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.

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.

The antitumor drug F14512 enhances cisplatin and ionizing radiation effects in head and neck squamous carcinoma cell lines.

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. The treatment of advanced stages HNSCC is based on surgical treatment combined with radiotherapy and chemotherapy or concomitant chemo-radiotherapy. However, the 5-year survival remains poor for advanced stages HNSCC and the development of new targeted therapies is eagerly awaited. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. This spermine moiety facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and reinforces topoisomerase II poisoning. Here we report the evaluation of F14512 toward HNSCC. MATERIALS AND METHODS: Four cell lines representative of head and neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and CAL27 (base of the tongue). PTS activity and specificity were evaluated by confocal microscopy and flow cytometry using the fluorescent probe F17073 which contains the same spermine moiety as F14512. Cytotoxicity, alone or in association with standard chemotherapeutic agents (cisplatin, 5FU), and radio-sensitizing effects were investigated using MTS and clonogenic assays, respectively. F14512 efficiency and PTS activity were also measured under hypoxic conditions (1% O2). RESULTS: In all 4 tested HNSCC lines, an active PTS was evidenced providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Interestingly, F14512 presents a 1.6-11-fold higher cytotoxic effect than the reference compound etoposide (lacking the spermine chain). It appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition experiments with spermine confirmed the essential role of the PTS in the cell uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to be synergistic and, for the first time, we demonstrated the significant radio-sensitizing potential of F14512. CONCLUSION: The spermine moiety of F14512 confers a targeted effect and a much better efficacy than etoposide in HNSCC lines. The synergistic effect observed in association with cisplatin and radiotherapy augurs well for the potential development of F14512 in HNSCC.

Acute respiratory disease syndrome with preoperative chronomodulated chemoradiotherapy in patients with esophageal cancer. Early termination of a phase I trial.

A phase I trial was initiated to establish the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of chronomodulated 5-fluorouracil and cisplatin given concurrently with preoperative radiotherapy in patients with esophageal cancer. Patients with stage I or II esophageal cancer received preoperative radiation therapy (28-30 daily 1.8-Gy fractions for a total of 50.4 or 54 Gy) and concurrent three fortnightly cycles of chronomodulated 5-fluorouracil (700-835 mg/m2 per day, d1-d4, with peak delivery at 4.00 am) and cisplatin (50 mg/m2, d1, with peak delivery at 4.00 pm) administered by a time-programmable pump. Ten patients were treated on this study. Two of six patients treated at the starting dose-level experienced acute DLTs (esophagitis, asthenia) which required de-escalation of 5-fluorouracil. Five patients out of ten experienced seven DLTs (severe esophagitis, asthenia, vomiting: 5/1/1) at any dose-level. The MTD was not assessed because the study was halted due to slow accrual. Finally, two patients deceased from an Acute Respiratory Distress Syndrome due to inadequate radiation therapy planning. Without definitively ruling out any possible impact of chronomodulation in that setting, our data reinforce the need of a better selection of patients aimed to be treated by CRT plus surgery.

[CyberKnife robotic stereotactic radiotherapy: technical aspects and medical indications]. / Radiothérapie stéréotaxique robotisée par CyberKnife : aspects techniques et indications.

In 2006, 3 sites have been selected by the Institut national of cancer (Lille, Nancy et Nice) to evaluate a radiotherapy robot, the CyberKnife. This machine, able to track mobile tumours in real time, gives new possibilities in the field of extra cranial stereotactic radiotherapy. Functionalities and medico economical issues of the machine will be evaluated during 2 years on the 3 sites.

[In vivo dosimetry and radiation therapy of breast cancer]. / Dosimétrie in vivo et radiothérapie des cancers du sein.

INTRODUCTION: Verification of absorbed dose in target volume is a key factor for quality assurance in radiotherapy. In vivo measurements allow evaluation of the variations in dose with time and variations between measured doses and calculated doses by TPS. The aim of this work were to evaluate reproducibility of patient positioning and to compare calculated doses by 2 different TPS. PATIENTS AND METHODS: Twenty patients were divided in 2 groups according to the thickness of their breast (mean SSD = 92.9 cm). In vivo measurement was performed within the first two sessions. RESULTS: Reproducibility of SSD evaluation was made on 12 beams between 2 fractions. With a tolerance margin of 0.5 cm, positioning errors were present in 33% (4/12). The 2 TPS were in agreement in 75% (30/40). CONCLUSION: In vivo dosimetry can be a very interesting tool to assess patients positioning variations and TPS dose calculation.

[Comparison of conventional and conformational dosimetry in radiotherapy of cerebral neoplasms]. / Comparaison entre dosimétries classique et conformationnelle dans l'irradiation de tumeurs cérébrales.

PURPOSE: We prospectively compared a conventional treatment planning (PT2D) and 3-dimensional conformal treatment planning (PT3D) for radiotherapy of cerebral tumours. PATIENTS AND METHODS: Patients treated between 1/10/98 and 1/4/99 by irradiation for cerebral tumours were analysed. For each case, we planned PT2D using conventional orthogonal x-ray films, and afterward, PT3D using CT scan. Gross tumor volume, planning target volume and normal tissue volumes were defined. Dose was prescribed according to report 50 of the International Commission on Radiation Units and Measurements (ICRU). We compared surfaces of sagittal view targets defined on PT2D and PT3D and called them S2D and S3D, respectively. Irradiated volumes by 90% isodoses (VE-90%) and normal tissue volumes irradiated by 20, 50, 90% isodoses were calculated and compared using Student's paired t-test. RESULTS: There was a concordance of 84% of target surfaces defined on PT2D and PT3D. Percentages of target surface under- or-over defined by PT2D were 16 and 13% respectively. VE-90% was decreased by 15% (p = 0.07) with PT3D. Normal brain volume irradiated by 90% isodose was decreased by 27% with PT3D (p = 0.04). CONCLUSION: For radiotherapy of cerebral tumors using only coplanar beams, PT3D leads to a reduction of normal brain tissue irradiated. We recommend PT3D for radiotherapy of cerebral tumors, particularly for low-grade or benign tumors (meningiomas, neuromas, etc.).

[Dosimetric quality control in stereotactic radiotherapy with the aid of radiosensitivity]. / Contrôle de qualité dosimétrique en radiothérapie stéréotaxique à l'aide de gels radiosensibles.

Typical dosimeters used in stereotactic radiation therapy, such as ionization chambers, films, and thermoluminescent diodes, allow basic physical measurements. They are, however, neither well suited to discern small target volumes with high dose gradient, nor suitable for three-dimensional (3D) dose measurements. Gel dosimetry is becoming more and more interesting, owing to magnetic resonance imaging (MRI). It permits isocenter position planning verification of accuracy and the precision of the 3D dose mapping in the brain (when irradiated in realistic conditions), especially when several different targets are concerned. Many authors have assessed stereotactic radiation therapy quality control using different gels, and different irradiation procedures. This paper consists of the review of these different methods to assess quality control. Gel dosimetry cannot provide absolute dose measurements. However, gels can be used to check the 3D dose mapping with a high degree of detail. In our experiment, the difference between the stereotactic frame center and the isocenter is about 1 mm. The difference between the theoretical isodoses obtained by the treatment planning system and the experimental isodoses obtained by the MRI gray level calibration is also about 1 mm, the order of magnitude of the MRI pixel size.

[Use of real-time system of portal imaging in the daily monitoring of patients treated by radiotherapy for thoracic cancer]. / 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%) patient's 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.

Technical note: magnetic resonance imaging of agarose gel phantom for assessment of three-dimensional dose distribution in linac radiosurgery.

An agarose gel phantom is used to evaluate the spatial distribution of the dose delivered by a linac radiosurgery device. Dependence of the absorbed dose on the T1 relaxation time is checked. T1 magnetic resonance images show the close correspondence between the actual absorbed dose distribution and the dose distribution expected by the treatment planning.