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.

Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and other prognostic indicators in squamous cell lung cancer.

Multivariate models of survival have been established for both small cell and non-small cell lung cancers. So far, no study has focussed on squamous cell types. Previous demonstrations of the prognostic value of the tissue polypeptide antigen (TPA) and, partially, of the carcinoembryonic antigen (CEA) are based on univariate analyses of survival. These analyses do not account for the other prognostic factors. In the present study, we report the combined influence of various clinical and biological characteristics on the survival duration of 360 patients with a newly diagnosed squamous cell carcinoma of the lung. The study comprised 29 variables, including age, sex, smoking habit (SH), symptoms at diagnosis, the Karnofsky performance status (KPS), weight loss (WL), radiological findings, various disease extent parameters (DEP), CEA and TPA. Preliminary univariate analyses showed that 20 variables were survival-related. The Cox proportional hazards regression analysis selected stage of disease, KPS, TPA, WL, the existence of bone metastases, and SH as independent factors of prognosis (global chi-square: 122.40, P = 0.0000). A second multivariate analysis, performed with the same covariates but excluding DEP, revealed previous pulmonary diseases and CEA to be, in addition to KPS, TPA, SH, and WL the next most influential prognostic determinants. Also in squamous cell lung cancer, classifications based on the Cox's prediction equation may improve individual counseling and patient selection for therapeutic trials. In this malignancy, TPA shows an independent and strong prognostic significance while CEA shares informations of diverse other prognostic factors and seems to be less important.

Yield of total body GA-67 scintigraphy in the staging of non-small cell lung cancer.

One hundred and one patients with histologically proved non-small cell lung cancer underwent whole body gallium-67 (TB Ga-67) scintigraphy as a part of their routine pretreatment evaluation. Twenty-eight of these patients were subsequently operated and pathologically staged for hilar and mediastinal disease. Two other patients underwent mediastinoscopy, but were judged unresectable at that time. All had computed tomography (CT) of the thorax, as well as radionuclide or CT scans of suspicious metastatic areas, and were carefully followed-up. When possible, a biopsy was performed of each suspected metastasis. Primary lung tumors concentrated Ga-67 in 94 patients. Sensitivity, specificity, and accuracy for hilar and mediastinal node metastases were 58%, 89%, and 77%, respectively. There were no false-negative gallium scans as regards secondary involvement of both liver and bone, whereas only 1 of the 4 brain metastases was detected by the technique. Sensitivity, specificity, and accuracy for all metastatic sites were 82%, 38%, and 56%, respectively. Fifty-five patients were classified as having a more advanced stage of disease by TB Ga-67 scintigraphy than at the initial clinical evaluation. However, 42 gallium-staged patients were ultimately re-classified differently according to all available clinical data. Using TB Ga-67 scintigraphy, 21 patients were found to have occult metastases which would not otherwise have been recognized; for the above reason, an unnecessary intervention was avoided in 6 of them.

Combination chemotherapy with methotrexate, adriamycin, cyclophosphamide and CCNU (MACC) for nonsmall cell lung cancer. 4-year experience with 92 patients.

Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated with a combination chemotherapy containing methotrexate, adriamycin, cyclophosphamide and CCNU (MACC). The regimen was administered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 51 weeks. The remaining 70 evaluable patients were nonresponders. These latter patients had a survival probability reduced to 29 weeks. Median time to progression for the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiolo-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosuppression, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively infrequent. Polychemotherapy with MACC regimen may benefit a few selected patients with NSCLC, but its overall antitumor efficacy appears to be very limited.

Continuation of chemotherapy versus supportive care alone in patients with inoperable non-small cell lung cancer and stable disease after two or three cycles of MACC. Results of a randomized prospective study.

Recommendations concerning the continuation of chemotherapy in nonresponding patients with non-small cell lung cancer (NSCLC) and stable disease after the first chemotherapy test are empirical and often conflicting. Between 1984 and 1987, 116 inoperable NSCLC patients were treated with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC regimen). After two or three cycles of therapy, 74 patients were judged to have stable disease and assigned at random either to chemotherapy maintenance with the same regimen (38 subjects) or to chemotherapy discontinuation (36 subjects). The two study groups were comparable for all the major prognostic factors. Median time to progression was 26 weeks for the chemotherapy group compared to 24 weeks for the nonchemotherapy group (P = NS). Median survival was prolonged in the treatment arm (47 weeks) compared to nontreatment arm (30 weeks), which was statistically nonsignificant. A patient self-assessment of the quality of life revealed a significantly worse tolerance to therapy and a better physical condition in the chemotherapy group. Objective MACC toxicity was significant with two treatment-related deaths. This study failed to demonstrate sufficient therapeutic benefits to justify the increased cost and toxicity of continuing treatment in nonresponding NSCLC patients.

Clinical value of a multiple biomarker assay in patients with bronchogenic carcinoma.

In 98 newly diagnosed patients with histologically proven bronchogenic carcinoma seen at Cuneo Hospital of Chest Diseases from July 1983 to December 1984, multiple biomarker assays were performed. Fiftynine cases had more than one carcinoembryonic antigen (CEA) and/or tissue polypeptide antigen (TPA) assay during the course of the disease, at 3- to 12-week intervals. A total of 209 CEA (91 pretreatment), 170 TPA (80 pretreatment), 62 human chorionic gonadotropin (HCG)-beta subunits and 60 lactate dehydrogenase (LDH) was assayed. In addition, serum samples were taken from 141 blood donors and their TPA values were used as a control. The percentages of elevated values were, respectively, 37%, 52%, 18%, and 25%. In 85% of the patients at least one biomarker was found to be higher than normal. Neither significant differences between mean biomarker levels in tumors of various histologic types nor positive intermarker correlations were found. The number of patients with elevated CEA, TPA, and LDH serum levels and their mean values increased significantly according to the disease extent. Among evaluated markers TPA showed the highest accordance to tumor burden. The raising of two markers was never associated with Stage I-II disease, except in one patient. Both CEA and TPA concentrations changed significantly during the course of the illness in relation to the clinical status assessment. Abnormal pretreatment levels of CEA, LDH, and particularly, TPA were independently and significantly associated with a poor outcome. Patients with abnormal levels of TPA and LDH and, to a lesser degree, TPA and beta-HCG had shorter survival as compared with patients with high TPA values, irrespective of the LDH and beta-HCG levels, although not significantly so.

Lack of clinical significance of gallium-67 uptake in non-small cell lung cancer.

To evaluate the clinical significance of tumor Ga-67 uptake, we studied 89 consecutive patients with a potentially resectable non-small cell lung cancer (NSCLC) by performing a whole body Ga-67 scan. For each scintigraphy, an overall Ga-67 accumulation index (T-N) and a volume independent index (T/Nr) were calculated. Both parameters were related to disease extent, response to subsequent treatment and host survival. With the exception of the significant correlations of T-N to both stage of disease and survival-the higher the T-N, the more advanced the disease and the worse the prognosis-no other relationship was found. Based on these findings, we conclude that, in NSCLC at least, gallium uptake is mainly dependent on tumor size and, therefore, of limited practical value.

MACC (methotrexate, doxorubicin, cyclophosphamide and lomustine) versus cis-platinum and etoposide in the treatment of advanced non-small cell lung cancer.

From June, 1982 to December, 1984, 35 consecutive patients with histologically proven non-small cell lung cancer (NSCLC) were treated either with methotrexate, adriamycin, cyclophosphamide and CCNU (MACC regimen) or cis-platinum and etoposide (DDP-VP16). The rates of objective responses were, respectively, 15% (3 partial responses out of 20 patients) and 13 (2 out of 15). Times to progression were significantly prolonged in the DDP-VP16 group (median: 29 weeks vs 11), with a trend to improvement in the median survival time (30 weeks vs. 17, P less than 0.1). Except for life-threatening leukopenia in 15% of the MACC patients and intractable vomiting in 47% of patients on cis-platinum based chemotherapy, no serious toxicity was observed. The DDP-VP16 combination seems to be more effective, but less well tolerated, than the MACC regimen and can be recommended for compliant patients with good prognostic factors.

Tumor markers in bronchogenic carcinoma. Superiority of tissue polypeptide antigen to carcinoembryonic antigen and carbohydrate antigenic determinant 19-9.

One hundred six patients with histologically proven bronchogenic carcinoma were tested for carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and carbohydrate antigenic determinant 19-9 (CA19-9). A total of 349 CEAs, 350 TPAs, and 317 CA19-9s were measured. In addition, sera were assayed from 57 patients with pulmonary benign diseases and their CEA, TPA, and CA19-9 levels were used as negative controls for specificity and accuracy. One hundred twenty healthy subjects provided our normal CA19-9 reference value. Sensitivity, specificity, and accuracy were obtained for CEA, TPA, and CA19-9, respectively. Significant intermarker correlations were found both at diagnosis and during follow-up, CEA and CA19-9 being the most closely related substances. The percentage of patients with elevated levels of TPA increased significantly according to tumor load. Individual values of TPA related significantly to the stage of disease. Concentrations of CEA, TPA, and CA19-9 varied significantly during the course of the illness in relation to treatment response; however, TPA showed the closest relationship to the clinical status assessments of the follow-up period. Abnormal pretreatment levels of TPA were significantly associated with a poor outcome. Biomarker combinations were clinically evaluated by calculating the mean of the percentage of the reference value for each combined marker. Using this method, any association of TPA with CEA and/or CA19-9 revealed neither a greater diagnostic accuracy nor a more reliable predictive capacity for the above clinical variables than TPA evaluated on its own. The authors believe that a single TPA assay should be added to the initial and subsequent clinical assessments of patients with bronchogenic carcinoma.