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Resume Les nouvelles techniques d’irradiation permettent de mieux conformer la dose aux contours de la tumeur. Le corollaire est une exigence accrue de precision. Des etudes recentes d’intercomparaison de plans de traitement ont souligne la necessite d’une harmonisation des pratiques de contourage. Une approche plus consensuelle repose sur l’utilisation de modalites d’imagerie adaptees, des recommandations de groupes experts et des atlas de segmentation automatiques, une harmonisation des decisions dosimetriques passant par l’utilisation d’abaques exhaustifs pour les organes a risque, et d’indices pour le choix des plans de traitement optimaux. A un echelon de plus, des programmes d’assurance qualite et de partage des donnees passant par l’utilisation de transferts de donnees DICOM RT (reseaux d’images) sont mis en place. La combinaison de plusieurs techniques d’irradiation differentes (par exemple, radiotherapie conformationnelle par modulation d’intensite [RCMI] + boost en CyberKnife ® et reirradiations), permettant de mieux irradier les tumeurs, necessite une documentation des doses cumulees grâce a des logiciels de sommation de dose. Une reelle prise de conscience s’est faite ces dernieres annees dans le sens de l’amelioration de la qualite des traitements, du partage des donnees et de l’harmonisation des pratiques.

Resume Objectif. – Validation de la dosimetrie biologique par rapport a la dosimetrie physique realisee sur 15 patients atteints d'hemopathie maligne et traites par irradiation corporelle totale avant transplantation medullaire. Materiel et methodes. – La dosimetrie biologique est realisee par le denombrement des aberrations chromosomiques lymphocytaires chez un sujet, comparees a celles observees chez des volontaires sains dont les lymphocytes ont ete irradies in vitro (courbes dose–effet). Les donnees humaines publiees sont fondees sur une evaluation retrospective des doses, avec de tres larges incertitudes sur la dose reellement delivree. L'irradiation corporelle totale avant transplantation de moelle osseuse est le seul modele humain de radiotherapie homogene d’un corps en totalite avec une connaissance parfaite de la dose delivree par dosimetrie physique. Nous avons utilise ce modele pour etablir la dosimetrie biologique avec les lymphocytes peripheriques circulants de 15 patients avant et apres la premiere fraction de 1,8 Gy, delivree par un accelerateur lineaire de 18 MV (debit de dose : 15,8 cGy·min –1 ). L'etablissement in vitro des courbes de reference a ete realise sur le sang de volontaires sains par deux methodes differentes : la cytogenetique classique, detectant les aberrations chromosomiques instables (dicentriques) et la methode de FISH-peinture du chromosome 4 avec marquage pancentromerique (hybridation in situ des chromosomes en fluorescence), detectant les aberrations chromosomiques stables (translocations). Les memes methodes ont ete utilisees pour les patients participant a l’etude, les anomalies chromosomiques etant denombrees a 0 Gy et apres la premiere fraction d'irradiation corporelle totale (1,8 Gy). Resultats. – Chez les volontaires, avant irradiation in vitro, on a note l’absence de dicentriques (1/1 091, soit 0,1 %), ainsi que le faible nombre de translocations du chromosome 4 (3/900, soit 2,5 % pour tout le genome apres extension grâce a la formule de Lucas). Chez les patients, avant irradiation in vivo, on a note 2 % de dicentriques (46/2 491) et 1,24 % (32/2 566) de translocations du chromosome 4, soit 11,48 % d'apres la formule de Lucas pour tout le genome. Cela temoigne probablement du passe therapeutique (chimiotherapie) de ces patients. Chez les 15 patients, pour une dose physique de 1,8 Gy, la dose biologiquement evaluee etait de 1,93 Gy (IC 95 % : 1,85–2,05) par la methode de cytogenetique classique et 2,02 Gy (IC 95 % : 1,75–2,15) par FISH. Conclusion. – La dosimetrie biologique est dans ce cas de figure en parfait accord avec la dosimetrie physique.

Resume Les tests de radiosensibilite tumorale mis au point dans les annees 80 ont repose sur les cultures cellulaires a partir de biopsies tumorales. Dans la plupart des cas, il n'a pu etre montre de correlation entre les donnees obtenues in vitro et la radiocurabilite. Actuellement, de nouveaux tests, bases sur des techniques differentes, sont en cours d'evaluation (mesure de l'apoptose radioinduite, hybridation in situ avec sondes fluorescentes). Les resultats preliminaires paraissent encourageants, mais il est vraisemblable qu'une correlation entre les resultats de ces tests et le controle locoregional du cancer sera difficile a etablir en raison du caractere multifactoriel de ce dernier.

High doses of ionizing radiation (> 40 Gy) cause severe lung fibrosis in approximately 5% of the cases. There is a twofold increase when chemotherapy is added to ionizing radiation. Lung fibrosis is due to the destruction of lung tissue by ionizing radiation but also to various cytokine effects (PDGF-beta, TGF-beta). Only a minority of patients (approximately 10%) with abnormal X-rays will experience clinical symptoms. The most important radiobiological parameters which accounts for pulmonary tolerance is the fraction size. Irradiation of the heart begets multifarious late sequelae which are often left unrecognized. Chronic pericarditis affects approximately 5% of the patients when the irradiation dose exceeds 40 Gy. Coronary artery disease can be diagnosed in 5 to 10% of the patients. This late complication is more likely to occur if the patient was young at the time of the irradiation or if other risk factors are associated. Valvular defects can be found in 15 to 30% of the patients. However, the mortality rate is very low (0.5%). Finally, conduction defects can also be seen in approximately 5% of the patients. It is very likely that the radiation dose given to the heart should not exceed 30 Gy if late sequelae are to be avoided.

Ionizing radiations have been reported as an in vitro apoptosis initiating stimulus in human lymphocytes. As the cytotoxicity of ionizing radiations and chemotherapeutic agents appears to be dependent on the efficacy of cell death induction, the manipulation of apoptosis initiation might be used as a means to supress some pathological process. In the present study the in vivo induction of gamma-ray mediated programmed cell death in humans is reported. The in vivo induction of apoptosis in peripheral blood lymphocytes (PBL) by ionizing radiations was investigated in 33 patients after each of two sessions (2 Gy and 4 Gy) of fractionated total body irradiation (FTBI) as part of their conditioning regimen before bone marrow transplantation. PBL committed to apoptosis were scored before irradiation (S1), 4 h (S2) and 24 h after 2 Gy (S3, 14-17 h after the second 2 Gy fraction). Nuclear morphology and chromatin-DNA were analysed by fluorescence microscopy immediately after blood sample withdrawal (I) and after 24 h in cell culture medium (II). When scored immediately after withdrawal, no circulating PBL with the apoptotic nuclear morphology were observed in S1 and S2 blood samples whereas S3 disclosed 21.9 +/- 11.7% of circulating lymphocytes with an apoptotic nuclear morphology. After 24 h in culture, S1 samples (before irradiation) generally contained less than 20% of apoptotic lymphocytes. A higher percentage of apoptotic cells was noted in some cases in relation with recent chemotherapy and possibly with pathology. After 24 h in culture, S2 and S3 samples contained 51.7 +/- 17.9% and 60.4 +/- 16.4% of apoptotic lymphocytes, respectively. These results confirm that ionizing radiations induce apoptosis in vivo in human lymphocytes and that the commitment to apoptosis can be determined after low doses (2 Gy) of therapeutic whole body irradiation. The results suggest that susceptibility to apoptosis induction by ionizing radiations could be related to previous therapy by cytotoxic drugs and possibly to the type of haematological malignancy.

International audience; With new irradiation techniques, the dose can be better matched to the contours of the tumour. The corollary is that greater precision is required. Recent intercomparison studies of treatment plans have emphasized the need to harmonise contouring practices. More of a consensus approach is based on using adaptive imaging modalities, expert group recommendations and automatic segmentation atlases, on harmonisation of dosimetric decisions through employing exhaustive nomograms for organs at risk, and on indexes for choosing optimal treatment plans. On another level, quality assurance and data pooling programmes have been set up, making use of DICOM-RT data transfer (image networks). The combination of several irradiation techniques (for example, intensity-modulated conformal radiation therapy plus CyberKnife((R)) boost and re-irradiation), making it possible to irradiate tumours better, requires the cumulative doses to be recorded by dose summation software. Real awareness has been achieved in recent years as regards improving the quality of treatment, pooling data and harmonising practices.

IMRT is a seducing treatment option in patients with Hodgkin lymphoma mediastinal masses due to the complex form of the tumour masses and their proximity to organs at risk such as the heart and the coronary arteries. This treatment delivery technique remains risky owing to respiratory movements and heart beats. The concomitant use of IMRT and respiratory gating is enticing, but a number of theoretical and practical hurdles remain to be resolved before it can be used in clinical daily practice.

To assess the clinical outcome of the involved-node radiotherapy (INRT) concept with the use of deep-inspiration breath-hold (DIBH) technique in patients with localized supra-diaphragmatic Hodgkin lymphoma.All were patients with stage I-II Hodgkin lymphoma and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy concept according to the European Organization for Research and Treatment of Cancer Guidelines and a spirometer dedicated to DIBH radiotherapy was used for every patient.Twenty-seven patients with Hodgkin lymphoma (26 patients with primary Hodgkin lymphoma, one with refractory disease), treated from November 2004 to October 2010, were retrospectively analysed. The median age was 27 years (range 16 to 54). Seventeen (63%) patients had stage I-IIA and 10 (37%) had stage I-IIB disease. All patients received two to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine. The median radiation dose to patients was 30,6 Gy (range: 19,8-40). Protection of various organs at risk was satisfactory. Median follow-up, 3-year progression-free and 3-year overall survival were 38 months (range: 7-70), 96% (95%CI: 79-99%) and 95% (95%CI: 75-99%), respectively. Recurrence occurred in one patient (mediastinal in-field relapse). There was one grade 3 acute toxicity (transient pneumonitis).Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using deep-inspiration breath technique and the involved-node radiotherapy concept. Longer follow-up is needed to assess late toxicity, especially for the heart and the coronary arteries.

To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supradiaphragmatic Hodgkin lymphoma.Patients with early-stage supradiaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing.Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20-40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4-94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80-99) and 92% (95% confidence interval: 78-97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case.Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation.

Multiple new developments in the treatments of patients with Hodkgin lymphoma have occurred in the last 10 years. Radiation treatments have become extremely precise in localized Hodgkin lymphomas, on the other hand, they have almost completely disappeared in advanced stages. For patients with refractory or recurrent disease, it is strongly advocated, whenever feasible, to deliver a mantle field radiation treatment after an autologous stem cell transplant to avoid any further recurrence of the disease.

Primary malignant non-hodgkin lymphoma involving the prostate is rare. Most of the time, it is associated with extraprostatic disease. We report a case of a 72-year-old patient presenting with acute lower urinary tract irritative symptoms, due to large B-cell lymphoma limited to the prostate. Combination of chemotherapy with extern beam radiotherapy provided long-term local control.

Presently, radiotherapy is rarely an upfront treatment in patients with lymphomas. The modern evolution of radiation treatment calls for the development of therapeutic niches in which radiotherapy remains absolutely necessary. The development of new imaging techniques and their use in radiation planning systems along with new sophisticated radiation delivery techniques such as IMRT and respiratory gating should permit an increased accuracy an increased accuracy in the treatment of tumor masses and a decrease in late normal tissue complications.

Validation of biological dosimetry versus physical dosimetry in malignant haemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT).The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cytogenetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations.Healthy volunteer lymphocytes, before irradiation, yielded 0.1% dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cytogenetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH.These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning.

To study the biologic and clinical effects of ionizing radiation on blood vessels.Data extracted from experimental and clinical reports and articles.Radiation-induced demise of endothelial cells is due to apoptosis. These cells are considered to be very radiosensitive. In vivo, however, the basal membrane might play a protective role. Early effects are characterized by swelling and shloughing of endothelial cells. Late effects are due to endothelial and smooth muscular cell proliferation. The underlying biologic mechanisms are little known. One hypothesis is the production of PDGF (platelet-derived growth factor) and FGF (fibroblast growth factor) by endothelial cells. Perivascular fibrosis might occur because of the TGF-beta production by endothelial cells and/or macrophages. Occurrence of late complications is probably multifactorial. Individual susceptibility to harmful effects of ionizing radiation, other vascular risk factors, and non optimal use of radiation treatment might contribute to the occurrence of late vascular complications. Modern radiotherapy using new techniques as the intensity modulation radiation therapy (IMRT) and the reduction of radiation doses and size of radiation fields should permit a dramatic reduction of vascular complications in cancer patients.Ionizing radiation treatments can lead to serious late vascular complications. A better understanding of the underlying biologic processes and newer radiation techniques might lead to fewer late complications in the very near future.

The aim of this study was to describe the radiological characteristics of breast cancers occurring after treatment of Hodgkin's disease (HD). This study identified 23 women (age range 28–70 years, mean age 40 years) with 29 breast cancers (22 infiltrating carcinomas, 5 in situ, 1 sarcoma, 1 indeterminate) who had previously undergone mantle irradiation (35–40 Gy) for HD. Clinical and mammographic data were reviewed by two radiologists. Dosimetry was available for 16 patients. Time from treatment of HD to the occurrence of breast cancer ranged from 15 months to 35 years (mean 18 years); 79 % were younger than 45 years and 76 % of cancers occurred between 10 and 25 years of follow-up. The physical examination was positive in 76 % and 6 patients had bilateral tumors (synchronous, n = 2; metachronous, n = 4). Eighty-three percent of mammograms (n = 24) were abnormal (microcalcifications, n = 72 %; opacity, n = 54 %; two inflammatory breast cancers). Seven cancers were only detected by mammography, but mammograms were normal in 4 patients. Breast cancer was located beyond or was overlapping radiation fields in 75 % of cases. Starting 10 years after mantle irradiation of women with HD, the follow-up should include annual clinical breast examination and mammography.

Various assays measuring tumor radiosensitivity were developed in the early eighties. These assays were based on cell cultures derived from tumor biopsies. In most studies there was no correlation between measured radiosensitivity and treatment outcome. New assays using new techniques (such as measurement of radiation-induced apoptosis, or fluorescence in situ hybridization) have been developed recently. Preliminary results are encouraging, but correlation with treatment outcome is expected to be difficult to demonstrate as multivarious clinical and biological parameters are involved in loco-regional control.

The treatment of synchronous esophageal and head and neck carcinomas is difficult.Retrospective study of 33 patients treated with esophagectomy for an intrathoracic squamous cells carcinoma discovered during pan-endoscopy for a synchronous head and neck cancer.In 7 cases (21%) it was advanced (pT3-4) esophageal cancers. The hospital mortality was 9%. Five year survival was 18% without stabilization of the survival curve, 60% of patients died of recurrence of tumor.Esophagectomy is suitable for usT1-2 tumors if surgery is also indicated for the head and neck tumor. Radiochemotherapy is indicated for advanced usT3-4 esophageal tumors or when the treatment of the head and neck tumor is not surgery.

High doses of ionizing radiation (40 Gy) cause severe lung fibrosis in approximately 5% of the cases. There is a twofold increase when chemotherapy is added to ionizing radiation. Lung fibrosis is due to the destruction of lung tissue by ionizing radiation but also to various cytokine effects (PDGF-beta, TGF-beta). Only a minority of patients (approximately 10%) with abnormal X-rays will experience clinical symptoms. The most important radiobiological parameters which accounts for pulmonary tolerance is the fraction size. Irradiation of the heart begets multifarious late sequelae which are often left unrecognized. Chronic pericarditis affects approximately 5% of the patients when the irradiation dose exceeds 40 Gy. Coronary artery disease can be diagnosed in 5 to 10% of the patients. This late complication is more likely to occur if the patient was young at the time of the irradiation or if other risk factors are associated. Valvular defects can be found in 15 to 30% of the patients. However, the mortality rate is very low (0.5%). Finally, conduction defects can also be seen in approximately 5% of the patients. It is very likely that the radiation dose given to the heart should not exceed 30 Gy if late sequelae are to be avoided.

The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less than 10 per cent of secondary MDS are usually observed in patients treated for Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by modern chemotherapeutic regimens is needed. Between January 1985 and January 1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE) were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi-agent chemotherapy and involved-field irradiation. The mean age was 54 years (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28 months after therapy. Thirteen patients were followed up for at least 5 years. Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic analysis was performed in two cases and showed-7 and 18q- in one case, t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy should not be recommended in patients with localized gastric non-Hodgkin's lymphoma due to the high risk of developing secondary myelodysplastic syndromes.

The multifocal origin of prostate cancer suggests a pan-organ defect in a tumor suppressor pathway. Although structural mutations in the p53 gene have been implicated in late-stage prostate cancer, little is known about the p53 response to genotoxic stress in normal human prostatic epithelial cells from which adenocarcinomas originate. We found that the majority (10 of 12) of epithelial cell cultures derived from histologically normal tissues of radical prostatectomy specimens failed to exhibit p53 accumulation in response to ionizing radiation. Epithelial cell cultures derived from benign prostatic hyperplasia and a primary prostatic adenocarcinoma also failed to accumulate p53 in response to ionizing radiation. In contrast, cultures of prostatic stromal cells derived from normal, benign prostatic hyperplasia, or adenocarcinoma tissues exhibited a 3-9-fold induction of p53 within 1-3 h after irradiation. Since p53 regulates a cell cycle checkpoint through the induction of the cyclin-cdk inhibitor p21, we examined p21 accumulation and cell cycle arrest following exposure to ionizing radiation. With one exception, epithelial cells that did not display increased p53 or p21 induction did not demonstrate a significant G1-S arrest in response to ionizing radiation, whereas stromal cells that accumulated p53 and p21 exhibited a large cell cycle arrest. These results indicate a functional difference between the DNA damage response of epithelial and stromal prostatic cells and suggest a possible mechanism for the increased susceptibility of prostatic epithelial cells to accumulate genetic alterations.

Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distant metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the primary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new local controls would develop distant metastasis. To investigate this concept, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating centers. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local control have been evaluated for 24 murine tumor systems. SF2s (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8 human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity assessed after injection of the cells into syngeneic murine hosts and xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled locally by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of patients studied was 222. The cumulative distributions of SF2s of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relationship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2s of murine and human tumor cell lines did not track with metastatic activity. Radiation sensitivity of clinical and laboratory tumors did not correlate with metastatic activity in studies of data from six centers.

From 1982 to 1991, 200 patients with squamous-cell esophageal cancers underwent operation. Sixteen prognostic parameters were prospectively collected and analyzed. The main aim of this study was to define the best preoperative criteria for selection for curative surgery and which patients would benefit most from radical resection. Squamous-cell head and neck carcinoma was associated in 43.5% of cases. Of these, 24% preceded the esophageal carcinoma while 19.5% were synchronous. Resection was curative (i.e. grossly complete) in 144 cases, palliative (leaving gross tumor behind) in 25 cases, and judged impossible in 31 cases. Twenty-one patients died during their hospitalization. Five-year survival, according to the Kaplan-Meier method, was 18 +/- 3.6% for all patients, and 27 +/- 4.8% for patients undergoing curative resection (including postoperative mortality). Palliative resections or invasion of adjacent organs, but not resection with positive lymph nodes, was thought to be synonymous with incurability. Multivariate analysis showed that the two principal statistically significant characteristics were the stage as determined by roentgenological and endoscopic evaluation (P = 0.003) (clearly assessable during initial work-up) and type of resection (complete or not) (P = 0.04). Tumor diameter, as determined on CT-scan (orthan 30 mm), was at the limit of statistical significance (P = 0.09). A second multivariate analysis of prognostic factors was conducted in 128 patients undergoing resection with curative intent and who survived the initial postoperative period. Roentgenologic/endoscopic staging alone emerged as being statistically significant (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

From May 1980 to December 1989, 107 consecutive patients with non-constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco-abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow-up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.

Fractionated total body irradiation was given to a patient with chronic myeloid leukemia as part of a conditioning regimen for bone marrow transplantation. The radiation treatment was discontinued after the third fraction (total dose: 385 cGy) and no bone marrow graft was given because of the patient's refusal. Peripheral blood lymphocyte levels were monitored for 3 months and lymphocyte subsets up to 50 days post-irradiation. Lymphocyte numbers reached the nadir 48 h after the last fraction and lymphopenia was still present 3 months later. All lymphocyte subsets (T, B, CD4 and CD8 cells) showed a similar decrease except for natural killer cells which exhibited a larger decline. The regenerative capacity of T cells, CD4 subset and natural killer cells was less than that of B cells and CD8 lymphocyte subsets.

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Twenty-eight patients with synchronous esophageal and head and neck epidermoid cancers have been treated by a combined protocol including esophagectomy. Seventy-nine percent received pre-operative chemotherapy, 50% had resection of the head and neck lesion at the same time as the esophagectomy and 79% received post-operative irradiation. Two patients died during the post-operative period (7%), and 1, 2 and 3-yr survival rate (Kaplan-Meier) was respectively 64, 32 and 27%. Contrary to our initial assumption, there was no significant decrease in survival compared to patients operated on for an isolated esophageal cancer. The patients were divided into 4 very simple prognostic groups based on the T and N stages of the clinical pre-therapeutic TNM classification: T1 or T2 for esophageal lesions and different T or N stages according to the prognosis for head and neck lesions. A study of each group tended to show that esophagectomy was beneficial except in cases of synchronous T2 esophageal cancer and locally advanced head and neck cancer (there was 2-yr survival in this group). The 28 patients studied represent a particular population which presented 91 cancerous localisations during the duration of the study (mean: 3.25 localisations per patient).

Early hematotoxicity following 4 to 8 courses of polychemotherapy has been analysed in 78 patients (mean age 32.5 years) treated for advanced stage Hodgkin's disease (53 stages III, 25 stages IV). Toxicity occurred in a third of the patients, and led to interrupt the treatment in one case out of 7, definitively in half of them. The thrombocyte lineage appeared the most sensitive to irradiation. Toxicity was proportional to the target volume (42% of upper and infra-diaphragmatic field versus 11.5% of one sided irradiation, P = 0.01). Toxicity was more frequent after infra-diaphragmatic irradiation (32% of para-aortic field, 43.75% of inversed Y field) than after mantle field (12.3%, P = 0.01). Tolerance to extended field irradiations seemed better in young patients. Sex, stage, type of chemotherapy did not influence toxicity in our series. Abnormalities of the blood count before irradiation was predictive of toxicity. While expecting development of megakaryocytic growth factors of autologous bone marrow transplantation, we suggest: 1) to achieve total lymphoïd irradiation in three periods (mantle field then lombo-aortic field-/+ spleen, then iliac and inguinal fields); 2) to wait, if possible, until normalization of the hemogram before starting the irradiation.

Intra-operative radiotherapy is being used more and more frequently; this raises the problem of the equivalence of these large doses delivered in a single fraction, especially when a second line, complementary external irradiation is planned afterwards. The linear quadratic (LQ) model is probably the most convenient way to compare 2 irradiation schedules delivered with different doses per fraction. However, in the case of intra-operative radiotherapy, one should question the use of the LQ equation; this model actually predicts a continuous bending of the survival curve, while most experimental curves show a trend towards exponential at high dose levels. As a result, with the very large doses (20-30 Gy) given here, the LQ model would lead to overestimate the efficacy--and the toxicity--of intra-operative irradiation. We thus propose to calculate the equivalent fractionated doses by combining 2 models; the LQ model, considered to be reliable up to 7 Gy, and the 2 components' target model, which tends towards an exponential at high dose level. Moreover, we must take into account the hypoxic component of the tumour, since the single fraction, intra-operative technique cannot benefit from the reoxygenation occurring during conventional fractionated irradiations. Calculations indicate that for a partially hypoxic tumour, the effect of a large dose (20-30 Gy) is very similar to the one which would be achieved by the same dose given in a conventionally fractionated way, increased by the dose necessary to compensate for the proliferation occurring during treatment. For healthy tissues, assuming that all cells are well oxygenated, the equivalent fractionated dose is, in particular, much higher for late responding tissues.1) there is little hope for sterilizing any carcinoma with only one fraction of 20-30 Gy; 2) however, intra-operative irradiation, focussing on a small volume, could contribute to the tumour eradication; 3) the intra-operative irradiation technique should, as much as possible, spare the neighbouring normal tissues, regarding the risks of long term complications.

Non-Hodgkin lymphomas (NHL) of the conjunctiva are rare. Radiotherapy is usually considered to be the choice of treatment in such situations. Reported here are 14 cases of conjunctival NHL, treated at the Institut Gustave-Roussy from 1981 to 1988. Mean age of the patients was 53 years. The series comprised 7 stages of IE, 4 stages of IIE and 3 stages of III. Histological types were mostly "low-grade" according to the Working Formulation (9 cases out of 14). The irradiation technique took advantage of a customized facial lead mask and of a direct anterior electron beam. A small cylindrical lead block, hanging some millimetres above the eye, shielded the cornea and the lens. Local control was achieved for 17 eyes treated (out of 19 irradiated), with a follow-up ranging from 5 to 90 months. The 2 relapses occurred in the same patient, and could be treated by a second line irradiation of the same type. Immediate tolerance was good. Late sequelae were rare and actually included 4 cases of cataract which clearly could not be entirely attributable to the treatment. In conclusion, this sophisticated technique appears to be efficient and non-toxic, since it was able to achieve an almost 100% local control rate, together with a very low percentage of late complications.

Up to now, radiation oncologists had at their disposal only a number of well-known histological and clinical factors in order to define the optimal dose which should be delivered to a given tumor. Recently, radibiological studies have suggested additional parameters which may play a major role in tumor radiocurability. These parameters are: the number of clonogenic cells, intrinsic radiosensitivity, hypoxia and proliferation kinetics. "Predictive" tests are being developed and evaluated for each of these parameters. The more advanced studies deal with intrinsic radiosensitivity; preliminary data show impressive variations in radiosensitivity within groups of clinically "homogeneous" tumors. Should these tests prove to be reliably predictive of radiocurability, it will be possible, in the near future, to propose to any given patient a "custom-made radiotherapy" adapted to the precise features of his or her tumor.

Objectifs Presenter l’etat de l’art de l’application aux images medicales d’une segmentation interactive issue de la morphologie mathematique. Materiels et methodes La morphologie mathematique est une branche du traitement d’images qui propose des outils puissants de segmentation interactive. La theorie mathematique sous-jacente, qui combine la morphologie mathematique (dont ligne de partage des eaux) et la theorie des graphes, est tres generale et peut etre appliquee a des images a dimensions multiples. L’utilisation de marqueurs permet d’introduire de maniere naturelle dans le processus de segmentation une information a priori sur les structures a contourer. Resultats L’outil developpe a ete implante dans un demonstrateur et applique a des images scanner. L’utilisateur placait des marques simples sur les images axiales coronales ou sagittales. La segmentation hierarchique 3D pyramidale etait ensuite calculee. Conclusion L’application de marqueurs augmente l’efficacite de la segmentation interactive d’images medicales par hierarchie de partition pour le contourage de zones anatomiques. Son extension potentielle aux differentes modalites d’imagerie, aux sequences incluant le temps, en font un outil d’interet pour differentes specialites d’organe et pour la radiotherapie.

Le but d u r a d i o t h e r a p e u t e est d ' e r a d i q u e r les ce l l u l es t u m o r a l e s d u v o l u m e i r rad ie e n ev i t an t (ou e n m i n i m i s a n t ) a u t a n t q u e fa i re s e peu t les c o m p l i c a t i o n s p r e c o c e s e t t a r d i v e s a u n i v e a u d e s t i s s u s sa ins s i t ues d a n s c e m e m e v o l u m e . L a f i b r o s e r a d i q u e e s t l 'un d e s m u l t i p l e s p a r a m e t r e s qu i v i e n n e n t s ' in t r iquer p o u r r e n d r e c o m p t e d e la tox i c i t e t a r d i v e d e la r a d i o t h e r a p i e .