[Non-metastatic advanced non-small cell lung carcinoma: systemic high-dose brachytherapy following curative external radiotherapy]. / Cancers bronchiques non à petites cellules localement évolués: curiethérapie de haut débit de dose complémentaire d'une radiothérapie externe à visée curative.

PURPOSE: To analyse retrospectively the local control, overall survival and immediate and long-term tolerance after a radiotherapy delivered with a curative intent systematically including a high-dose rate brachytherapy. PATIENTS AND METHODS: From January 1993 to January 1995, 50 patients (45 males-five females, median age: 61) with non-small cell lung cancers, inoperable for tumour reasons, non-metastatic, were included in the protocol. Following external radiotherapy (55-65 Gy conventional fractionation), all the patients received high-dose rate brachytherapy delivering 14 to 24 Gy using fractions of 7 Gy. RESULTS: Immediate tolerance was good. Two months after the end of the treatment, five patients suffered from massive haemorrhages and three others experienced a mucosal necrosis (two tracheal sites). Tumour response was observed endoscopically in 88% of the cases (38/50) and was complete in 38%. Median survival of complete responders was 15 months. In the mean follow-up period of 24 months, five patients were still alive with no evidence of disease (median survival: 30 months). Most of the patients died from distant metastases (33/50: 66%). CONCLUSION: Systematic use of endoluminal high-dose rate brachytherapy in addition to external radiotherapy did not improve survival. The gain in the local control rate was counteracted by an increase in haemorrhages and mucosal necroses. Improving techniques and dosimetry, and combining different methods which have proved their efficiency, should result in improvements in survival. Quality of life would be part of the analysed parameters in any future study.

Puzzles in the clinical pharmacokinetics of fluorouracil.

The pharmacokinetics of fluorouracil (5FU) were studied in two groups of patients, the administration of 105 i.v. as daily bolus (x5) or 5-day continuous infusions. The 5FU pharmacokinetics were extremely variable from day to day, i.e. from one bolus to the next or during the continuous infusion, especially in some patients. The variations were lower for the daily bolus, but still remained high. The pharmacokinetics of cisplatin, given simultaneously during continuous infusions did not show the same variability; therefore the variability could be specific for 5FU. The role of implantable subcutaneous ports as the most probable source of this extraordinary variability is discussed. We hypothesise that in some patients the implantable subcutaneous ports used for 5FU infusion, could cause transient and extremely high plasma concentrations, exacerbated by the very short half life of the drug and by saturation of its catabolism.

[Pneumoconiosis and exposure to wood]. / Pneumoconiose et exposition au bois.

The authors report a case of an employee in the wood processing industry. The clinical presentation was respiratory with dyspnoea on effort. The chest x-ray showed bilateral interstitial changes. Following bronchioalveolar lavage electron microscopic studies showed evidence of silica particles. Respiratory function tests showed pulmonary performance of 51%-64% of theoretical values depending on the test used. His working position involved the up keep of the boilers and also the drainage of the silos for wood dust. The wood used was corupixa, a brazilian wood containing crystalline silica; 0.1% in fresh wood dust. Numerous analyses have specified the percentage of silica in the ashes in magma. The diagnosis of pneumoconiosis of the silicotic type was sustained. The occupational risk linked to using this type of wood should be understood and the need to take protective measures for the employees concerned.

Evaluation of a prediction model of cisplatin dose based on total platinum plasma concentration.

The aim of this study was to validate prospectively a model of cisplatin dose adjustment. 27 patients (63 courses) with lung cancer were treated by a 5 day continuous infusion of cisplatin and etoposide. The dose of cisplatin was adjusted in order to reach a target plasma concentration of total platinum (TP) of 2000 mu/l at the end of the infusion. The target concentration was reached with a mean bias of 2.7% and a precision of 7.8%. The results were compared with those of a population of 38 patients (97 courses) with lung cancer and treated with the same protocol of chemotherapy, but without dose adjustment. The average dose adjustment was an increase of cisplatin dose of 20.2%. This augmentation was most important during the first course, decreasing during the following courses. There was also an increase in the etoposide AUC, although its dose was not modified. Toxicity to polymorphonuclear cells was significantly increased and was linked to etoposide AUC.

Total vertebrectomy for en bloc resection of lung cancer invading the spine.

We describe a technique of total vertebrectomy for en bloc resection of a non-small cell lung cancer with vertebral invasion through a combination of thoracic and enlarged posterior approaches, and present our entire experience of total and partial vertebrectomy for tumors invading vertebral bodies or the costovertebral angle.

Airflow obstruction in chalkpowder and sugar workers.

Our aim was to investigate the relationship between suspected occupational hazards and airflow obstruction in industrial workers. The study was a cross-sectional survey of 314 male workers from a chalkpowder plant (n = 158) and from a sugar refinery (n = 156). Occupational exposure to chalkpowder and sugar dust was assessed by individual job classification. Outcome variables included respiratory symptoms and routine spirometric parameters. Statistical analysis was done for each industry separately. Overall, mean pulmonary function parameters fell either within or above the normal range in both industries. However, analysis by job classification showed that in the chalkpowder plant, all indices of airway obstruction declined significantly with increasing dustiness. Additionally, workers in the dustiest workplace (chalk sacking) had significantly lower airflow parameters than workers from other workstations. In the sugar refinery, workers exposed to sugar dust in the sugar cube manufacture workstation had significantly lower forced expiratory volume in 1 s (FEV1) (p = 0.02) than the non-exposed ones. For both industries, the proportion of subjects complaining of cough and/or phlegm was greater among the most exposed subgroups than among the remaining workers but the differences were not statistically significant. In conclusion, coupling spirometry to job classification proved useful in disclosing a relationship between airflow obstruction and exposure to either chalkpowder or sugar dust in industrial workers.

Comparison of two dose prediction models for cisplatin.

Cisplatin toxicity could be decreased by adjusting its dosage to each patient. For this purpose, a limited sampling method was established and validated based on a Bayesian approach taken using the values of assays during a 5-day continuous infusion of cisplatin. Using this method, a dosing model to achieve a target plasma concentration of total platinum (Pt) was evaluated retrospectively; the calculated dose of cisplatin was 95.0 to 104.8% of the actual dose. This model was then studied prospectively and the actual plasma Pt concentration reached at the end of the infusion was 94.9% of the target concentration. A strong correlation was observed between the clearance of Pt and the calculated clearance of creatinine or Cockroft index (p = 1.7 x 10(-11), and this correlation was used to develop another cisplatin dosing model. With this model the actual concentration reached at the end of the infusion was 85.3% of the theoretical concentration. The Bayesian approach gave reliable results for most clinical uses, whereas the creatinine based model has to be improved.

CA-50 and CA-19.9 as tumour markers: which is preferable?

CA-50 (Kit IRMA Stena Diagnostic, cut-off value: 16 U/ml) and CA-19.9 (Kit SPAC Mallinckrodt were compared in a prospective study including 323 cancer patients (56% metastatic) and 120 patients with non neoplastic disease. The CA-50 and CA-19.9 sensitivities were 41.8% and 39% respectively; the CA-50 sensitivity was greater in the cancers of the gastro-intestinal (GI) tract (61.3% versus 51.6% alpha less than 0.00001) and did not differ in the other cases. The CA-19.9 specificity was greater (77.5% versus 64.2% alpha less than 0.0001), due to a greater specificity in the case of respiratory diseases (86.7% versus 66.7% alpha less than 0.0001). A good correlation was found between the serum levels of the two markers in each group of patients (cancer r = 0.78, alpha less than 0.001; benign diseases r = 0.69, alpha less than 0.001). This study has shown a close correlation between these two markers; the reliabilities of CA-50 and CA-19.9 were similar, particularly in the gastro-intestinal diseases (58.3% versus 51.3%). In conclusion, CA-50 and CA-19.9 are both good markers of cancers of the GI tract. Their simultaneous assay would be useless.

Five-day continuous infusion of cisplatin and etoposide in non-small cell lung cancer. A phase II trial.

Cisplatin (CDDP) and etoposide are synergistic in vitro: the aim of this study was to evaluate the efficacy of a continuous infusion (C.I.) of these 2 drugs in inoperable non-small cell lung cancer. Patients were to receive 3 courses of CDDP 20 mg/m2/d in 1 l saline x 5d and etoposide 50 mg/m2/d in 21 saline x 5d--both in C.I.--every 3-4 weeks. Thirty patients have entered the study. Four were inevaluable for response. One patient got complete remission, 15 partial remission, 8 no change and 2 progressive disease. The response rate was 53.3% overall (95% confidence interval: 35-71%), and 61.5% for 26 assessable patients. Toxicity appeared to be acceptable despite 52% transient neutropenia--one patient died during aplasia--and 78% grade 1 to 3 nausea or vomiting. Treatment was stopped in only one case, and modified in 6 others. The high response rate that we observed, supports the idea of potentiation of the antineoplastic effect of CDDP and etoposide by C.I., in non-small cell lung cancer. These results must be confirmed in larger series before definitive conclusions can be drawn.

Analysis of CA-125 levels in the sera of patients with non-ovarian carcinomas and non-malignant diseases.

CA-125 is known as a marker of ovarian carcinoma; it is useful in monitoring response to treatment and it is even said to be a means of detecting ovarian carcinomas. We have studied the serum levels of CA-125 in 260 patients with advanced carcinomas (excluding ovarian cancer) and in 120 patients with non-malignant diseases (excluding gynaecological diseases). Our cut-off value was 20 IU/ml. Sensitivity was 0.53 and Specificity only 0.38; sensitivity was high in lung cancer (0.56), in breast cancer (0.46) and in cancer of the stomach (0.91). Five percent of the cancer patients had values higher than 233.5 IU/ml. Sensitivity was correlated with the presence of a metastatic disease (p less than 0.001). A second assay was obtained in 163 cases; a concordance between the variation of the serum level and the clinical evolution was found in 65% cases. A high rate of false positive values was found in cases of acute pneumonia (0.74) and of gastro-intestinal diseases (0.41). In view of these results, the optimal threshold value was set at 65 IU/ml. CA-125 appears to be a useful marker in the monitoring of advanced non-ovarian carcinomas.

Serum levels of CA-50, CA-19.9, CA-125, neuron specific enolase and carcinoembryonic antigen in lung cancer and benign diseases of the lung.

The serum levels of five markers (CA-50, CA-19.9, CA-125, Enolase (NSE) carcinoembryonic antigen (CEA) were studied in 96 lung cancer patients and in 60 patients with benign diseases of the lung: sensitivity was 0.44, 0.41, 0.54, 0.23 and 0.38 respectively; specificity was 0.67, 0.87, 0.47, 0.93 and 0.97 respectively. Serum levels of CA-125 over 20 U/ml were found in 74% of patients with acute pneumonia. A good parallel existed between the clinical evolution of lung cancer and the variations in the serum level of CA-50, CA-19.9 and NSE. Although the pretreatment result was elevated, successive assays of the marker allowed the clinical evolution to be followed. Conflicting results were found with CA-125 and to a lesser extent with CEA. A close correlation existed between the serum levels CA-50 and CA-19.9 in the 2 groups of patients. In the absence of a specific marker for lung cancer, complementary information can be provided by means of a simultaneous determination of CEA, NSE, CA-19.9--or CA-50--and CA-125.

[CA-125 in non-ovarian benign and malignant pathology: study on 380 patients]. / Le CA-125 en pathologie bénigne et maligne non ovarienne: étude portant sur 380 patients.

CA-125, a serum marker of epithelial ovarian cancer, was studied by a radioimmunometric method: the sensitivity and specificity of the assay was studied in 260 patients with non ovarian carcinomas and 120 patients with non malignant diseases. The ideal threshold value has been discussed. Levels higher than 20 UI/ml (cut-off value) have been found in 53% of cases. Sensitivity falls to 25% if the cut-off value is 65 UI/ml. The serum levels correlated well with the existence of a metastatic disease (P less than 0.001). A second assay allowed to study in 163 cases the correlation between the variations of the serum level and the clinical evolution; a good correlation was found except in case of stable disease. High levels have also been found in patients with benign diseases, most of all in cases of pneumonia and severe liver cirrhosis.

Serum levels of CA-50, CA-19.9, CA-125, CA-15.3, enolase and carcino-embryonic antigen in non neoplastic diseases of the lung.

There is not as yet a specific marker for lung cancer. We tested the specificity of six serum markers using radio-immunological assays (CA-50, CA-19.9, CA-125, CA-15.3, Enolase, CEA) in 60 patients with non-neoplastic diseases of the lung (COPD: 28 patients, acute pneumonia: 23 patients, allery: 9 patients). No correlation was found between the percentage of false positivities on the one hand, and sex, age and smoking habits on the other. CA-125 proved to be positive in 74% of acute pneumonia cases. The rate of false positive values is low with CEA (3.3%), Enolase (6.7%) and CA-15.3 (5%) and therefore the cut-off value we chose for these markers was adequate. This is not the case with CA-50, CA-19.9 and CA-125, for which we observed a high rate of false positive values (33.3%, 13.3% and 53.3% respectively) and for which higher cut-off values must be adopted.

[Blood levels of CA-50, CA-19.9, CA-125, enolase, CA-15.3 and carcinoembryonic antigen in non-cancerous bronchopulmonary pathology]. / Taux sériques du CA-50, CA-19,9, CA-125, énolase, CA-15,3 et antigène carcino-embryonnaire en pathologie broncho-pulmonaire non tumorale.

At present we do not possess a specific marker of broncho-pulmonary cancers. We propose to test the specificity of six serum markers labelled by radio-immunological methods (CA-50, CA-19.9, CA-125, CA-15.3, enolase, ACE) in 60 patients suffering from non-tumoural broncho-pulmonary disorders: chronic airflow obstruction = 28, acute infective bronchopulmonary disorders = 23, allergy = 9. We have not found any correlation between the percentage of false positives and sex, age or smoking. On the other hand, the CA-125 was often found to be positive in cases of acute pneumonia. Overall the frequency of false positives with ACE (3.3%) enolase (6.7%) and CA-15.3 (5%) is weak. The threshold of positivity obtained is adequate. This is not the case with CA-50 (33.3%), CA-19.9 (13.3%) and above all CA-125 (53.3%), for these we suggest new thresholds of positivity.

[Iatrogenic pneumothorax after puncture of the breast]. / Pneumothorax iatrogène après ponction du sein.

The authors describe a very rare aetiology of iatrogenic pneumothorax occurring during breast puncture for cytology. They review the principal origins of iatrogenic pneumothorax and describe the composition of the chest wall beneath the breast.