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PurposeTo evaluate the results of 15 years of experience with proton beam radiotherapy in the treatment of intraocular melanoma, and to determine univariate and multivariate risk factors for local failure, eye retention, and survival.MethodsA total of 368 cases of intraocular melanoma were treated with proton beam radiotherapy at Centre Lacassagne Cyclotron Biomedical of Nice, France, between 1991 and 2006. Actuarial methods were used to evaluate rate of local tumor control, eye retention, and survival after proton beam radiotherapy. Cox regression models were extracted to evaluate univariate risk factors, while regularized least squares algorithm was used to have a multivariate classification model to better discriminate risk factors.ResultsTumor relapse occurred in 8.4% of the eyes, with a median recurrence time of 46 months. Enucleation was performed on 11.7% of the eyes after a median time of 49 months following proton beam; out of these, 29 eyes were enucleated due to relapse and 16 due to other causes. The univariate regression analysis identified tumor height and diameter as primary risk factors for enucleation. Regularized least squares analysis demonstrated the higher effectiveness of a multivariate model of five risk factors (macula distance, optic disc distance, tumor height, maximum diameter, and age) in discriminating relapsed vs nonrelapsed patients.ConclusionsThis data set, which is the largest in Italy with relatively long-term follow-up, demonstrates that a high rate of tumor control, survival, and eye retention were achieved after proton beam irradiation, as in other series.

Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002.Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1--D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1--D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3.A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years.For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.

To report the clinical features and outcomes of iris melanomas treated by proton beam therapy. A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon, Department of Ophthalmology, in 36 patients treated by proton beam therapy for presumed (n = 29) and confirmed (n = 7) iris melanomas between July 1997 and October 2010. Ciliary body melanomas with iris involvement were excluded. The patients’ mean age was 54.4 years (range, 22–82 years). The average tumor diameter was 3.8 mm (range, 2.5–8.0). The iridocorneal angle was invaded by the tumor in 47 % of cases (n = 17), the ciliary body in 17 % of cases (n = 6), and the sclera in 3 % (n = 1). Raised intraocular pressure was present before treatment in 11.1 % of cases (n = 4). Tumor biopsy was performed in 19 % of cases (n = 7). Four patients had undergone an initial incomplete surgical excision of tumor before radiotherapy. Surgical preparation of the eye with tantalum ring positioning had been performed in all cases 3–4 weeks before irradiation. The prescribed dose was 60 Cobalt Gray Equivalent (CGE) of proton beam radiotherapy delivered in four fractions on four consecutive days. The median follow-up was 50 months (mean 60.5, range 15–136). One patient (2.7 %) was lost to follow-up. None of the patients showed tumor progression, local recurrence, or metastasis. None of the patients required secondary enucleation. Cataract was developed in 62 % of patients, glaucoma in two cases (6 %) after irradiation, and hyphema with the aggravation of pre-existing glaucoma in one patient. No patients developed neovascular glaucoma. Proton beam therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable rate of complications. Longer follow-up studies on a larger series is necessary to consolidate these results.

Small choroidal melanomas have a better prognosis than large tumours. However, these small tumours can spread, often late in their course. The aim of the study was to analyse survival and tumour characteristics of six cases of late metastatic diseases after conservative treatment.A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon among 523 patients treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with 106 (Ru/Rh) (15) for uveal melanomas. We have selected patients with small choroidal melanoma (thickness≤3 mm and diameter≤9 mm) (59 patients), who have developed hepatic metastases (six of 59).At the time of diagnosis, median age was 57 years (range, 37-82 years). The mean tumour thickness was 2.9 mm (range 2.5-3 mm), and the mean diameter was 7 mm (5-8 mm). Orange pigment was observed in four cases, subretinal fluid was observed in two cases, and one tumour touched the optic disc. Five patients had proton beam therapy. One patient had beta brachytherapy (106 Ru/106 Rh). Average follow-up was 8.3 years (range 4.2-11.8 years). None of the six patients developed local tumour recurrence. The mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9-14.6 years). The average time from treatment of primary tumour to detection of liver metastasis was 7 years (range 3.9-12 years). The mean survival time from the diagnosis of metastasis was 35.2 months (range 9-101 months). Small melanoma-related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at 15 years in our series.Despite a small tumoral size and an early and effective local treatment, six of 59 small choroidal melanomas have developed metastasis after local treatment. Small tumours represent a significant risk of metastasis.

In an effort to clarify the relationship between sensitivity of human tumour cells to low-LET and to fast neutron irradiation, 10 human tumour cell lines were exposed to cobalt gamma-rays and to 60 MeV (p -Be+) neutron beam. The data were pooled with results of 31 human tumour cell lines previously published. The analysis of date using the linear-quadratic model indicated that not only alpha values increased after neutron irradiation, but so did beta values too, although to a lesser extent. The mean inactivation dose (MID) was derived for each cell line from the linear-quadratic parameters after low-LET and high-LET exposure. MID values following neutron irradiation were closely correlated to those after gamma-ray irradiation. In these 41 cell lines, the extreme values of RBE derived by the ratio of MID varied by a factor of 3 among the cell lines. RBE was positively correlated to photon MID, meaning that intrinsically radiation resistant tumour cells have a higher neutron RBE, on average. Similar findings were observed if alpha ratios were used instead of MID ratios. In addition, the RBE/dose variations were more marked in cells with the higher RBE. Taken together, these data suggest that, although considerable variations exist among human tumour cell lines, intrinsically radioresistant cells are relatively more sensitized when exposed to high LET beams than radioresponsive tumours. An 'intrinsic gain factor' may thus be expected in irradiating radiation resistant tumours with fast neutrons, in addition to the hypoxic or kinetic gain factors. Because the quadratic component is still present after neutron irradiation, we suggest using MID ratio as a reference RBE when comparing survival curves of cells exposed to radiations of different qualities.

Summary The proton therapy facility of the Centre Antoine-Lacassagne in Nice began treatment of ocular tumors in June 1991. Up to October 1995, a total number of 600 patients were treated. An overview of the cases treated during the first 4 years of activity is given and the main problems encountered in the field, possibly interacting with the accuracy and reliability of the dose distribution, are listed.

Little is known about the action of charged particles of very high linear energy transfer (LET) on human cells and, in particular, the relationship between DNA damage and reproductive death. The aim of this study was to measure the biological efficiency of a low-energy argon beam (E = 7.1 MeV/nucleon, LET = 1590 keV/micron) produced at GSI, Darmstadt, on a human melanoma cell line (CAL4) established in our Institute. Two different methods were used: the micronucleus (MN) test and the colony-forming assay. The MN test, using the cytochalasin-block method, is a measure of genotoxic damage. MN are scored in binucleate cells (BNC) and are formed from acentric fragments or whole chromosomes that have not been incorporated into daughter nuclei at mitosis. The colony-forming assay quantifies reproductive death. Parallel experiments were run with cobalt gamma-rays for comparison. After Co irradiation, the MN-free BNC dose-response curve coincided with that of the loss of colony-forming ability, suggesting the potential of the former as a predictive test of cell killing. After Ar irradiation, there was a dissociation between the two effects, especially at high doses: cell death was greater than the frequency of BNC with MN. The inactivation cross-section was 74 microns2; it was 39 microns2 for MN yield. Therefore, the relative biological effectiveness (RBE) was higher for cell killing than for MN yield (0.8 and 0.5, respectively at a Co dose of 3 Gy). The total MN count in BNC followed the same pattern of response as the fraction of BNC with MN.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation therapy with positively charged particles implies that the Bragg peak be spread out to deliver a homogeneous dose to the tumour. The spread-out Bragg peak (SOBP) has a higher linear energy transfer (LET) than the entrance beam. In addition, there is an LET gradient from proximal to distal SOBP. The aim of this study is to find out whether these small LET variations lead to differences in radiation response. Human melanoma cells (CAL4) were exposed to 65 MeV proton beams produced by the cyclotron Medicyc at five different positions: 2 mm depth corresponding to the entrance, 15, 20, 25 and 26.8 mm depth corresponding to four different positions in the half-modulated SOBP. Survival curves were generated using the in vitro colony method and fitted with the linear-quadratic model. Survival differences were observed at high doses; they were statistically significant at a dose of 8 Gy. With respect to the entrance position (2 mm), the relative biological effectiveness (RBE) at 1% survival was 1.09, 1.12, 1.19 and 1.27 at 15, 20, 25 and 26.8 mm in the SOBP, respectively. Whereas RBE values in the SOBP greater than 1.0 relative to the entrance beam represent a small biological advantage to be added to the well-known physical advantage of high energy proton beams; the RBE gradient along the SOBP would imply that the distal end of the tumour would receive a higher biologically equivalent dose than the proximal end, despite a homogeneous physical dose, especially at the high doses per fraction given in ocular melanomas. Although the increase in effectiveness with depth is mild, it should be kept in mind during eye treatment planning, in case a critical target is present at the extreme end of the SOBP.

Summary The organization of a networking for patient recruitment is a main concern for a new facility using charged particles. The experience of choroidal melanoma in Nice demonstrates the possibility to create “de novo” a protontherapy center treating a sufficient number of patients. The influence of the opening of new facilities is analyzed.

Diffuse and multifocal patterns of conjunctival melanoma may not be treatable with standard eye-sparing methods. The purpose of this study was to evaluate the usefulness of proton beam radiation therapy as an alternative to exenteration. Twenty patients with extended conjunctival melanoma were treated by proton beam irradiation. Most cases were T3 tumours which were not accessible to brachytherapy due to their extension, localisation with fornical or caruncular involvement. Only 2 patients had a tumour limited to the bulbar conjunctiva. Both were recurrent tumours with multiple lesions. Sixteen cases were recurrences after various pre-treatments. The area of the conjunctiva which was suspected to have microscopic disease was treated by 31 Gy in 6 fractions. The “high risk” areas with a clinically detectable tumour (primary target volume) were treated by an additional boost using a smaller beam size and applying 2 fractions up to 45 Gy. An individually shaped compensator was brought into the beam to modify the range of the protons so that the eye was irradiated only at a depth of 2 mm. The mean follow-up time was 38.1±26.6 months (median 34 months). Recurrent disease occurred in 6 cases (30%); 2 of them outside the irradiated volume, 3 within the target volume treated by 31 Gy, and just one in the primary target volume treated by 45 Gy. An exenteration followed only in two patients (10%). 6 patients (30%) suffered from metastatic disease and 4 (20%) of them have died by now. During follow up we found no statistically significant association between the occurrence of local recurrence after proton radiotherapy and the development of metastases. Best corrected visual acuity remained stable in 12 cases (60%); in 14 patients the best corrected visual acuity was 0.25 or better. A sicca-syndrome developed in 19/20 patients. However, only 10/20 patients used artificial tears more than 5×/d. A focal cataract developed in 7 patients (35%). There was eyelash loss in the area of irradiated eyelids. In 4 cases a limbal stem cell deficiency occurred with the consequence of corneal vascularisation. Proton radiotherapy may serve as an alternative to exenteration in case of T3 and diffuse T1 or T2 conjunctival melanomas.

The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients.To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors.The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPG s according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers.This article is a summary version of the full document presenting the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concern the place of fine needle aspiration biopsy in preoperative diagnosis, the place of cervical lymph node area surgical treatment, the place of postoperative irradiation and neutron therapy in the treatment of unresectable tumors and also the place of medical imaging, especially RMI, for the diagnosis of these tumors.

A total of 69 families affected by uveal melanoma have been reported in the literature. This report describes two additional families. In addition to presenting these cases, which constitute exceptions, the paper reviews the literature.Two families, each with two affected members, were analysed in this retrospective study. The pedigree of each family has been pieced together.Considering the low incidence of familial uveal melanoma in the general population, it seems unlikely that inherited genetic factors are responsible for the condition; this question remains difficult to resolve.The characteristics of each family history are described and compared with the literature data. The mode of possible inheritance is discussed. Both the histopathology and anatomical location are studied, after which we discuss the body of evidence to establish whether there is an inherited cancer predisposition syndrome in patients with familial uveal melanoma.The statistical likelihood of such an uncommon tumour occurring independently in two or more family members leads us to believe that some cases of familial uveal melanoma may go unrecognized, and that reports on too few families have been published worldwide to prove the existence of a single mendelien gene. However, appropriate tissue samples, such as blood and tumour samples, should be obtained and conserved for present or future cytogenetic and molecular genetic studies.

International audience; Recently, radiotherapy possibilities have been dramatically increased by software and hardware developments. Improvements in medical imaging devices have increased the importance of three-dimensional (3D) images as the complete examination of these data by a physician is not possible. Computer techniques are needed to present only the pertinent information for clinical applications. We describe a technique for an automatic 3D reconstruction of the eye and CT scan merging with fundus photographs (retinography). The final result is a "virtual eye" to guide ocular tumor protontherapy. First, we make specific software to automatically detect the position of the eyeball, the optical nerve, and the lens in the CT scan. We obtain a 3D eye reconstruction using this automatic method. Second, we describe the retinography and demonstrate the projection of this modality. Then we combine retinography with a reconstructed eye, using a CT scan to get a virtual eye. The result is a computer 3D scene rendering a virtual eye into a skull reconstruction. The virtual eye can be useful for the simulation, the planning, and the control of ocular tumor protontherapy. It can be adapted to treatment planning to automatically detect eye and organs at risk position. It should be highlighted that all the image processing is fully automatic to allow the reproduction of results, this is a useful property to conduct a consistent clinical validation. The automatic localization of the organ at risk in a CT scan or an MRI by automatic software could be of great interest for radiotherapy in the future for comparison of one patient at different times, the comparison of different treatments centers, the possibility of pooling results of different treatments centers, the automatic generation of doses-volumes histograms, the comparison between different treatment planning for the same patient and the comparison between different patients at the same time. It will also be less time consuming.

AIMS To assess the cellular proliferation using the monoclonal antibody Ki-67, in paraffin embedded uveal melanomas irradiated by proton beam, as well as in non-irradiated uveal melanomas. METHODS 30 enucleated eyes were included for histopathological study and Ki-67 immunostaining. Patients were enucleated between 1991 and 1996 for uveal melanoma, 14 after proton beam irradiation and 16 without treatment (control group). The mean follow up period was 2.5 years after diagnosis and 1 year after enucleation. RESULTS A significant relation was found between Ki-67 score and mitotic index ( r = 0.56, p = 0.001), histological largest tumour diameter ( r = 0.38, p = 0.03), fibrosis ( r = −0.35, p = 0.05), absence of tumoral pigmentation (p = 0.05), and presence of vascular thrombosis (p = 0.03). The Ki-67 score was significantly higher in the non-irradiated group (p = 0.01) and in the group of patients whose cause of enucleation was tumoral evolution (p = 0.005) compared with the group of patients enucleated after neovascular glaucoma. The Ki-67 score was very high in a case of orbital recurrence of uveal melanoma and metastatic death. 70% of metastasised tumours showed a Ki-67 score higher than the median value. CONCLUSION Ki-67 labelling is a reliable method of estimating the proliferative activity in uveal melanomas after proton beam irradiation. The Ki-67 score is significantly correlated with prognostic variables (mitotic index and histological largest tumour diameter), and with radiation effects after proton beam irradiation.

From the theoretical point of view, the Faraday cup (FC) is an absolute instrument for fluence measurements of proton beams. As the FC is easily manufactured it can be considered an `in-house' calibration system. Moreover, at the moment no national standards for proton dosimetry are available. Up to now the experimental tests of these instruments show that much study still has to be done to better understand their use in reference dosimetry. To investigate the possibility of using an FC as a secondary standard, an FC was jointly designed by the `TERA Collaboration' and `Centre Antoine-Lacassagne' (Nice, France) to evaluate the main parameters of the instrument. A comparison between two FCs of different designs - the `TERA FC' and the `Nice FC' - and an ionization chamber (IC) used for routine proton dosimetry was carried out. Results show that the two FCs agree to within 1.5 - 3.6%. While the differences between FC and IC are larger - 6% for the `TERA FC' and 8.2% for the `Nice FC', the FC giving a lower dose evaluation - they follow the same trend shown by the calorimetric measurements. The data show that once the beam characteristics are defined, the fluence measurements are reproducible and show a good accuracy.

Summary Neutron capture irradiation aims to selectively destroy tumor cells using 10 B(n,α) 7 Li nuclear reactions produced within themselves. Following the capture reaction, an α particle and a, 7 Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 μ m. These captures, used exclusively with a ‘slow’ neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an ‘epithermal’ neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10 B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

Summary V79 cells were exposed to fast neutrons generated by 60 MeV p → Be produced by the cyclotron Medicyc at four different depths: 1.3, 25.8, 72.2 and 116.8 mm. Survival was assessed by the in vitro colony method. Mean inactivation doses ( MID ) were significantly different among the four points. The ratio of MID was used to determine the relative efficiency of the neutron beam at these points. Compared to 25.8 mm depth, a 40% increase in biological effect was observed at the superficial point versus a 14 to 16% decrease in effect for the deeper points. This is ascribed to absorption of low energy neutrons near the surface and to beam hardening with depth. Taking in consideration the relative physical dose delivered, these findings suggest that skin-sparing may be markedly reduced and that the lower effectiveness with depth should be kept in mind when dealing with deep tumours.

A number of data measuring survival of animal or human cells to low LET ionizing radiation have demonstrated that these cells may be hypersensitive to doses below 1 Gy, possibly due to the absence of an inducible repair mechanism, which is observed at higher doses. The production of micronuclei (MN) in cells exposed to ionizing radiation reflects genotoxic damage. Moreover, the micronucleus assay is sensitive to low radiation doses. We have exposed 10 human tumour cell lines to doses ranging between 0.12 and 4 Gy. Using cytochalasin B to block the cells in a binucleate phase, we have scored the fraction of binucleate cells (BNC) expressing MN, as well as the number of MN per BNC, as a function of γ-ray dose. Experimental points were fitted with a binomial equation. Doses from 1 to 4 Gy were fitted separately from those below 1 Gy, and the initial slopes after both fits were compared. Taken together, the initial slopes of MN induction after low-dose (LD) irradiation were not different from those after high-dose (HD) irradiation. Only in one cell line was a significant increase in MN production detected after LD irradiation. This cell line had the shallowest linear term after HD irradiation. It appeared that the likeliness of expressing hypersensitivity at LD was correlated with the quadratic term of MN induction at HD, which does not contradict an inducible repair hypothesis. However, the failure of observation of a significant hypersensitivity at LD for nine cell lines, and the high variability of response at LD suggests that this occasional effect may be influenced by other factors as well.

A total of 25 patients with inoperable cervical cancer were treated by daily radiotherapy (2 Gy); sensitisation was obtained by administration of 5 mg cisplatin 30 min before each irradiation session. The total cumulative dose of cisplatin varied between 50 and 150 mg. A complete kinetic profile (0-24 h) of platinum (Pt) was established after the first dose and at the end of treatment for 22 patients. Pt was quantified by atomic absorption spectrophotometry using Zeeman-effect background correction for trace analysis. The total Pt AUC0-24h increased from 1.53 +/- 0.77 to 7 +/- 3.55 micrograms.h.ml-1 between the start and the end of treatment (P less than 0.001). Ultrafilterable Pt (Pt UF) rose from 0.079 +/- 0.038 to 0.138 +/- 0.095 microgram.h.ml-1 (P less than 0.01). Elimination half-lives were unchanged for total Pt but rose for Pt UF; these kinetic modifications in Pt UF did not correlate with any significant change in individual serum creatinine levels. No clear correlation was found between the cumulative cisplatin dose and tumor levels measured in 13 patients, and the tumor cisplatin dose did not correlate with response to treatment. Patients with hematological toxicity were characterised by an increase in their residual Pt UF level during treatment. Overall, our findings strengthen the notion of Pt UF kinetic variability during repeated treatment.

Evaluation of loco-regional results obtained by radiotherapy for 31 patients with inoperable epidermoid lung cancer revealed objective remission (over 50%) in only 25% of patients. These results emphasize the limited effectiveness of radiotherapy in such cases and point out the need for increased research in radiotherapy techniques if survival rates are to be improved.

The thymidine labelling index (LI), representing the percentage of cells in the DNA-synthesis phase, was measured in vitro prior to therapy in 87 patients with squamous cell carcinoma of the head and neck, who were treated between 1977 and 1982. The LI was not related to patient age, site of the tumour, clinical stage or histological grade. Overall survival was 44.5%. Univariate analysis demonstrated that survival was affected by the following factors: (1) age: patients older than 55 had a better outcome (p = 0.03); (2) site of the tumour (p = 0.005): laryngeal tumours had the best survival; (3) clinical stage (p = 0.05). Histological grade did not influence the survival (p = 0.41). Patients having a tumour LI higher than 15.5% (mean + 1 S.D.) had a significantly lower survival than patients with lower tumour LI (p = 0.008). A multivariate analysis using the Cox model showed that clinical stage and LI kept their prognostic impact with regard to survival. Finally, survival after relapse was lower in patients with a high tumour LI. These results demonstrate that a high tumour proliferation rate is an additional factor influencing the disease outcome in head and neck carcinoma. Patients with bad prognosis defined by this parameter could be offered a more energetic treatment.

SISGRAD, the interactive computer system of the Antoine-Lacassagne Cancer Center Radiotherapy Department, has been operational since January 1982. It completes the computerized dosimetry system installed several years earlier and is fully integrated with the institution's central network. SISGRAD is in charge of surveillance of the radiotherapy treatments given by the Center's three radiotherapy units (1400 patients per year); it is also used for administrative purposes in the Department and physically connects all of the Department's operating stations. SISGRAD consists of a series of microcomputers connected to a common mass memory; each microcomputer is used as an intelligent console. SISGRAD was developed to guarantee that the treatments comply with prescriptions, to supply extemporaneous dosimetric data, to improve administrative work, and to supply banks with data for statistical analysis and research. SISGRAD actively intervenes to guarantee treatment quality and helps to improve therapy-related security factors. The present text describes the results of clinical use over a 4-year period. The consequences of integration of the system within the Department are analyzed, with special emphasis being placed on SISGRAD's role in the prevention and detection of errors in treatment prescription and delivery.

Two new permanent cell lines derived from squamous cell carcinomas of the tongue, CAL 27 and CAL 33, have been established in culture. Both cell lines were isolated in standard culture media without epidermal growth factor or fibroblast feeder layer to avoid obtaining clones of more differentiated cells. Analysis of the morphology, ultrastructure, karyotype and immunohistochemical properties of these two cell lines demonstrated that they are both well characterized, uncontaminated by HeLa cells, and do in fact correspond to transformed epithelial cells that have conserved certain characteristics of the original Malpighian epithelium. CAL 27 and CAL 33 have relatively long doubling times (35 and 43 h respectively). Their response to 14 drugs used for cancer chemotherapy was evaluated by a short term assay based on tritiated thymidine incorporation after exposure to the drugs. CAL 27 was more resistant than CAL 33 in all cases but one. Although cytogenetic examination revealed both lines to be malignant, neither CAL 27 nor CAL 33 produced colonies in soft agar; both lines were tumorigenic after inoculation into nude mice. This study clearly demonstrates the diversity of cancers of a given histologic form, in agreement with the diversity noted previously in vivo. Isolated without the use of any selection criteria, these cell lines constitute appropriate models for the study of human tumors.