact of TPA was evaluated by assaying the marker in the serum of 563 patients with a newly diagnosed bronchogenic carcinoma. The group included patients with squamous cell cancers and others with tumors of diverse or undefined histologies. Raised levels of TPA were clearly associated with a shortened survival, even adjusting for the stage of disease. A Cox's proportional hazards regression analysis, incorporating all major prognostic factors, selected TPA as an independent survival predictor. In the regression model, however, TPA was less important than disease extent, KPS and weight loss. Another multivariate analysis was made in a subgroup of 121 patients who, because of poor KPS or advanced age, had undergone a limited staging workup; TPA came out as the first most important factor. This study shows that TPA is an important prognostic factor and that it should be included among laboratory data evaluated in lung cancer studies.

Circulating levels of the soluble interleukin 2 receptor (sIL-2R) could provide an in vivo measure of the immunologic response to human tumors. We performed a total of 326 sIL-2R serum assays in 126 patients with lung cancer (67 at diagnosis, 59 during and after treatment), 112 patients with pulmonary benign diseases, and 63 voluntary healthy subjects. Patients with lung cancer had a median value of sIL-2R of 791 U/ml, which was superior to that of both controls (398 U/ml, p less than 0.001) and patients with noninflammatory benign diseases (583 U/ml, p less than 0.02). However, infectious pulmonary disorders, such as tuberculosis and pneumonia, were associated with the highest values of the substance (median, 1150 U/ml; p less than 0.001). At the diagnosis of lung cancer, sIL-2R correlated neither with the stage of disease nor with the cell type. On the contrary, posttreatment levels of the receptor were significantly related to disease status (RO = .41, p less than 0.002), particularly in the subgroup of nonsurgical patients (RO = .48, p less than 0.001). Patients with abnormal sIL-2R levels had a nearly significant reduction in survival as compared with patients with normal values (p less than 0.1). Measurements of sIL-2R could be useful in monitoring patients under treatment for bronchogenic carcinoma, as well as in prognostication. In this setting, sIL-2R might open a new class of biologic markers, providing information that is complementary to those of the more classic tumor-derived markers.

Information on the correlation between bronchoscopically visible aspects, histopathologic classification, and diagnostic yield is very scarce. To contribute to the knowledge of the subject, we reviewed the bronchoscopic charts of 1,045 patients with lung cancer who were seen in the years from 1983 to 1989 at the Bronchology Service of the A. Carle Hospital. Tumors were more often located centrally and superiorly. No preference as to side was found. Squamous carcinomas were, by far, the most frequent cell type. Forceps biopsies, brushings, and washings were positive in 79 percent, 38 percent, and 32 percent of the obtained specimens, respectively. Bronchoscopically, squamous and small-cell carcinomas were more often visualized as central tumor-like lesions, which were better diagnosed by forceps biopsies. Adenocarcinomas, on the contrary, were more frequently peripheral and showed infiltrative, compressive, or aspecific findings. In these latter tumors, cytologic studies were more fruitful. Large-cell anaplastic carcinomas had an intermediate behavior. Cell type, endoscopic appearance, and diagnostic success are interrelated features. Visible characteristics at bronchoscopy can therefore anticipate the more likely histotype and guide the diagnostic approach.

A study of tissue polypeptide antigen (TPA) serum levels was conducted in patients with various cell types of bronchial carcinoma. A total of 548 assays (226 pretreatment) were evaluated. In all, the sensitivity of the test at diagnosis was 61 percent. It varied considerably in relation to the extent and site of disease. Individual pretreatment values of TPA correlated significantly with the stage of disease. Similarly, posttreatment TPA values related to disease evolution. In small cell carcinoma, eight of the 29 meaningful changes in follow-up levels of TPA preceded clinical recognition of disease status variations. Raised pretreatment values of TPA were significantly associated with a shortened survival. These results indicate that TPA may contribute to staging, monitoring, and prognosis of lung cancer.

Forty-five consecutive patients (17 non-smokers and 28 smokers) affected by pulmonary silicosis with limited profusion of radiologic small opacities of "p" type underwent physical examination; resting standard pulmonary function tests (PFT); and progressive, multistage, treadmill-based exercise testing (ET). Results show that, in 78 percent of all patients, maximum oxygen uptake (VO2max) was below 80 percent of predicted, and in most cases this was accompanied by a reduction of anaerobic threshold and/or oxygen pulse. In our group, VO2max predicted was uncorrelated with PFT parameters, symptoms and x-ray picture. No significant differences in response to exercise were observed between smokers and non-smokers. Therefore, exercise was limited by factors other than ventilatory limitation. It is concluded that ET is not more sensitive than PFT for assessing ventilatory impairment in patients with early, simple silicosis, even though it may be valuable for providing information about other sources of exercise limitation.