Weekly chemotherapy with cisplatin and paclitaxel in advanced NSClC: a phase II study.

BACKGROUND: This phase II study was designed to assess the activity and toxicity of administration of the cisplatin/paclitaxel combination in advanced non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included: age up to 70 years, pathological diagnosis of NSCLC, inoperable disease or post-operative tumour recurrence, performance status < or =2, no severe co-morbidity, no previous chemotherapy, and informed consent. Treatment consisted of intravenous infusion of cisplatin, 25 mg/m2, and paclitaxel, 80 mg/m2, every week. Chemotherapy was continued until completion of a 22-week treatment plan, disease progression, persistent toxicity, or patient refusal. RESULTS: Forty-nine patients entered the study. They received a median of 14 cycles (range 0-22). For both drugs, the median dose-intensity was 75% of projected. Toxicity was generally acceptable, and never life threatening. Alopecia was the most common side effect, followed by anemia, leukopenia, and nausea/vomiting. Twenty patients responded (40.8% response rate), with three complete, pathologically documented responses. The estimated median time to progression was 35 weeks (95% CI: 29-41); the median survival time was 56 weeks (95% CI: not calculable), with a 2-year survival rate of 46.1%. CONCLUSIONS: When given on a weekly basis, the cisplatin/paclitaxel combination is well tolerated, active, and associated to remarkably long survivals.

A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer. Cuneo Lung Cancer Study Group (CuLCaSG)

Combination chemotherapy with anti-proliferative agents is the usual treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anti-cancer activity of conventional cytotoxic drugs, with no increase of specific toxicity. Following a pilot study of feasibility, we now report the results of a randomised trial evaluating MACC chemotherapy, as originally described, versus the same regimen+LND. 151 patients with advanced NSCLC were assigned at random to the two treatment arms. LND 150 mg was given orally three times daily. Treatment was continued until progression of disease, unacceptable toxicity or refusal by the patient (median number of cycles of MACC, three for both arms; median duration of LND administration, 8 weeks in the arm concerned). Actual dose intensities (DI) of MACC and LND were, respectively, 100 and 83% of those intended (median values). There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient, but no correlation between the duration of treatment with LND and its DI. DIs of LND and MACC were not correlated with each other. In all, 15 objective responses (one complete and four partial responses in the MACC group, 10 partial responses in patients on MACC+LND) were observed. Median progression-free survivals were 20 weeks (confidence interval, CI 14-22) for the group on LND and 17 weeks (CI 12-17) for the control group (non-significant difference). Median overall survivals were, respectively, 30 weeks (CI 23-40) and 27 weeks (CI 22-34), P = non-significant. Toxicity was as expected by the use of MACC, and similar in both arms, except for more severe anaemia and gastric toxicity in the group on MACC+LND. Other uncommon side-effects, seen only in this latter group, were mild to moderate and reversible and included myalgia, asthenia, testicle pain, headache, visual troubles, incubi and dizziness. Subjective tolerance to the treatment, and perception of physical and psychological well-being were rated similarly by patients of both groups. MACC plus LND is a moderately active regimen in advanced NSCLC, with a foreseeable and reversible toxicity of low-medium grade. Potential enhancements of anti-tumour efficacy of chemotherapy, and possible host survival benefits derived from the use of LND are not substantiated by the results of this trial.

Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution.

The Karnofsky's index of performance status (KPS) and the Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) are widely used methods of assessing the functional status of cancer patients. In this study, we compare their predictive validity, and suggest a table of transformation between scales. 536 consecutive lung cancer patients were assigned both KPS and ECOG PS scores before, during and after treatment (in all, 1656 assignments). Patients were accurately staged at diagnosis, and carefully re-evaluated at each follow-up visit. Multiple clinical, laboratory and instrumental data were recorded along with performance status assessments. Survival times were measured from the pathological diagnosis. KPS and ECOG PS assignments were strongly related to each other (Spearman R = -0.869). Correlation between scales persisted unchanged in pretreatment and post-treatment assessments, advanced and limited diseases, response or non-response to treatment, and different assessors (R indices ranging from -0.825 to -0.901). A three-point conversion table showed the highest rate of success with an overall percentage of agreement exceeding 84% (grade 1: KPS = 100, 90, 80 and ECOG PS = 0, 1; grade 2: KPS = 70, 60 and ECOG PS = 2; grade 3: KPS < 60 and ECOG PS = 3, 4). Both univariate and multivariate analyses of survival documented the predictive validity of the two scales. However, KPS showed less ability than ECOG PS to discriminate patients with different prognosis. Because of the better predictive ability shown in this study, ECOG PS should be preferred to KPS. A general consensus on the scale to use could avoid problems of conversion, which is not always easy and free of errors.

Haemostatic abnormalities in lung cancer: prognostic implications.

Both experimental and clinical data have shown that coagulation disorders are common in patients with cancer although clinical symptoms occur rarely. A prethrombotic state is probably involved in the mechanism of metastatic spread. Anticoagulant treatment, with either warfarin or heparin, has been shown to have a positive influence in small cell lung cancer. The purpose of this study was to evaluate the prethrombotic state as a possible marker of the outcome of lung cancer. Pretreatment prothrombin time (PT), partial thromboplastin time (PTT), antithrombin III (AT-III), platelet blood count (P), fibrinogen (F) and D-dimer (DD) were prospectively recorded in a series of 286 consecutive patients with a new primary lung cancer. Other recorded variables (32 in all) consisted of a set of anthropometric, clinical, physical, laboratory, radiological and pathological data. All patients were carefully followed up, and their subsequent clinical course recorded. Spearman rank correlation tests between coagulation factors were weakly significant, or more often non-significant. The best correlation index was that between PT and PTT (ra = -0.25). Univariate analyses of survival showed that a prolonged value of PT (P = 0.00167) and higher values of F (P = 0.00143) and DD (P = 0.0005) were associated with a poor prognosis. A few, weak relationships between well-known prognostic variables and coagulation abnormalities were also found. Because of the weakness of this correlation pattern, coagulation factors emerged in all the Cox's regression analyses as important predictors of survival, regardless of the number and type of cofactors used. A prethrombotic state (depicted by a prolongation of PT and increase of DD) is confirmed in this study as an aggravating condition in lung cancer. Studies attempting to reverse possible haemostatic abnormalities with the use of anticoagulants are justified by the present data.

Detection of suspected primary lung cancer by scintigraphy with indium-111-anti-carcinoembryonic antigen monoclonal antibodies (type F023C5)

Immunoscintigraphy with 111In-labeled anti-CEA-Mab (F023C5i) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was centrally located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies.

Aspects of quality-of-life in patients with lung-cancer - a 3 observer evaluation study.

Only 5 to 10 % of patients with lung cancer can expected to be cured by radical treatments. In the remaining subjects the potential survival benefit of the treatment must be weighed, taking into consideration the possible deterioration of their quality of life (QL). A problem arising from this evaluation is the subjective variability of measurements. We distributed 279 QL instruments to 71 patients, their relatives, and the doctors responsible for their management. Each instrument bore 3 simple questions concerning patients' treatment tolerance, physical well-being, and psychological condition. We collected in all 267, 252, and 147 questionnaires completed by patients, doctors, and relatives, respectively. Correlations between replies were all statistically significant. Patients and relatives manifested the highest degree of interobserver agreement, while doctors and relatives the lowest. Differences in the QL assessment from different observers were also highly significant. Relatives were generally the most pessimistic raters. In comparison with patients, doctors judged more favourably treatment tolerance, but estimated quite similarly physical well-being and the emotional status. Doctors were the most reliable raters of chemotherapy tolerance, on the basis of the highest degree of correlation between their replies and the standard grading of toxicity. The results of this study may help physicians dealing with incurable patients with lung cancer to give the most appropriate weight to potentially differing perceptions of QL.

Nuclear medicine imaging in lung cancer.

The evaluation of the anatomical dissemination of lung cancer has a pivotal role in the choice of the most appropriate treatment modality. The techniques of nuclear medicine are founded on the use of different radiopharmaceuticals capable of exploiting the specific characteristics of malignant tissues. They may recognise diverse cell densities, growth rates, metabolic pathways, antigenic and surface receptor expressions. In the past, the use of Co-57-bleomycin and, then, of (67)Gallium has encountered a mixed acceptance among nuclear medicine specialists, with favourable reports claiming their utility, and others with more sceptical opinions. It is generally admitted that both Co-57-bleomycin and (67)Gallium scintigraphies are quite sensitive and rather accurate. Their use, however, is almost abandoned in favour of more innovative and encouraging approaches, including non-specific radio-tracers ((201)Thallium and Tc-99m-sestamibi), substances useful in particular clinical applications (the somatostatin analogues I-123-tyr(3) and the In-111 octreotide for neuronendocrine tumours), radio-labelled monoclonal antibodies, and the recently introduced positron emission tomography. Promising results with each of these techniques need to be further substantiated, before their entering into clinical practice. However, the abundance of choices offered by nuclear medicine might reasonably bring forward the ideal noninvasive test. We review the many scintigraphic methods investigated so far and their clinical significance.

Usefulness of tissue polypeptide antigen in staging, monitoring, and prognosis of lung cancer.

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.

Cranial computed tomography as a part of the initial staging procedures for patients with non-small-cell lung cancer.

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.

Prognostic value of the tissue polypeptide antigen in lung cancer.

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.

Serum biomarkers facilitate the recognition of early- stage cancer and may guide the selection of surgical candidates: a study of carcinoembryonic antigen and tissue polypeptide antigen in patients with operable non-small cell lung cancer.

OBJECTIVES: Copious literature shows that in lung cancer many serum markers, especially the cytokeratin degradation products, correlate with the extent of disease. In 1995, we suggested the possibility of predicting the resectability of non-small cell lung cancer by measuring the plasma level of the tissue polypeptide antigen, a marker of the cytokeratin family. This study was designed (1) to confirm the earlier data in a new prospective evaluation, (2) to comparatively assess another classic biomarker (ie, the carcinoembryonic antigen), and (3) to incorporate their results into the preoperative evaluation of non-small cell lung cancer. METHODS: We analyzed the database of a single institution over a 5-year period (1994-1998) in a community-based hospital and second referral level institution for a province of 500,000 people. The database included 124 consecutive patients (105 men) with pathologically documented lung cancer (50% with adenocarcinoma) accurately staged, clinically judged operable or potentially operable, and eventually operated on. Anthropometric, clinical, and laboratory data (including the carcinoembryonic antigen and tissue polypeptide antigen serum levels) and the results of a complex staging workup were prospectively recorded. Receiver-operating characteristic curves and diagnostic formulas were used for data analysis. RESULTS: Computed tomography of the thorax, upper part of the abdomen, and brain was the most accurate preoperative method to assess tumor resectability (receiver-operating characteristic area: 0.76, 95% confidence intervals: 0.67-0.86, P =.000; accuracy rate: 77%, confidence intervals: 69%-84%). Tissue polypeptide antigen was also predictive for tumor resectability (receiver-operating characteristic area: 0.62, 95% confidence intervals: 0.51-0.73, P =.035; accuracy rate at a threshold level of 110 U/L: 65%, 95% confidence intervals: 56%-73%). Carcinoembryonic antigen was diagnostic only at the extreme values of its distribution (accuracy rate at a level up to 10 ng/mL: 69%, 95% confidence intervals: 60%-77%). The probability of finding resectable disease at the time of the operation increased from 78% (baseline computed tomography-based probability) to 83% when the concentration of tissue polypeptide antigen was lower than 90 U/L and to 85% when the concentration of carcinoembryonic antigen was below 10 ng/mL. The probability of discovering an advanced disease increased from 68% (baseline computed tomography-based probability) to 89% when tissue polypeptide antigen levels were abnormal and to 100% when carcinoembryonic antigen concentrations were higher than 10 ng/mL. Conversely, the predictability of computed tomography was diminished by contrasting biomarker results, requiring further clinical investigations. CONCLUSIONS: Computed tomography remains the gold standard for the preoperative evaluation of non-small cell lung cancer, although it may significantly underestimate the real tumor extension. The addition of the easy and inexpensive tissue polypeptide antigen test (with or without carcinoembryonic antigen) is capable of correcting this underestimation and helps to decide whether to completely rely on computed tomography or order additional clinical investigations.

Prognostic value of stage grouping and TNM descriptors in lung cancer.

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.

The tissue polypeptide antigen serum test in the preoperative evaluation of non-small cell lung cancer. Diagnostic yield and comparison with conventional staging methods.

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.

Exercise testing in radiologically-limited, simple pulmonary silicosis.

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.

Diagnostic, morphologic, and histopathologic correlates in bronchogenic carcinoma. A review of 1,045 bronchoscopic examinations.

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.

Soluble interleukin 2 receptor in lung cancer. An indirect marker of tumor activity?

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.

Anti-CEA immunoscintigraphy might be more useful than computed tomography in the preoperative thoracic evaluation of lung cancer. A comparison between planar immunoscintigraphy, single photon emission computed tomography (SPECT), and computed tomography.

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.

Lung tumor markers of cytokeratin origin: an overview.

Lung tumor markers fall into several categories including oncofetal proteins, structural proteins and their fragments, enzymes, membrane antigens, peptide and non-peptide hormones. Cytokeratins (CK) are well known structural proteins whose degradation gives rise to soluble fragments, measurable in the blood of patients and capable of cancer marking. Among them, Tissue Polypeptide Antigen (TPA), Tissue Polypeptide-Specific Antigen (TPS) and Cytokeratin-19-Fragments (Cyfra 21-1) are the most studied CK fragments' complexes. This article will review biological characteristics and clinical properties of these substances, emphasizing as their concentration in the peripheral blood might reflect the mass of tumor, the rate of cancer cell lysis, and other potentially unfavorable tumor characteristics. Assaying the concentration of CK fragments in the blood is an easy and effective way to assess lung cancer and monitor its clinical evolution.

Serum biomarkers of non-neuron-endocrine origin in small-cell lung cancer: a 16-year study on carcinoembryonic antigen, tissue polypeptide antigen and lactate dehydrogenase.

BACKGROUND: Biomarkers of non-neuron-endocrine origin are measured only occasionally in the sera of patients with small-cell lung cancer (SCLC). An exception to this rule is carcinoembryonic antigen (CEA), for which, however, there is no consistent evidence. Based on such a premise, we decided to review the Cuneo Lung Cancer Study Group 16-year-experience with non-neuron-endocrine markers in SCLC. METHODS: a total of 619 CEA, 621 tissue polypeptide antigen (TPA), and 616 lactate dehydrogenase (LDH) serum assays were obtained from 160 consecutive SCLC at diagnosis, during, and after treatment. Demographic, clinical, laboratory, and tumoral correlates were also available for another 25 pretreatment and 14 posttreatment variables. RESULTS: bivariate correlation analyses showed that LDH and TPA were significantly related to each other, and both of them were also correlated with disease extent, and treatment response. LDH correlation indexes were higher than that of TPA, especially those regarding the parameters of disease extent. CEA was correlated only with the category of treatment response. Receiver-operating characteristic (ROC) analysis confirmed the correlation between stage disease at diagnosis and both LDH (P = 0.000) and TPA (P = 0.002), while the treatment failure was better recognized by TPA (P = 0.000). In univariate analysis, both LDH and TPA were correlated with survival (P = 0.000 and 0.092, respectively); however, only LDH remained significant in multivariate analysis (P = 0.012). CONCLUSIONS: the evidence from this study does not suggest a routine CEA test in SCLC. LDH remains particularly useful and it should be kept in use. Finally, data on TPA is insufficient to advocate its systematic use in this type of malignancy.

Therapeutic options for regionally advanced non-small cell lung cancer.

The optimal treatment for regionally advanced non-small cell lung cancer (NSCLC, Stage IIIa/IIIb) remains unknown. Proposed approaches include surgery, radiotherapy, chemotherapy, and combinations of these. No treatment modality, however, has ever shown other than modest or minimal beneficial effects. When differences between new and old treatments appear trivial, as in the management of the locally advanced NSCLC, controlled studies are necessary to select the best approach. This review is based on a systematic overview of data from randomized trials comparing different treatment modalities. The following six points emerged from the cited literature. (1) It is sufficiently proved that chemotherapy alone prolongs survival in patients with both locally advanced and metastatic disease. (2) Although it is probably true that radiation therapy is better than no active treatment, this idea is supported by very limited evidence. (3) Although it is probably also true that radiotherapy alone is not worse than chemotherapy alone, this is another insufficiently proved issue. (4) The possible superiority of chemo-radiotherapy to chemotherapy alone or to supportive care is also poorly documented. (5) There is abundant evidence that chemo-radiotherapy is better than radiotherapy alone (however, this information may be unhelpful if point 2, or 3 remains unclarified). (6) Although neoadjuvant treatments have improved resectability and may ensure overall better results, the surgical cure, either alone or in combination with chemotherapy or chemo-radiotherapy, is another unproved option. Based on the above six points, it was concluded that new randomized studies are urgently needed to confirm the possible superiority of chemo-radiotherapy to chemotherapy. Only after such a validation, will the many ongoing trials, designed to prove the possible superiority of local surgical control to the more traditional approaches based on thoracic irradiation, have a practical sense.