Thierry Sarrazin

Extracranial Stereotactic Radiotherapy: Preliminary Results with the CyberKnife®

In the field of radiation oncology, equipment for fractionated radiotherapy and single-dose radiosurgery has become increasingly accurate, together with the introduction of robotized treatments. A robot is a device that can be programmed to carry out accurate, repeated and ad-justed tasks in a given environment. Treatment of extracranial lesions involves taking into account organ mobility (tumor and healthy tissue) whilst retaining the ability to stereotactically locate the target. New imaging techniques (single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), positron emission tomography (PET)) provide further relevant information to slice images (computed tomography (CT) scans, MRI) for target definition. Hypo-fractionated treatments can only be used for curative treatment if the target is accurately defined and tracked during treatment. The CyberKnife® is a non-invasive system of radiosurgery and fractionated stereotactic radiotherapy. For intracranial lesions treated by single-dose radiosurgery, it has been used to treat meningioma, acoustic neuromas, pituitary adenoma, metastases, arteriovenous malformations and refractory pain (trigeminal neuralgia). More than 10,000 patients have been treated worldwide. Currently, the most significant developments are in the field of extracranial stereotactic radiotherapy (lung, liver, reirradiation, prostate, etc.). Clinical results obtained in the Cyberknife Nord-Ouest program after 1 year of experience are presented.

Clinical outcomes after Gamma Knife surgery for idiopathic trigeminal neuralgia: review of 76 consecutive cases

OBJECT Stereotactic radiosurgery is an increasingly used, and the least invasive, surgical option for patients with trigeminal neuralgia (TN). In this study, the authors performed a retrospective evaluation of the safety and efficacy of this method for idiopathic TN. METHODS The authors reviewed data from 76 patients with idiopathic TN who underwent Gamma Knife surgery (GKS). The mean age of the patients was 64 years (range 27-83 years). All patients had typical features of TN. Thirty patients (39.5%) had previously undergone surgery. The intervention consisted of GKS on the retrogasserian cisternal portion of the fifth cranial nerve. The mean maximum GKS dose used was 85.1 Gy (range 75-90 Gy). RESULTS Patients were followed-up from 6 to 42 months (mean 20.3 months) after GKS. Complete pain relief was achieved in 83.1% of the patients within 1 year, 70.9% within 2 years, and 62.5% within 3 years. Patients who underwent previous surgery demonstrated a lower rate of pain relief (p < 0.05). Twenty patients (26.3%) reported pain recurrence between 6 and 42 months after treatment. New or worsened persistent trigeminal dysfunction developed after GKS in 16 patients (21%); 8 of these patients described some facial numbness/not bothersome, and 8 reported some facial numbness/somewhat bothersome. None of the patients developed troublesome dysesthesia or anesthesia dolorosa. CONCLUSIONS Gamma Knife surgery for idiopathic TN proved to be safe and effective and was associated with a particularly low rate of complications.

Utilisation d'un système d'imagerie en temps réel dans le contrôle quotidien de patients traités par irradiation pour un cancer thoracique

PURPOSE: Retrospective analysis of the results obtained with daily interactive use of portal imaging for monitoring thoracic cancer radiotherapy. MATERIALS AND METHODS: A Siemens electronic portal imaging system called Beamviewplus was used daily in 15 lung cancer patients for each X-ray field. Out of the 714 expected portal images, 585 (82%), were obtained and printed. RESULTS: We counted 94 errors in the 585 successful controls (16%). Four main classes of errors were identified: irradiation field placement (47 cases, 50%), shielding placement (30 cases, 32%) patients position on the till examining table (14 cases, 15%), and selection of the energy (3 cases, 3%). Forty percent of these errors were potentially serious in terms of treatment volume and vital organ protection. CONCLUSION: Only portal imaging control could easily detect errors because they occurred randomly. We thus consider the use of this daily system helpful for patient management.

Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.

SummaryThe poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and increases topoisomerase II poisoning. Here, F14512 was evaluated in pediatric HGG and neuroblastoma cell lines. PTS activity and specificity were evaluated using a fluorescent spermine-coupled probe. The cytotoxicity of F14512, alone or in combination with ionizing radiation and chemotherapeutic agents, was investigated in vitro. The antitumor activity of F14512 was assessed in vivo using a liver-metastatic model of neuroblastoma. An active PTS was evidenced in all tested cell lines, providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Competition experiments confirmed the essential role of PTS in the cell uptake and cytotoxicity of F14512. This cytotoxicity appeared greater in neuroblastoma cells compared with HGG cells but appeared independent of PTS activity levels. In vivo evaluation confirmed a marked and prolonged antitumoral effect in neuroblastoma cells. The combinations of F14512 with cisplatin and carboplatin were often found to be synergistic, and we demonstrated the significant radiosensitizing potential of F14512 in the MYCN-amplified Kelly cell line. Thus, F14512 appears more effective than etoposide in pediatric tumor cell lines, with greater efficacy in neuroblastoma cells compared with HGG cells. The synergistic effects observed with platinum compounds and the radiosensitizing effect could lead to a clinical development of the drug in pediatric oncology.

Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments

PURPOSE The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans.

Radiothérapie stéréotaxique extracrânienne: la place du CyberKnife®

RésuméEn 2006, l’Institut national du cancer a lancé un appel d’offres portant sur la radiothérapie stéréotaxique extracrânienne. Trois sites ont été sélectionnés pour implanter et évaluer un robot de radiothérapie, le CyberKnife®. Cette machine capable de suivre des tumeurs mobiles en temps réel ouvre de nouvelles perspectives dans le champ de la radiothérapie stéréotaxique, notamment dans sa composante extracrânienne. Les fonctionnalités de cet équipement et le coût de sa mise en œuvre vont ètre évalués sur une période de deuxanssur les trois sites considérés.AbstractIn 2006, three sites were selected by the French Institut national du cancer to evaluate the CyberKnife robotic radiotherapy system. This device, able to track mobile tumours in real time, offers new possibilities in the field of extracranial stereotactic radiotherapy. The device’s functionalities, as well as medical and economical issues, will be evaluated for two years on the three sites.

Role of radiosurgery in the management of pineal region tumours: indications, method, outcome.

Numerous tumour types can occur in the pineal region. Because these tumours are uncommon and heterogeneous, it is often difficult to establish optimal treatment strategies based on comparative clinical trials. To date, the role of radiosurgery for the treatment of pineal region tumours remains controversial. This report of a 10-year single-department experience and review of the literature focuses on the spectrum of pathologic features found in these pineal parenchymal tumours and on the interest of radiosurgery in their management. Considering pineocytomas, although these tumours have been considered to be radioresistant to fractionated radiotherapy, our results are in agreement with similar results reported in the literature in suggesting that radiosurgery may be an alternative to surgical resection or an adjuvant therapy when the resection is not optimal. When dissemination occurs after radiosurgery, however, craniospinal radiation and chemotherapy are necessary. Radiosurgery has also proven its interest in the treatment of germinomas as an alternative to encephalic radiotherapy with limited long-term damage. Regarding the other pathologies, radiosurgery can be considered as part of a multimodal treatment including surgery, chemo-radiotherapy and its role still has to be clearly defined.

Abstract ID: 222 Clinical implementation of a Monte Carlo based QA platform for validation of Tomotherapy and Cyberknife treatment plans

INTRODUCTION This work describes the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, including a semi-automatic plan evaluation module based on dose constraints for organs-at-risk (OAR). METHODS The Monte Carlo-based platform Moderato [1] is based on BEAMnrc/DOSXYZnrc and allows for automated re-calculation of doses planned with Tomotherapy and Cyberknife techniques. The Prescription/Validation module generates a set of dose constraints based on the anatomical region and fractionation scheme considered. Upon achievement of the planning, dose results are displayed with visual warnings in case of constraint violation. The system was tested on 83 patient cases in order to evaluate the influence of difference in calculation algorithms on OAR constraints. RESULTS The first results with the Tomotherapy plans allowed for detecting and correcting a problem with the CT Hounsfield units when using a large reconstruction diameter (a CT artifact that lead to air voxels with an overestimated density). The Cyberknife results also showed some dose differences associated with different energy thresholds between Moderato and the Monte Carlo algorithm used in the Treatment Planning Station. Regarding OAR constraints, re-calculation generated few violations in thoracic, pelvic and abdominal cases. However, in spinal and head cases, significant differences can appear (-11% to +6%) on optic pathways and spinal cord, leading to doses above the limits. CONCLUSIONS The Moderato platform constitutes a promising tool for the validation of plan quality, offering both dose re-calculation and OAR constraints evaluation. First results show the importance of this verification for some specific regions. Further work is ongoing to optimize the quantity and relevance of the information displayed, before fully introducing the system in clinical routine.