[An original contention system for hadron therapy]. / Un système de contention original applicable à l'hadronthérapie.

In hadron therapy centers that have only fixed horizontal beams (i.e. most carbon ions centers and protons centers of first generation), the angulations of the beam remain technically limited, especially for the treatment of children under general anaesthesia with posterior-oblique (40 degrees or so) beams in supine position. We have been developing recently an original positioning system allowing for treatment with posterior-oblique beams, either from right or left directions, by keeping the child in the adequate position.

[Quality assurance of a virtual simulation software: application to IMAgo and SIMAgo (ISOgray)]. / Assurance qualité d'un logiciel de simulation virtuelle: application à IMAgo et SIMAgo (ISOgray).

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.

[Image registration for radiation therapy: Practical aspects and quality control]. / Recalage d'images en radiothérapie: considérations pratiques et contrôle de qualité.

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.

Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies.

PURPOSE: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.

[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.

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.

[Virtual simulation: means and methodology]. / Simulation virtuelle: moyens et méthodologie.

State of the art imaging and computer systems coupled with the development of superior visualisation and multiplane reconstruction software have opened new perspectives in treatment planning. "Virtual simulation" of the irradiation technique allows definition in 3D of the optimised geometrical characteristics of the treatment beams with respect to anatomical structures of the patient. One can then visualise the beam direction and target volume coverage in the "virtual patient", leading to very precise radiotherapy. However, this "three dimensional" approach requires not only technical means, but also a methodology and an appropriate system of quality assurance for each step of the treatment planning, as well as significant multidisciplinary input.

[Glossary of conformal radiotherapy]. / Glossaire de la radiothérapie conformationnelle.

Most of the concepts and terms related to conformal radiotherapy were produced by English-speaking authors and eventually validated by international groups of experts, whose working language was also English. Therefore, a significant part of this literature is poorly accessible to the French-speaking radiation oncology community. The present paper gathers the 'official' definitions already published in French, along with propositions for the remaining terms which should be submitted to a more formal and representative validation process.

[Conformal radiotherapy of brain tumors]. / La radiothérapie conformationnelle des tumeurs cérébrales.

Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy.

[Determination of target volume in pediatric radiotherapy: application to brain tumors]. / La détermination des volumes-cibles en radiothérapie pédiatrique: application aux tumeurs cérébrales.

Pediatric tumors have enjoyed considerable improvements for the past 30 years. This is mainly due to the extensive use of combined therapeutical modalities in which chemotherapy plays a prominent role. In many children, local treatment including radiotherapy, can nowadays be adapted in terms of target volume and dose to the "response" to an initial course of chemotherapy almost on a case by case basis. This makes precise recommendation on local therapy highly difficult in this age group. We will concentrate in this paper on brain tumors in which chemotherapy is of limited value and radiotherapy still plays a key-role.

[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.

[Involved-node radiotherapy combined with deep-inspiration breath-hold technique in patients with Hodgkin lymphoma]. / Optimisation de la radiothérapie involved-node grâce à l'inspiration profonde bloquée dans la maladie de Hodgkin.

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

[Intensity-modulated radiotherapy and involved-node concept in patients with Hodgkin lymphoma: experience of the Gustave-Roussy Institute]. / Optimisation de l'« involved-node radiotherapy ¼ par l'utilisation de la modulation d'intensité dans le lymphome hodgkinien localisé : expérience de l'institut Gustave-Roussy.

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

[Intensity modulated radiotherapy as adjuvant post-operative treatment for retroperitoneal sarcoma: acute toxicity]. / Radiothérapie avec modulation d'intensité dans le traitement postopératoire des sarcomes rétropéritonéaux: profil de toxicité aiguë.

PURPOSE: To assess the acute toxicity of intensity modulated radiotherapy as post-operative adjuvant treatment for retroperitoneal sarcoma. PATIENTS AND METHODS: Patients who received adjuvant intensity modulated radiotherapy from January 2009 to September 2010 were retrospectively reviewed. RESULTS: Fourteen patients entered the study (seven primary tumours and seven relapses). All tumours were liposarcoma and had macroscopically complete resection, epiploplasty was systematically realized. Median tumour size was 21 cm (range: 15-45), median planning target volume was 580 cm(3) (range: 329-1172) and median prescribed dose was 50.4 Gy (range: 45-54). Median follow-up was 11.5 months (range: 2-21.4). Acute toxicity was mild: acute digestive toxicity grade 1-2 occurred in 12/14 patients (86%). However, there was no weight loss of more than 5% during radiotherapy and no treatment interruption was required. Two months after completion of radiotherapy, digestive toxicity grade 1 remained present in 1/14 patients (7%). One case of grade 3 toxicity occurred during follow-up (transient abdominal pain). Three relapses occurred: two were outside treaded volume and one was both in and outside treated volume. CONCLUSIONS: Intensity modulated radiotherapy in the postoperative setting of retroperitoneal sarcoma provides low acute toxicity. Longer follow-up is needed to assess late toxicity, especially for bowel, kidney and radio-induced malignancies.

[Dose delivered to the patient by megavoltage cone beam computed tomography imaging]. / Dose délivrée au patient lors de l'acquisition d'images par tomographie conique de haute énergie.

PURPOSE: To study the dose delivered by a megavoltage cone beam computed tomography imaging system (MVCBCT) installed on a Oncor Impression linac (Siemens). MATERIALS AND METHODS: The acquisition of MVCBCT images was modelled in a treatment planning system by 67 photon beams (6 MV). A study was conducted to: compare the calculated and measured dose at the centre of a cylindrical phantom; compare the calculated and measured dose distributions in the Alderson-Rando phantom (pelvis); study the influence of MVCBCT image acquisition for the repositioning of a prostate cancer patient treated by 3D conformal radiotherapy (prescribed dose of 74 Gy), on the dose-volume histograms (DVH) for the treatment plus seven MVCBCT (protocol D1-3 and weekly), treatment plus 37 MVCBCT (one for each day of treatment). RESULTS: The difference between calculated and measured doses at the centre of the cylindrical phantom was less than 3%. A deviation of 7% maximum was found between the dose distribution calculated in the Rando phantom and the measured doses normalized at the beam isocentre. The dose delivered at the isocentre was equal to 3,7 cGy for a "5 MU" protocol, with a maximum dose of 6 cGy. In the case of the patient considered, the acquisition of 37 MVCBCT corresponded to an additional mean dose to the PTV of 1.2 Gy for a protocol "5MU" with a significant influence on the DVH. CONCLUSION: In view of this study, it appears that the doses delivered in frequent use of MVCBCT must be taken into account by the radiation oncologist in assessing the therapeutic dose delivered to the target volume and organs at risk.

Breast carcinoma in women previously treated for Hodgkin's disease: clinical and mammographic findings.

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