Feasibility of home delivery of pemetrexed in patients with advanced non-squamous non-small cell lung cancer.

OBJECTIVES: To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). MATERIALS AND METHODS: Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. RESULTS: 52 patients (UK & Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (non-compliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. CONCLUSION: HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management.

Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

Eighth international mesothelioma interest group.

The eighth International Mesothelioma Interest Group (IMIG) meeting was held in Chicago, IL, United States, in 19-22 October 2006 to discuss mesothelioma - the cancer often linked to asbestos exposure. It is a very aggressive malignancy with a median survival of less than 1 year from diagnosis. Millions of people have been exposed worldwide to asbestos, especially during the second half of the twentieth century when asbestos use increased significantly. The tons of asbestos utilized in the past remain a health hazard for current and future generations because asbestos is difficult to be disposed off. This makes asbestos and mesothelioma research a public health issue in addition to a medical problem. Moreover, the very high costs of asbestos litigation have a significant impact on the whole economy. In the United States, up until 2001, defendant companies had paid 54 billion dollars in claims and estimated future liabilities ranged from 145 to 210 billion. Therefore, asbestos research is of great interest to a large audience that includes patients, millions of asbestos-exposed individuals, scientists, physicians, public health officials, politicians, unions of asbestos workers, lawyers and the public at large. During the past few years, there has been significant progress in understanding the process of mineral fiber carcinogenesis and mesothelioma pathogenesis. With improved understanding of the pathogenesis of mesothelioma, new diagnostic, preventive and therapeutic options are being developed. A total of 247 papers were presented at the IMIG: the abstracts of these presentations were published in Lung Cancer, Supplement 1, October 2006. Here, experts in different disciplines critically review some of the most exciting presentations of the IMIG meeting. The result is a comprehensive review of the research field of asbestos carcinogenesis and mesothelioma, and of the progress that has been made in recent years in both basic and clinical sciences.

Nonmalignant pleural lesions due to environmental exposure to asbestos: a field-based, cross-sectional study.

The aim of the present study was to investigate the frequencies of asbestos-related benign pleural diseases in villagers environmentally exposed to asbestos and the factors affecting these frequencies. A field-based, cross-sectional study was designed. In total, 991 villagers from 10 villages, randomly chosen from 67 villages with known use of asbestos-containing white soil in central Anatolia (Turkey), were investigated. The type of asbestos in the white soil was determined for each village, as well as air-borne fibre concentrations. The villagers were investigated with small-size chest roentgenograms and epidemiological features were recorded. The air-borne fibre levels were generally low. Despite this, pleural plaques were found in 14.4% of the villagers, 10.4% had diffuse pleural fibrosis and 0.4% asbestosis. The significant variables for plaques were age, sex, type of asbestos fibre, e.g. actinolite and tremolite, and exposure duration, while there was a negative relationship with cumulative exposure. The variables affecting diffuse pleural fibrosis were age, exposure duration and cumulative exposure. In conclusion, villagers exposed to environmental asbestos have high frequencies of pleural plaques and diffuse pleural fibrosis, similar to occupationally exposed asbestos cohorts. Different types of asbestos appear to result in different frequencies of pleural lesions.

Effect of delays on prognosis in patients with non-small cell lung cancer.

BACKGROUND: The effect of delay on survival in lung cancer remains uncertain. It is suggested that prompt management of non-small cell lung cancer (NSCLC) can influence prognosis. This study was undertaken to examine the relation between delay and prognosis in patients with NSCLC and to investigate the delay time from first symptom and from first hospital visit to start of treatment. METHODS: Two types of delay (symptom to treatment delay and hospital delay) were investigated in 466 patients treated for NSCLC at two institutions in central Sweden. Delays in relation to clinical characteristics were compared and the effects of delay times and other relevant factors on survival were assessed in multivariate analyses. RESULTS: Thirty five per cent of patients received treatment within 4 weeks of the first hospital visit and 52% within 6 weeks. Median symptom to treatment delay was 4.6 months and median hospital delay 1.6 months. Older age, advanced tumour stage, and non-surgical treatment were independently related to poor survival. Both prolonged hospital delay and symptom to treatment delay provided additional information when considered separately. In a final multivariate model only increased symptom to treatment delay gave significant information of a better prognosis. There was an association between a short delay and a poor prognosis which was most pronounced in patients with advanced disease. CONCLUSION: When considering the whole study population and all stages of tumour together, shorter delay was associated with a poorer prognosis. This is likely to reflect the fact that patients with severe signs and symptoms receive prompt treatment. These findings indicate that the waiting time for treatment in patients with NSCLC is longer than recommended.

Exposure to tremolite asbestos and respiratory health in Swedish dolomite workers.

OBJECTIVES: Deposits of carbonate rock like limestone and dolomite may contain tremolite asbestos. This study assessed the exposure to tremolite asbestos and the respiratory health of Swedish dolomite workers. METHODS: 95% of 137 eligible workers at two dolomite producing companies completed a self administered questionnaire that included questions on respiratory symptoms and were examined with spirometry as well as chest radiography. Total exposure to dust was gravimetrically measured and the tremolite asbestos content of the dust was assessed with polarisation and phase contrast microscopy. RESULTS: Dolomite dust concentrations were moderate (median 2.8 mg/m3) and tremolite asbestos concentrations were generally below the limit of detection (<0.03 fibres/ml). Somewhat higher values, around 0.1 fibres/ml, were obtained in manual stone sorting and bagging. Respiratory symptoms suggestive of chronic bronchitis were more related to smoking than to estimates of individual exposure to dust. The mean vital capacity was 0.2 l lower than expected after adjustment for sex, age, height, and smoking but the decline in lung function was not associated with current or cumulative exposure to dust in a clear cut way. Two definite cases of pleural plaques and one possible case of simple pneumoconiosis were noted, but the plaques could not be attributed exclusively to exposure to tremolite asbestos. CONCLUSIONS: Dolomite mining and milling may indeed entail low levels of exposure to tremolite asbestos, but this exposure was not a strong determinant of respiratory symptoms, lung function, or pneumoconiosis in exposed Swedish workers. This was true also for dolomite dust. The hazards of exposure to tremolite asbestos may vary across deposits, however, and additional studies at other sites of carbonate rock exploitation are warranted.

[Screening for lung cancer--new possibilities with new methods!]. / Screening för lungcancer--helt nya möjligheter med nya metoder!

Screening for lung cancer has been regarded as unwarranted for many years. With new techniques, this is no longer the case. Screening with low dose CT scanning has been used in Japan and New York, among many places, for a number of years. We here describe some results. New lung cancers were found in 0.6 per cent of all participants in both studies at the yearly repeat scan. The tumors have been very small, almost all in Stage I, and survival is very good. Thus, the results are promising, and trials in Sweden will hopefully begin before long.

Increased risk for cancer following sarcoidosis.

Little is known about the cancer risk following sarcoidosis. In a retrospective cohort study, we tested the hypothesis of an increased risk for malignant lymphomas, lung cancer as well as cancer in other organs frequently involved in sarcoidosis. Four hundred seventy-four patients from an incidence study 1966-1980 and 8,541 patients identified in the Swedish Inpatient Register (IPR) 1964-1994 were linked to the Cancer Register, the Register of Causes of Death, and the Register of Total Population. Relative risks were estimated using standardized incidence ratios (SIR). The overall relative risks for cancer were similar and elevated in both cohorts (IPR presented), SIR = 1.3; 95% confidence interval (CI) 1.2 to 1.4. For lung cancer and non-Hodgkin's lymphoma, the relative risk was doubled during the first decade of follow-up. Thereafter, the risk for lung cancer was significantly decreased whereas the risk for non-Hodgkin's lymphoma equaled unity. Throughout follow-up, elevated risks were found for melanoma (SIR = 1.6; 95% CI 1.0 to 2.3) and nonmelanoma skin cancer (SIR = 2.8; 95% CI 2.0 to 3.8). An increased risk was also found for liver cancer (SIR = 1.4; 95% CI 0.8 to 2.2). Thus, sarcoidosis appears to be associated with a significantly increased risk for cancer in affected organs. Chronic inflammation is a putative mediator of this risk.

Chlamydia pneumoniae may be associated with lung cancer. Preliminary report on a seroepidemiological study.

Material from 117 consecutive patients with lung cancer was investigated with respect to serological markers for chronic Chlamydia pneumoniae infection. Specific C. pneumoniae IgA antibodies were found significantly more often in patients with lung cancer than in control groups with coronary heart disease and in healthy controls, even after adjustment for smoking. The results suggest that chronic C. pneumoniae infection is common in patients with lung cancer.

Mesothelioma: cases associated with non-occupational and low dose exposures.

OBJECTIVES: To estimate the importance of low dose exposure to asbestos on the risk of mesothelioma. METHODS: A review of the literature. RESULTS AND CONCLUSIONS: There is no evidence of a threshold level below which there is no risk of mesothelioma. Low level exposure more often than not contains peak concentrations which can be very high for short periods. There might exist a background level of mesothelioma occurring in the absence of exposure ot asbestos, but there is no proof of this and this "natural level" is probably much lower than the 1-2/million/year which has been often cited.

Environmental asbestos exposure and malignant pleural mesothelioma.

Asbestos-related benign and malignant pleural diseases are endemic in some rural parts of central Turkey because of environmental exposure to asbestos fibres. We report here epidemiological data on 113 patients with diffuse malignant pleural mesothelioma (DMPM) diagnosed in our clinic in Eskisehir, located in central Turkey. Of the 113 patients, 59 were men and 54 women (male:female ratio = 1). Ninety-seven patients (86%) had non-occupational asbestos exposure; all were living in villages. Their mean age was 56 years. As the patients had been exposed to asbestos from birth, the latency period was equivalent to the age of the patients. Twenty-eight patients (29%) had lived in villages their entire lives. The other 69 (71%) had been born in a village but migrated to the city or had given up white-soil usage for various reasons. The mean exposure time was 55 years for those with a long exposure period and 25 years for those with a short exposure period, but there was no significant difference between the age of the disease appearance for both groups (55 and 56 years, respectively). Thus, the latency time of mesothelioma due to environmental exposure to asbestos was longer than that due to occupational exposure, but independent of the length of exposure. Soil samples from 67 villages were analysed, comprising a population of 10,120 villagers. Tremolite and some other types of asbestos were found. In conclusion, DMPM in our region is due to mainly to environmental exposure to asbestos. The risk is substantial as a large proportion of the villagers are exposed. After smoking, asbestos exposure is one of the most serious health hazards in our rural population.

Malignant mesothelioma due to environmental exposure to erionite: follow-up of a Turkish emigrant cohort.

The incidence of malignant mesothelioma is extremely high in some Turkish villages where there is a low-level environmental exposure to erionite, a fibrous zeolite. The best known example is the village of Karain. However, since epidemiological studies are difficult to perform in Turkey, the incidence and the dose-response curve have not been thoroughly examined. A small cohort of immigrants from Karain who have lived in Sweden for many years were studied. Exposure data, i.e. the time residing in Karain, and hospital records including pathological diagnosis, were recorded. The cohort consisted of 162 people. During the observation time, 18 deaths occurred, 14 (78%) of which were due to malignant pleural mesothelioma. In addition, there were five patients with mesothelioma who were still alive, one of whom had a peritoneal mesothelioma. Thus, the risk of mesothelioma is 135-times and 1,336-times greater in males and females, respectively, than for the same sex and age groups in Sweden. The risk increased with duration of residence.

The impact of pleurodesis in malignant effusion on respiratory function.

Pleurodesis of malignant pleural effusion provides for a substantially better quality of life compared to onging exudation with the need for repeated evacuation of fluid. Successful pleurodesis leads to permanent cessation of fluid production as a result of the formation of fibrous adhesion between the lung and costal pleura which in theory, however, might restrict lung mobility. In patients with poor lung function, or with need for bilateral pleurodesis, the apprehension of further impairment of lung function often arises. The aim of this study was to evaluate the effects of pleurodesis on lung function. Therefore 10 patients with malignant pleurisy with very limited tumour were investigated. They were without radiological signs of tumour infiltration in the lung parenchyma, without visible tumour growth in the pleural space during thoracoscopy and had undergone a successful one-sided pleurodesis. Respiratory function tests were performed at different times, 1-102 months after pleurodesis. The assessment consisted of: static and dynamic spirometry, exercise testing with blood gas determination and radiospirometry. Spirometric values were slightly low, but in general within the reference limits. Blood gas determination showed no signs of alveolar hypoventilation. Radiospirometry showed a slight attenuation of activity in the treated lung but similar turnover of gas of the treated vs. the untreated side. The study showed that pleurodesis in malignant pleurisy has only minor impact on respiratory function.