European Code Against Cancer and scientific justification: third version (2003).
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Adult↗
Biomedical subjects
M Tubiana
Publications and source records attributed to M Tubiana.
Measuring progress against cancer in Europe: has the 15% decline targeted for 2000 come about?
BACKGROUND: Against a background of increasing cancer rates in the mid-1980s, Europe Against Cancer launched an ambitious programme aiming to reduce cancer mortality by 15% by the year 2000. A programme of activities and research, focussing on three major themes [prevention (particularly tobacco control), screening, and education and training], was developed together with the European Code Against Cancer. METHODS: To evaluate the outcome of the programme, all cancer mortality data were abstracted for each member state of the European Union (EU) until the most recent year available. For each gender group in each member state, age-specific rates were estimated for 2000. For each country-gender grouping, the standardized mortality rate (SMR) and expected numbers of deaths in 2000 were calculated based on the age-specific rates for 1985 and the population estimates for 2000. The ratio of the SMR in 2000 to that of 1985, was used as the measure to compare mortality rates. RESULTS: In 1985, there were 850 194 cancer deaths in the EU. Based solely on demographic considerations, this number was expected to rise to 1 033 083 in the year 2000. Between 1985 and 2000, the number of cancer deaths increased in both men (+12%) and women (+9%). The target of a 15% reduction in the expected numbers of cancer deaths in the EU was not met, although the 10% reduction in number of deaths expected in men and 8% in women, along with a 11% reduction in risk of cancer death in men and a 10% reduction in women, was noteworthy. Only Austria and Finland achieved the 15% reductions in deaths in both men and women. The UK and Luxembourg (where the small population and annual number of deaths make interpretation difficult) came close to meeting these targets, as did Italy. Portugal and Greece had the poorest performance, with increases in each gender group. CONCLUSIONS: Cancer deaths in the EU were expected to rise from 850 194 in 1985 to 1 033 083 in 2000. It is estimated that there will be 940 510 cancer deaths that year, due to the decline in risk observed since 1985. The Europe Against Cancer programme appears to have been associated with the avoidance of 92 573 cancer deaths in the year 2000. With few exceptions, most countries are experiencing declining trends in cancer death rates, which seem set to continue, at least in the near future. Renewed tobacco control efforts are clearly needed for women, and there is a strong case for the introduction of organized breast and cervix screening programmes in all member states. Continuing to emphasize prevention within cancer control will help to promote the continuing decline in death rates in the future.
Adolescent↗
Late mortality in Hodgkin's disease: can we reduce it?
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Hodgkin Disease↗
[Jean-Claude Savoie].
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Clinical Medicine↗
[Health and the city: physical health and mental health].
In France, city size has very little bearing on the mortality rate as a function of age and life expectancy and it is in large cities that these indicators are the most favorable. No increase in maternal or infant mortality rates or deaths due to cancers has been observed in large cities. The lower mortality rate linked to respiratory and cardiovascular diseases in large urban areas contradicts the fears concerning the impact of air pollution. Deaths linked to lifestyle are less frequent in big cities, which could be due to social structures (socio-professional level: the proportion of white-collar workers and professionals is higher in bigger cities than in the suburbs or small cities). However, although the overall mortality rate is lower, it should be emphasized that there is in large cities a greater incidence of sexually transmitted diseases, AIDS and certain infectious diseases (because of social diversity and the fact that certain individuals seeking anonymity and marginality are drawn to large cities). In terms of mental health, the breakdown of family structures, instability, unemployment, the lack of parental authority and failing schools render adolescents vulnerable and hinder their social integration. When the proportion of adolescents at risk is high in a neighborhood, individual problems are amplified and social problems result. In order to restore mental and social health to these neighborhoods, ambitious strategies are necessary which take into account family and social factors as well as environmental ones. At the present time, when physical health is constantly improving, the most pressing problems are those related to lifestyle and mental health which depend for a large part on social factors.
France↗
[The precautionary principle: advantages and risks].
The extension of the precautionary principle to the field of healthcare is the social response to two demands of the population: improved health safety and the inclusion of an informed public in the decision-making process. The necessary balance between cost (treatment-induced risk) and benefit (therapeutic effect) underlies all healthcare decisions. An underestimation or an overestimation of cost, i.e. risk, is equally harmful in public healthcare. A vaccination should be prescribed when its beneficial effect outweighs its inevitable risk. Mandatory vaccination, such as in the case of the Hepatitis B virus, is a health policy requiring some courage because those who benefit will never be aware of its positive effect while those who are victims of the risk could resort to litigation. Defense against such accusations requires an accurate assessment of risk and benefit, which underlines the importance of expertise. Even within the framework of the precautionary principle, it is impossible to act without knowledge, or at least a plausible estimation, of expected effects. Recent affairs (blood contamination, transmissible spongiform encephalitis by growth hormone, and new variant of Creutzfeldt-Jacob disease) illustrate that in such cases the precautionary principle would have had limited impact and it is only when enough knowledge was available that effective action could be taken. Likewise, in current debates concerning the possible risks of electromagnetic fields, cellular phones and radon, research efforts must be given priority. The general public understands intuitively the concept of cost and benefit. For example, the possible health risks of oral contraceptives and hormone replacement therapy were not ignored, but the public has judged that their advantages justify the risk. Estimating risk and benefit and finding a balance between risk and preventive measures could help avoid the main drawbacks of the precautionary principle, i.e. inaction and refusal of innovation, highly restrictive administrative procedures, and a waste of funds on the search for the utopian goal of zero risk. Other drawbacks are more insidious. The precautionary principle could contribute to a general feeling of anxiety and unease in the population. It could be used by campaigns to manipulate public opinion in favor of a particular commercial interest or ideology. Furthermore, practitioners and public policy makers could be led to make choices not dictated by a search for the optimal solution but rather a solution that would protect them from future accusations (the so-called umbrella phenomenon). On the international level, the precautionary principle must not be used to mask protectionism. Nevertheless, a clear advantage of the precautionary principle is that it requires decision-makers to explain the rationale behind their decisions, to quantify the risks, and to provide objective information. However, the physician must not be tempted to make patients sign documents certifying that they have been given all relevant information on his or her diagnosis and treatment. This example underlines the role of legal texts and jurisprudence in the application of the precautionary principle. Finally, the precautionary principle implies new obligations for the State. In the field of health and healthcare, the State must undertake actions based on fully open and undisguised decision-making and provide complete information to the public. A pplication of the precautionary principle requires much discernment because the final outcome can be beneficial or harmful, depending on the way it is implemented. The precautionary principle, and its applications, must be precise and detailed within a well-defined framework.
Adult↗
Radiation risks in perspective: radiation-induced cancer among cancer risks.
The majority of the public in industrial countries believes that pollution and low doses of radiation are threats to good health. As a matter of fact, when these putative risks are compared to those originating from lifestyle, they appear very small. In particular, the risks associated with low doses of irradiation, even when they are assessed with the most pessimistic models, appear extremely small. Public anxiety is fuelled by the uncertainty regarding the magnitude of this risk and the use of the linear no threshold (LNT) hypothesis, which gives credence to the concept that even the smallest doses are harmful. There are a number of scientific and epidemiological data currently under debate that are not consistent with the LNT hypothesis. For example, no difference in the incidence of cancers or of birth defects has been observed between regions with low or high natural irradiation. This inconsistency between perceptions and data underlines the role of psychological factors studied since 1957 which should be placed in the perspective of the public's present attitude toward risk and technology. Social amplification or attenuation of risk may occur in several ways. Fearful concern about radiation began in 1955, with the beginning of the Cold War, when the possibility of a nuclear holocaust appeared very real. Analysis of the data shows that these fears of technology could have a detrimental effect; they should therefore be investigated and understood.
Cause of Death↗
[Health and environment].
The impact of the environment (air, water, food pollution) on health is a major concern in contemporary society. Unfortunately, there are relatively few objective epidemiological data on this subject and their accuracy is limited. Risks are often not quantified, whereas in public health the quantitative assessment of the various risks and benefits must provide the bases for a global strategy. Actual risks should be distinguished from putative risks and, when the risks are putative, an effort should be made to ascertain the upper and lower limits of the risk. The validity of a linear no threshold relationship for assessing putative risks should be discussed and, whenever appropriate, other relationships should be considered. Since emotional reactions often pervade environmental issues, which in turn are exploited for political or commercial reasons, it is not surprising that any statement or action may provoke violent debate. It is serious to underestimate the importance of a risk, since appropriate measures may not be put in place. However, it is equally serious to overestimate it because this can provoke unjustified fears, a pervasive unease, and a rejection of certain technologies, even to the point of discrediting science. It can lead therefore to a questioning of progress by instilling fears about any innovation, as well as facilitating the manipulation of public opinion for financial or ideological reasons, and finally to distortions in budget allocations and public health actions. Confronted with this situation, the Academy's role should be threefold. a) Whenever necessary, point out the need for an increase in appropriate fundamental research. When epidemiological data are uncertain, analyse the cause of these uncertainties and advocate appropriate development in statistical methodologies and epidemiological research, which could ascertain the upper limit of the putative risk. The lack of knowledge often results in public anxiety; this reaction should be investigated and psychosociological research must be encouraged and supported. b) Inform the scientific community and the public; fight against misinformation and sensationalism in the news, and take advantage of the Internet to this end. Encourage openness and transparency in the preparation of scientific reports and dialogue with the stakeholders. c) Better define the role and the place of experts, ensure their independence, monitor their competence and make sure they represent the various fields involved. When reports are conflicting, the Academy should be ready to organize a forum for analysing the roots of these disagreements and to delineate the limits of the uncertainties.
Aging↗
Conformal radiotherapy and intensity-modulated radiotherapy--clinical data.
Conformal radiotherapy (CRT) is based on three hypotheses: (i) a higher rate of local control can improve the survival rate; (ii) dose escalation can increase tumor control; and (iii) CRT allows the delivery of higher doses by decreasing the incidence of late effects. These postulates are now supported by several data. Three-dimensional conformal radiotherapy (3D-CRT) has markedly progressed since its introduction two decades ago. However, there are situations for which 3D-CRT cannot produce a satisfactory treatment plan because of complex target volume shapes or the close proximity of sensitive normal tissues. This is why intensity-modulated radiation therapy (IMRT) was introduced. Its aim is to overcome the limitations of 3D-CRT by adding modulators of beam intensity to beam shaping. IMRT can achieve nearly any dose distribution; however, the role of the planner remains crucial. CRT has been investigated mainly for prostate cancers and head and neck cancers. By and large, the clinical data, although still limited, seem to confirm the advantages of this type of radiotherapy. Dose escalation in prostate cancers improves the local control rate without increasing late effects and for this cancer site IMRT appears to be a significant advance over conventional 3D-CRT. In head and neck cancers the clinical data are still scarce but encouraging. CRT should be investigated in breast cancers with the aim of reducing the incidence of late effects. The available data underline the great potential for major progress in 3D-CRT and IMRT. The techniques are still costly and time consuming, nevertheless they merit investigation since their cost should decrease. Efforts should be concentrated on the specification of robust optimization criteria, taking into account clinical and radiobiological data.
Dose Fractionation, Radiation↗
[ [In Process Citation]
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Journal Article↗
[Conclusions. The precautionary principle: its advantages and risks].
The proposed extension to health of the precautionary principle is the reaction to two social demands: the desire for greater health safety and for more transparency in the decision making process by associating the public. In medical care, all decisions are based on the balance between cost (dangers induced by the treatment) and benefit (the therapeutic effect). It is as dangerous to overestimate the cost, in other words the risks, as it is to underestimate them. The same problem is encountered in public health. If a vaccination is to be prescribed, the beneficial effects must outweigh the risks; however, these risks are inevitable and have been known to exist since the 18th century, but they have been accepted for the public good. It takes courage to make a vaccination mandatory because those who benefit from it will never know, while those who suffer from its ill effects could take legal action. In order to counter accusations, an evaluation must be made beforehand of the risks and benefits, which underlines the important role of expert opinion. Within the framework of the precautionary principle, actions cannot be taken in ignorance and, at the very least, plausible estimations must be made. The analysis of several recent events (contaminated blood, BSE, growth hormone and Creutzfeldt-Jacob disease) shows that the precautionary principle would have had a very limited impact and that only once there was sufficient knowledge was action made possible. The same is true concerning current debates (the possible risks associated with electromagnetic fields, mobile phones and radon); in these three cases, no country in the world has invoked the precautionary principle, but rather the priority has been given to research. The public understands quite readily the cost/benefit relationship. In the case of oral contraceptives, or hormone replacement therapy the public was aware of their possible health risks but judged that the advantages outweighed the risks. The estimation of risks and benefits, the putting into proper perspective the possible risks that can be incurred from any given action, enables the main pitfalls of the precautionary principle to be avoided: the opposition to progress and the refusal of innovation, ever greater bureaucracy, and the waste of funds in the pursuit of an utopian "zero risk". Other drawbacks are more insidious: increased anxiety in the population, the manipulation of opinion by campaigns fomented by commercial or ideological interests, the influencing of practitioners and decision-makers to choose not the best solution but rather the one that will protect them from any future accusations. At the international level, efforts must be made to avoid that the precautionary principle be used for protectionist reasons. Nevertheless, the precautionary principle can have advantages, such as motivating decision-makers in the public or private sector to explain and quantify their reasoning, and to give objective information. However, the medical practitioner should not be tempted to ask that documents be signed as proof of the information given. This example underlines the possible dangers of the strict application of the law in certain cases and the importance of the role of jurisprudence. The precautionary principle will also impose new obligations on the State, which also must conform to the requirements of proportionality between risk and action, transparency and information in the field of care and health. The application of the precautionary principle will require good judgment because the way it is implemented will determine whether its outcome will be for the better or the worse. That is why it is indispensable that jurists, medical practitioners, and scientists work together so that the precautionary principle will be as precisely defined and codified as possible.
Decision Making↗
Link between local recurrence and distant metastases in human breast cancer.
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Breast Neoplasms↗
The link between local recurrence and distant metastases in human breast cancer.
PURPOSE: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination. METHODS AND MATERIALS: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients. RESULTS: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year at initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type. CONCLUSIONS: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases' emergence, and death, which shows that tumors with or without LR have similar biological characteristics.
Adult↗
The rationale for early diagnosis of cancer--the example of breast cancer.
The main advantage of early diagnosis of cancer is the reduction of tumor size at initial treatment and thereby an increase in the proportion of patients without distant dissemination. This benefit is illustrated by the example of breast cancer. A model of its natural history was built using data extracted from the files of over 4000 patients followed in the same institution for 20 to 35 years. The model was used to quantify the impact of tumor size, histologic grade, and lymph node involvement on the probability of distant spread. The relationships were found to be highly significant. The model also and unexpectedly revealed that the tumors progress while they grow; avoiding histologic progression is therefore another advantage of early diagnosis. The model showed that residual tumor can be a nidus for distant dissemination, and that consistency between the prediction of the model and the results of post-operative radiotherapy is satisfactory. Conversely to what is often stated, the benefits of post-operative radiotherapy appear to be greater for small tumors, even in the absence of lymph node involvement, than for large ones. The model could be used to help improve screening strategies, but more data are required, in particular for the young age range.
Brain Neoplasms↗
Cancer prevention.
Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole.
Adult↗
Goralatide (AcSDKP), a negative growth regulator, protects the stem cell compartment during chemotherapy, enhancing the myelopoietic response to GM-CSF.
The aim of our study was to investigate the protection afforded to the bone marrow by Goralatide (AcSDKP), an inhibitor of hemopoietic stem cell proliferation, when administered alone or in combination with a growth factor (granulocyte/macrophage colony-stimulating factor [GM-CSF]) during iterative cycles of Ara-C (cytarabine) treatment. In control mice receiving the inhibitor alone without Ara-C, the number of granulocytes was reduced during treatment, and a surge in number of peripheral blood cells was observed after its completion. Peripheral hematological responses were monitored during 3 consecutive cycles of Ara-C chemotherapy and the resultant nadir and recoveries. Analysis of variance of the treatment effects pooled over the 3 cycles showed that a treatment regimen in which the inhibitor was administered during the myelotoxic periods of chemotherapy confirmed the existence of a surge after completion of administration of the inhibitor and showed a significant protective effect. When the cycles of chemotherapy plus Goralatide were followed by GM-CSF, the recovery from leukopenic nadirs was accelerated and the white blood cells and granulocyte levels were markedly increased over those observed in control mice and in mice treated either with Goralatide alone or with GM-CSF alone. The differences were highly significant. A consistent and significant increase (p < 0.001) in platelet count was also noted in animals given Goralatide in conjunction with Ara-C or Ara-C + GM-CSF. After three treatment cycles, this response to the CSF was far better in mice treated by the inhibitor than when CSF was given alone, suggesting a protection of the stem cell pool.
Animals↗
The hazy dawn of brachytherapy.
The discovery of radium by Pierre and Marie Curie in December 1898 opened a new era in science and within a few years provided medicine with a new means of tumor treatment. Their personal contribution to the start and early development of clinical applications should not be overlooked. The Curies did not limit their support to providing radium sources to medical pioneers but took a deep interest in the horizons of radium therapy. Pierre was one of the first to search for and demonstrate a biological effect of radium radiation. He investigated the radioactivity of the waters of hydrotherapeutic resorts. Marie took care of the measurement of the medical sources personally, convinced that the result of the treatment depends on the precise knowledge of the amount of radium applied. Her perseverance resulted in the establishment of the Institut du Radium (1909) in which, besides the physico-chemical laboratory, a biological department was set up. The latter became the Fondation Curie (1920), a leading medical center of treatment and training, with an integrated team of physicists, radiobiologists and clinicians led by Regaud. One hundred years after the discovery of radium, patients benefit today from the extensive clinical experience that has been collected over the years and from sophisticated developments in application techniques, dosimetry and quality assurance; the professional risk has been precisely assessed and the improvements in material and procedure have enabled the medical personnel to work in hazard-free conditions. This outcome results from the continuous progress that the pioneers gave impulse to. This paper intends to recall their efforts and achievements, as well as the difficulties and the problems they encountered during the first 2 decades when the sturdy foundations of brachytherapy were built.
Animals↗
The report of the French Academy of Science: 'Problems associated with the effects of low doses of ionising radiation'.
In 1995 the French Academy of Science published a report on 'Problems associated with low doses of ionising radiation'. This report aroused interest among French-speaking scientists and a translation in English was published a year later. The report pointed out that an important issue in radioprotection was not whether to accept or reject the linear no-threshold model but rather to test its validity. The aim of this review is to analyse the report and its recommendations, and to briefly indicate the progress which has been made and the questions which remain open. Three areas of the report are covered in this review: DNA repair, carcinogenesis and epidemiological data.
Animals↗