Childhood malignancies in the EUROCARE study: the database and the methods of survival analysis.

This paper describes the database of children with cancer in the EUROCARE study and the methodology used to analyse and report survival. This is the first systematic evaluation of survival after childhood cancer on a large scale in Europe: approximately 45,000 cases were included, diagnosed between 1978 and 1992 (34,814 cases diagnosed in 1978--1989 and an additional set of 9495 cases diagnosed in 1990--1992) and followed-up until 1995. Data were provided from 34 population-based registries (four specialised for childhood cancer registrations and one specialised registry for childhood leukaemia) in 17 countries of Europe (where there was national coverage in 10 countries). Quality of the data was fairly good, given the general differences among the countries and their health systems, thereby allowing for comparisons between them. Among cases diagnosed in 1978--1989, overall 2.0% were lost to follow-up, 91.8% were microscopically diagnosed and 93.4% of alive cases had at least 5 years of observation. Survival proportions (observed survival) were calculated for each of the countries involved, by age group (0, 1--4, 5--9, 10--14 years), gender, different time periods and selected diagnostic groups. Age-standardised cumulative survival rates and European averages (weighted and pooled) were also computed. Cox regression models were used to evaluate geographical and temporal differences. The EUROCARE database represents a unique source of information on survival of childhood cancer patients in Europe, intercountry differences and time trends in survival.

Survival of children with Wilms' tumour in Europe.

A total 2535 cases of Wilms' tumours registered in children aged 0--14 years by 34 population-based cancer registries in 16 countries of Europe in 1978--1992 and followed-up until the end of 1994 were included in this EUROCARE study. Overall 5-year observed survival of all children diagnosed in 1985--1989 was 83%, 95% confidence interval (CI) 80--85. Relatively large differences were observed between the European countries, with significantly lower survival of patients registered in the formerly socialist countries, Estonia, Poland and Slovakia. Overall European survival was slightly lower in comparison with results reported from the USA and Australia, which demonstrate a potential for improvement. Over the study period, overall survival adjusted for age, sex and country has increased significantly. This favourable trend is attributed primarily to improvements in treatment, particularly to the introduction of new chemotherapeutic agents.

Survival of children with malignant germ cell, trophoblastic and other gonadal tumours in Europe.

Collaborators of the EUROCARE study had provided records on 1263 cases of germ cell, trophoblastic and other gonadal neoplasms, registered in 34 cancer registries in 16 European countries over the period 1978--1992 and followed-up until the end of 1994. Observed 5-year actuarial survival for 490 cases diagnosed in 1985-1989 was 80% (95% confidence interval (CI)=(76, 83)). The corresponding figures were calculated for the intracranial and intraspinal germ cell tumours (68%, 95% CI=(57, 76)), other non-gonadal germ cell tumours (76%, 95% CI=(68, 82)), gonadal germ-cell tumours (89%, 95% CI=(85, 93)) and gonadal carcinomas (50%, CI=(24, 76)). Relatively large differences in survival were observed between age-sex subgroups, which also differed with histology, with extremely poor survival of young children with intracranial and intraspinal germ cell tumours. Lower survival was observed in the countries with formerly socialist economies. Time trends in survival were examined for the entire study period, including only the cases registered in the large contributing registries. For all germ cell tumours, the risk ratios calculated in the Cox regression analysis were markedly lowered for the years after the reference period of 1978--1981. The improved outcome is attributed to treatment advances.

Incidence of childhood cancer in Ho Chi Minh City, Vietnam, 1995-97.

Incidence rates of childhood cancer for the city of Ho Chi Minh are presented for the first time. For the 3-year period 1995-97, a total of 302 cancer cases were registered in children under 15 years of age, with a male to female ratio of 1.1. The overall crude rate was 78.8 and the age-standardised incidence rate was 88.4 per million person-years, which was low in comparison with other countries in eastern Asia and with the predominantly white population of Australia. Leukaemia (principally acute lymphocytic), brain tumours and lymphomas were the most common childhood neoplasms, which is consistent with the pattern observed in other registries of the region. The rate of retinoblastoma was higher than in the other regional registries. On the other hand, no cases of hepatocellular carcinoma were registered.

Exposure to Agent Orange and occurrence of soft-tissue sarcomas or non-Hodgkin lymphomas: an ongoing study in Vietnam.

Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper.

Six- and seven-membered 1-oxa-4-aza-2-silacyclanes as possible correctors of adaptational mechanisms.

The biological activity of eight 1-oxa-4-aza-2-silacyclanes with the OSiCH(2)N fragment including 6-membered 2-sila-5-morpholinones (1-3) and 4-acyl-2-silamorpholines (4-6)and previously unknown 7-membered derivatives of salicylic acid (7, 8) was studied. Compounds 1 and 3-6 show the certain antihypoxic action. Compounds 2 (40 mg/kg), 4 (20 mg/kg), 6 (40 mg/kg), 7 (20 mg/kg) and 8 (40 mg/kg) reduce the physical serviceability of intact animals. Compound 1 (20 mg/kg) influences the physical serviceability in a moderate-positive way on the background of chlorophos-poisoning. Compounds 5-8 displayed protective properties against chlorophos-poisoning at the LD(50) dose and compounds 2, 4, 5, 7 at the LD(100) dose. Influence of compounds 1 and 2 on the emotional-research behavior of mice was studied.

Plantar melanoma: a case-control study in Paraguay.

In Paraguay, the plantar surface of the foot is the most common site for malignant melanoma, as it is in several other populations worldwide, most notably in those of African descent. Here, we report the results of the first case-control study of plantar melanoma, carried out in Paraguay. Sixty incident, histologically confirmed cases of plantar melanoma and 256 hospital controls were recruited in 11 hospitals throughout the country during 1988-93. Information was collected on general demographic, social, and lifestyle variables, on external exposures of feet (shoewear, work activities, injuries), and on some constitutional factors (skin, eye and hair color, and pigmented lesions of the feet). Few of the factors examined appeared to be associated with the risk of plantar melanoma. Adjusted for possible confounders, the strongest association was found for reported injuries (odds ratio [OR] = 40.9, 95 percent confidence interval [CI] = 14.8-112.7) and for occurrence of naevi on the soles (OR = 5.9, CI = 2.5-14.3). Walking barefoot did not seem to contribute to the risk although an outdoor workplace was associated with an increased melanoma occurrence (OR = 2.3, CI = 1.1-4.8). Future studies should be aware of problems of recall bias with respect to previous injuries, and ensure that evaluation of pigmentation of the sole is carried out blind to case/control status.

The international classification of childhood cancer.

The International Classification of Childhood Cancer (ICCC) updates the widely used Birch and Marsden classification scheme. ICCC is based on the second edition of the International Classification of Diseases for Oncology (ICD-O-2). The purpose of the new classification is to accommodate important changes in recognition of different types of neoplasms, while preserving continuity with the original classification. The grouping of neoplasms into 12 main diagnostic groups is maintained. The major changes are: (1) intracranial and intraspinal germ-cell tumours now constitute a separate subgroup within germ-cell tumours; (2) histiocytosis X (Langerhans-cell histiocytosis) is excluded from ICCC; (3) Kaposi's sarcoma is a separate subgroup within soft-tissue sarcomas; (4) skin carcinoma is a separate subgroup within epithelial neoplasms; (5) "other specified" and "unspecified" neoplasms are now usually separate sub-categories within the main diagnostic groups. Draft copies of the ICCC were distributed to some 200 professionals with interest and expertise in the field and their comments are considered in this final version. This classification will be used for presentation of data in the second volume of the IARC Scientific Publication "International Incidence of Childhood Cancer." A computer programme for automated classification of childhood tumours coded according to ICD-O-1 or ICD-O-2 is now available from IARC.

Improving survival for childhood cancer in Slovakia.

Data from the National Cancer Registry of Slovakia were used to evaluate survival for 2,958 childhood cancer patients registered between 1968 and 1987 and aged 0-14 years at diagnosis. Actuarial survival rates were computed for children diagnosed in 4 successive 5-year periods and compared. Overall 5-year survival rose from 20% for the period 1968-1972 to 46% for the period 1983-1987. The increase was statistically significant in age groups 1-4, 5-9 and 10-14 years. Survival for children aged less than l year also increased slightly, but this was not statistically significant. In most of the major diagnostic groups, survival increased markedly. Five-year survival rose significantly for leukaemias, lymphomas, CNS neoplasms, Wilms' tumours, bone tumours, soft-tissue sarcomas and germ-cell tumours. Despite this progress, survival in Slovakia remains lower than the corresponding figures from registries in Western Europe and the United States.

Mapping in epidemiological studies and control of cancer: experiences from Slovakia.

This article reviews our experience with the use of the cancer atlas of Slovakia, published in 1989 which presented simultaneously the cancer incidence and mortality rates derived from national population-based cancer registries. Contrary to all expectations, the role of the environmental pollution was confirmed only for nonmelanoma skin cancer and arsenic exposure. Valuable information was obtained also for the study of dynamics of cancer distribution, which revealed a shift in the incidence of stomach cancer to the east and its replacement with colorectal cancer in the western part of the country. Of enormous importance for the comprehensive cancer care and control is the knowledge of incidence and mortality rates at the level of individual districts.

Patterns of cigarette sales and lung cancer mortality in some central and eastern European countries, 1960-1989.

BACKGROUND: Remarkable increases in lung cancer risk recently have been observed in the Central and Eastern European (CEE) area. This study examines the patterns of lung cancer mortality rates and cigarette sales in 1960-1989 in seven CEE countries with a total population of 97.5 million and 43,000 deaths from lung cancer in the last year under study. METHODS: Trends in cigarette sales and mortality rates from lung cancer in seven CEE countries were compared for the years 1960-1989. RESULTS: Among males, recent lung cancer death rates were the highest in Europe, and trends by country largely reflected the varied prevalence and duration of smoking in previous decades. For females, lung cancer mortality rates were much lower, although there were exponential rate increases. In the more recent birth cohorts, there were some declines in mortality rates among males, but not among females. CONCLUSIONS: The rising cigarette consumption through the 1960s, 1970s, and, in some countries, the 1980s is accompanied in most of the countries by rising lung cancer mortality rates for young adults. This increasing cigarette consumption will determine future trends in lung cancer, which will increase well beyond the turn of the century and will continue longer for females than for males. This outlook underlines the urgent need for comprehensive lung cancer prevention with the concerted control of smoking as a priority. The role of cofactors and their interaction with smoking deserve further exploration.

Thyroid cancer in Slovakia, 1968-1990: incidence, mortality and histological types.

Data on thyroid cancer incidence and mortality from the national cancer registry in Slovakia have been analysed for 1968-90, representing one of the first such descriptive epidemiological studies from Eastern Europe. The incidence of thyroid cancer has increased over this period, particularly among women, from approximately 1.5 to 2.5 per 100,000. These increases occurred primarily in papillary carcinomas, and to a lesser extent follicular carcinomas; the greatest proportional increase was in the younger age groups. In contrast to data reported from other areas, mortality also increased over the same period. The reasons for such increases are not evident, but the increases in mortality certainly indicate the potential for improvements in the treatment of thyroid cancer in Slovakia, as well as further study on the aetiological factors involved in the disease.

Epidemiological features of gastric and oesophageal cancers in Slovakia.

Data from Slovakia were analysed to determine whether, in accordance with observations made in western Europe and the United States, there is an increasing occurrence of tumours around the oesophagogastric junction. However, the increase in oesophageal cancers in this area was found to be attributable to squamous cell carcinomas. This is in keeping with observations made in central and eastern Europe of an increase in the incidence of tobacco- and alcohol-related cancers.

Oral and pharyngeal cancer incidence in Slovakia 1968-1989.

Slovakia currently has one of the highest incidence rates of oral cancer in Europe. Incidence data from the Slovakian Cancer Registry relating to oropharyngeal cancer are analyzed for the period 1968-1989 to examine trends in the incidence of these malignancies, representing the first such reported time-series from Central Europe. Over this period, rates in males have increased from 4.5 per 100,000 in 1968-1970 to 17.9 per 100,000 in 1987-1989, with more marked increases noted amongst middle-aged males (35 to 64 years), among whom rates have increased from 6.8 to 47.9 per 100,000 over the same period. Rates in women have been relatively low and stable. Changes in rates in men follow a period during the 1950s and 1960s when there was a marked increase in alcohol and tobacco consumption. The magnitude of the increases have resulted in oropharyngeal cancer becoming an important public health problem in Slovakia and emphasizes the importance of measures to prevent further increases in the consumption of tobacco and alcohol.

The role of the registry in the study of relation between cancer and environment experiences from Slovakia.

Highly complete and detailed data on cancer incidence collected in National Cancer Registry of Slovakia in the years 1968-1988 contributed largely to the study of the relations between cancer occurrence and environment. The study of temporal trends of age-adjusted rates revealed the rapid increase of overall cancer incidence and mortality rates in males influenced mainly by extreme increase and high proportion of lung cancer. The lower but increasing overall incidence rates in females could be related to the increase in breast, other skin and genital organs cancers, while the stabilized mortality trends were caused by improving prognosis of these major cancers in females. The possible role of environmental factors in adults could be stressed also by the temporal trends of childhood malignancies which remained fairly stable during the same period. The role of environmental factors in cancer etiology is further documented with the dramatically increasing incidence of malignant skin melanoma caused probably by the overexposition to the sunlight and with prevailing incidence of the majority of cancer sites in urban areas. Finally, the significantly increased incidence rates of other skin cancers are shown in two districts and in both sexes in relation to the environment, highly polluted with arsenic.

[Incidence of malignant tumors in Slovakia. I. Levels and trends 1968-1989]. / Incidencia zhubných nádorov na Slovensku. I. Hodnoty a trendy v rokoch 1968-1989.

In the period from 1968-1989 an increase in the overall incidence of malignant tumors was recorded in men. Of the individual localizations a particularly marked increase was recorded in tumors of the lung, followed by tumors of the oral cavity, pharynx, esophagus, pancreas, urinary bladder, kidney (related to smoking), as well as of the testis and prostate gland. In women the values of overall incidence were lower and the trends were relatively stabilized. This is due to the relatively slow increase in the incidence in cancer of the breast and female reproductive organs and to the slight increase in cancer of the lung. Cancer of the kidney, urinary bladder and pancreas exhibited increased incidence. Low values, stabilized and even decreasing trends were recorded in the incidence of cancer of the oral cavity, pharynx, esophagus, and larynx, as compared to values found in men. In both sexes the incidence of cancer of the stomach showed a pronounced decrease, while the incidence of cancer of the colon and rectum was increasing. A smaller or greater rise was found also in the incidence of tumors of the hematopoietic and lymphatic tissues (except Hodgkins's disease). The trends observed in the incidence of malignant tumors in Slovakia are suggestive of their uncontrolled course, not affected by preventive measures. Yet the findings provide important information for directing the measures so as to aim at localizations of priority. (Tab. 2, Fig. 7, Ref. 20.)

Survival rates for childhood malignancies in Slovakia.

Survival rates (SR) for population-based series of 1564 cases of cancer in children aged 0-14, diagnosed during the decade 1978-1987 in Slovakia and derived from the National Cancer Registry, were examined. The overall 5-year SR (all types of childhood malignancies combined) was 49.8%. Different SR were ascertained for leukemias -43.8%, lymphomas -59.1%, CNS tumors -42.7% and for other remaining diagnostic groups and subgroups of childhood malignancies. Generally, the SR were slightly better for girls than for boys. Cancer patients being diagnosed during the first two years of age showed worse prognosis with a 5-year survival rate of 36.8% as compared to 52.6% for children aged 2-14 at diagnosis. Differences in 5-year survival were also found between urban and rural areas: 56.8% and 48.8%, respectively. The 5-year SR increased during the study period from 48.5% for 1978-1982 to 50.0% for 1983-1987. Comparison of SR from Slovakia with the corresponding rates observed recently in some developed countries indicated possibilities to improve prognosis of childhood malignancies in this country.

Development of registration and cancer incidence rates and trends in Slovakia.

The development of cancer registration, from the introduction of obligatory notification and the establishment of National Cancer Registry of Slovakia, is described. The activity of the registry is illustrated by the list of publications which have emanated from this institution in recent years. The survey is completed by the analysis of the incidence rates of individual cancer sites in the last 5-year period (1984-1988) and by their trends in the decade 1979-1988. The positive role of the registry in the establishment of a cancer control programme and the investigation of cancer epidemiology is stressed.