A new single crystal diamond dosimeter for small beam: comparison with different commercial active detectors.

Recent developments of new therapy techniques using small photon beams, such as stereotactic radiotherapy, require suitable detectors to determine the delivered dose with a high accuracy. The dosimeter has to be as close as possible to tissue equivalence and to exhibit a small detection volume compared to the size of the irradiation field, because of the lack of lateral electronic equilibrium in small beam. Characteristics of single crystal diamond (tissue equivalent material Z = 6, high density) make it an ideal candidate to fulfil most of small beam dosimetry requirements. A commercially available Element Six electronic grade synthetic diamond was used to develop a single crystal diamond dosimeter (SCDDo) with a small detection volume (0.165 mm(3)). Long term stability was studied by irradiating the SCDDo in a (60)Co beam over 14 h. A good stability (deviation less than ± 0.1%) was observed. Repeatability, dose linearity, dose rate dependence and energy dependence were studied in a 10 × 10 cm(2) beam produced by a Varian Clinac 2100 C linear accelerator. SCDDo lateral dose profile, depth dose curve and output factor (OF) measurements were performed for small photon beams with a micro multileaf collimator m3 (BrainLab) attached to the linac. This study is focused on the comparison of SCDDo measurements to those obtained with different commercially available active detectors: an unshielded silicon diode (PTW 60017), a shielded silicon diode (Sun Nuclear EDGE), a PinPoint ionization chamber (PTW 31014) and two natural diamond detectors (PTW 60003). SCDDo presents an excellent spatial resolution for dose profile measurements, due to its small detection volume. Low energy dependence (variation of 1.2% between 6 and 18 MV photon beam) and low dose rate dependence of the SCDDo (variation of 1% between 0.53 and 2.64 Gy min(-1)) are obtained, explaining the good agreement between the SCDDo and the efficient unshielded diode (PTW 60017) in depth dose curve measurements. For field sizes ranging from 0.6 × 0.6 to 10 × 10 cm(2), OFs obtained with the SCDDo are between the OFs measured with the PinPoint ionization chamber and the Sun Nuclear EDGE diode that are known to respectively underestimate and overestimate OF values in small beam, due to the large detection volume of the chamber and the non-water equivalence of both detectors.

Small fields output factors measurements and correction factors determination for several detectors for a CyberKnife® and linear accelerators equipped with microMLC and circular cones.

PURPOSE: The use of small photon fields is now an established practice in stereotactic radiosurgery and radiotherapy. However, due to a lack of lateral electron equilibrium and high dose gradients, it is difficult to accurately measure the dosimetric quantities required for the commissioning of such systems. Moreover, there is still no metrological dosimetric reference for this kind of beam today. In this context, the first objective of this work was to determine and to compare small fields output factors (OF) measured with different types of active detectors and passive dosimeters for three types of facilities: a CyberKnife(®) system, a dedicated medical linear accelerator (Novalis) equipped with m3 microMLC and circular cones, and an adaptive medical linear accelerator (Clinac 2100) equipped with an additional m3 microMLC. The second one was to determine the kQclin,Qmsr (fclin,fmsr) correction factors introduced in a recently proposed small field dosimetry formalism for different active detectors. METHODS: Small field sizes were defined either by microMLC down to 6 × 6 mm(2) or by circular cones down to 4 mm in diameter. OF measurements were performed with several commercially available active detectors dedicated to measurements in small fields (high resolution diodes: IBA SFD, Sun Nuclear EDGE, PTW 60016, PTW 60017; ionizing chambers: PTW 31014 PinPoint chamber, PTW 31018 microLion liquid chamber, and PTW 60003 natural diamond). Two types of passive dosimeters were used: LiF microcubes and EBT2 radiochromic films. RESULTS: Significant differences between the results obtained by several dosimetric systems were observed, particularly for the smallest field size for which the difference in the measured OF reaches more than 20%. For passive dosimeters, an excellent agreement was observed (better than 2%) between EBT2 and LiF microcubes for all OF measurements. Moreover, it has been shown that these passive dosimeters do not require correction factors and can then be used as reference dosimeters. Correction factors for the active detectors have then been determined from the mean experimental OF measured by the passive dosimeters. CONCLUSIONS: Four sets of correction factors needed to apply the new small field dosimetry formalism are provided for several active detectors. A protocol for small photon beams OF determination based on passive dosimeters measurements has been recently proposed to French radiotherapy treatment centers.

Comparison of organs' shapes with geometric and Zernike 3D moments.

The morphological similarity of organs is studied with feature vectors based on geometric and Zernike 3D moments. It is particularly investigated if outliers and average models can be identified. For this purpose, the relative proximity to the mean feature vector is defined, principal coordinate and clustering analyses are also performed. To study the consistency and usefulness of this approach, 17 livers and 76 hearts voxel models from several sources are considered. In the liver case, models with similar morphological feature are identified. For the limited amount of studied cases, the liver of the ICRP male voxel model is identified as a better surrogate than the female one. For hearts, the clustering analysis shows that three heart shapes represent about 80% of the morphological variations. The relative proximity and clustering analysis rather consistently identify outliers and average models. For the two cases, identification of outliers and surrogate of average models is rather robust. However, deeper classification of morphological feature is subject to caution and can only be performed after cross analysis of at least two kinds of feature vectors. Finally, the Zernike moments contain all the information needed to re-construct the studied objects and thus appear as a promising tool to derive statistical organ shapes.

[History of radiosurgery]. / Historique de la radiochirurgie.

Within the last decades, radiosurgery, also known as stereotactic radiotherapy, has become more and more popular as a non-invasive treatment of small benign tumours, arteriovenous malformations, metastases, and also some functional neurological structures, such as the fifth cranial nerve for trigeminal neuralgesia. It allows precisely delivering very high dose in a small volume under stereotactic conditions with minimal irradiation of tissue around the area. The first equipment devoted to radiosurgery was the Leksell Gamma Knife®. It is now challenged by some linear accelerators providing radiosurgery technology, such as the CyberKnife®, the Novalis Tx® radiosurgery platform, and the True Beam® linear accelerator.

[Contribution of registered and/or fused images to radiotherapy]. / Apport du recalage et/ou de la fusion d'images à la radiothérapie.

The quality of treatment that one can realize today in conformal radiotherapy, can be reached only if one has access to 3D imaging allowing a precise determination of the volume of the organs at risk and of the GTV. For this reason, one has access to anatomical imaging, CT or MRI, and functional and metabolic imaging, PET or SPECT imaging. CT gives the electronic density of the tissues, which is essential to ensure a very precise calculation of dose distribution. Its insufficiency in the visualization of the tumour and some anatomical structures makes necessary the registration of these images with MRI of which distortions are sufficiently weak to be usable in radiotherapy. The registration will be usable only if images of each modality are realised with the patient in treatment position, except for brain, where only CT, on which is based the registration, must be done in treatment position. The images registration is also called images fusion by some authors. Others consider fusion of images as a way to display registered images on a screen, specially for CT images and PET, and MRI and SPECT. Nevertheless, the fusion of images is a function offered by some softwares. It allows obtaining a single volume of voxels from those of the registered images (CT and MR images). This volume is not usable in radiotherapy because it keeps only partially the contributions of the CT scan images and the MRI. At least, if one wants to visualize the active parts of a tumour or to make the difference between fibrosis and tumour left or recurrence after radiotherapy or chemotherapy, it is necessary to use PET or SPECT. To define correctly the CTV using these images, one must realize the anatomical localization of the metabolic abnormalities, which they highlight with a registration based on CT or MRI. The difficulties to obtain the registration of these images led the manufacturer to propose mixed machines allowing realizing, at the same time, a CT imaging and a PET or a SPECT imaging with the patient in treatment position.

[Chordomas of the base of the skull and upper cervical spine. 100 patients irradiated by a 3D conformal technique combining photon and proton beams]. / Les chordomes de la base du crâne et du rachis cervical haut. A propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons.

OBJECTIVE: To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS: Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival. CONCLUSION: In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.

[Results of salvage stereotactic radiosurgery in 14 patients with grade III or IV gliomas]. / Résultats de l'irradiation en conditions stéréotaxiques de rattrapage de 14 patients atteints d'un gliome de grade III ou IV.

AIMS: To determine local control and overall survival rates of 14 patients treated for a grade III or IV glioma relapsing in a previously irradiated area and re-irradiated by stereotactic radiosurgery. PATIENTS AND METHODS: From January 1997 to October 2001, 14 patients (median age 52 Years, age range 49-58 Years, Karnofski performance score 80 to 100) received radiosurgery for a relapse of grade III (3 patients) and or grade IV (10 patients) malignant gliomas. Before relapse, all patients had undergone surgery and had been given with a classical radiation protocol. Median maximum diameter and Volume of the tumors were 38.5mm (24-86mm) and 7cm3 (2-35cm3), respectively. RESULTS: Median maximal dose at the isocenter and median minimal dose at the periphery of the lesion were 21Gy (16-38Gy) and 13Gy (9-17Gy), respectively. Mean follow-up was 8.5 Months (1-29). Median overall survival was 11.6 Months; 6-Month, 1- and 2-Year overall survival rates were 85p.100, 36p.100 and 12p.100, respectively. At univariate analysis, only histological grade was a significant prognostic factor of overall survival (p=0.03). Median disease-free survival was 8.2 Months while 6-Month and 1-Year disease-free survival rates were 69p.100 and 14p.100, respectively. According to univariate analysis, histological grade (p=0.033) and minimal dose delivered at the margin of the target Volume (p=0.02) were prognostic factors for disease-free survival. Two patients developed a symptomatic radionecrosis. CONCLUSION: Radiosurgery of relapsed primitive high-grade brain tumors is efficient and overall survival rates were encouraging.

[First-line radiosurgery of brain metastases. Interest and results of reduced dose]. / Irradiation stéréotaxique de première intention des métastases cérébrales. Intérêt et résultats d'une réduction de la dose délivrée.

BACKGROUND: The minimal radiosurgical dose required to control cerebral metastases remains unknown. The aim of this study was to test whether a lower peripheral dose than usually delivered could effectively control these lesions or not. PATIENTS AND METHODS: One hundred and eighty patients presenting 356 lesions were give first-line radiosurgery between 1995 and 2001 in Pitié-Salpêtrière hospital using a 10 MV LINAC. Mean age was 59 years, sex-ratio was 1.65, mean KI was 70. The lung was the most frequent primary site (n=85), followed by melanoma (n=29), kidney (n=21), digestive tract (n=14), breast (n=11), and others (n=20). Seventy-six percent of the patients presented 1 or 2 lesions. Mean tumor Volume was 5.5 cm3. Mean peripheral dose was 14.8Gy, mean isocenter dose was 21.6Gy. RESULTS: Median survival was 7.6 months, local control rate was 90% at 6 months, 76% at 1 Year and 70% at 2 years. Median "neurological disease free" survival was 15 months. Multivariate analysis demonstrated the influence of two parameters on survival: number of lesions (p=0.001) and KI (p=0.04). The only parameter significantly correlated with disease-free survival was the number of isocenters (p=0.005). Morbidity (grade 2 RTOG) was 7.2% with no perimortality. CONCLUSIONS: Low peripheral doses delivered by radiosurgery may control brain metastases with the same efficacy and fewer side-effects as the doses usually reported in the literature.

[Automatization and robotics of the set-up and treatment of patients irradiated for brain and base ot the skull tumors]. / Automatisation et robotisation du placement et de la mise en place des patients irradiés pour une tumeur de l'encéphale et de la base du crâne.

Progresses of the three-dimensional imageries and of the software of planning systems makes that the radiotherapy of the tumours of brain and the base of skull is increasingly precise. The set-up of the patients and the positioning of the beams are key acts whose realization can become extremely tiresome if the requirement of precision increases. This precision very often rests still on the visual comparison of digital images. In the near future, the development of the automated systems controlled by robots should allow a noticeable improvement of the precision, safety and speed of the patient set-up.

[Comparison with dose-volume histograms of two conformal irradiation techniques used for the treatment of T2N0M0 nasopharyngeal cancer, one with association of photons and protons and another with photons alone]. / Comparaison par les histogrammes dose-volume de deux techniques d'irradiation conformationnelle des cancers du nasopharynx classés T4N0M0, l'une par photons et protons et l'autre par photons seuls.

Purpose- There is a relationship between the local control rate of the nasopharyngeal cancer and the total dose delivered within the tumoral volume. In contrast, the relation between the dose and the irradiated volume and the risk of complication is not clearly defined. That is why, in patients presenting with a locally advanced nasopharyngeal cancer, we compared the dose-volume distribution of irradiated tissues, obtained from two 3D conformal irradiation techniques. Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and 2 females, with a median age of 32 years and presenting with a T4N0M0 nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons and protons beams and the platin-based chemotherapy was delivered in three intravenous injections at d1, 22, 43 of the irradiation. To calculate the dosimetry, a CT scan and a MRI were performed in all the patients. The gross tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by protons. According to dose-volume histograms obtained from the dosimetry planning by protons and photons and from the theoretical dosimetry by photons lonely, for the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves, chiasm, internal ears, brainstem, temporal lobes), we compared the averages of the maximum, minimum and mean doses and the averages of the volumes of organs of interest encompassed by different isodoses.Results- Calculated averages of minimum, maximum and mean doses delivered within GTV were superior for the treatment with combined photons and protons than with photons alone. The average GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association compared to photons alone. The conformation ratio (tissue volume encompassed by the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association compared to 5.7 with photons alone. For the CTV2, there were no differences in different criteria according to the both irradiation techniques. For the critical, radiosensitive organs, the comparison of the majority of the criteria was in favour of the association of protons and photons. Overall, 78% of the criteria were in favour of the association.Conclusion- For locally advanced nasopharyngeal cancer without clinical adenopathy, irradiation by photons and protons increases the tumor volume irradiated at the prescribed dose and decreases the volume or critical organs irradiated and the total dose delivered within them.

[The influence of age on radiation-induced cognitive deficit:experimental studies on brain irradiation of 30 gy in 10 sessions and 12 hours in the Wistar rat at 1 1/2, 4 and 18 months age]. / Influence de l'âge sur les troubles cognitifs radio-induits: études expérimentales avec irradiation cérébrale de 30 gy en 10 seances et 12 jours chez le rat Wistar de 1 1/2, 4 et 18 mois.

The objective of this study was to determine the influence of age on the learning and memory dysfunction induced by cranial radiation in the male Wistar rat. Ninety-six 45-day-old, 70 4-month-old, and 78 18-month-old male rats were divided in two equal groups: (i) irradiated and (ii) control. A course of whole-brain radiation therapy (30 Gy in 10 fractions over 12 days) was administered to the irradiated group, while the control group received sham irradiation. Sequential behavioral studies including one and two-way avoidance tests were undertaken before and after the 7 months following radiation. The results suggest that radiation induced progressive and irreversible memory dysfunction in elderly (18-month-old) rats, but this effect was partial or almost reversible in the 4-month-old and 45-day-old rats, respectively. In return, the learning dysfunction was age non-dependent despite the fact that is occurs more rapidly in the young (45 days, 4 months) rats.

[Intracerebral radiotherapy under stereotaxic conditions]. / Radiothérapie intracérébrale en conditions stéréotaxiques.

Stereotactic radiosurgery is used for treating several brain diseases. Radiosurgery is a non-invasive alternative to surgery for brain metastases, and randomized trials are on going to assess the role of radiosurgery. Radiosurgery has been advocated for patients with small benign meningioma or with vestibular schwannoma, but there is no proof of efficacy and safety of radiosurgery in comparison with other treatments. Radiosurgery can obliterate 80-90% of small arteriovenous malformations, but no information exists on the survival of treated compared with untreated patients. The limited information available suggests that radiosurgery should be fully evaluated in well-designed prospective studies.

[Gross tumor volume and clinical target volume in brachytherapy of malignant tumors]. / Le volume tumoral macroscopique et le volumecible anatomoclinique dans le cadre de la curiethérapie des tumeurs malignes.

Tumours treated with radioactive implants are in most cases small and accessible to clinical examination or endoscopy. Gross tumour volume is consequently mainly determined clinically or with endoscopy. Imaging may also be useful, with classical techniques, as mammography, or with CT-scan or MRI. Clinical target volume includes gross tumour volume and a 5-10 mm margin. Distribution of dose is estimated on the basis of images performed after implantation, classically with two orthogonal films of the implant. It can then be optimised. Dose-volume histogram of gross tumour volume and critical organs can be obtained with a CT-scan or a MRI of the implant, which may be difficult to perform because of implantation material and dummy sources.

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience.

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Radiosurgery for re-irradiation of brain metastasis: results in 54 patients.

PURPOSE: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory. PATIENTS AND METHODS: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2-70). Median age was 53 years (24-80), and median Karnofski performance status (KPS) 70 (60-100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6-59) and 1.2 cc (0.1-95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8-23), and median maximal dose 21.2 Gy (14- 42). RESULTS: Median follow-up was 9 months (1-57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia. CONCLUSION: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.

[Use of multimodality imagery in radiotherapy]. / Utilisation de l'imagerie multimodalité en radiothérapie.

The quality of treatment that one can realize today in conformal radiotherapy, can be reached only if one has access to 3D imaging allowing a precise determination of the volume of the organs at risk and of the GTV. For this reason, one has access to anatomical imaging, CT or MRI, and functional and metabolic imaging, PET or SPECT imaging. CT gives the electronic density of the tissues, which is essential to ensure a very precise calculation of dose distribution. Its insufficiency in the visualization of the tumor and some anatomical structures makes necessary the registration of these images with MRI of which distortions are sufficiently weak to be usable in radiotherapy. The registration will be usable only if images of each modality are realized with the patient in treatment position, except for brain, where only CT, on which is based the registration, must be done in treatment position. At least, if one wants to visualize the active parts of a tumor or to make the difference between fibrosis and tumor left or recurrence after radiotherapy or chemotherapy, it is necessary to use PET or SPECT. To define correctly the CTV using these images, one must realize the anatomical localization of the metabolic abnormalities, which they highlight with a registration based on CT or MRI. The difficulties to obtain the registration of these images led the manufacturer to propose mixed machines allowing to realize, at the same time, a CT imaging and a PET or a SPECT imaging with the patient in treatment position.

[Effect of Ginkgo biloba extract (EGb 761) on rats in an experimental model of acute encephalopathy after total body irradiation]. / Effet de l'extrait de Ginkgo biloba (EGb 761) chez le rat sur un modèle expérimental d'encéphalopathie aiguë après irradiation corporelle totale.

PURPOSE: To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in an experimental model of acute encephalopathy following total body irradiation in rats. MATERIAL AND METHODS: Ninety four-month-old rats received 4.5 Gy total body irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed test, was performed after irradiation. Orally treatment was started one day (study A) or twenty two days (study B) after irradiation and repeated daily for twelve days. In the irradiated group, three subgroups were defined according to the treatment received: EGb 761 (50 mg/kg), EGb 761 (100 mg/kg), water. RESULTS: This work comprised two consecutive studies. In study A (45 rats) the one-way avoidance test was administered daily from day 7 to day 14. In study B (45 rats) the behavioural test was performed from day 28 to day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated with water demonstrated a significant delay in a learning the one-way avoidance test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats treated with EGb 761 (50 mg/kg; P < 0.0017) or EGb 761 (100 mg/kg; P < 0.0002). The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated rats, treated with water or EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat, which persists fourteen days after TBI. This effect is prevented by the administration of EGb 761 (50 or 100 mg/kg) started twenty-four hours after irradiation.

[First treatment for brain metastases by stereotactic radiosurgery]. / Traitement premier des métastases cérébrales par irradiation en conditions stéréotaxiques.

Local control of brain metastases is better with first treatment by stereotactic radiosurgery than with radiosurgery for recurrence. We reported a retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery realised in first intention. From January 1994 to December 1997, 26 patients presenting with 43 metastases underwent radiosurgery. The median age was 61 years and the median Karnofsky index 70. Primary sites included: lung (12 patients), kidney (7 patients), breast (2 patients), colon (1 patient), melanoma (2 patients), osteosarcoma (1 patient), it was unknown for one patient. Seven patients had extracranial metastases. Twenty-one sessions of radiosurgery have been realized for one metastase, and 9 for two, three or four lesions. The median diameter was 21 mm and the median volume 1.8 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Forty-two metastases were evaluable for response analysis. The overall local control rate was 90.5% and the 1-year, 2- and 3-year actuarial rates were 85% and 75%. In univariate analysis, theorical radioresistance was significantly associated with better local control (100% versus 77%, p < 0.05). All patients were evaluable for survival. The median survival rate was 15 months. Four patients had a symptomatic oedema (RTOG grade II). Two lesions have required a surgical excision. In conclusion, low dose radiosurgery (14 Gy delivered at the periphery of metastasis) can be proposed in first intention for brain metastases, in particularly for theorical radioresistant lesions.

[Radiotherapy using a combination of photons and protons for locally aggressive intracranial tumors. Preliminary results of protocol CPO 94-C1]. / Radiothérapie des tumeurs intracrâniennes localement agressives par une combinaison de photons et de protons. Résultats préliminaires du protocole CPO 94-C1.

PURPOSE: From October 1993 through July 1998, 48 assessable adult patients with non-resectable aggressive intracranial tumors were treated by a combination of high dose photon + proton therapy at the Centre de Protonthérapie d'Orsay. PATIENTS AND METHODS: Grade 1 and 4 gliomas were excluded. Patients benefited from a 3D dose calculation based on high-definition CT and MRI, a stereotactic positioning using implanted fiducial markers and a thermoplastic mask. Mean tumor dose ranged between 63 and 67 Gy delivered in five weekly sessions of 1.8 Gy in most patients, according to the histological types (doses in Co Gy Equivalent, with a mean proton-RBE of 1.1). RESULTS: With a median 18-month follow-up (range: four-58 months), local control in tumors located in the envelopes and in the skull base was 97% (33/34), and in parenchymal tumors, 43% (6/14) only. Two patients (5%) presented with a clinically severe radiation-induced necrosis (temporal lobe and chiasm). CONCLUSION: In our experience, high-dose radiation combining photons and protons is a safe and highly efficient procedure in selected malignancies of the skull base and envelopes.