Moyed Miften

Radiation-Associated Liver Injury

The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

RADIATION DOSE-VOLUME EFFECTS IN THE STOMACH AND SMALL BOWEL

Published data suggest that the risk of moderately severe (>or=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.

Radiation-Associated Kidney Injury

The kidneys are the dose-limiting organs for radiotherapy to upper abdominal cancers and during total body irradiation. The incidence of radiotherapy-associated kidney injury is likely underreported owing to its long latency and because the toxicity is often attributed to more common causes of kidney injury. The pathophysiology of radiation injury is poorly understood. Its presentation can be acute and irreversible or subtle, with a gradual progressive dysfunction over years. A variety of dose and volume parameters have been associated with renal toxicity and are reviewed to provide treatment guidelines. The available predictive models are suboptimal and require validation. Mitigation of radiation nephropathy with angiotensin-converting enzyme inhibitors and other compounds has been shown in animal models and, more recently, in patients.

Quality assurance for image-guided radiation therapy utilizing CT-based technologies: A report of the AAPM TG-179

PURPOSE Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. METHODS The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. RESULTS This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances. CONCLUSION A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

Patient dose and image quality from mega-voltage cone beam computed tomography imaging

The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.

Feasibility of optimizing the dose distribution in lung tumors using fluorine‐18‐fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions

The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits. However, in the other patient, critical structure dosage from the nonuniform dose prescription exceeded dose-volume/function limits, and greatly exceeded that from the uniform dose prescription. Strict compliance to dose-volume/ function limits would entail reducing dose proportionality to the FDG-PET activity distribution, thereby theoretically reducing the duration of local control. Thus, even though it appears feasible to tailor lung tumor dose to the FDG-PET activity distribution, despite SPECT restrictions, strict adherence to dose-volume/function limits could compromise the effectiveness of functional image guided radiotherapy.

A region growing method for tumor volume segmentation on PET images for rectal and anal cancer patients.

The application of automated segmentation methods for tumor delineation on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images presents an opportunity to reduce the interobserver variability in radiotherapy (RT) treatment planning. In this work, three segmentation methods were evaluated and compared for rectal and anal cancer patients: (i) Percentage of the maximum standardized uptake value (SUV% max), (ii) fixed SUV cutoff of 2.5 (SUV2.5), and (iii) mathematical technique based on a confidence connected region growing (CCRG) method. A phantom study was performed to determine the SUV% max threshold value and found to be 43%, SUV43% max. The CCRG method is an iterative scheme that relies on the use of statistics from a specified region in the tumor. The scheme is initialized by a subregion of pixels surrounding the maximum intensity pixel. The mean and standard deviation of this region are measured and the pixels connected to the region are included or not based on the criterion that they are greater than a value derived from the mean and standard deviation. The mean and standard deviation of this new region are then measured and the process repeats. FDG-PET-CT imaging studies for 18 patients who received RT were used to evaluate the segmentation methods. A PET avid (PETavid) region was manually segmented for each patient and the volume was then used to compare the calculated volumes along with the absolute mean difference and range for all methods. For the SUV43% max method, the volumes were always smaller than the PETavid volume by a mean of 56% and a range of 21%-79%. The volumes from the SUV2.5 method were either smaller or larger than the PETavid volume by a mean of 37% and a range of 2%-130%. The CCRG approach provided the best results with a mean difference of 9% and a range of 1%-27%. Results show that the CCRG technique can be used in the segmentation of tumor volumes on FDG-PET images, thus providing treatment planners with a clinically viable starting point for tumor delineation and minimizing the interobserver variability in radiotherapy planning.

Comparison of RTP dose distributions in heterogeneous phantoms with the beam Monte Carlo simulation system

Therapeutic treatment plan evaluation is often based on examining the radiotherapy treatment planning (RTP) system dose distributions in the target and surrounding normal structures. To study the effects of tissue inhomogeneities on photon dose distributions, we compared FOCUS RTP system dose distributions from the measurement‐based Clarkson and model‐based MultiGrid Superposition (MGS) algorithms with those from the beam Monte Carlo code system in a set of heterogeneous phantoms. The phantom inhomogeneities mimic relevant clinical treatment sites, which include lung slab, lung‐bone slab, bone‐lung slab, mediastinum, and tumor geometries. The benchmark comparisons were performed in lung densities of 0.20 and 0.31g/cm3, and a bone density of 2.40g/cm3 for 5×5cm2 and 10×10cm2,6− and 15‐MV photon beams. Benchmark comparison results show that the MGS model and beam doses match better than 3% or 3 mm, and the MGS model is more accurate than the Clarkson model in all phantoms. The MGS model, unlike the Clarkson model, predicts the build‐down and build‐up of dose near tissue interfaces and penumbra broadening in lung associated with high energy beams. The Clarkson model overestimates the dose in lung by a maximum of 10% compared to beam. Dose comparisons suggest turning‐off the effective path length inhomogeneity correction in the Clarkson model for lung treatments. PACS number(s): 87.53.–j, 87.53.Bn

Evaluation of a commercial biologically based IMRT treatment planning system

A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose-volume optimization, plans with equivalent target coverage obtained using the biologically based TPS demonstrate improved dose distributions for the majority of normal structures.

Commissioning of the Varian TrueBeam linear accelerator: a multi-institutional study.

PURPOSE Latest generation linear accelerators (linacs), i.e., TrueBeam (Varian Medical Systems, Palo Alto, CA) and its stereotactic counterpart, TrueBeam STx, have several unique features, including high-dose-rate flattening-filter-free (FFF) photon modes, reengineered electron modes with new scattering foil geometries, updated imaging hardware/software, and a novel control system. An evaluation of five TrueBeam linacs at three different institutions has been performed and this work reports on the commissioning experience. METHODS Acceptance and commissioning data were analyzed for five TrueBeam linacs equipped with 120 leaf (5 mm width) MLCs at three different institutions. Dosimetric data and mechanical parameters were compared. These included measurements of photon beam profiles (6X, 6XFFF, 10X, 10XFFF, 15X), photon and electron percent depth dose (PDD) curves (6, 9, 12 MeV), relative photon output factors (Scp), electron cone factors, mechanical isocenter accuracy, MLC transmission, and dosimetric leaf gap (DLG). End-to-end testing and IMRT commissioning were also conducted. RESULTS Gantry/collimator isocentricity measurements were similar (0.27-0.28 mm), with overall couch/gantry/collimator values of 0.46-0.68 mm across the three institutions. Dosimetric data showed good agreement between machines. The average MLC DLGs for 6, 10, and 15 MV photons were 1.33 ± 0.23, 1.57 ± 0.24, and 1.61 ± 0.26 mm, respectively. 6XFFF and 10XFFF modes had average DLGs of 1.16 ± 0.22 and 1.44 ± 0.30 mm, respectively. MLC transmission showed minimal variation across the three institutions, with the standard deviation <0.2% for all linacs. Photon and electron PDDs were comparable for all energies. 6, 10, and 15 MV photon beam quality, %dd(10)x varied less than 0.3% for all linacs. Output factors (Scp) and electron cone factors agreed within 0.27%, on average; largest variations were observed for small field sizes (1.2% coefficient of variation, 10 MV, 2 × 2 cm(2)) and small cone sizes (<1% coefficient of variation, 6 × 6 cm(2) cone), respectively. CONCLUSIONS Overall, excellent agreement was observed in TrueBeam commissioning data. This set of multi-institutional data can provide comparison data to others embarking on TrueBeam commissioning, ultimately improving the safety and quality of beam commissioning.