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Purpose: Virtual simulation process is often used to prepare three dimensional conformal radiation therapy treatments. As the quality of the treatment is widely dependent on this step, it is mandatory to perform extensive controls on this software before clinical use. The tests presented in this work have been carried out on the treatment planning system ISOgray (DOSIsoft), including the delineation module IMAgo and the virtual simulation module SIMAgo., Material and Methods: According to our experience, the most relevant controls of international protocols have been selected. These tests mainly focused on measuring and delineation tools, virtual simulation functionalities, and have been performed with three phantoms: the Quasar Multi-Purpose Body Phantom, the Quasar MLC Beam Geometry Phantom (Modus Medical Devices Inc.) and a phantom developed at Hospital Tenon., Results: No major issues have been identified while performing the tests. These controls have emphasized the necessity for the user to consider with a critical eye the results displayed by a virtual simulation software. The contrast of visualisation, the slice thickness, the calculation and display mode of 3D structures used by the software are many factors of uncertainties., Conclusion: A virtual simulation software quality assurance procedure has been written and applied on a set of CT images. Similar tests have to be performed periodically and at minimum at each change of major version.

Objectives: The impact of learning effects on the variability of costs of new health technologies in a prospective payment system (PPS) through the case of intensity modulated radiation therapy (IMRT) was studied., Methods: A series of consecutive patients treated in nine medical centers was enrolled in a prospective study. Direct costs were assessed from the perspective of the healthcare providers. We used a two-level model to explain the variability of costs: patients nested within centers. Learning effects at the center level were considered through a fixed effect (the learning curve slope) and a random effect (the initial cost level). Covariates were introduced to explain the patterns of variation in terms of patient characteristics., Results: The mean direct cost of IMRT was 5,962 euro (range, 2,414 euro-24,733 euro). Manpower accounted for 53 percent of this cost. Learning effects explained 42 percent of the variance between centers (which was 88 percent of the total variance) and were associated with a substantial decrease in treatment costs. The mean initial treatment direct cost was 6,332 euro in centers with a previous experience of IMRT, whereas it was 14,192 euro in centers implementing IMRT for the first time. Including logistics costs and overhead, the full cost of IMRT was 10,916 euro. Average reimbursement was 6,987 euro., Conclusions: Learning effects are a strong confounding factor in the analysis of costs of innovative health technologies involving learning effects. In a PPS, innovative health technology involving learning effects necessitates specific reimbursement mechanisms.

These last years, the new irradiation techniques as the conformal 3D radiotherapy and the IMRT are strongly correlated with the technological developments in radiotherapy. The rigorous definition of the target volume and the organs at risk required by these irradiation techniques, imposed the development of various image guided patient positioning and target tracking techniques. The availability of these imaging systems inside the treatment room has lead to the exploration of performing real-time adaptive radiation therapy. In this paper we present the different image guided radiotherapy (IGRT) techniques and the adaptive radiotherapy (ART) approaches. IGRT developments are focused in the following areas: 1) biological imaging for better definition of tumor volume; 2) 4D imaging for modeling the intra-fraction organ motion; 3) on-board imaging system or imaging devices registered to the treatment machines for inter-fraction patient localization; and 4) treatment planning and delivery schemes incorporating the information derived from the new imaging techniques. As this paper is included in the "Cancer-Radiotherapie" special volume dedicated to the lung cancers, in the description of the different IGRT techniques we try to present the lung tumors applications when this is possible.

The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.

An economic evaluation of intensity modulated radiotherapy (IMRT) in head and neck cancer was carried out to assess the cost of treatment and compare it to reimbursement paid to hospitals in the French Prospective Payment System. Planning required in average 20 hours of work for the physician and 6 hours for the radiation oncologist. Radiation consisted of 33 fractions in average and required 29 hours of work for the radiotherapy technician, 8 hours for the physician and 3 hours for the radiation oncologist. Mean cost of IMRT treatment was estimated at euro 10,916 (euro 2,773 for planning and euro 8,143 for radiation). The variability of costs was important and was in a large extent attributable to learning effects. As more patients were treated, unit cost of treatment was decreasing. In the French Prospective Payment System, mean reimbursement of IMRT was euro 6,987. For 70 % of the patients, reimbursement did not offset the cost of treatment. A financial support for hospitals implementing the technique is essential during the whole learning period.

The development of conformal radiotherapy techniques (CRT) and intensity modulated CRT requires an accurate delineation of target structures and organs at risk. Thus, additional information provided by anatomical and/or functional imaging modalities can be used for volume of interest determination combined with traditionally used Computed Tomography imaging (CT): for instance, functional or morphological Magnetic Resonance Imaging (f MRI or m MRI) or Positron Emission Tomography (PET). A prerequisite to the simultaneous use of this information is image registration. Due to the differences between the images and the information they provide, a quality control of image registration process for radiotherapy is mandatory. The purpose of this article is to present the difficulties in implementing such controls and to show the necessity for a clinical validation on patient's images. The last part of this work presents the possible interest in using f MRI to help radio-oncologists in the treatment planning for gliomas associated to image coregistration and quality control considerations.

Target localization has become increasingly important in the advent of IMRT, as treatment margins are reduced and target doses are increased with high-dose gradients outside this target volume. The in-room CT on rails-LINAC system allows CT imaging while the patient remains immobilized in the treatment position just prior to treatment. The anatomic inter- and intra-fractional variations can be therefore quantified during a course of treatment. The position of the tumour can be checked and corrected before the fraction. In case of modification of tumour shape, a re-planning of the treatment is also feasible. However, several issues remain: the integration with routine clinical treatment due to a lack of software tools, the frequency of imaging, and the cost-efficiency ratio. The clinical experience is yet very limited but CT-image-guided radiotherapy appears promising for prostate, brain and spinal tumours.

Purpose: To evaluate the role of beam orientation optimization and the role of virtual volumes (VVs) aimed at protecting adjacent organs at risk (OARs), and to compare various intensity-modulated radiotherapy (IMRT) setups with conventional treatment with anterior and posterior fields and three-dimensional conformal radiotherapy (3D-CRT)., Methods and Materials: Patients with mediastinal masses in Hodgkin's disease were treated with combined modality therapy (three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] before radiation treatment). Contouring and treatment planning were performed with Somavision and CadPlan Helios (Varian Systems, Palo Alto, CA). The gross tumor volume was determined according to the prechemotherapy length and the postchemotherapy width of the mediastinal tumor mass. A 10-mm isotropic margin was added for the planning target volume (PTV). Because dose constraints assigned to OARs led to unsatisfactory PTV coverage, VVs were designed for each patient to protect adjacent OARs. The prescribed dose was 40 Gy to the PTV, delivered according to guidelines from International Commission on Radiation Units and Measurements Report No. 50. Five different IMRT treatment plans were compared with conventional treatment and 3D-CRT., Results: Beam orientation was important with respect to the amount of irradiated normal tissues. The best compromise in terms of PTV coverage and protection of normal tissues was obtained with five equally spaced beams (5FEQ IMRT plan) using dose constraints assigned to VVs. When IMRT treatment plans were compared with conventional treatment and 3D-CRT, dose conformation with IMRT was significantly better, with greater protection of the heart, coronary arteries, esophagus, and spinal cord. The lungs and breasts in women received a slightly higher radiation dose with IMRT compared with conventional treatments. The greater volume of normal tissue receiving low radiation doses could be a cause for concern., Conclusions: The 5FEQ IMRT plan with dose constraints assigned to the PTV and VV allows better dose conformation than conventional treatment and 3D-CRT, notably with better protection of the heart and coronary arteries. Of concern is the "spreading out" of low doses to the rest of the patient's body.

Intracranial gliomas account for less than 2% of primary solid tumors in adults, but are among the most frequent causes of death from cancer in children. Their increasing incidence and the weak impact of treatments on the prognosis justify all the efforts expended to improve results. Surgery, radiation therapy (RT) and chemotherapy are proposed as first-line therapy, according to indications and modalities that remain controversial. In this palliative setting, the only consensus is to search for an optimal efficacy/toxicity ratio. Finally, after a very variable duration of local control depending on the histologic type, recurrence is virtually inevitable, with mainly local progression. The prognosis is then generally dismal, with a median survival of less than 6 months. Although re-operation is efficient for the rapid relief of symptoms, it is often rejected. After or in the absence of surgery, different chemotherapy schedules are proposed according to the histologic type and the patient's general status and objective response rates are very limited, except in the case of oligodendrogliomas. Re-irradiation has a rather bad reputation: even as first-line therapy, total doses never exceed 60 Gy in 30 fractions of 2 Gy over six weeks (conventional fractionation). The main reasons are concerns about increasing unacceptable late neurologic complications and the absence of a demonstrated dose-effect beyond this threshold. However, some arguments have led clinicians to consider lifting the ban on re-irradiation. Among adult patients receiving focal RT for low-grade gliomas, late neurologic toxicity was recently evaluated prospectively using a battery of neurocognitive tests. Compared with the initial status, no significant deleterious effects were observed with a follow-up of at least 3 years. In addition, studies on primates demonstrated that the spinal cord was capable of repairing, at least partially, RT-induced injury. There appears to be room for further irradiation: the results of re-irradiation in more than 300 patients have been documented. The techniques used, patient selection and re-irradiation modalities reported were varied: interstitial brachytherapy or intraoperative-RT within the surgical bed, conformal 3D RT, stereotactic-RT delivered in one or several fractions. Treatment efficacy and toxicity endpoints were very heterogeneous. Nevertheless, with a clearly defined prospective assessment, re-irradiation seems possible without any unacceptable clinical neurotoxicity under the following conditions: a good general status (WHO 0-1); at least a one-year disease-free interval; an initial WHO grade 2 or 3 histology with a maximal tumor diameter not exceeding 3 cm. In this very selective setting, re-irradiation is possible at a dose of 30 to 40 Gy, if possible in stereotactic mode, with a hypofractionated schedule (less than 4 Gy/fraction). Median survival exceeding one year is expected, the main endpoint being the control of symptoms and quality of life.

Purpose: The aim of this work was to establish the acquisition, calculation and 3D compensator manufacturing optimum parameters. This methodology is based on virtual simulation and 3D dosimetry., Materials and Methods: The material used is a helicoidal CT (PQ 5000-Marconi), a virtual simulation system (AcQsim version 4-Marconi), a Treatment Planning System (Dosigray), a linear accelerator Saturne 43 (Varian, CGR), an automated milling system for compensator filters (Autimo 2.5 D-HEK), a water tank phantom (wellhofer) and an homogeneous phantom with simple patterns in order to simulate the obliquity surface of patient body. The compensator was composed by granulate tin because this material ensures a good profile modulation. The compensation plane has been calculated at 80% to dose profile. The compensator thickness profile has been calculated with different acquisition (slice thickness, pitch factor), calculation (attenuation coefficient, bixel) and fabrication parameters (drill diameter, specification of milling system)., Results: After this preliminary study, we have defined the optimum parameters for the compensator realization. We have observed that the slice thickness, bixel size and drill diameter are the parameters that mainly affect the profiles homogeneity. The choice of parameters with smaller dimensions S = 3 mm; B = 3 mm, F = 3 mm, improve the profiles homogeneity. Though, for manufacture times compatible with the clinical routine, the selected parameters are S = 5 mm, B = 6 mm and F = 6 mm. Compensator can be used for any type of Linac. However, one must pay attention on their realization and their positioning on the beam central axis.

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Purpose: To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children., Methods and Materials: Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months)., Results: The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia., Morbidity: Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes., Conclusion: In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.

Purpose: To evaluate repeat radiosurgery (RS2) for cerebral arteriovenous malformations (AVMs) after failure of initial radiosurgery (RS1)., Methods and Materials: Between 1986 and 2000, 41 patients underwent RS2. Nine patients were not assessable: seven had insufficient follow-up (RS2 in 1999 and 2000) and two had no recent control angiography data. Thus, 32 (78%) of 41 patients were assessed. Most lesions (29 [90%] of 32) were supratentorial: 22 (69%) on the left, 8 (25%) on the right, and 2 on the midline (6%). The patients had Spetzler-Martin Grade 1-5 (median Grade 3). The symptoms before RS1 included hemorrhage in 20 (63%), epilepsy in 10 (31%), progressive neurologic deficits in 2 (6%), and headaches in 6 (19%). Five patients had two or more symptoms. Twenty-two patients (69%) had received other treatment before RS1, including neurosurgery in 3 patients (9%) and one to six embolizations in 19 patients. At RS1, the median largest nidus dimension was 2.7 cm (range 0.8-5). The median volume was 2.7 cm(3) (range 1.2-9.9). The median time from RS1 to RS2 was 52 months (range 12-126). Between RS1 and RS2, 7 (22%) of 32 patients experienced bleeding. The same irradiation technique was used for RS1 and RS2, except for 2 patients who underwent RS2 at another institution. Circular 15-MV X-ray minibeams (range 6-20 mm) and coronal arcs were used. RS1 was monoisocentric in 75% of cases and multiisocentric in 25%. At RS2, the median largest nidus dimension was 3 cm (range 1.4-5). The median volume was 4.2 cm(3) (range 0.8-13.4). RS2 was monocentric in 72% of cases and multiisocentric in 28%. After RS2, the median follow-up was 19.5 months (range 0-79; mean 25.3)., Results: After RS2, the obliteration rate was 59.3% (19 of 32). The median time to arteriographic obliteration was 21 months (range 12-96). The survival rate was 97% (31 of 32). Five of the 13 patients with a nonobliterated nidus experienced complications; 3 had bleeding (9%) and 2 without prior neurologic deficits developed partially regressive neurologic deficits. One patient with a previously existing deficit developed an additional new partially regressive neurologic deficit after an episode of bleeding. Thus, 3 (9%) of 32 patients had neurologic complications. Moderate-grade parenchymal changes at MRI increased after RS2 (88.2% vs. 57.7% after RS1; p = 0.10, not significant). However, necrosis-like changes did not significantly increase. After RS1 failure, salvage may be attempted by embolization, neurosurgery, or RS2. RS2 should be considered after the second successive annual angiogram if reduction of the nidus is <25%., Conclusion: The results after RS2 are encouraging. A multidisciplinary approach is mandatory to reduce the initial failure rate and to choose the modality and timing of salvage treatment.

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.

Modulated intensity dose distributions are obtained by inverse planning. It requires an inversion algorithm and an objective function that can be physical or biological. The biological objective functions aim at quantifying the probability of the favourable end of the treatment. The inversion algorithm used is analytical and is based on the mathematical analysis of the singular values decomposition. It proposes as many solutions as there are elementary beams. From the Tumour Control Probability, Normal Tissue Complication Probabilities and complication free tumour control, three biological assessment functions of the proposed solutions are compared with the least square difference between the prescribed and obtained dose distributions. We used a simplified irradiation configuration: Brahme's dose prescription (2D modelling of a prostate) and 9 beams (1D). The choice by mean of biological criterion of the optimal solution makes it possible to increase the average dose in the tumour, so as its homogeneity compared to physical optimisation. Conversely, the organs at risk are then less protected. The laying down of relevant constraints makes it possible to obtain satisfactory dose distributions. Concerning the validity of the models and data used, some limitations appear. At present time, it seems to exclude the use in clinical routine of an only biological optimisation. The future availability of new biological data will allow the development and in particular the clinical use of biological optimisation.

The recent evolutions of the imaging modalities, the dose calculation models, the linear accelerators and the portal imaging permit to improve the quality of the conformal radiation therapy treatment planning. With DICOM protocols, the acquired imaging data coming from different modalities are treated by performant image fusion algorithms and yield more precise target volumes and organs at risk. The transformation of the clinical target volumes (CTV) to planning target volumes (PTV) can be realised using advanced probabilistic techniques based on clinical experience. The treatment plans evaluation is based on the dose volume histograms. Their precision and clinical relevance are improved by the multi-modality imaging and the advanced dose calculation models. The introduction of the inverse planning systems permitting to realise modulated intensity radiation therapy generates highly conformal dose distributions. All the previously cited complex techniques require the application of rigorous quality assurance programs.

Background and Purpose: Between 20 to 50% of cerebral arteriovenous malformations treated with radiosurgery (RS) fail to obliterate 2 to 5 years after irradiation. Patients are not protected against the risks leading to treatment. Two therapeutic options can be used to eradicate the persisting nidus: micro-surgery and a second irradiation. Our group has reirradiated 39 such patients., Material: From 1989 to 2000, 39 patients have been reirradiated (14 females and 25 males; median age 31 years). There were more left lesions: 59% than right (35%) and 5% on midline. The most frequent locations were: temporal 12 cases; parietal 8 cases; frontal 7 cases; thalamus 7 cases. The predominant first symptoms were hemorrhage (68.5%) and seizure (15.8%). Prior RS, 21/39 patients had embolization (53.8%) and 3 surgery. Method. Treatment has been performed with the same system for the first and the second radiosurgery for 37 patients. Planification and dosimetry improved during that period. The level of dose was similar for the 2 RS. MRI has been used as a non invasive follow-up tool., Results: Only 28 patients were evaluable because 7/39 patients had the second radiosurgery in 1999 or in 2000 and data were lacking at the time of writing for 4 patients. Obliteration rate was 17/28 (60.7%). Nine patients bled between the two radiosurgery procedures., Complications: 4 new regressive deficits occurred after the second radiosurgery. The rate of parenchymal changes were higher, after the second radiosurgery. Except one patient who died of a non-related affection 2 years after obliteration of his cerebral arteriovenous malformation, thus 38/39 patients were alive., Conclusion: This series was small compared to the potential number of candidates suffering from failure of the first radiosurgery, but the results are promising.

The aim of this paper is to analyze retrospectively the reasons for the failure in cerebral arteriovenous malformations radiosurgery. Several factors are evoked and discussed mainly: inaccurate target, intentional partial irradiation, repermeabilization of a previously embolized cerebral arteriovenous malformation. The results suggest the necessity of a complete irradiation of the nidus. The strategy of partial volume irradiation should be avoided, even if it necessitates lowering of the doses in large cerebral arteriovenous malformations. Accuracy in the target determination is required and a complete stereoangiography is necessary.

We present a review of current technological progress enabling improvement in the quality of stereotactic irradiations: imaging fusion; individual adaptation of dosimetric planning to the shape of the target thanks to several collimation systems, spatial modulation of the beam with the use of multileaf microcollimators, beam intensity modulation, robotisation of the materials, owing to hardware and software developments.

Background and Purpose: The purpose was to present the successive steps of dosimetric planning and the different means used to allow the choice of the best solution among several planning projects considering the anatomical and clinical features of arteriovenous malformation. Method. Four successive steps were: A study of these factors for 5 different plannings of a clinical case using different isocenters is presented and the results are discussed., Conclusion: For complex arteriovenous malformations several hours are often necessary to permit physicians/radiotherapists to elaborate planning which is often a compromise among several solutions.

Purpose: To study dosimetric implications of our group dose prescription methodology on a series of 408 cerebral arteriovenous malformations., Material: and method. Between January 1990 and July 1998, 408 patients with cerebral arteriovenous malformations that had never been irradiated before, were treated radiosurgically in a single fraction at Tenon Hospital. 223 patients were treated with a single isocentre and 185 with multiple isocenters. Dosimetric characteristics have been studied as a function of the global quality index of planning, defined our group as the standard deviation of the differential dose volume histogram calculated in the lesion., Results: One percent correlation obtained between some dosimetric data and the global quality index of planning allowed to modelize by linear equations the connection between this quality index and minimum isodose in the lesion, mean doses and isodoses in the underdosed part of the lesion and in the complete lesion. This was done for mono isocentric cases and multi isocentric cases., Conclusion: Before the choice of the therapeutic dose and prescription isodose, it is therefore possible from the global quality index of planning to foresee isodoses modelized by the defined equations. So, the radiotherapist can compensate using the prescription since conformity is not perfect and thus attenuate healthy tissues overdosage.

Background and Purpose: After a review of the main radiosurgical published series, to evaluate our own series of 705 patients with cerebral arteriovenous malformations treated by radiosurgery alone or in combination with embolization or surgery., Patients: and method. From January 1984 to December 1998, 705 patients were treated by a multidisciplinary team including neurosurgeons, neuroradiologists, radiophysicians and radiotherapists. Age of revelation of the cerebral arteriovenous malformations ranged between birth to 73 years (mean 27, median 25). Age at time of radiosurgery ranged between 7 and 75 years (mean 33, median 31). There were 410 males for 295 females (sex- ratio 1.4). Symptoms of revelation were hemorrhage for 59%, seizures for 23%, headaches for 14% and progressive deficits for 4%. Discovery of cerebral arteriovenous malformation was fortuitous in 4% of cases. Repartition following Spetzler's grading was 12% in grade I, 36% in grade II, 40% in grade III, 12% in grade IV and 0% in grade V. Maximal size ranged between 4 and 60 mm (mean 23, median 20). Volume ranged between 0.2 and 24.3 cc (mean 3.8, median 2.8). Majority of cerebral arteriovenous malformations were large size (42% with size higher than 25 mm) and large volume (54% higher than 10 cc. 54% of patients had treatment prior radiosurgery: 38% had embolization, 10% were operated, 4% were treated by radiosurgery (reirradiation) and 3% were operated and embolized., Results: Overall complete obliteration rate was 55%. The obliteration rate was correlated with size (77% for cAVMs lower than 15 mm, 62% for cerebral arteriovenous malformations between 15 and 25 mm, and 44% for cerebral arteriovenous malformations higher than 25 mm), with volume (94% for cerebral arteriovenous malformations lower than 1 cc, 64% between 1 and 4 cc, 48% between 4 and 10 cc, and 62% for cerebral arteriovenous malformations higher than 10 cc), dose at reference isodose, minimal dose, morphological parameters (presence of dural components, arteriolovenous fistula, plexiform angioarchitecture, arterial steal, arterial recruitment, deep exclusive drainage, venous plicature, venous confluence, venous ectasia, venous reflux), sectional topography and good recovery of the target. Embolization was a confusion factor not associated with obliteration rate. After multivariate analysis, only Dmin and complete coverage of the cerebral arteriovenous malformations were correlated with obliteration rate. Delay of obliteration was significantly correlated after multivariate analysis with Dmin, complete coverage, arteriolovenulary angioarchitecture (positive correlation) and venous ectasia (negative correlation)., Conclusion: Overall complete obliteration rate is unreliable data to assess efficacy of radiosurgical method in the tretment of cerebral arteriovenous malformations. The obliteration rate must be interpretated after stratification on several morphological and dosimetric parameters.

Purpose: To evaluate dosimetric consequences generated by the automatic definition based on lesion coverage of prescription isodose. A clinical series of 124 arteriovenous malformations was analysed. Plan quality was quantified by the standard deviation of the differential dose volume histogram calculated in the lesion., Material and Methods: We define two quantitative protocols based on lesion coverage for the automatic definition of prescription isodose using a volumetric definition of coverage (90% of lesion volume), and an isodose-based definition proposed by RTOG (prescription isodose equals minimum isodose in the lesion divided by 0.9)., Results: We have evaluated the plans obtained for these two protocols, calculating several dose-volume indices. These indices are presented as a function of dose-volume histogram standard deviation in order to quantify the consequences of their variations for this representative series of plans. The margin our team tolerates is such that the sum of underdosed lesion and overdosed healthy tissues factors remains lower than one. Protocol based on volumetric coverage gives results situated within this margin. Protocol based on RTOG definition produces conformation indices that could be greater than 1., Conclusion: The absolute dose would be decided taking into account examined dose-volume indices and clinical data. A protocol for automatic definition of prescription isodose using volumetric lesion coverage seems to be more judiciously adapted to arteriovenous malformation conformal plans in stereotactic conditions because of variations observed in the overdosage of healthy tissues.

Several stereotactic irradiation techniques, using Linacs with the patient in lying and sitting position and a Gamma Knife Unit, were compared with regard to mono-isocentric three-dimensional dose distributions. Three types of target volumes, a sphere and two ellipsoids, were used for the comparisons. All three targets were centered on a real head, reconstructed from transversal CT scans. The ARTEMIS 3D Treatment Planning System, developed by the Tenon Hospital, Paris, was used for the dosimetry and the dose-volume histogram (DVH) calculation. For the comparative study, several quantitative parameters were used, derived from the dose-volume histogram calculation. Differential DVHs were plotted for each target volume and beam arrangement. Irradiation techniques were compared by deriving quantitative parameters from the DVHs such as mean and integral dose delivered to the target and normal tissue irradiated, as well as by the relative volume of the examined areas. All techniques used in this study produced very similar dose distributions. The small differences confirm the capability of the studied techniques to produce the same irradiation effects. By changing from the spherical target shape to a more elliptical shape, more of the normal tissue was irradiated with higher doses. For elliptical cases we therefore identified a need for more conformal stereotactic planning.

The definition of criteria and of a methodology dedicated to the quantitative evaluation of conformal stereotactic treatment plans is presented. We implemented the 'Receiver Operating Characteristics' (ROC) analysis, already used in medical imaging, for the quantitative evaluation of irradiation treatment plans. This implementation is based on data provided by dose-volume histograms (DVH). Three techniques, each one using a different dosimetric criterion, were defined for the choice of a reference isodose for a given treatment plan. We used this ROC analysis for the selection of the most conformal treatment plan and its reference isodose among the treatment plans proposed for one patient. This study revealed the interest of ROC analysis based on dose-volume histograms for the quantitative evaluation of treatment plans.

An innovative computerized dosimetric database (DDB) is proposed to enable the analysis of the stereotactic radiosurgical dose distributions; it contains relationships between the irradiation parameters and the dose-volume data. Dose-volume data provide guidance to the physicist-physician team by facilitating the initialization of the irradiation parameters and the treatment planning. The presented DDB contains dose-volume data such as the 70% isodose widths and the 70%-30% isodose penumbra along the right-left, anterior-posterior, and superior-inferior directions as a function of the irradiation parameters defined by the user. In order to demonstrate the usefulness of the DDB, the effects of the collimator diameter, the number of arcs, and their length on the shape of the prescription isodose surface are shown and are related to practical considerations for the treatment plan. However, the presented DDB is one example that can be generated by the DDB system. The planner can define as many different DDBs as he/she wishes, which can then be used for different investigations. This type of DDB enables us to investigate the irradiation technique used, to compare different irradiation techniques, to inspect the feasibility of planning different lesion types, or to define some dosimetric rules. The DDB provides useful interactive guidelines for the treatment planning process and replaces the voluminous dosimetric atlas. It has now been in clinical use for a year in a conformal procedure which automatically proposes collimator diameters, arc positions, and lengths allowing rapid conformal planning.

A Linac stereotactic irradiation space is characterized by different angular separations of beams because of the geometry of the stereotactic irradiation. The regions of the stereotactic space characterized by low angular separations are one of the causes of ill-conditioning of the stereotactic irradiation inverse problem. The singular value decomposition (SVD) is a powerful mathematical analysis that permits the measurement of the ill-conditioning of the stereotactic irradiation problem. This study examines the ill-conditioning of the stereotactic irradiation space, provoked by the different angular separations of beams, using the SVD analysis. We subdivided the maximum irradiation space (MIS: (AA)AP x (AA)RL = 180 degrees x 180 degrees) into irradiation subspaces (ISSs), each characterized by its own angular separation. We studied the influence of ISSs on the SVD analysis and the evolution of the reconstruction quality of well defined three-dimensional dose matrices in each configuration. The more the ISS is characterized by low angular separation the more the condition number and the reconstruction inaccuracy are increased. Based on the above results we created two reduced irradiation spaces (RIS: (AA)AP x (AA)RL = 180 degrees x 140 degrees and (AA)AP x (AA)RL = 180 degrees x 120 degrees) and compared the reconstruction quality of the RISs with respect to the MIS. The more an irradiation space is free of low angular separations the more the irradiation space contains useful singular components.

Objective: The aim of this study was to retrospectively analyze the reasons for the failure of radiosurgical treatment of cerebral arteriovenous malformations (AVMs)., Methods: Seventeen cases of noncured AVMs were reviewed 3 years after radiosurgical treatment. Follow-up ranged from 33 to 54 months (mean, 44.3 mo). Lesion dimensions varied from 9 to 55 mm (mean, 29.2 mm). The lesions were located in critical or near-critical brain regions. Angiography was performed under Talairach's stereotactic conditions. Two large AVMs bled 36 and 39 months after receiving irradiation, respectively. These two AVMs had been incompletely irradiated., Results: Retrospectively, in four cases (23.5%) we observed errors in determining AVM target shape and size because of inaccurate definition of the nidus and/or because of stereoangiographic incompleteness (absence of external carotid artery injections). In five large and/or irregularly shaped AVMs (29.4%), a strategy of partial volume irradiation had been used. In one patient (5.8%), we observed the recanalization of previously embolized AVMs. In another case (5.8%), the target had been partially missed. The AVMs in one case (5.8%) had been treated with an ineffective peripheral dose. In one (5.8%), the failure occurred because of the lesion angio-architecture. In four cases (23.5%), no evident reasons for failure were determined., Conclusion: The results of this study suggest the necessity of complete irradiation of the nidus. The strategy of partial volume irradiation might be avoided, even if it necessitates lowering the doses to treat large AVMs. Accuracy in the target determination is required, and complete stereoangiography is necessary.

We began intracranial stereotactic irradiation under the direction of O Betti 11 years ago. At the present time, we believe it is interesting to present the methodologies of the SALT (Saint-Anne-Lariboisière-Tenon) group. Up to the present time we have irradiated 693 patients using a single fraction. Arteriovenous malformations (AVMs) represented the majority (90%) of treated lesions. Irradiation protocol has little changed since 1986, and the localization of the target volume was performed in the neurosurgery department of St Anne Hospital, France. The stereotactic images (computerized tomography [CT], angiography) were sent to the radiotherapy department of Tenon Hospital through the French public digital network NUMERIS. Protocol was realized using the stereotactic ARTEMIS-3D/Dosigray TPS. The lesion volume was filled by one or more spherical or elliptical subvolumes using the "Associated Target Methodology". The interactive adjustment of subvolumes was based on the 3D graphical representations of the lesion. The direct optimization of the irradiation space was performed by managing parameters provided by the DDB (Dosimetric Data Base) such as the number of arcs, their angular position, as well as the starting and the ending point of each arc. The evaluation of the calculated dose distribution was made using quantitative parameters. The second method of optimization was based on the minibeam intensity modulation using a mathematical theory of inverse problems and singular value decomposition (SVD) analysis. At the present time, due to technical reasons, linear accelerators do not permit the modulation of intensity of arctherapy. Thus we transformed the profiles of irregular forms into rectangular profiles of modulated ponderation, with each optimized plan being evaluated before its implementation. The criteria of evaluation were derived from the differential and cumulative dose volume histograms (DVH). The DVHs permitted the evaluation of the volumes of underdosage and overdosage inside the lesion and in the healthy tissue, respectively. Using DVHs, we have defined parameters such as the conform factor and the homogeneity index. We stress that the methodology of protocol optimization is valid for single or multiple fractions as well as for intra- and extra-cranial irradiation.

Embolization was used to reduce the size of brain arteriovenous malformations (AVMs) prior to radiosurgical treatment in 125 patients who were poor surgical candidates or had refused surgery. Of these patients, 81% had suffered hemorrhage, and 22.4% had undergone treatment at another institution. According to the Spetzler-Martin scale, the AVMs were Grade II in 9.6%, Grade III in 31.2%, Grade IV in 30.4%, and Grades V to VI in 28.8% of the cases. Most embolizations were performed using cyanoacrylate delivered by flow-guided microcatheters. Radiosurgery was performed using a linear accelerator in 62 patients treated by the authors, and 34 patients were treated at other institutions using various methods. Embolization produced total occlusion in 11.2% of AVMs and reduced 76% of AVMs enough to allow radiosurgery. Radiosurgery produced total occlusion in 65% of the partially embolized AVMs (79% when the residual nidus was < 2 cm in diameter). Embolizations resulted in a mortality rate of 1.6% and a morbidity rate of 12.8%. No complications were associated with radiosurgery. The hemorrhage rate for partially embolized AVMs was 3% per year. No patient with a completely occluded AVM experienced rehemorrhage. Angiographic follow-up review of AVMs embolized with cyanoacrylate demonstrated a 11.8% revascularization rate, occurring within 1 year. It is concluded that after partial embolization with cyanoacrylate, the risk of hemorrhage from the residual nidus is comparable to the natural history of AVMs and that the residual nidus can be irradiated with results almost as good as for a native AVM of the same size.

We have treated in 1990 and 1991, 84 arteriovenous malformations (AVMs) by radiosurgery. Irradiation was realized by 5 to 7 arcs with 15 MV X rays circular minibeams of a GE-CGR Saturne 43 Linac diameter, at 100 cm 6 to 20 mm; the Betti arm chair and the Talairach frame. The prescribed peripheral dose containing the nidus was 25 Gy corresponding to the 60-70% isodose range (100% was the maximum dose). For the irradiation planning we used the 'associated targets methodology' and the ARTEMIS-3D TPS, both of which have been developped in the radiotherapy departement of the Tenon hospital. Evaluation was performed in February 1995, the follow-up range was 38 to 62 months. In 1990, 46 cases were treated for cure and were all evaluable, whereas in 1991, among the 38 irradiated cases one patient was not evaluable because of lack of arteriographic control. Thus this series consisted in 84 evaluable cases. The overall obliteration rate was 65/84 (78%), partial obliteration was seen in 18/84 (21%) and no change in 1 case. According to AVM volume, obliteration rate was: AVMs < 4200 mm3: 82% (46/56). For lesions > 4200 mm3 it was 68% (19/28). In one isocenter irradiation, the obliteration rate was 42/47 (89%); whereas it was 23/37 (62%) in multi-isocenters treatments. The obliteration rate was better for not previously treated cases: 39/44 (89%) than for previously treated nidus (mostly embolisation) 65% (26/40). In 23 spheroid AVMs obliteration rate was 87% (20/23) in 43 ellipsoid AVMs the obliteration rate was 77% (33/43); and in irregular rounded nidus, it was 67% (12/18). The peripheral dose of 25 Gys has been used in 78 cases (93%), the obliteration rate was 63/78 (81%); in 6 other cases treated with 15-23.5 Gy, it was 2/6 (33%). We observed two recurrences of haemorrhage at 4 and 6 months after radiosurgery (recurrent haemorrhage rate 2/84 = 2.4%) with total neurological recovery in one of the two patients. One patient died of myocardial infarctus 11 months after radiosurgery (there was a partial obliteration of his AVM at 8 months after radiosurgery). There was no AVM related death. One patient developed an epilepsy.

Purpose: A modified teletherapy unit to achieve total body irradiation with a vertical beam in a conventional treatment room., Methods and Materials: A standard 60C teletherapy unit has been modified to achieve total body irradiation with a vertical beam in a conventional treatment room. Patients are treated in prone and supine positions. Removal of the adjustable collimator assembly of this standard machine provides a circular field of 196 cm in diameter at 167 cm from the source. Second, the machine has been elevated by about 50 cm on a metallic base to enlarge irradiation field to obtain 248 cm in diameter at 210 cm from the source, and to encompass tall patients under better conditions. A special lead conical beam flattening filter, 10-mm thick at the center, was designed to compensate the spatial inhomogeneity of the beam. An instantaneous dose rate of 6.10(-2) Gy/min is attained at the L4 level (midplane) in an average 20-cm thick patient with a source activity of 5099 RHM (air kerma rate of 44.8 Gy.h-1.m2). Between February 2, 1984 and December 27, 1990, 244 total body irradiations were performed either by single dose (n = 69, 10 Gy were given to midplane at L4 level in about 6 to 8 h, 8 Gy to the lungs), or by fractionated dose (n = 175, 12 Gy were given in 6 fractions over 3 consecutive days to midplane at L4 level, 9 Gy to the lungs)., Results: The dose distribution is similar than the ones obtained by a linear accelerator with patients lying on their sides., Conclusion: Patients were treated in a comfortable and highly reproductible position. Organ shielding was easily achievable. This could be a less expensive and reasonable alternative to linear accelerator.

Background: The role of radiotherapy alone in the sterilization of anal canal epidermoid carcinomas of 5 cm or more remains to be assessed. Thus, the outcomes of patients treated with radiotherapy alone (RT) versus those treated with preoperative radiotherapy and surgery (RS) were compared retrospectively., Methods: Between 1972 and 1990, 185 patients were treated with curative intent either with RT alone (n = 147) or with RS (n = 38). The Mean tumor length was 6.18 +/- 1.14 cm and was significantly longer in the RS group (6.55 +/- 1.29 cm) than in the RT group (6.08 +/- 1.08 cm) (P = 0.02). The median follow-up was 77 +/- 57 months and 93 +/- 60 months (P = 0.23) for the RT and RS groups, respectively. For the RT group, the first course of radiotherapy was 40 to 45 Gy in the pelvis for 4 to 5 weeks; after a rest of 4 to 6 weeks, radiotherapy was boosted an additional 15 to 20 Gy for 2 weeks. The RS patients received 40 to 45 Gy in the pelvis for 4 to 5 weeks, then received surgery after a median period of 54 days., Results: The overall 10-year cancer specific survival rates were 58% in the RT group and 66% in the RS group (P = 0.48). The T-stage 10-year cancer specific survival rates were 68% in the RT group and 67% in the RS group for T2 tumors (P = 0.96); 57% in the RT group and 53% in the RS group for T3 tumors (P = 0.85); and 42% in the RT group and 40% in the RS group for T4 tumors (P = 0.05). In the RS group, the local control rate was 75% (3/4) for T2 tumors; 74% (17/23) for T3 tumors; and 82% (9/11) for T4 tumors. In the RT group, the local control rate was 77% (34/44) for T2 tumors; 70% (58/82) for T3 tumors; and 60% (12/20) for T4 tumors. In the RT group, the anal conservation rate was 61% (27/44) for T2 tumors, 59% (48/82) for T3 tumors, and 55% (11/20) for T4 tumors. Local tumoral control and a functioning anus were present in 72 out of 147 (49%) patients [52% (23/44) for T2 patients, 52% (43/82) for T3 tumors, and 30% (6/20) for T4 patients]. In the RS group, the grade 3 complication rate was 9% (13/146) and in the RS group, 5% (2/38)., Conclusion: For patients with T4 tumors, preoperative radiotherapy and surgery seemed to be better in terms of survival and local tumor control rate, but the difference was not significant probably because the number of patients in the RS group was small. For these large tumors, the treatment should probably be more aggressive, combining chemotherapy and radiation therapy, but the increase of local control in relation with the addition of cytotoxic chemotherapy to irradiation is not proved.

Purpose: To assess the influence of instantaneous total-body irradiation dose rate in hematological malignancies, we randomized 157 patients according to different instantaneous dose rates., Methods and Materials: Between December 10, 1986 and December 31, 1989 157 patients have undergone a total-body irradiation before bone-marrow transplantation according to two different techniques: either in one fraction (1000 cGy given to the midplane at the level of L4, and 800 cGy to the lungs) or in six fractions (1200 cGy over 3 consecutive days to the midplane at the level of L4, and 900 cGy to the lungs). Patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 vs. 15 cGy/min) and fractionated (3 vs. 6 cGy/min) TBI groups; there were 77 cases for the LOW and 80 for the HIGH groups, with 57 patients receiving single-dose (28 LOW, 29 HIGH) and 100 patients receiving fractionated total-body irradiation (49 LOW, 51 HIGH)., Results: As of July 1992, 16 (10%) of 157 patients developed cataracts after 17 to 46 months, with an estimated incidence of 23% at 5 years. Four (5%) of 77 patients in the LOW group, 12 (15%) of 80 patients in the HIGH group developed cataracts, with 5-year estimated incidences of 12% and 34%, respectively (p = 0.03). Ten (18%) of 57 patients in the single-dose group, and 6 (6%) of 100 patients in the fractionated group developed cataracts, with 5-year estimated incidences of 39% and 13%, respectively (p = 0.02). When the subgroups were considered, in the single-dose group, 3 (11%) of 28 LOW patients, and 7 (24%) of 29 HIGH patients developed cataracts, with 5-year estimated incidences of 24% and 53%, respectively; in the fractionated group, 1 (2%) of 49 LOW patients, and 5 (10%) of 51 HIGH patients developed cataracts, with 5-year estimated incidences of 4% and 22%, respectively (single-dose LOW vs. single-dose HIGH vs. fractionated LOW vs. fractionated HIGH, p = 0.006). There was no statistically significant difference in terms of 5-year estimated cataract incidence between the patients receiving steroids and those not (30% vs. 25%, p = 0.22). Multivariate analyses revealed that the instantaneous dose rate was the only independent factor influencing the cataractogenesis (p = 0.04)., Conclusion: We conclude that the total-body irradiation regimen (instantaneous dose rate and/or fractionation) may have an influence on the development of cataracts following bone-marrow transplantation.

During 1990 we treated 49 cases of arterio-veinous malformations (AVMs) using radiosurgery. We employed 15 MV X-Ray minibeams of a Saturne 43 Linac, eight additional collimators, 6-20 mm, the O Betti armchair and the Talairach stereotactic frame. Irradiation consisted of delivering 25 Gy at the periphery of the nidus corresponding to the 60-70% peripheral isodose range. We used the "Associated Target Methodology" and the three-dimensional treatment planning system Artemis-3D, both of which have been developed in our radiotherapy department. In December 1992, 44 out of 49 patients who had been treated were available for analysis with a 2-3-year follow-up. The overall obliteration rate was 33/44 (75%). According to the number of isocenters the obliteration rate was: 22/26 (85%) for one isocenter. In 18 multi-isocenters irradiation cases overall obliteration rate was 11/18 (61%). Two isocenters were used in nine of these 18 cases, the obliteration rate was 6/9; while when three isocenters were used it was 2/4 and in five cases of four isocenters irradiation the obliteration rate was 3/5. Obliteration rate for lesions < or = 4200 mm3 was 31/37 (84%). For greater volumes (5500 mm3 to 19000 mm3; median 9200 mm3) the obliteration rate was 2/7 whereas three others were partially (75 to 90%) obliterated and two remained inchanged. Before radiosurgery 21 cases received other treatment (mostly embolizations), the obliteration rate in this group was 15/21 (71.5%) while in previously untreated AVMs it was 18/23 (78%). A control arteriography was performed between 6 to 18 months after radiosurgery in 44 patients; three others refused the arteriography but are alive and well; two others had palliative irradiation, one of whom is dead. Out of 28 AVMs checked between 6 to 12 months 17/28 were obliterated (61%). In four cases, epilepsy was the first symptom; one has not suffered a further crisis whereas three others experienced a decrease in the number of crises. Two patients had recurrence of bleeding four and six months after irradiation (recurrence rate 2/44 = 5%). There were no lasting neurological consequences.

A new radiosurgical methodology, the "associated targets methodology" has been developed and tested by our group for the irradiation of complex cerebral arteriovenous malformations using our treatment planning system Artemis-3D. For the treatment of the arteriovenous malformations we used 15 MV photons generated by a Saturne 43 Linac, eight additional collimators (6-20 mm in diameter), the Betti fixation seat and the Talairach stereotactic frame. The successive steps of the associated targets' methodology are: -the prescription of a peripheral minimal therapeutic effective dose corresponding to the 60-70% cumulated isodose range; -the compartmentalization of the target volume into several sub-volumes, each of them having its own isocenter, collimator, irradiation space and isocenter dose weight; -the 3-dimensional computation and graphics requirements, and dose volume analysis; -the optimization evaluation criteria taking into account the dose inside and outside of the lesion. Two treatment planning software versions of Artemis-3D exist; the first one was developed for the sitting position and later for the supine treatment position, the second version is a multi-modalities imagery radiosurgical treatment planning system based on more powerful computers. Different types of stereotactic frames have been integrated. Three-dimensional visualization, stereotactic CT imaging, and angiography can be used for the sitting or supine position. We started using this methodology in 1990, and treated 44 patients during that year. For 26 single isocenter arteriovenous malformations, the obliteration rate was 22/26 (85%). In the 18 multi-isocenters irradiation cases, the overall obliteration rate was 11/18 = 61%. An example of successfully irradiated complex arteriovenous malformation is discussed to illustrate the methodology. With this three-dimensional methodology we have improved the results obtained during the first period (1986 to 1989) of our radiosurgical practice in which we used a two dimensional planification approach.

To stereotactically irradiate ellipsoidal inclined arteriovenous malformations (AVMs) with a single isocenter one can use an adjusted inclined irradiation space with a reduced angular range of arcs. If one uses the maximum available irradiation space it is necessary to weight some of the arcs in order to closely encompass the lesion. It has been found that there is a relationship between the lesion inclination angle beta and the weights of arcs. Conversely when the beta angle is known, the weights of the arcs can be determined in advance by means of weighting vectors. The dose volume analysis shows that the isodose volumes remain constant for the different weighting vectors except for the 10% isodose volume which increases slightly as the linear weighting vector's slope alpha increases. Moreover, this procedure permits the optimization of the superimposition between the lesion and the reference isodose. These results enable the construction of an "a priori knowledge" database that can be included in an optimization algorithm procedure.

One hundred fifty-seven patients referred to the Department of Radiation Oncology of the Hôpital Tenon, Paris, France, between December 10, 1986 and December 31, 1989 for total-body irradiation (TBI) were treated according to the following two techniques: (1) either in one fraction (1000 cGy administered to the midplane at L4 and 800 cGy to the lungs) or (2) in six fractions (1200 cGy on 3 consecutive days to the midplane at L4 and 900 cGy to the lungs). The patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 versus 15 cGy/min) and hexafractionated (3 versus 6 cGy/min) TBI groups. There were 77 patients in the LOW group and 80 in the HIGH group, with 57 patients receiving single-dose TBI (28 LOW and 29 HIGH) and 100 patients receiving fractionated-dose TBI (49 LOW and 51 HIGH). In March 1991, the 4-year relapse-free and overall survival rates were 58.4% and 52.1%, respectively. The 4-year relapse-free survival and survival rates were 54.9% and 50.7% in the LOW group; 61.9% and 53.5% in the HIGH group (P = 0.69 and 0.82, respectively); 60.3% and 50.4% in the single-dose group; and 57.9% and 53.3% in the fractionated group (P = 0.65 and 0.78, respectively). There was no difference in the incidence of graft versus host disease, interstitial pneumonitis, or venoocclusive disease either between the LOW and the HIGH groups or between the single-dose and fractionated-dose TBI groups. The 4-year estimated cataract incidence was significantly higher in the single-dose HIGH instantaneous dose rate group than in the LOW instantaneous dose rate TBI group (P = 0.049). Multivariate analyses showed that instantaneous dose rate and fractionation do not influence the relapse-free and overall survival rates or the incidence of interstitial pneumonitis.

Between May 1986 and March 1987, 46 small and medium sized cerebral arteriovenous malformations (AVM) were treated by radiosurgery in Paris. The stereotaxic coordinates of the lesions were determined according to the method of J. Talairach and the total radiation dose was delivered on spherical or ovoid target volumes with minibeams of 18 MV photons, using the technique developed by Osvaldo Betti. A review of the cases was undertaken in december 89. Twenty-one patients had previously been treated by embolization and/or surgery (46.6%). During the 25 to 40 months follow-up there were only 2 recurrences of bleeding (4.3). Control arteriography was performed in 38 cases (38/46 = 82.6%). There were thirteen cases of total disappearance of the AVM (13/36 = 34.2%), 17 incomplete obliterations (44.7%) and 9 (23%) arteriographies failed to show any radiological improvement. Eight patients had no arteriographic follow-up: 2 of them experienced a recurrence of bleeding and died before the planned arteriography, 1 was lost to follow-up and 5 patients refused control arteriography. A multidisciplinary team is needed to study the shape, the volume, the hemodynamic features of the AVM and the dosimetry in order to attain the best definition of the target volume and of the dose distribution. It seems that when the target volume included the nidus and the venous collector, follow-up arteriography results were satisfactory. Even though the optimum dose is yet to be determined, our results imply that a dose distribution allowing for 25 grays at the periphery of the AVM (isodose 70%) seems sufficient provided that the target volume is included within the 25.00 Gy isodose curve.

Stereoradiotherapy is the stereotaxy guided high-dose irradiation of small (less than 3 cm) intracerebral lesions. Its aim is to induce necrosis or sclerosis inside the target volume. Several techniques permit us to obtain a steep dose gradient between the lesion and the adjacent healthy cerebral parenchyma. They use minibeams (diameter less than 3 cm) of different types of radiations: protons (Kjellberg from Harvard, since 1962); gamma rays of cobalt 60 (Leksell from Stockholm, since 1968); and X-rays from a linear accelerator (Betti from Buenos-Aires, since 1982). The most commonly treated lesions are arterio-venous malformations, hypophyseal adenomas and low grade parenchymatous tumors. The stereotaxic technique is the only means by which to insure that these high dose irradiations, administered in a single session, are actually delivered to the small lesions situated in the cerebral parenchyma.