L Lu

Longitudinal Changes in Tumor Perfusion Pattern during the Radiation Therapy Course and its Clinical Impact in Cervical Cancer

PURPOSE To study the temporal changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns during the radiation therapy (RT) course and their influence on local control and survival in cervical cancer. METHODS AND MATERIALS DCE-MRI was performed in 98 patients with Stage IB(2)-IVA cervical cancer before RT (pre-RT) and during early RT (20-25 Gy) and mid-RT (45-50 Gy). Signal intensity (SI) from the DCE-MRI time-SI curve was derived for each tumor voxel. The poorly perfused low-DCE tumor subregions were quantified as lower 10th percentiles of SI (SI10). Local control, disease-specific survival, and overall survival were correlated with DCE parameters at pre-RT, early RT, and mid-RT. Median follow-up was 4.9 (range, 0.2-9.0) years. RESULTS Patients (16/98) with initial pre-RT high DCE (SI10 >or=2.1) had 100% 5-year local control, 81% disease-specific survival, and 81% overall survival, compared with only 79%, 61%, and 55%, respectively, in patients with pre-RT low DCE. Conversion from pre-RT low DCE to high DCE in early RT (28/82 patients) was associated with higher local control, disease-specific survival, and overall survival (93%, 74%, and 67%, respectively). In comparison with all other groups, outcome was worst in patients with persistently low DCE from pre-RT throughout the mid-RT phase (66%, 44%, and 43%; p = 0.003, 0.003, and 0.020; respectively). CONCLUSION Longitudinal tumor perfusion changes during RT correlate with treatment outcome. Persistently low perfusion in pre-RT, early RT, and mid-RT indicates a high risk of treatment failure, whereas outcome is favorable in patients with initially high perfusion or subsequent improvements of initially low perfusion. These findings likely reflect reoxygenation and may have potential for noninvasive monitoring of intra-treatment radio-responsiveness and for guiding adaptive therapy.

Predicting outcomes in cervical cancer: a kinetic model of tumor regression during radiation therapy.

Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S(2) < 0.70 vs. S(2) > or = 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T(1/2) < 22 days versus T(1/2) > or = 22 days, P < 0.001). The 6-year disease-specific survival was 73% versus 41% with S(2) < 0.70 versus S(2) > or = 0.70 (P = 0.025), and 87% vs. 52% with T(1/2) < 22 days versus T(1/2) > or = 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy.

Using NanoDot dosimetry to study the RS 2000 X-ray Biological Irradiator

Abstract Purpose: To use NanoDot dosimeters to study the RS 2000 X-ray Biological Irradiator dosimetry characteristics and perform in vivo dosimetry for cell or small animal experiments. Methods and materials: We first calibrated the Landauer NanoDot™ Reader by irradiating some NanoDot dosimeters with a set of known doses at specific positions defined by the irradiator. A group of five NanoDot dosimeters were placed at five specific positions where the dose rates were known and provided by the irradiator. Each group was irradiated for a set of times respectively. By correlating the readings of dosimeters with the given irradiated doses, we established the dose-reading relationship for the irradiator under the specific running condition. The established calibration curve was validated by exposing arbitrary known doses to a set of dosimeters, using the Landauer NanoDot™ Reader to measure the doses, and then making the comparison between the two doses. To study the dose gradient of the X-ray inside the irradiated target (dose variation/cm), we placed dosimeters under different thicknesses of water-equivalent bolus and irradiated them, then measured the doses to determine the dose gradient. Results: Using the method described above, we were able to calibrate the Landauer InLight NanoDot™ Reader and use NanoDot dosimeters to measure the actual doses delivered to the targets for the cell/small animal experiments that use the RS 2000 X-ray Biological Irradiator. Conclusions: NanoDots are ideal dosimeters to use for in vivo dosimetry for cell/small animal irradiation experiments. The dose decrease inside the animal tissue is about 20% per cm.

Outcome Prediction of Cervical Cancer: Kinetic Model of Tumor Regression during Radiation Therapy

Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S(2) < 0.70 vs. S(2) > or = 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T(1/2) < 22 days versus T(1/2) > or = 22 days, P < 0.001). The 6-year disease-specific survival was 73% versus 41% with S(2) < 0.70 versus S(2) > or = 0.70 (P = 0.025), and 87% vs. 52% with T(1/2) < 22 days versus T(1/2) > or = 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy.

SU-G-JeP2-12: Quantification of 3D Geometric Distortion for 1.5T and 3T MRI Scanners Used for Radiation Therapy

PURPOSE To quantify the magnitude of geometric distortion for MRI scanners and provide recommendations for MRI imaging for radiation therapy METHODS: A novel phantom, QUASAR MRID3D [Modus Medical Devices Inc.], was scanned to evaluate the level of 3D geometric distortion present in five MRI scanners used for radiation therapy in our department. The phantom was scanned using the body coil with 1mm image slice thickness to acquire 3D images of the phantom body. The phantom was aligned to its geometric center for each scan, and the field of view was set to visualize the entire phantom. The dependence of distortion magnitude with distance from imaging isocenter and with magnetic field strength (1.5T and 3T) was investigated. Additionally, the characteristics of distortion for Siemens and GE machines were compared. The image distortion for each scanner was quantified in terms of mean, standard deviation (STD), maximum distortion, and skewness. RESULTS The 3T and 1.5T scans show a similar absolute distortion with a mean of 1.38mm (0.33mm STD) for 3T and 1.39mm (0.34mm STD) for 1.5T for a 100mm radius distance from isocenter. Some machines can have a distortion larger than 10mm at a distance of 200mm from the isocenter. The distortions are presented with plots of the x, y, and z directional components. CONCLUSION The results indicate that quantification of MRI image distortion is crucial in radiation oncology for target and organ delineation and treatment planning. The magnitude of geometric distortion determines the margin needed for target contouring which is usually neglected in treatment planning process, especially for SRS/SBRT treatments. Understanding the 3D distribution of the MRI image distortion will improve the accuracy of target delineation and, hence, treatment efficacy. MRI imaging with proper patient alignment to the isocenter is vital to reducing the effects of MRI distortion in treatment planning.

SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy.

Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types.

SU-E-J-274: Image Distortion Quantification and Image Registration QA in GammaKnife Radiosurgery Using A Modus GRID3D Phantom

PURPOSE To quantify image distortion in MRI and CT images used in GammaKnife radiosurgery planning with a Modus GRID3D phantom. METHODS Image distortion in GammaKnife radiosurgery can affect treatment efficacy by inaccurately depicting tumors and organs at risk in the brain. It is therefore important that a quantified QA check on image distortion be performed periodically. A commercial 3-dimensional grid phantom and its associated software, GRID3D (Modus Medical Devices Inc.), was used in determining image distortion on the MRI machines and the CT-simulator that are used clinically for GammaKnife treatment planning. The GammaKnife head frame and frame box were placed on the phantom and imaged on each MRI and CT machine according to GammaKnife imaging protocols used clinically at our institution. The obtained images were imported into the GRID3D Image Distortion Analysis System where the distortion of each image set was calculated. The calculation works by quantifying the 3D spatial deviation between the reconstructed image sets and the programs reference phantom. For registration QA, the CT and MR image sets were registered with each other. The regular analysis of grids alignment allows us to evaluate the quality of image registration from MRI to CT (commonly used in the Gamma Knife preplan scheme) and vice versa. RESULTS Distortion analysis using the GRID3D phantom numerically represented image distortion in the x, y, and z direction for each MRI machine and CT simulator used clinically for GammaKnife treatments. The spatial deviation between images in each direction is generally less than or equal to 1 mm when the imager is functioning properly. Image registration QA using the GRID3D phantom proves to be very efficient. CONCLUSION The quantified image distortion check is important and should be incorporated into routine QA practice. It is especially important to perform this check immediately after a major machine upgrade.

SU-E-T-536: Inhomogeneity Correction in Planning of Gamma Knife Treatments for Acoustic Schwannoma

PURPOSE To find out the dose difference on targets and organs at risk for the treatment of acoustic schwannoma if the inhomogeneity correction (Convolution algorithm) is applied. METHODS Images of patients treated for acoustic schwannoma with Gamma Knife using TMR 10 algorithm were retrieved from database and replanned with Convolution and TMR 10 algorithm respectively. These patients were treated using a preplan scheme in following: (1) Before the actual treatment day, using the MRI image that was taken without a head frame on the patients skull, a pre-treatment plan was made based on the default skull coordinates in the Gamma Knife treatment planning system (LGP); (2) then on treatment day, a head frame was placed on the patients skull, and a CT image was taken. The CT image with head frame was registered and fused with the completed preplan; (3) the treatment plan was finalized and the treatment was delivered. To find out the dosimetry impact of inhomogeneity correction, we used the retrieved CT images to replan the treatment using Convolution algorithm in LGP software version 10.1.1. The dose distributions and the dose volume histograms for targets and OARs were compared for these two dose calculation algorithms. RESULTS The dose calculated with the Convolution algorithm in general is slightly lower than the one from TMR 10 around the boney area. The effect from the inhomogeneity correction is observable but not significant, and varies with the location of the tumor. CONCLUSION Inhomogeneity correction slightly improve the dose accuracy for acoustic schwannoma Gamma Knife treatments although the correction may not be very significant. Our Result provides evidence for dose prescription adjustment to treat acoustic schwannoma. The actual clinical outcome of switching from using TMR10 to using Convolution needs to be further investigated.

SU‐E‐T‐216: A Clinical Dosimetry Analysis of Total Body Irradiation for Leukemia Patients

PURPOSE Perform a retrospective dosimetry study of total body irradiation (TBI) on leukemia and bone marrow transplant patients. METHODS The in vivo dosimetry data of 129 patients treated with TBI between 2008 and 2011 were retrieved from the database and analyzed. These patients were mostly treated with the regime of a single fraction or 6 fractions with some exceptions of 8-fraction or 2-fraction treatments depending on the protocols that were applied. For every fraction of treatment, 10 pairs of diode dosimeters were used to monitor the doses to the mid-line of head, neck, arms, mediastinum, left lung, right lung, umbilicus, thigh, knee, and angle for both AP and PA fields. The doses to the midline of the above body parts were considered to be the average of the AP and PA readings of each diode pair. Dose deviation from the prescribed value for each body part was studied by plotting the histogram of the frequency versus deviation and comparing this with the dose delivered to the midline of the umbilicus to where the dose was prescribed. The correlation of dose deviation to body part thickness was also studied. RESULTS The dose differences between measurement and prescription for all body parts are mostly less than 10%. The dose inhomogeneity on different body parts could be manually improved by using compensators but the method is cumbersome. The dose deviation in many histograms ranging from about -10% to 10% indicates some incongruity of dose distribution. This could be due to the method of using lead compensators for a manual dose adjustment which could not ideally compensate different body thicknesses everywhere. CONCLUSION The conventional TBI could give uniform dose to the major body parts under the in vivo dosimetry monitoring at the level of 10%, but the treatment procedure is cumbersome and time consuming.

SU‐GG‐T‐85: Anisotropy Function Verification of I‐125 Brachytherapy Source with Film Dosimetry

Purpose: For eye plaque implant with fixed source locations and orientations on the plaque, the variation of anisotropy function may significantly affect the brachy dose distribution following the TG43‐U1 algorithm. TLD‐based dosimetry for the brachy source anisotropy functions generally involves significant measurement time. In this study, we explore a convenient film‐based dosimetry verification of the anisotropy function for eye plaque I‐125 source, on a timely manner prior to the brachytherapytreatment planning. Method and Materials: EDR2 films (Kodak) were used to measure the dose distribution of I‐125 seeds (Amersham, model 6711). The center and alignment of the cylindrical I‐125 seed on the film dose plane were determined based on the anisotropic and symmetrical dose distribution fact. Then along the circles with radius R = 1cm, 2cm, 3cm from the seed center, point dose reading were taken to calculate the anisotropy function table and compared to published data (TG43‐U1). Results: For the comparisons between our film measurement data and the published data, the relative differences between the two data were small at radius R = 1cm i.e. mean ± STD as 0.9% ± 1.2%, while increasing with larger R — mean ±STD as 7.3% ± 6.5% at R = 2cm, and 11.3% ± 9.7% at R = 3cm. This increasing deviation trend with larger radius was anticipated considering the fact that more angle range will fall below the film lower dose response threshold at larger radius. Conclusion: The preliminary results showed that film dosimetry can give fairly precise estimation of the seed Anisotropy Function Table, as compared to the published data. For dosemeasurement at different radius from the seed, the film exposure time needs to be adjusted, avoiding the measureddose region exceeding the film dose responsive range.