Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma. PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy. RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy. CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.

[Course and distribution of mortality of pleural mesothelioma in The Netherlands, 1970-1987]. / Verloop en spreiding van de sterfte aan pleura-mesotheliomen in Nederland, 1970-1987.

In this article the sex- and age-specific trends and geographical distribution of asbestos related pleural mesothelioma mortality in the Netherlands between 1970 and 1987 are investigated. For men total mortality increased from 10.8 per million during 1970-1978 to 20.9 per million during 1979-1987. The highest mortality occurred with 147.7 per million in 1987 in the age group between 65 and 74 years. Mortality rates for the age group between 55 and 64 years amounted to 96.5 per million in 1987. The geographical distribution over the country showed a strong concentration of male mesothelioma cases in the regions with many harbours, shipyards and heavy industries round Amsterdam, IJmuiden, Rotterdam, Dordrecht and Walcheren. Using linear regression techniques, it was calculated that several thousands new mesothelioma cases will occur in the Netherlands during the next two decades. A significant decrease in mesothelioma mortality can not be expected before 2010.

The influence of the diagnostic technique on the histopathological diagnosis in malignant mesothelioma.

In the histopathology of malignant mesotheliomas three different types (epithelial, connective tissue and mixed type) are distinguished. Some authors believe all tumours to be of mixed type, but consider that due to inadequate sampling or small biopsies this may be missed frequently. In this study the relationship between the histopathological diagnosis and the amount of tissue examined was investigated. In a series of 124 cases of malignant pleural mesothelioma a high percentage of mixed type tumours was found (55%). In cases where the decisive diagnostic procedure had been an Abrams biopsy (the "small-specimen" technique) mixed-type histology was found in 36%. If thoracoscopy, thoracotomy or autopsy (the "large-specimen" techniques) had delivered a definite diagnosis, mixed-type histology was found in 63%. Apparently diagnosing the mixed-type variety depends on the amount of tumour tissue obtained. However, the assumption that all mesotheliomas are of mixed type cannot be confirmed.

Mitoxantrone in malignant pleural mesothelioma: a study by the EORTC Lung Cancer Cooperative Group.

46 patients with malignant pleural mesothelioma were entered in a phase II study of mitoxantrone 14 mg/m2 every 3 weeks. Histology was confirmed by a pathology panel. None of the patients had received previous chemotherapy. Toxicity was mainly mild gastrointestinal and haematological side-effects. Out of 34 patients evaluated for response, only 1 partial response was recorded. Mitoxantrone at this dose and schedule has marginal activity in malignant mesothelioma.

[localized fibrous tumors of the pleura]. / Gelokaliseerde fibreuze tumoren van de pleura.

The localized fibrous tumour of the pleura, also named localized fibrous mesothelioma or fibroma of the pleura, is a very rare tumour with a benign behaviour. Its origin, clinical behaviour and prognosis are very different from malign mesothelioma. In a 33-year period 22 patients with this diagnosis were surgically treated. The prognosis was excellent. In this article the clinical and radiological signs, as well as the diagnosis and therapy are discussed.

Trends and geographical patterns of pleural mesotheliomas in the Netherlands 1970-87.

The sex and age related trends and geographical distribution of asbestos related mortality from pleural mesothelioma in the Netherlands between 1970 and 1987 were investigated. Deaths from pleural malignancies recorded by the Dutch Central Bureau of Statistics (CBS) were used and death rates were age adjusted per year by the indirect method. Standardised mortality ratios (SMRs) were computed for 43 regions over the period 1979-86. For men, total mortality increased from 10.8 per million in the period 1970-8 to 20.9 per million during 1979-87. The highest mortality occurred in the group aged between 65 and 74 with 147.7 per million in 1987. The death rate for the group aged between 55 and 64 was 96.5 per million in 1987. For women, total death rates for pleural mesothelioma showed a moderate increase from 2.5 per million in the period 1970-8 to 3.6 per million during 1979-87. The highest mortality occurred in the group aged over 65, fluctuating around 10-15 per million. For men and women under 45 mortality was very low and presented no upward trend. The geographical distribution over the country for the period 1979-86 showed a pattern with a clear concentration of deaths from mesothelioma in men, in conurbations with many harbours, shipyards, and heavy industry near the river mouths and along the North Sea Coast.

Malignant pleural mesothelioma in the southwestern part of The Netherlands.

This report is the result of an analysis of the medical records of 124 patients presenting with a malignant pleural mesothelioma. Information about asbestos exposure was available in 104 of them, which appeared to be positive in 95 (91%). The median duration of exposure was 34 yrs. The median latent period was 41 yrs. The median survival was 11 months while different ways of treatment could not prolong survival. The most common radiologic findings were pleural effusions, while in some patients contralateral effusions or pleural thickening was found. Pleural plaques or asbestosis were seen in a minority of the patients. In this series a relatively high percentage of mixed type mesotheliomas was found (56%). Large biopsies will often show both epithelial and connective tissue type elements. Concerning diagnostic procedures we recommend beginning with cytology of pleural fluid, which can easily be obtained together with an Abrams biopsy. If this does not give a definite diagnosis thoracoscopy or thoracotomy will be indicated.

Malignant peritoneal mesothelioma: a series of 19 cases.

The clinical data, diagnostic procedures and survival are reported in 19 cases diagnosed as malignant peritoneal mesothelioma. All patients were men and 74% had an occupational exposure to asbestos, whereas in 26% no information about asbestos exposure was available. The median interval between asbestos exposure and the diagnosis appeared to be 44.7 years (range 18-49 years). The most common presenting symptoms were abdominal pain, weight loss and dysphagia. Most patients presented with a large amount of ascites. In the majority of patients no therapy except pain relief was given and the median survival from the time of diagnosis was 6 months (range: 0-29 months). Some patients received surgery or chemotherapy, which however did not prolong survival. Only in 2 patients survival exceeded 1 year, although these patients did not receive therapy. The autopsy findings of some patients showed that there were positive abdominal lymph nodes in 2 of them, while in no case positive thoracic lymph nodes were found. The relative short survival period from the time of the first diagnosis in contrast to malignant pleural mesotheliomas is probably the reason for the absence of distant metastases. In this series only in a minority of patients cytology of the ascites was positive and often a laparotomy had to be done. Since cytologic specimens are often negative, we suggest that in patients suspected of a malignant peritoneal mesothelioma, laparoscopy with directed biopsies is the diagnostic procedure of first choice.

Benign localized mesothelioma of the pleura.

Eleven cases of benign localized mesotheliomas of the pleura are described. Ten patients were asymptomatic and discovered by routine X-rays. In eight cases the tumour was localized in the visceral pleura and all tumours showed only a benign mesenchymal component. Non-neoplastic epithelial structures can become entrapped within the tumour. A benign clinical behaviour and an excellent prognosis could be expected after surgical resection.

Familial balanced insertion (5;10) and monosomy and trisomy (10) (q24.2----q25.3).

The phenotype of a boy with monosomy of a small segment of chromosome (10) (q24.2----q25.3) is described. In his family a balanced insertion (5;10) is found in three generations. Moreover there are two persons who are trisomic for the same small segment of chromosome 10 for which the boy is monosomic.

Experiences with observer variation in mesothelioma panels.

The voting system used in the Dutch Mesothelioma Panel and in those of the European Communities and the IARC in the UK to estimate the probability of the histopathological diagnosis of malignant mesothelioma is described. Five categories are used: A: definite B: probable C: possible D: improbable E: definitely not The voting system facilitates measurement of probability and comparison of opinions, and good or reasonable agreement between panel members is achieved. Second viewing of the slides usually increases agreement. The percentages of dubious diagnoses are less when sufficiently large amounts of tissue are available.