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Resume Objectif Etudier si l’IRM de contraste quantitative avec modelisation pharmacocinetique ameliore la fiabilite de l’imagerie T2 pour localiser le cancer de prostate non palpable dans la zone peripherique (ZP) et dans la zone de transition (ZT) et estimer son volume. Materiels et methodes Vingt-trois patients (PSA :8,91 ± 6,2 ng/ml) avec cancer de prostate non palpable ont beneficie d’une IRM prostatique endorectale avec imagerie T2 et de contraste avant prostatectomie radicale. Chaque niveau d’evaluation (apex, partie moyenne, base) a ete divisee en huit territoires (24 territoires par prostate et 552 territoires pour les 23 patients). La localisation et le volume des foyers tumoraux de plus de 0,2 cc presents sur les pieces de prostatectomie ont ete retrospectivement correles a leur aspect en IRM sur les 552 territoires etudies. Les parametres dynamiques quantitatifs du modele pharmacocinetique incluaient la permeabilite vasculaire (Ktrans), la concentration maximale de gadolinium ([Gd]) apres 60 secondes de perfusion, et le lavage du contraste (Kep). Une etude univariee et multivariee a ete ensuite realisee pour determiner les facteurs predictifs du cancer. Resultats Les valeurs moyennes de Ktrans, [Gd] et Kep etaient significativement superieures dans les 58 foyers tumoraux superieurs a 0,2 cm3 de la ZP et de la ZT (p Conclusion Par rapport a l’imagerie T2, la modelisation quantitative de l’IRM dynamique ameliore la localisation du cancer de la prostate non palpable de plus de 0,2 cm3, mais sans difference significative pour les cancers de la ZT. Au-dela de ce volume, la correlation entre le volume tumoral IRM et celui de la piece est faible.

Objectif de l’etude La categorisation des maladies prises en charge dans nos services de radiotherapie permet d’adapter les delais de traitement et de definir des priorites en cas de reduction des plages horaires. Ces reductions, programmees ou non, conduisent a une impossibilite d’effectuer la planification recommandee pour les traitements longs en radiotherapie prostatique. Nous avons donc etudie l’etalement et le fractionnement des cancers prostatiques irradies dans notre centre en 2014. Materiel et methode A partir des dossiers de 238 patients, nous avons selectionne ceux des 61 en situation de recidive postoperatoire (51) ou n’ayant pas recu d’hormonotherapie concomitante car atteints d’un cancer de pronostic favorable selon la classification de D’Amico (10). Resultats L’etalement classique prevu de 7,03 semaines en moyenne avec un ecart-type (σ) de 0,9 en fonction de la prescription (64 a 76 Gy) a ete en realite de 8,8 semaines en moyenne (σ = 0,75). L’analyse descriptive de notre population a montre que si on faisait abstraction des semaines de debut et de fin de traitement, le nombre de seances hebdomadaire pour un meme patient varie de trois (10 % ; σ = 0,9) a cinq (33 % ; σ = 1,5). La modalite la plus frequente etant de quatre (56 % ; σ = 1,7). Conclusion Les contraintes machines sont a l’origine de ce faible taux de patients recevant un etalement classique. Considerant nos imperatifs cliniques, techniques, l’etat d’avancee des connaissances et de la recherche actuelle, existe-t-il un autre etalement « ideal » pour les radiotherapies prostatiques que celui en cours actuellement dans nos services, hypo-fractionnement par exemple ?

Resume Chez les patients traites pour maladie de Hodgkin, les tumeurs radio-induites representent la premiere cause de deces apres 10 ans. Ce risque ne doit plus etre ignore. La premiere tumeur radio-induite a ete decrite des 1902, ce risque a cependant ete ensuite sous-evalue. Les radiations ionisantes ont alors ete utilisees pour des affections diverses, tant malignes que benignes. Depuis, de nombreuses etudes epidemiologiques ont permis de mieux evaluer les risques des traitements. A partir d'une revue de la litterature, nous avons compare les risques relatifs de developper une tumeur radio-induite en fonction du type de tissu, de la dose, de l'âge et des maladies associees. Les organes les plus sensibles a la transformation semblent etre la thyroide, le systeme nerveux central, le sein, l'os et le poumon, ce dernier principalement chez les fumeurs. Le nombre de tumeurs radio-induites augmente, dans la plupart des cas, avec la dose. Les risques sont plus importants pour les irradiations de l'enfant et de l'adulte jeune et majeurs pour les patients traites pour retinoblastome. Si le risque de tumeur induite ne doit pas modifier la place de la radiotherapie dans le traitement des tumeurs malignes, une reflexion sur les volumes et les doses doit etre entreprise pour en limiter l'incidence. Pour les affections benignes, l'indication d'une radiotherapie doit etre posee avec une extreme prudence, surtout chez les patients jeunes.

With an experience of more than 25 years for the pioneers (and more than 14 years in France), permanent implant brachytherapy using iodine 125 seeds (essentially) is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. The possible extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group has now been confirmed by several studies. Moreover, for the other patients in the intermediate-risk group and for the patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best ways to escalate the dose. Different permanent implant brachytherapy techniques have been proposed; preplanning or real-time procedure, loose or stranded seeds (or both), manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints, which have been recently redefined by the international societies, such as the GEC-ESTRO group. Mid- and long-term results, which are now available in the literature, indicate relapse-free survival rates of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3 to 5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome, which may significantly alter the quality of life of the patients, and last several months. In spite of those drawbacks, with excellent long-term results, low rates of incontinence and impotence, and emerging new indications (focal brachytherapy, salvage brachytherapy after localized failure of an external irradiation), permanent implant prostate brachytherapy can be expected to be proposed to an increasing number of patients in the next future.

Objectifs Evaluer l’efficacite et la toxicite d’une irradiation prostatique par Cyberknife® ou curietherapie en traitement de rattrapage des recidives locales de cancers de prostate initialement traites par radiotherapie. Methodes Entre 2011 et 2015, 28 patients initialement traites par irradiation prostatique et presentant une recidive exclusivement locale de leur cancer ont ete re-irradies par Cyberknife® (n = 18) ou curietherapie a haut debit de dose (HDD) (n = 10). Le schema de re-irradiation etait de 35 Gy en 5 fractions de 7 Gy par jour. La reponse biologique (variation post re-irradiation du PSA), la survie sans recidive biologique definie selon les criteres de Phoenix (nadir PSA post-irradiation +2 ng/mL), ainsi que les toxicites aigues et tardives cotees selon l’echelle CTCAE 4.03 ont ete evaluees. Resultats Apres un suivi median de 15,5mois (EI = 7–28), 9 (90 %) patients traites par CHDD et 13 (72,2 %) patients traites par Cyberknife® ont eu une reponse biologique positive. Deux (11,1 %) patients traites par Cyberknife® ont stabilise leur PSA. Chez les patients en reponse biologique positive apres CHDD, le nadir du PSA etait de 0,66 ng/mL (EI = 0,23–1,13), atteint en 6 mois (EI = 5–8). Quatre (44,4 %) patients ont eu une recidive biologique survenue en 19,5 mois (EI = 11,5–26) ( Figure 1 ). Nous avons note une seule complication urinaire G3 transitoire. Apres Cyberknife®, le nadir du PSA chez les patients en reponse biologique positive ou stabilisation etait 1,00 ng/mL (EI = 0,42–2,4) et fut atteint en 7,5 mois (EI = 4,5–10). Cinq (33,3 %) patients ont recidive biologiquement en 7 mois (EI = 6–14). Trois patients ont connu une complication ≥ G3 resolutive (urinaire : 2 G3 et 1 G4). Aucun patient n’a connu de complication sexuelle ou digestive ≥ G3. Conclusion La re-irradiation des recidives locales des cancers de prostate est une technique faisable et relativement peu toxique. Cependant, d’autres investigations sont necessaires pour confirmer ces resultats de facon prospective.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

To determine whether quantitative dynamic contrast-enhanced MRI improves the performance of T2W-MRI for the localisation of non-palpable prostate cancer (PCa) and for the estimation of tumor volume.Twenty-three patients (PSA: 8.91+/-6.2ng/m) with a non-palpable cancer underwent endorectal MRI with T2W and dynamic contrast enhanced (DCE) imaging before radical prostatectomy. Each level of evaluation (apex, mid-portion, base) was divided in eight areas (24 areas per prostate and 552 areas for the 23 patients). Localisation and volume of tumor foci greater than 0,2cc present on the radical prostatectmoy specimens were retrospectively correlated to their MR appearance on the 552 evaluated areas. The dynamic parameters included capillary permeability (K(trans)), maximum concentration of gadolinium after 60s of perfusion ([Gd]) and wash-out (K(ep)). Uni- and multivariate analysis were performed to determine which parameters were predictive of PCa.Mean values of K(trans), K(ep) and [Gd] were significantly higher in the 58 tumor foci greater than 0,2 cm(3) of the PZ and the TZ (all p0.05). Logistic regression for each zone provides provided a value of the area under the ROC curve of 0.83 for the PZ and 0.81 for the TZ (0.7 and 0.75, respectively, for the T2W imaging), only significant for the PZ (p0.002). Sensitivity and specificity were 79 and 77% for the PZ, 62.5 and 94% for the TZ. Above 0,2 cm(3), tumor volume on dynamic MR showed a mean difference of 51+/-100% (range: -145 to +248%).Quantitative dynamic MRI is more accurate than T2W imaging for tumor localisation of non-palpable cancer greater than 0,2 cm(3), but the difference is only significant for the PZ. Above this volume, correlation between tumor volume measured on dynamic MRI and that on the specimen is poor.

Whereas it has been proposed almost one century ago, brachytherapy for prostate cancer has only recently emerged, especially thanks to endorectal echography, allowing to visualize seed implantation, to the development of seeds for permanent delivery and of micro-sources for high-dose rate delivery, and also to the development of three-dimension dosimetry programs allowing real-time implantations. For selected patients with localized prostate cancer (PSA10, Gleason7, no extracapsular extension, volume50-60 g), prostate brachytherapy with permanent implants (iodine 125 or, less frequently, palladium 103) gives results which appear at 10-15 years comparable to those of surgery. Incontinence and impotence rates appear lower than those of classical surgery. However, the first post-implant months are usually accompanied by urinary toxicity that should not be minimized. High-dose rate brachytherapy (HDR) could find its indications, in combination with conformal radiotherapy, in the treatment of more advanced forms, presenting an intermediate risk. It could also be an alternative to brachytherapy with permanent implants for the low-risk forms mentioned above, especially in developing countries where the cost of radioactive seeds slows down the use of this technique. Brachytherapy for prostate cancer should, therefore, find more and more indications, because of the increased incidence of prostate cancer, due to population ageing, of the increased proportion of localized forms, due to better detection, of the patient's request for less toxicity, and of the expecting lowering of the costs, which are now equivalent to those of surgery and should further lower.

To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria.From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters.In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age70 years (P0.00001) and D90200 Gy (P0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml.The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age70 years and D90200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

La radiotherapie a pendant longtemps occupe une place primordiale dans le traitement des cancers du testicule. Elle est actuellement reservee aux seminomes, la chimiotherapie ayant totalement bouleverse la prise en charge des tumeurs germinales non seminomateuses. On constate egalement une evolution des pratiques concernant cette tumeur avec une reduction de ses indications au profit de la chimiotherapie pour les stades evolues, ainsi qu’une recherche d’une moindre toxicite pour les stades initiaux ou elle occupe encore une large place. Une reduction du champ et une diminution de la dose delivree sont les deux principaux objectifs permettant de conserver la fiabilite de cette option therapeutique tout en diminuant ses effets secondaires. C’est au stade initial, de loin le plus frequent, que la radiotherapie conserve sa place privilegiee avec un taux de reponse complete de 99 %. L’irradiation prophylactique sus-diaphragmatique en cas d’atteinte retroperitoneale de meme que l’irradiation du creux susclaviculaire ne sont plus recommandees. La premiere etait a l’origine d’une toxicite cardiaque a plus ou moins long terme, la deuxieme ne se justifie plus en raison du faible taux d’atteinte sus-claviculaire. Elle se limite actuellement a la region retroperitoneale selon des modalites plus simples permettant d’en diminuer les effets secondaires.

To study the number of migrating seeds, the anatomical site of migration and possible predictive parameters of migration, after prostate cancer brachytherapy using a loose-seed (I125) implantation technique.The charts of the 170 patients consecutively treated by the Institut Curie/Hospital Cochin/Hospital Necker Group between September 1, 2001 and August 31, 2002, were analysed. All seeds having migrated to the lungs and seen on the chest X-ray systematically performed at 2 months, have been recorded, as well as the seeds lost by the urines (after sieving) or in the sperm (condom).Among 12,179 implanted seeds, 44 were found to have migrated (0.36%). Most of the migrating seeds (32/44; 73%), were found in the lungs. Overall, one or several seed migrations were observed in 35 patients (21% of the total number of patients in this series). In the majority of cases (77%), only one seed migrated. A significant relationship (P = 0.04) was found between the number of migrating seeds and the number of implanted ones (or with the prostate volume, but those two parameters were closely linked in our series). More specifically, a significant relationship (P = 0.02) could be demonstrated between the number of seeds implanted at the periphery of the prostate and the number of seeds migrating to the lungs.The percentage of migrating seeds observed in this series is low, actually one of the lowest found in the literature when using the loose-seed technique. There was no clinical consequences and the loss of-usually-only one seed is very unlikely to alter the quality of the dose distribution. However, the predominance of pulmonary migrations in our series led us to slightly modify our implantation technique. We now try to avoid too "peripheral" seed implantations, due to the risk of migration towards the periprostatic veins, and subsequently to the lungs.

To study different methods of CT and MR images fusion in patient treated by brachytherapy for localized prostate cancer. To compare the results of the dosimetric study realized on CT slices and images fusion.Fourteen cases of patients treated by I125 were retrospectively studied. The CT examinations were realized with contiguous section of 5mm thickness, and MR images were obtained with a surface coil with contiguous section of 3 mm thickness. For the images fusion process, only the T2 weighted MR sequence was used. Two processes of images fusion were realized for each patient, using as reference marks the bones of the pelvis and the implanted seeds. A quantitative and qualitative appreciation was made by the operators, for each patient and both methods of images fusion. The dosimetric study obtained by a dedicated software was realized on CT images and all types of images fusion. The usual dosimetric indexes (D90, V100 and V150) were compared for each type of image.The quantitative results given by the software of images fusion showed a superior accuracy to the one obtained by the pelvic bony reference marks. Conversely, qualitative and quantitative results obtained by the operators showed a better accuracy of the images fusion based on iodine seeds. For two patients out of three presenting a D90 inferior to 145 Gy on CT examination, the D90 was superior to this norm when the dosimetry was based on images fusion, whatever the method used.The images fusion method based on implanted seed matching seems to be more precise than the one using bony reference marks. The dosimetric study realized on images fusion could allow to rectify possible errors, mainly due to difficulties in surrounding prostate contour delimitation on CT images.

The prognosis of locally advanced cervix cancers is poor with metastatic and local recurrence risks. Recent publications reported that concurrent chemotherapy and pelvic radiation increased local control compared to radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We report 92 cases of patients with locally advanced cervix cancer treated between 1986 and 1998 at the Institut Curie.Concurrent chemoradiation was exclusive in 51 cases and added to surgery in 41 cases. Chemotherapy with 5FU-Cisplatin-Mitomycin C-Vindesin (protocol A) was performed for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B).Median follow-up was 64 months (6-149 months). Five-year disease-free survival rate was 47% and local control rate was 70%. Disease-free survival was correlated with therapeutic response. After exclusive chemoradiation, the good responsive patients had a better DFS (54% vs 26%, p = 0.018). In the surgery group, those patients with sterilized lymph nodes and tumours had also a higher DFS (76% vs 47%, p = 0.036). Toxicity was higher with protocol A.From our study, it appears that local control of advanced cervix cancers is better with combined chemoradiotherapy but disease-free survival stays low according to the metastatic evolution. Metastasis without local recurrence remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with radiotherapy.

In the last decade, brachytherapy emerged as a particularly appealing new way ot treating localized prostate cancer. Recently published 10-12 years biochemical control results appear to be superimposable to the best percentages achieved by surgery or conformal radiotherapy, with a small percentage of complications. This applied to severely patients. Only patients with T1/T2, PSA10 ng/mL, and Gleason score7 should be proposed such a treatment. The potential benefit of exploring patients with a endorectal coil MRI is being evaluated. The number of positive biopsies is also a parameter which should probably be considered in the therapeutic choice. Moreover, a prostate volume60 g, hip mobility limitations, a urinary obstructive syndrome and previous transurethral resection lead to difficulties in technical implantation and therefore must be taken into account when discussing brachytherapy. In conclusion, for adequately selected patients, brachytherapy offers a particularly applied alternative to surgery and external radiotherapy, with satisfactory long term biochemical control rates and limited complications.

Uterine sarcoma is a rare disease and survival is poor. From 1975 to 1995, 73 uterine sarcomas were treated at the Curie Institute, and we analysed prognostics factors of survival.Seventy-one patients underwent primary surgery, in most cases a radical non conservative surgery and a lymphadenectomy. Every patient had an irradiation (external beam irradiation and/or brachytherapy), and 24 patients received adjuvant chemotherapy. We observed that youngest patients had more leiomyosarcomas and low histologic grade tumours. Median survival was 42 months, and 5-years survival and local control were 36 and 68% respectively. Pelvic recurrences were most often before 2 years. This series demonstrates the impact of adjuvant irradiation on local control. This impact was stronger if the tumour had a high histologic grade (p0.01). However, irradiation, as well as chemotherapy, had no impact on the survival.The study confirmed that irradiation enable a better local control. However modalities of radiation therapy (brachytherapy and/or external beam radiotherapy, dose, volume), are still controversed.

Radical prostatectomy remains the 'golden standard' therapy for localized prostate carcinoma for patients with a survival rate of more than ten years. However, because of the complications inherent in this surgical procedure, prostatectomy is presently increasingly challenged by various radiotherapy procedures. In the last decade, more sophisticated conformal therapy techniques have been proposed for prostate cancer patients. In parallel, for highly selected patients, brachytherapy is being promoted by an increasing number of medical centers. In fact, brachytherapy techniques for prostate cancers can be traced back to 1911, but recently developed techniques offer reliability and reproducibility, with satisfactory results in terms of tumor control and reduced toxicity, in selected patients. We present here the different techniques that are available today in prostate cancer brachytherapy.

Although the first radiation-induced solid tumor was reported as early as 1902, the risk of second tumor has been underestimated by radiation oncologists who treated large numbers of patients with either benign or malignant diseases. Since then, numerous epidemiological studies yielded better knowledge of the risks of radiation-induced malignancies. For instance, radiation-induced tumors are the first cause of death 10 years after treatment for Hodgkin's disease. We present here a literature review of the risks of radiation-tumors in various organs, related to the irradiation dose, age, and associated diseases. The most sensitive organs are the thyroid, central nervous system, breast, bone, and lung, especially in smokers. Higher risks are observed with increasing doses, the shape of the dose-response curve depending on the tumor type, when the irradiation is performed in children or young adults and in patients with retinoblastomas. The risk of radiation-induced tumors should lead the radiation oncology committee to reconsider the dose and technique of irradiation and to reduce the use of ionizing radiation in benign diseases.

Thirty one patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of carboplatin (CBDCA) and etoposide (VP16) at tumor progression. Carboplatin and etoposide (CE) were given, each at a dose of 100 mg/m2/day from day 1 to 3. The response was evaluated at each course and a minimum of three course was required to definite stable patient. Tolerance was evaluated in 31 patients. None had renal or auditory toxicity. Side effects consisted of grade III hematologic toxicity in 6 patients (19%), and grade III hepatic toxicity in one patient. No grade IV WHO toxicity was observed. All 31 patients could be evaluated for therapeutic response. A partial response was noted in 4 patients during 13, 34 +, 35 + and 51 + weeks. Ten patients had stable disease after a minimum of 3 courses (19 to 37 weeks). The rate of partial response (PR) and stabilisation (S) was 45% (14/31). The median time to tumor progression (MTTP) for responding and stable patients was 28 weeks. The median survival time (ST) for the entire group was 45 weeks and over 51 weeks for PR and S patients.

Two types of "severe accidental irradiation" can be schematically described: high dose localized irradiations and accidental total body overexposure. Actually, these two pathologies may coexist, and may be associated with external or internal radioactive contamination, and with all the "catastrophe medicine" syndromes. For high dose localized irradiation, physicians must manage as well as possible complex surgical procedures which unfortunately cannot always avoid being mutilating. For total body overexposure, haematological problems are at the forefront. In according with various situations, hematological growth factors or even allogeneic bone marrow transplantation will be discussed in specialized haematology (and transplant) units. The optimal management of severe accidental irradiation victims implies a close--and rapidly organized--cooperation between general practitioners, firemen, intensive care units, radiopathologists, specialist surgeons (hand and burns) and haematologists.

In 1994, late effects of radiotherapy should be limited to an acceptable rate of benign and non-disabling complications. In almost all cases, this goal can be presently reached, owe to recent technological and radiobiological advances. The precise adaptation of irradiated volume, dose, fractionation and total duration of treatment should avoid severe post-radiotherapeutic toxicity. The identification of subgroups of patients with high susceptibility to ionizing radiations should soon allow the radiotherapists to take up the challenge of a both efficient and non-toxic irradiation.

Inactivation of both alleles of the retinoblastoma susceptibility gene ( RB1 ), localised on chromosome band 13q14, is the crucial event for the development of retinoblastoma, a malignant tumour that originates from embryonal retinal cells.1, 2 Germinal mutation of one allele leads to a predisposition to retinoblastoma. Tumour development is initiated by inactivation of the second allele. In most families, the tumour predisposition segregates as an autosomal dominant trait with high (90%) penetrance3 and affected subjects usually develop bilateral multifocal tumours. Rare instances of familial retinoblastoma with low penetrance and variable expressivity have been described. In such families, patients develop retinoblastoma later than classical familial cases, there is a high rate of unilateral cases, and phenotypically normal obligate carriers are observed.4 A family with several cases of retinoblastoma has been identified (fig 1). Four members of the family were affected; three had unilateral retinoblastoma (III.5, IV.12, and IV.13), diagnosed at 12, 12, and 24 months, respectively, and one had bilateral retinoblastoma (IV-6), which developed at 11 months. Thus, with the exception of patient IV.13, the age of onset was not delayed compared to an average of less than 12 months in the majority of familial retinoblastoma. There were no cases of spontaneous osteosarcoma in this family, a secondary tumour recurrently found in patients with predisposition to retinoblastoma.5 However, the retinoblastoma of patient IV.6 was treated by radiotherapy (45 Gy) and 10 years later an osteosarcoma occurred in the irradiated field. It is well established that a germline mutation in the RB1 gene dramatically increases the probability of developing a radiation induced osteosarcoma.6 After ophthalmic examination of unaffected family members, no case of retinoma/retinocytoma, which may represent benign proliferation or tumour regression, was found. Altogether, these observations suggest the presence of a germline RB1 mutation linked to incomplete …

We report three examples of toxic acute colitis which occurred after ingestion of colocynth (Citrullus colocynthis) for ritual purposes. The prominent clinical feature was dysenteric diarrhoea; colonoscopic changes included congestion and hyperaemia of the mucosa with abundant exudates but no ulceration or pseudopolyp formation. A causal relationship between colonic injury and the intake of colocynth was supported by the following features: (1) the pharmacology of the colocynth extract ingested; (2) the temporal relationship between colocynth intake and clinical onset (eight to 12 h); (3) the rapid recovery within three to six days, with normal endoscopy at day 14; (4) the absence of other possible causes for the observed patterns, except in one case, in which a concomitant intestinal infection with Clostridium perfringens Type A was discovered; (5) the specific pathological features. Colonic biopsies taken 27, 44, and 72 h after colocynth intake showed: erosions with fibrino-purulent exudate, early fibrosis of the lamina propria, hyaline thickening of the superficial epithelial basal membrane. These pathological features completely disappeared within 14 days in all three cases.

Forty-six cases of non-surgical malignant glioma were treated by several repeated infusion of non-superselective intra-arterial chemotherapy using HECNU, followed by conventional radiotherapy. Chemotherapy was well tolerated immediately. Good responses rate was 46% for the whole group, but was higher in anaplastic astrocytomas (71%) than in glioblastomas (43%). The median survival for responders was 17 months, and clinical improvement was observed in a large majority of them. Later, neurological or ophthalmological ipsilateral complications of varying severity were observed in 8.7% and 15% of the cases respectively. Despite these complications the treatment was generally well tolerated and gave in responders a longer survival with better comfort.

Six patients with scleroderma (Barnett's type I and II) associated with hepatopathy are reported. Primary biliary cirrhosis was confirmed in four cases and was probably present in one case, while cirrhosis of unknown origin was present in the sixth patient. The outcome was fatal in two cases. Salivary secretions were reduced in all six cases, and a diagnosis of Gougerot-Sjögren's disease was confirmed in four patients. The frequency with which this triple association has been reported suggests that its incidence has been underestimated.