[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.

Positive clinical experience with misonidazole in brachytherapy and external radiotherapy.

We performed a clinical evaluation of Misonidazole (MISO) radiosensitization in brachytherapy and two schedules of hypofractionated external radiotherapy in 3 non randomized studies. MISO (1 g/m2/d) was administered to patients with ENT tumors treated by brachytherapy, two applications of 35 Gy each with an interval of 1 month. For 46 patients with tumor responses less than 50% (in the largest dimension) at time of second application, 21 received MISO and 25 did not. For these poorly radiosensitive tumors, the addition of MISO significantly increased the rate of complete remission from 9/25 (36%) in controls to 14/21 (67%) (p less than 0.05). We studied MISO with radiation hypofractionation for conservative breast cancer with 4 fractions over 17 days (5 Gy on days 1, 3 and 6.5 Gy on days 15 and 17). Brachytherapy alone was delivered three weeks later. MISO (1 g/m2/d) was given to 38 patients with 87 acting as controls. Radiosensitization was measured by mean tumor diameter at brachytherapy, which showed a residual mass of 33% in the group without MISO and only 17% in the group with MISO (p less than 0.05). We also studied MISO with radiation hypofractionation for large ENT tumors with 14 fractions over 45 days, 2 sessions with a 4 hour interval per day for totals of 6 Gy on days 1 and 3; 8 Gy on days 15, 17, 29, 31; and 6 Gy on day 45. MISO (1 g/m2/d) was given to 49 patients with 21 acting as controls. MISO increased the rate of complete remission from 7/21 (33%) in controls to 32/49 (65%) (p less than 0.02).

The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients.

An ongoing randomized study of a specific regimen of hypofractionated radiation therapy (IHF) versus classical or standard radiation therapy (IC) for breast cancer was begun in the Department of Radiation Therapy of the Necker Hospital, Paris France, in January 1982. Breast cancer patients entered into this study received either IC to deliver 45 Gy in 25 fractions over 33 days or a specific IHF regimen to deliver 23 Gy in 4 fractions over 17 days. As of June 1989, 525 patients had been entered into the study. The first 230 patients treated from 1982 through December 1984 had a minimum follow-up of 4 years (range: 4 to 7 years). Preliminary analysis of the results in these first 230 patients are presented. The distribution of patients in this initial group according to clinical staging, associated treatments, and pathological nodes is as follows: T1 = 22%, T2 = 61%, T3 + T4 = 17%, palpable nodes = 28%, inflammatory signs = 7%, surgical treatment = 79% (mastectomy = 35%, tumorectomy + Ir.192 = 44%), radiation alone + neoadjuvant chemotherapy = 21%, N+ = 50% of patients undergoing surgery. Loco-regional recurrences developed in 7% (9/125) of patients in the IHF group and in 5% (5/105) of patients in the IC group. Complications were minor. The addition of the percentage of each complication noted results in a total of 23% for the IHF group and 19% for the IC group (one patient could present several complications). As we had previously observed when comparing these two fractionation regimens in other studies with other tumors, these preliminary results showed no evident difference in the effectiveness and rate of complications whether IHF or IC was used to treat patients with breast cancer.

Split course interstitial brachytherapy with a source shift: the results of a new iridium implant technique versus single course implants for salvage irradiation of base of tongue cancers in 55 patients.

Between January 1973 and December 1984, 55 patients with prior irradiation of the oropharynx underwent salvage irradiation for recurrent (26 patients) or second cancers (29 patients) of the base of tongue. The initial irradiation had delivered from 45 to 80 Gy to the base of tongue. One of two techniques of Iridium implantation was used for salvage. Single course implants, delivering 60 Gy, were used until June 1981 in a total of 31 patients. After June 1981, split course implants with a source shift were used in 24 patients in the hope of decreasing treatment complications. The first and second course of the split course implants delivered 35 and 30 Gy, respectively, at a 1-month interval. The active lines of the second implant were placed parallel to and between the position of the lines of the first implant. This shift in the source position resulted in a more uniform dose within the treated volume with a 60% reduction in the high dose sleeves. The overall 3-year survival was 19% (28% T less than or equal to 3 cm). The overall local failure rate was 45.5% (25/55). The difference between the local failure rate after single course implants (52%) and after split course implants (37.5%) was not statistically significative. The response observed after the first course of a split course implant proved to be a reliable indication of the probability of achieving local control after a full course of treatment: 2/14 failures (14%) if the response was greater than or equal to 75% versus 7/10 (70%) if the response was less than 75% (p less than 0.01). The only complication noted in the 40 patients achieving immediate local control after either implant technique was mucosal necrosis. The introduction of split course implants was followed by a two and a half fold decrease in the incidence of necrosis: 43% (9/21) in the single course group and 16% (3/19) in the split course group (p = 0.05). Interstitial brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the base of tongue even when the tumor arises in a zone that has previously received high dose irradiation. The use of split course implants with a shift in the position of the active lines at the time of the second implant significantly decreases the risk of radionecrosis.

Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase.

PURPOSE: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. METHODS AND MATERIALS: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. RESULTS: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase 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. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.

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.

[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.

[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.

[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.

[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.

[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.

[Radiotherapy-induced cognitive dysfunction in 4-months-old male Wistar rats]]. / Dysfonctionnement cognitif radio-induit chez le rat Wistar mâle âgé de 4 mois.

PURPOSE: Behavioral dysfunction of memory process arising 4 months after whole brain irradiation (30 Gy/10 fractions/12 days) has been demonstrated in 16-27 month old rats, as compared with non irradiated rats. This study was therefore aimed at delivering the same irradiation in young rats and comparing results with those previously obtained in old rats. MATERIAL AND METHODS: Thirty-three 4-month old rats were included into the study. Eighteen received whole brain irradiation (30 Gy/10 fractions/12 days), and 18 were given sham irradiation. Sequential behavior studies were done before irradiation and during the 7 months following irradiation. RESULTS: Significant decrease in memory function was observed in irradiated rats 1 month (p < 0.001), 3 months (p < 0.013), and 6 months (p = 0.007) post-irradiation. This was accompanied by learning deficit 1 month (p = 0.01), 4.5 months (p = 0.03), and 7 months (p = 0.009) post-irradiation. CONCLUSION: Response to radiation therapy observed in young rats differed from that observed in old rats. Young rats showed earlier decrease in memory function than old rats, but this deficit was followed by partial recovery. Learning deficits also arised earlier in young rats than in old rats. In two cases this deficit was permanent.

[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.

[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.

[Importance of radiotherapy in stereotactic conditions (radiosurgery) in brain metastasis: experience and results of the Hôpital Pitié-Salpêtrière Group]. / Intérêt de la radiothérapie en conditions stéréotaxiques (radiochirurgie) des métastases cérébrales: expérience et résultats du groupe hospitalier Pitié-Salpêtrière.

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.

[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.