T.R. McNutt

High-Resolution, Small Animal Radiation Research Platform With X-Ray Tomographic Guidance Capabilities

PURPOSE To demonstrate the computed tomography, conformal irradiation, and treatment planning capabilities of a small animal radiation research platform (SARRP). METHODS AND MATERIALS The SARRP uses a dual-focal spot, constant voltage X-ray source mounted on a gantry with a source-to-isocenter distance of 35 cm. Gantry rotation is limited to 120 degrees from vertical. X-rays of 80-100 kVp from the smaller 0.4-mm focal spot are used for imaging. Both 0.4-mm and 3.0-mm focal spots operate at 225 kVp for irradiation. Robotic translate/rotate stages are used to position the animal. Cone-beam computed tomography is achieved by rotating the horizontal animal between the stationary X-ray source and a flat-panel detector. The radiation beams range from 0.5 mm in diameter to 60 x 60 mm(2). Dosimetry is measured with radiochromic films. Monte Carlo dose calculations are used for treatment planning. The combination of gantry and robotic stage motions facilitate conformal irradiation. RESULTS The SARRP spans 3 ft x 4 ft x 6 ft (width x length x height). Depending on the filtration, the isocenter dose outputs at a 1-cm depth in water were 22-375 cGy/min from the smallest to the largest radiation fields. The 20-80% dose falloff spanned 0.16 mm. Cone-beam computed tomography with 0.6 x 0.6 x 0.6 mm(3) voxel resolution was acquired with a dose of <1 cGy. Treatment planning was performed at submillimeter resolution. CONCLUSION The capability of the SARRP to deliver highly focal beams to multiple animal model systems provides new research opportunities that more realistically bridge laboratory research and clinical translation.

Modeling dose distributions from portal dose images using the convolution/superposition method

Post-treatment dose verification refers to the process of reconstructing delivered dose distributions internal to a patient from information obtained during the treatment. The exit dose is commonly used to describe the dose beyond the exit surface of the patient from a megavoltage photon beam. Portal imaging provides a method of determining the dose in a plane distal to a patient from a megavoltage therapeutic beam. This exit dose enables reconstruction of the dose distribution from external beam radiation throughout the patient utilizing the convolution/superposition method and an extended phantom. An iterative convolution/superposition algorithm has been created to reconstruct dose distributions in patients from exit dose measurements during a radiotherapy treatment. The method is based on an extended phantom that includes the patient CT representation and an electronic portal imaging device (EPID). The convolution/superposition method computes the dose throughout the extended phantom, which allows the portal dose image to be predicted in the EPID. The process is then reversed to take the portal dose measurement and infer what the dose distribution must have been to produce the measured portal dose. The dose distribution is modeled without knowledge of the incident intensity distribution, and includes the effects of scatter in the computation. The iterative method begins by assuming that the primary energy fluence (PEF) at the portal image plane is equal to the portal dose image, the PEF is then back-projected through the extended phantom and convolved with the dose deposition kernel to determine a new prediction of the portal dose image. The image of the ratio of the computed PEF to the computed portal dose is then multiplied by the measured portal dose image to produce a better representation of the PEF. Successive iterations of this process then converge to the exiting PEF image that would produce the measured portal dose image. Once convergence is established, the dose distribution is determined by back-projecting the PEF and convolving with the dose deposition kernel. The method is accurate, provided the patient representation during treatment is known. The method was used on three phantoms with a photon energy of 6 MV to verify convergence and accuracy of the algorithm. The reconstructed dose volumes agree to within 3% of the forward computation dose volumes. Furthermore, this technique assumes no prior knowledge of the incident fluence and therefore may better represent the dose actually delivered.

Calculation of portal dose using the convolution/superposition method.

The convolution/superposition method was used to predict the dose throughout an extended volume, which includes a phantom and a portal imaging device. From the calculated dose volume, the dose delivered in the portal image plane was extracted and compared to a portal dose image. This comparison aids in verifying the beam configuration or patient setup after delivery of the radiation. The phantoms used to test the accuracy of this method include a solid water cube, a Nuclear Associates CT phantom, and an Alderson Rando thorax phantom. The dose distribution in the image plane was measured with film and an electronic portal imaging device in each case. The calculated portal dose images were within 4% of the measured images for most voxels in the central portion of the field for all of the extended volumes. The convolution/superposition method also enables the determination of the scatter and primary dose contributions using the particular dose deposition kernels for each contribution. The ratio of primary dose to total dose was used to extract the primary dose from the detected portal image, which enhances the megavoltage portal images by removing scatter blurring. By also predicting the primary energy fluence, we can find the ratio of computed primary energy fluence to total dose. Multiplying this ratio by the measured dose image estimates the relative primary energy fluence at the portal imager. The image of primary energy fluence possesses higher contrast and may be used for further quantitative image processing and dose modeling.

Effects of Prostate-Rectum Separation on Rectal Dose From External Beam Radiotherapy

PURPOSE In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate (e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice. METHODS AND MATERIALS Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans. RESULTS In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% (p < .05). In the simulation studies, a prostate-rectum separation of 10 mm was sufficient to reduce the mean rectal volume receiving 70 Gy by 83.1% (p <.05). No additional reduction in the average rectal volume receiving 70 Gy was noted after 15 mm of separation. In addition, spacer placement allowed for increased planning target volume margins without exceeding the rectal dose tolerance. CONCLUSION Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.

Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study

BACKGROUND Neurocognitive toxicity from radiation therapy (RT) for brain tumors may be related to damage to neural progenitor cells that reside in the subventricular zone and hippocampus. This prospective study examines the relationship between RT dose to neural progenitor cell niches, temporal lobes, and cerebrum and neurocognitive dysfunction following cranial irradiation. METHODS Standardized assessments of motor speed/dexterity, verbal memory, visual perception, vocabulary, and visuospatial working memory were conducted in 19 pediatric patients receiving cranial RT and 55 controls at baseline and 6, 15, and 27 months following completion of RT. Prescription doses ranged from 12 Gy to 59.4 Gy. Linear mixed effects regression model analyses were used to examine the relationships among neuropsychological performance, age, and radiation dose to the subventricular zone, hippocampus, temporal lobes, and cerebrum. RESULTS Performance on all neuropsychological tests, except vocabulary, was significantly reduced in patients relative to controls, particularly among younger children. Performance on motor speed/dexterity decreased with increasing dose to hippocampus (P < .05) and temporal lobes (P < .035). There was also a significant relationship between (i) reduced performance on verbal learning and increasing dose to the cerebrum (P = .022) and (ii) reduced performance on visual perception and increasing dose to the left temporal lobe (P = .038). There was no association between radiation dose to evaluated structures and performance on vocabulary or visuospatial working memory. CONCLUSIONS These prospective data demonstrate a significant association between increasing RT dose to hippocampus and temporal lobes and decline in neurocognitive skills following cranial irradiation. These findings have important implications for trials, including RTOG 0933 (hippocampal-sparing whole brain radiation therapy for brain metastases).

Use of Respiratory-Correlated Four-Dimensional Computed Tomography to Determine Acceptable Treatment Margins for Locally Advanced Pancreatic Adenocarcinoma

PURPOSE Respiratory-induced excursions of locally advanced pancreatic adenocarcinoma could affect dose delivery. This study quantified tumor motion and evaluated standard treatment margins. METHODS AND MATERIALS Respiratory-correlated four-dimensional computed tomography images were obtained on 30 patients with locally advanced pancreatic adenocarcinoma; 15 of whom underwent repeat scanning before cone-down treatment. Treatment planning software was used to contour the gross tumor volume (GTV), bilateral kidneys, and biliary stent. Excursions were calculated according to the centroid of the contoured volumes. RESULTS The mean +/- standard deviation GTV excursion in the superoinferior (SI) direction was 0.55 +/- 0.23 cm; an expansion of 1.0 cm adequately accounted for the GTV motion in 97% of locally advanced pancreatic adenocarcinoma patients. Motion GTVs were generated and resulted in a 25% average volume increase compared with the static GTV. Of the 30 patients, 17 had biliary stents. The mean SI stent excursion was 0.84 +/- 0.32 cm, significantly greater than the GTV motion. The xiphoid process moved an average of 0.35 +/- 0.12 cm, significantly less than the GTV. The mean SI motion of the left and right kidneys was 0.65 +/- 0.27 cm and 0.77 +/- 0.30 cm, respectively. At repeat scanning, no significant changes were seen in the mean GTV size (p = .8) or excursion (p = .3). CONCLUSION These data suggest that an asymmetric expansion of 1.0, 0.7, and 0.6 cm along the respective SI, anteroposterior, and medial-lateral directions is recommended if a respiratory-correlated four-dimensional computed tomography scan is not available to evaluate the tumor motion during treatment planning. Surrogates of tumor motion, such as biliary stents or external markers, should be used with caution.

Increased Subventricular Zone Radiation Dose Correlates With Survival in Glioblastoma Patients After Gross Total Resection

PURPOSE Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients. METHODS AND MATERIALS The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years). RESULTS Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS and OS among patients who underwent STR or biopsy. CONCLUSION A mean radiation dose of 40 Gy or greater to the ipsilateral SVZ was associated with a significantly improved PFS and OS in patients with GBM after GTR.

Towards real-time radiation therapy: GPU accelerated superposition/convolution

We demonstrate the use of highly parallel graphics processing units (GPUs) to accelerate the superposition/convolution (S/C) algorithm to interactive rates while reducing the number of approximations. S/C first transports the incident fluence to compute the total energy released per unit mass (TERMA) grid. Dose is then calculated by superimposing the dose deposition kernel at each point in the TERMA grid and summing the contributions to the surrounding voxels. The TERMA algorithm was enhanced with physically correct multi-spectral attenuation and a novel inverse formulation for increased performance, accuracy and simplicity. Dose deposition utilized a tilted poly-energetic inverse cumulative-cumulative kernel, with the novel option of using volumetric mip-maps to approximate solid angle ray casting. Exact radiological path ray casting decreased discretization errors. We achieved a speedup of 34x-98x over a highly optimized CPU implementation.

SmartArc-Based Volumetric Modulated Arc Therapy for Oropharyngeal Cancer: A Dosimetric Comparison With Both Intensity-Modulated Radiation Therapy and Helical Tomotherapy

PURPOSE To investigate the roles of volumetric modulated arc therapy with SmartArc (VMAT-S), intensity-modulated radiation therapy (IMRT), and helical tomotherapy (HT) for oropharyngeal cancer using a simultaneous integrated boost (SIB) approach. METHODS AND MATERIALS Eight patients treated with IMRT were selected at random. Plans were computed for both IMRT and VMAT-S (using Pinnacle TPS for an Elekta Infinity linac) along with HT. A three-dose level prescription was used to deliver 70 Gy, 63 Gy, and 58.1 Gy to regions of macroscopic, microscopic high-risk, and microscopic low-risk disease, respectively. All doses were given in 35 fractions. Comparisons were performed on dose-volume histogram data, monitor units per fraction (MU/fx), and delivery time. RESULTS VMAT-S target coverage was close to that achieved by IMRT, but inferior to HT. The conformity and homogeneity within the PTV were improved for HT over all strategies. Sparing of the organs at risk (OAR) was achieved with all modalities. VMAT-S (along with HT) shortened delivery time (mean, -38%) and reduced MU/fx (mean, -28%) compared with IMRT. CONCLUSION VMAT-S represents an attractive solution because of the shorter delivery time and the lower number of MU/fx compared with IMRT. However, in this complex clinical setting, current VMAT-S does not appear to provide any distinct advantage compared with helical tomotherapy.

Use of image registration and fusion algorithms and techniques in radiotherapy: Report of the AAPM Radiation Therapy Committee Task Group No. 132

Image registration and fusion algorithms exist in almost every software system that creates or uses images in radiotherapy. Most treatment planning systems support some form of image registration and fusion to allow the use of multimodality and time‐series image data and even anatomical atlases to assist in target volume and normal tissue delineation. Treatment delivery systems perform registration and fusion between the planning images and the in‐room images acquired during the treatment to assist patient positioning. Advanced applications are beginning to support daily dose assessment and enable adaptive radiotherapy using image registration and fusion to propagate contours and accumulate dose between image data taken over the course of therapy to provide up‐to‐date estimates of anatomical changes and delivered dose. This information aids in the detection of anatomical and functional changes that might elicit changes in the treatment plan or prescription. As the output of the image registration process is always used as the input of another process for planning or delivery, it is important to understand and communicate the uncertainty associated with the software in general and the result of a specific registration. Unfortunately, there is no standard mathematical formalism to perform this for real‐world situations where noise, distortion, and complex anatomical variations can occur. Validation of the software systems performance is also complicated by the lack of documentation available from commercial systems leading to use of these systems in undesirable ‘black‐box’ fashion. In view of this situation and the central role that image registration and fusion play in treatment planning and delivery, the Therapy Physics Committee of the American Association of Physicists in Medicine commissioned Task Group 132 to review current approaches and solutions for image registration (both rigid and deformable) in radiotherapy and to provide recommendations for quality assurance and quality control of these clinical processes.