Purpose
Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of the concurrent use of bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas.
Methods and Materials
After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg IV) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in 5 fractions after the first cycle of bevacizumab.
Results
Twenty-five patients (20 GBM and 5 AG) median age of 56 years (range, 30 to 80) and median KPS 90 (range, 70 to 100) received a median of 7 cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment due to: grade 3 CNS intratumoral hemorrhage, wound dehiscence and bowel perforation. Other non-hematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously-irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression free survival was 65%; median overall survival was 12.5 months and 1-year survival was 54%.
Discussion
Bevacizumab in combination with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control and survival suggest that this regimen is active in recurrent malignant glioma.
We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.
We describe in this paper an alternative method for routine dynamic multi-leaf collimator (DMLC) quality assurance (QA) using an electronic portal imaging device (EPID). Currently, this QA is done at our institution by filming an intensity-modulated radiotherapy (IMRT) test field producing a pattern of five 1-mm bands 2 cm apart and performing a visual spot-check for leaf alignment, motion lags, sticking and any other mechanical problems. In this study, we used an amorphous silicon aS500 EPID and films contemporaneously for the DMLC QA to test the practicality and efficacy of EPID vis-à-vis film. The EPID image was transformed to an integrated dose map by first converting the reading to dose using a calibration curve, and then multiplying by the number of averaged frames. The EPID dose map was then back-projected to the central axis plane and was compared to the film measurements which were scanned and converted to dose using a film dosimetry system. We determined the full-width half-maximum (FWHM) of each band for both images, and evaluated the dose to the valley between two peaks. We also simulated mechanical problems by increasing the band gap to 1.5 mm for some leaf pairs. Our results show that EPID is as good as the film in resolving the band pattern of the IMRT test field. Although the resolution of the EPID is lower than that of the film (0.78 mm/pixel vs 0.36 mm/pixel for the film), it is high enough to faithfully reproduce the band pattern without significant distortion. The FWHM of the EPID is 2.84 mm, slightly higher than the 2.01 mm for the film. The lowest dose to the valley is significantly lower for the EPID (15.5% of the peak value) than for the film (28.6%), indicating that EPID is less energy independent. The simulated leaf problem can be spotted by visual inspection of both images; however, it is more difficult for the film without being scanned and contrast-enhanced. EPID images have the advantage of being already digital and their analysis can easily be automated to flag leaf pairs outside tolerance limits of set parameters such as FWHM, peak dose values, peak location, and distance between peaks. This automation is a new feature that will help preempt MLC motion interlocks and decrease machine downtime during actual IMRT treatment. We conclude that since EPID images can be acquired, analyzed and stored much more conveniently than film, EPID is a good alternative to film for routine DMLC QA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.