System BrainLAB Research Articles

Phase II trial of functional imaging-optimized stereotactic fractionated radiotherapy plus temozolomide for recurrent high-grade glioma

1552 Background: Stereotactic fractionated radiotherapy (SFRT) is a valuable treatment option for recurrent high-grade glioma. Its therapeutic ratio might be improved by functional imaging-optimized treatment planning. After this approach has been evaluated in 16 patients, additional chemotherapy with temozolomide was added to the regimen in a single-institution phase II trial. Methods: 16 patients entered the SFRT alone trial, 30 patients received SFRT plus temozolomide. For treatment planning with the BrainLAB system, the gross tumor volume was defined by C11-methionine PET/CT/MRI image fusion. Maximum diameter was less than 4 cm. Mean age was 50 years. 37 patients had glioblastoma multiforme, 8 anaplastic astrocytoma and 1 anaplastic oligodendroglioma. Previous radiotherapy dose was 54–60 Gy (median interval to retreatment 17 months). Total dose was 30 Gy in 6 fractions. Temozolomide 200 mg/m2/day every 28 days was started before SFRT with 1–2 cycles. After SFRT, 4+ cycles were added. Patients were followed with MRI or CT every other cycle. Results: Median survival was 11 months for patients who received SFRT plus temozolomide and 6 months for patients treated with SFRT alone (p=0.02). No acute neurologic toxicity grade II or higher was observed. No grade IV hematologic toxicity was observed. Signs of radionecrosis were observed in 3 patients. However, surgical resection revealed both tumor and necrosis. Conclusions: This is the first study of functional imaging-optimized SFRT plus temozolomide. It demonstrates the feasibility and safety of this approach. Our institutional retrospective comparison suggests a significant survival advantage from combined modality treatment which needs to be confirmed prospectively. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharmaceuticals

Phase II trial of functional imaging-optimized stereotactic fractionated radiotherapy plus temozolomide for recurrent high-grade glioma

1552 Background: Stereotactic fractionated radiotherapy (SFRT) is a valuable treatment option for recurrent high-grade glioma. Its therapeutic ratio might be improved by functional imaging-optimized treatment planning. After this approach has been evaluated in 16 patients, additional chemotherapy with temozolomide was added to the regimen in a single-institution phase II trial. Methods: 16 patients entered the SFRT alone trial, 30 patients received SFRT plus temozolomide. For treatment planning with the BrainLAB system, the gross tumor volume was defined by C11-methionine PET/CT/MRI image fusion. Maximum diameter was less than 4 cm. Mean age was 50 years. 37 patients had glioblastoma multiforme, 8 anaplastic astrocytoma and 1 anaplastic oligodendroglioma. Previous radiotherapy dose was 54–60 Gy (median interval to retreatment 17 months). Total dose was 30 Gy in 6 fractions. Temozolomide 200 mg/m2/day every 28 days was started before SFRT with 1–2 cycles. After SFRT, 4+ cycles were added. Patients were followed with MRI or CT every other cycle. Results: Median survival was 11 months for patients who received SFRT plus temozolomide and 6 months for patients treated with SFRT alone (p=0.02). No acute neurologic toxicity grade II or higher was observed. No grade IV hematologic toxicity was observed. Signs of radionecrosis were observed in 3 patients. However, surgical resection revealed both tumor and necrosis. Conclusions: This is the first study of functional imaging-optimized SFRT plus temozolomide. It demonstrates the feasibility and safety of this approach. Our institutional retrospective comparison suggests a significant survival advantage from combined modality treatment which needs to be confirmed prospectively. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharmaceuticals

Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: first clinical experience

Purpose ( a) To implement a fully automatic method to integrate 11C-methionine positron emission tomography (MET-PET) data into stereotactic radiation treatment planning using the commercially available BrainLAB System, by means of CT/MET-PET image fusion. ( b) To validate the fully automatic CT/MET-PET image fusion technique with respect to accuracy and robustness. ( c) To give a short glance at the clinical consequences for patients with brain tumors. Methods and materials In 12 patients with brain tumors (9 meningeomas, 3 gliomas), CT, MRI, and MET-PET were performed for stereotactic fractionated radiation treatment planning. The CT and MET-PET investigations were performed using a relocatable mask for head fixation. Fifteen external reference markers (5 on each lateral and 5 on the frontal localizer plate) that could be identified in CT and MET-PET were applied on the stereotactic localizer frame; the marker positions were exactly defined for both investigations. The MRI/CT fusion was done completely automatically. The CT/MET-PET fusion was performed using two different methods: The gold standard was the CT/PET fusion based on the reference markers, and the test method was the automatic, intensity-based CT/PET fusion, independent of the external markers. The markers visible on CT and transmission PET were matched using a point-to-line matching algorithm. To quantify the amount of misregistration, the two fusion methods were compared by calculating the mean value of deviation between corresponding points inside a cubic volume of interest of ≥512 cm 3 defined within the cranial cavity. The gross tumor volume (CT/MRI) outlined on CT and T1-MRI with contrast medium was compared with the gross tumor volume (PET) defined in the reoriented MET-PET data sets. The clinical impact of MET-PET in tumor volume definition for stereotactic radiotherapy will be discussed. Results The fully automatic integration of MET-PET into stereotactic radiation treatment planning was successfully realized in all patients investigated. Mean deviation of the intensity-based automatic CT/PET fusion compared with the external marker–based gold standard was 2.4 mm; the standard deviation was 0.5. The algorithm’s robustness was evaluated, and the discrepancy of fusion results due to different initial image alignments was determined to be below 1 mm inside the test volume of interest. In patients with meningiomas and gliomas, MET-PET was shown to deliver additional information concerning tumor extension. Conclusion The precision of the automatic CT/PET image fusion was high. A mean deviation of 2.4 mm is acceptable, considering that it is approximately equal to the pixel size of the PET data sets. MET-PET improves target volume definition for stereotactic fractionated radiotherapy of meningiomas and gliomas.

57. Physical and dosimetric aspects of quality assurance in stereotactic radiotherapy

A quality assurance system in stereotactic radiosurgery and stereotactic fractionated radiotherapy, concerning the physical and dosimetric aspects, may be divided into three elements: (1) the preparation of reliable basic data for the computerized treatment planning system; (2) a control of the accelerator parameters prior to patient treatment; (3) preparation of the optimal treatment plan with the treatment planning system. Due to the small size of the beams formed by circular collimators (7.5–35 mm diameter, BrainLab System) the smallest available detectors should be used for measurements – a diamond diode (0.3 mm thickness) and a 0.015 cm3 ionization chamber (PTW Freiburg) are adequate to measure precisely TMR curves, beam profiles and output factors required for the treatment planning system BrainScan. The full control of accelerator parameters (Clinac 2300 C/D) necessary to safely carry out the treatment requires a comprehensive list of tests (an extended list of weekly checks including Winston-Lutz test). Testing procedure carried out with a set of specialized devices (Med-Tec, Radak, BrainLab) takes about two hours. Proper accelerator check and regulations allow for very precise patient positioning. Treatment planning (with the treatment planning system BrainScan) is based on a series of CT and MR scans with target volume and organs at risk marked on each slice by the radiotherapist. The planner has to select the positions of isocentres (up to 3), collimator diameters, number and range of the arcs. Additional parameters for optimization procedure are the total dose proportions delivered by each arc. The treatment plan evaluation is based on the analysis of DVHs for target volume and also for organs at risk (orbits, optical nerves, brain stem) in order to minimize the dose and volume irradiated. It was accepted that the dose uniformity factor, defined as a ratio Dmin/Dmax within the target volume, should be not less than 0.8, and should approach 0.9 as much as possible. The above-presented system of quality control, specifying tolerance limits of controlled parameters, assures safe and precise dose delivery in stereotactic radiotherapy.