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The risk of developing a tumor of the nervous system in humans is analysed in several studies of populations, exposed to ionising radiation for medical reasons, or exposed to military or occupational radiation. The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia). The type of radiation-induced tumors is variable, but meningioma is more frequent after low doses and glioma and sarcoma after higher doses used in the treatment of neoplastic diseases. A dose-effect relationship appeared between the risk of tumor of the nervous system and the radiation dose. The risk was higher when radiation was delivered at a younger age. Much less data are available after radiotherapy in the adulthood, but an increased risk of cerebral tumor appears in the series of ankylosing spondylitis patients. As for the exposures to radiodiagnosis exams, the main problem is the risk of cerebral tumor in children whose mother has undergone abdominal or pelvic X-rays during pregnancy. No risk of neurologic tumor was found in the A-bomb survivors irradiated at Hiroshima and Nagasaki. Occupational exposure to ionising radiation has been incriminated in the first radiologists exposed to high doses. In nuclear industry workers, the results of epidemiological studies are contradictory and at the present time it is not possible to link their radiologic exposure with a risk of tumor of the nervous system. In populations living near nuclear plants, mortality due to tumors of the nervous system was not increased.

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

Epidemiological studies have shown the role of alcohol in esophageal cancer in the West of France. Experiments were undertaken on Wistar rats to study the effect of locally consumed alcoholic beverages on the esophagus. Neither histological modifications, precancerous lesions nor cancer were observed in the animals. There was no significant excess of benign or malignant tumours in treated animals when compared with controls.

There is strong epidemiological evidence that oesophageal cancer in the West of France is related to alcohol consumption. Various laboratory studies have been undertaken in connection with this finding. Samples of the spectrum of alcoholic drinks consumed in the region, notably apple cider and its distillates, were collected from retail outlets and from farms: several distillates produced under experimental conditions in the laboratory were also examined. These samples were analysed for the presence of selected nitrosamines; small amounts were found for the most part in beer, which is little consumed in Normandy and Brittany. Mutageniticy tests on the apple cider based drinks and on other commercially available alcoholic beverages (beer excepted), have shown a weak response, for the most part in farm distillates, that can be attributed neither to nitrosamines nor to polycyclic aromatic hydrocarbons, but to some other as yet unidentified compounds.

Carbon ion therapy is an innovative radiation therapy. It has been first proposed in the forties by Robert Wilson, however the first dedicated centres for human care have been build up only recently in Japan and Germany. The interest of carbon ion is twofold: 1) the very sharp targeting of the tumour with the so called spread out Bragg peak that delivers most of the beam energy in the tumour and nothing beyond it, sparing very efficiently the healthy tissues; 2) the higher relative biological efficiency compared to X rays or protons, able to kill radioresistant tumour cells. Both properties make carbon ions the elective therapy for non resectable radioresistant tumours loco-regionally threatening. The technical and clinical experience accumulated during the recent decades is summarized in this paper along with a detailed presentation of the elective indications. A short comparison between conventional radiotherapy and hadrontherapy is proposed for the indications which are considered as priority for carbon ions.

The radiobiological properties of the hadrons (neutrons, protons, carbon ions) led to their therapeutic use in sarcomas, as a referent therapy or as an alternative to photon therapy. An extensive review of the literature has been conducted to assess the present indications and the perspectives for hadrontherapy. Compared to photons, neutrons are characterized by a higher biological efficiency that is on particular importance for these tumours usually considered as radio-resistant. Neutrons have been considered as a standard therapy for sarcoma' patients, contra-indicated for surgery or with a definitive R2 resection, but their indications and use have been restricted due to the occurrence of late severe toxicities related to their poor ballistic' properties. Thanks to their physical properties (Bragg Peak), protons are characterized by a higher conformity index compared to photons (and neutrons) with optimal organs at risk preservation that permits a dose escalation. Protontherapy is to date the standard of care for base of skull, spinal and paraspinal sarcomas. Carbon ions combined both advantages from protons and neutrons. Literature data permits to consider this radiation modality as a referent therapy for unresectable sarcomas. The ongoing diffusions of protons and carbon ions radiotherapy facilities will permit to offer these therapies to more patients and to conduct studies that are warranted to determine their indications and their results.

The epidemiological studies on cancer incidence or mortality among workers in the nuclear industry have been reviewed in a comparative manner. The results concerning workers monitored for external radiation or internal contamination and those on female workers have been analysed separately. A lower cancer risk was found in most studies, which is explained by the "healthy worker effect"; no difference was found between the workers with or without a radiation record. A high rate was found for a few cancers at specific sites, but results were variable in the different studies and no relationship was found between cumulative dose and excess mortality due to cancer. A link between ionizing radiation, multiple myeloma and prostatic cancer was indicated in more than one study; in the latter case, there might be a relationship with internal contamination, especially by tritium. In spite of the difficulties and limitations involved, it is important to pursue these studies and pool them, in order to directly evaluate the risks of cancer following exposure to low-dose radiation and low dose rates, instead of calculating these by extrapolation from high doses.

In order to test the qualities of the 2 assays, in the same laboratory and on the same tumors, a single-point dextran-coated charcoal radioligand binding assay (RLA-DCC) and Abbott enzyme immunoassay (EIA) were used for more than two years to perform estrogen receptor determinations on cytosols from 2,134 breast cancers. Statistical analysis of the data was performed according to the method of Passing-Bablock. The final regression curve between EIA (y) and RLA-DCC (x) was excellent y = 1.187 X fmol/mg of protein. However, from 1986 to 1988, a great variability was observed for this correlation. We report the study of this variability, which could be explained by several factors, especially calibration problems for the immunoassay kits and changes in our technical team. The binding assay appears to be more sensitive to the technicians' experience than the immunoassay. Technical points are discussed, particularly cytosol preparation and KCl presence or absence in the homogeneisation buffer. The conditions allowing for optimal correlation and routine determination fiability can therefore be defined.