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The aim of this work is to study the dosimetric effect from generated synthetic computed tomography (sCT) from magnetic resonance (MR) images using a deep learning algorithm for Gamma Knife (GK) stereotactic radiosurgery (SRS). The Monte Carlo (MC) method is used for dose calculations. Thirty patients were retrospectively selected with our institution IRB's approval. All patients were treated with GK SRS based on T1-weighted MR images and also underwent conventional external beam treatment with a CT scan. Image datasets were preprocessed with registration and were normalized to obtain similar intensity for the pairs of MR and CT images. A deep convolutional neural network arranged in an encoder-decoder fashion was used to learn the direct mapping from MR to the corresponding CT. A number of metrics including the voxel-wise mean error (ME) and mean absolute error (MAE) were used for evaluating the difference between generated sCT and the true CT. To study the dosimetric accuracy, MC simulations were performed based on the true CT and sCT using the same treatment parameters. The method produced an MAE of 86.6 ± 34.1 Hundsfield units (HU) and a mean squared error (MSE) of 160.9 ± 32.8. The mean Dice similarity coefficient was 0.82 ± 0.05 for HU > 200. The difference for dose-volume parameter D95 between the ground true dose and the dose calculated with sCT was 1.1% if a synthetic CT-to-density table was used, and 4.9% compared with the calculations based on the water-brain phantom.

Tumor response to radiation treatment (RT) can be evaluated from changes in metabolic activity between two positron emission tomography (PET) images. Activity changes at individual voxels in pre-treatment PET images (PET1), however, cannot be derived until their associated PET-CT (CT1) images are appropriately registered to during-treatment PET-CT (CT2) images. This study aimed to investigate the feasibility of using deformable image registration (DIR) techniques to quantify radiation-induced metabolic changes on PET images. Five patients with non-small-cell lung cancer (NSCLC) treated with adaptive radiotherapy were considered. PET-CTs were acquired two weeks before RT and 18 fractions after the start of RT. DIR was performed from CT1 to CT2 using B-Spline and diffeomorphic Demons algorithms. The resultant displacements in the tumor region were then corrected using a hybrid finite element method (FEM). Bitmap masks generated from gross tumor volumes (GTVs) in PET1 were deformed using the four different displacement vector fields (DVFs). The conservation of total lesion glycolysis (TLG) in GTVs was used as a criterion to evaluate the quality of these registrations. The deformed masks were united to form a large mask which was then partitioned into multiple layers from center to border. The averages of SUV changes over all the layers were 1.0  ±  1.3, 1.0  ±  1.2, 0.8  ±  1.3, 1.1  ±  1.5 for the B-Spline, B-Spline  +  FEM, Demons and Demons  +  FEM algorithms, respectively. TLG changes before and after mapping using B-Spline, Demons, hybrid-B-Spline, and hybrid-Demons registrations were 20.2%, 28.3%, 8.7%, and 2.2% on average, respectively. Compared to image intensity-based DIR algorithms, the hybrid FEM modeling technique is better in preserving TLG and could be useful for evaluation of tumor response for patients with regressing tumors.

Current commercially available planning systems with Monte Carlo (MC)-based final dose calculation in IMRT planning employ pencil-beam (PB) algorithms in the optimization process. Consequently, dose coverage for SBRT lung plans can feature cold-spots at the interface between lung and tumor tissue. For lung wall (LW)-seated tumors, there can also be hot spots within nearby normal organs (example: ribs). This study evaluated two different practical approaches to limiting cold spots within the target and reducing high doses to surrounding normal organs in MC-based IMRT planning of LW-seated tumors. First, "iterative reoptimization", where the MC calculation (with PB-based optimization) is initially performed. The resultant cold spot is then contoured and used as a simultaneous boost volume. The MC-based dose is then recomputed. The second technique uses noncoplanar beam angles with limited path through lung tissue. Both techniques were evaluated against a conventional coplanar beam approach with a single MC calculation. In all techniques the prescription dose was normalized to cover 95% of the PTV. Fifteen SBRT lung cases with LW-seated tumors were planned. The results from iterative reoptimization showed that conformity index (CI) and/or PTV dose uniformity (UPTV) improved in 12/15 plans. Average improvement was 13%, and 24%, respectively. Nonimproved plans had PTVs near the skin, trachea, and/or very small lung involvement. The maximum dose to 1cc volume (D1cc) of surrounding OARs decreased in 14/15 plans (average 10%). Using noncoplanar beams showed an average improvement of 7% in 10/15 cases and 11% in 5/15 cases for CI and UPTV, respectively. The D1cc was reduced by an average of 6% in 10/15 cases to surrounding OARs. Choice of treatment planning technique did not statistically significantly change lung V5. The results showed that the proposed practical approaches enhance dose conformity in MC-based IMRT planning of lung tumors treated with SBRT, improving target dose coverage and potentially reducing toxicities to surrounding normal organs.

The purpose of this study was to perform comprehensive measurements and testing of a Novalis Tx linear accelerator, and to develop technical guidelines for com-missioning from the time of acceptance testing to the first clinical treatment. The Novalis Tx (NTX) linear accelerator is equipped with, among other features, a high-definition MLC (HD120 MLC) with 2.5 mm central leaves, a 6D robotic couch, an optical guidance positioning system, as well as X-ray-based image guidance tools to provide high accuracy radiation delivery for stereotactic radiosurgery and stereotactic body radiation therapy procedures. We have performed extensive tests for each of the components, and analyzed the clinical data collected in our clinic. We present technical guidelines in this report focusing on methods for: (1) efficient and accurate beam data collection for commissioning treatment planning systems, including small field output measurements conducted using a wide range of detectors; (2) commissioning tests for the HD120 MLC; (3) data collection for the baseline characteristics of the on-board imager (OBI) and ExacTrac X-ray (ETX) image guidance systems in conjunction with the 6D robotic couch; and (4) end-to-end testing of the entire clinical process. Established from our clinical experience thus far, recommendations are provided for accurate and efficient use of the OBI and ETX localization systems for intra- and extracranial treatment sites. Four results are presented. (1) Basic beam data measurements: Our measurements confirmed the necessity of using small detectors for small fields. Total scatter factors varied significantly (30% to approximately 62%) for small field measurements among detectors. Unshielded stereotactic field diode (SFD) overestimated dose by ~ 2% for large field sizes. Ion chambers with active diameters of 6 mm suffered from significant volume averaging. The sharpest profile penumbra was observed for the SFD because of its small active diameter (0.6 mm). (2) MLC commissioning: Winston Lutz test, light/radiation field congruence, and Picket Fence tests were performed and were within criteria established by the relevant task group reports. The measured mean MLC transmission and dynamic leaf gap of 6 MV SRS beam were 1.17% and 0.36 mm, respectively. (3) Baseline characteristics of OBI and ETX: The isocenter localization errors in the left/right, posterior/anterior, and superior/inferior directions were, respectively, -0.2 ± 0.2 mm, -0.8 ± 0.2 mm, and -0.8 ± 0.4 mm for ETX, and 0.5 ± 0.7 mm, 0.6 ± 0.5 mm, and 0.0 ± 0.5 mm for OBI cone-beam computed tomography. The registration angular discrepancy was 0.1 ± 0.2°, and the maximum robotic couch error was 0.2°. (4) End-to-end tests: The measured isocenter dose differences from the planned values were 0.8% and 0.4%, measured respectively by an ion chamber and film. The gamma pass rate, measured by EBT2 film, was 95% (3% DD and 1 mm DTA). Through a systematic series of quantitative commissioning experiments and end-to-end tests and our initial clinical experience, described in this report, we demonstrate that the NTX is a robust system, with the image guidance and MLC requirements to treat a wide variety of sites - in particular for highly accurate delivery of SRS and SBRT-based treatments.

Purpose: Tumor control probability (TCP) models have been proposed to evaluate and guide treatment planning. However, they are usually based on the dose volume histograms (DVHs) of the planning target volume (PTV) and may not properly reflect the substantial variation in tumor burden from the gross tumor volume (GTV) to the microscopic extension (ME) and to the margin of PTV. In this study, the authors propose a TCP model that can account for the effects of setup uncertainties and tumor cell density decay in the ME region., Methods: The proposed TCP model is based on the total surviving clonogenic tumor cells (CTCs) after irradiation of a known dose distribution to a region with a CTC distribution. The CTC density was considered to be homogeneous within the GTV, while decreasing exponentially in the ME region. The effect of random setup uncertainty was modeled by convolving the dose distribution with a Gaussian probability density function, represented by a standard deviation, sigma. The effect of systematic setup uncertainty was modeled by summing each calculated TCP for all potential offsets in a Gaussian probability, represented by sigma. The model was then applied to simplified cases to demonstrate the concept. TCP dose responses were calculated for various GTV volumes, DVH shapes, CTC density decay coefficients, probabilities of lymph node metastasis, and random and systematic errors. The slopes of the dose falloff to cover the CTC density decay in the ME region and the margins to compensate setup errors were also analyzed in generalized cases., Results: The sigmoid TCP dose response curve shifted to the right substantially for a larger GTV, while modestly for cold spots in DVH. A dose distribution with a uniform dose within the GTV, and a linear dose falloff in the ME region, tended to cause a minimal TCP deterioration if a proper dose falloff slope was used. When the dose falloff slope was less steep than a critical slope represented by kT, the D50, which is the prescription dose at TCP=50%, and gamma50, which is the TCP slope at TCP=50%, varied little with different dose falloff slopes. However, both D50 and gamma50 deteriorated fast when the slopes were steeper than kT. The random setup error tended to shift the TCP curve to the right, while the systematic error tended to compress the curve downward. For combined random and systematic errors, we demonstrated that based on the model, a margin of mean square root of (0.75 sigma)2 + (1.15 sigma)2 added to the GTV was found to cause a TCP change corresponding to 2% drop at TCP=90%, or 0.5 Gy shift in D50., Conclusions: This study conceptually demonstrated that a TCP model incorporating the effects of tumor cell density variation and setup uncertainty may be used to guide radiation treatment planning.

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow-up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general-purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient-related clinical factors. In addition the database is web-based and accessible by multiple users, facilitating its convenient application and use.

Purpose: To use probability density function (PDF) to model motion effects and incorporate this information into treatment planning for lung cancers., Material and Methods: PDFs were calculated from the respiratory motion traces of 10 patients. Motion effects were evaluated by convolving static dose distributions with various PDFs. Based on a differential dose prescription with relatively lower dose to the clinical target volume (CTV) than to the gross tumor volume (GTV), two approaches were proposed to incorporate PDFs into treatment planning. The first approach uses the GTV-based internal target volume (ITV) as the planning target volume (PTV) to ensure full dose to the GTV, and utilizes the motion-induced dose gradient to cover the CTV. The second approach employs an inhomogeneous static dose distribution within a minimized PTV to best match the prescription dose gradient., Results: Motion effects on dose distributions were minimal in the anterior-posterior (AP) and lateral directions: a 10-mm motion only induced about 3% of dose reduction in the peripheral target region. The motion effect was remarkable in the cranial-caudal direction. It varied with the motion amplitude, but tended to be similar for various respiratory patterns. For the first approach, a 10-15 mm motion would adequately cover the CTV (presumed to be 60-70% of the GTV dose) without employing the CTV in planning. For motions < 10-mm, an additional PTV with a margin inversely related to the motion was needed to cover the CTV. The second approach was used for motions > 15-mm. An example of inhomogeneous static dose distribution in a reduced PTV was given, and it showed significant dose reduction in the normal tissue without compromising target coverage., Conclusions: Respiratory motion-induced dose gradient can be utilized to cover the CTV and minimize the lung dose without the need for more sophisticated technologies.

Unlabelled: PET with (18)F-FDG has been used in radiation treatment planning for non-small cell lung cancer (NSCLC). Thresholds of 15%-50% the maximum standardized uptake value (SUV(max)) have been used for gross tumor volume (GTV) delineation by PET (PET(GTV)), with 40% being the most commonly used value. Recent studies indicated that 15%-20% may be more appropriate. The purposes of this study were to determine which threshold generates the best volumetric match to GTV delineation by CT (CT(GTV)) for peripheral NSCLC and to determine whether that threshold can be generalized to tumors of various sizes., Methods: Data for patients who had peripheral NSCLC with well-defined borders on CT and SUV(max) of greater than 2.5 were reviewed. PET/CT datasets were reviewed, and a volume of interest was determined to represent the GTV. The CT(GTV) was delineated by using standard lung windows and reviewed by a radiation oncologist. The PET(GTV) was delineated automatically by use of various percentages of the SUV(max). The PET(GTV)-to-CT(GTV) ratios were compared at various thresholds, and a ratio of 1 was considered the best match, or the optimal threshold., Results: Twenty peripheral NSCLCs with volumes easily defined on CT were evaluated. The SUV(max) (mean +/- SD) was 12 +/- 8, and the mean CT(GTV) was 198 cm(3) (97.5% confidence interval, 5-1,008). The SUV(max) were 16 +/- 5, 13 +/- 9, and 3.0 +/- 0.4 for tumors measuring greater than 5 cm, 3-5 cm, and less than 3 cm, respectively. The optimal thresholds (mean +/- SD) for the best match were 15% +/- 6% for tumors measuring greater than 5 cm, 24% +/- 9% for tumors measuring 3-5 cm, 42% +/- 2% for tumors measuring less than 3 cm, and 24% +/- 13% for all tumors. The PET(GTV) at the 40% and 20% thresholds underestimated the CT(GTV) for 16 of 20 and 14 of 20 lesions, respectively. The mean difference in the volumes (PET(GTV) minus CT(GTV) [PET(GTV) - CT(GTV)]) at the 20% threshold was 79 cm(3) (97.5% confidence interval, -922 to 178). The PET(GTV) at the 20% threshold overestimated the CT(GTV) for all 4 tumors measuring less than 3 cm and underestimated the CT(GTV) for all 6 tumors measuring greater than 5 cm. The CT(GTV) was inversely correlated with the PET(GTV) - CT(GTV) at the 20% threshold (R(2) = 0.90, P < 0.0001). The optimal threshold was inversely correlated with the CT(GTV) (R(2) = 0.79, P < 0.0001)., Conclusion: No single threshold delineating the PET(GTV) provides accurate volume definition, compared with that provided by the CT(GTV), for the majority of NSCLCs. The strong correlation of the optimal threshold with the CT(GTV) warrants further investigation.

Background and Purpose: To develop and evaluate a technique and procedure of using gated-CT images in combination with PET image to determine the internal target volume (ITV), which could reduce the planning target volume (PTV) with adequate target coverage., Patients and Methods: A skin marker-based gating system connected to a regular single slice CT scanner was used for this study. A motion phantom with adjustable motion amplitude was used to evaluate the CT gating system. Specifically, objects of various sizes/shapes, considered as virtual tumors, were placed on the phantom to evaluate the number of phases of gated images required to determine the ITV while taking into account tumor size, shape and motion. A procedure of using gated-CT and PET images to define ITV for patients was developed and was tested in patients enrolled in an IRB approved protocol., Results: The CT gating system was capable of removing motion artifacts for target motion as large as 3-cm when it was gated at optimal phases. A phantom study showed that two gated-CT scans at the end of expiration and the end of inspiration would be sufficient to determine the ITV for tumor motion less than 1-cm, and another mid-phase scan would be required for tumors with 2-cm motion, especially for small tumors. For patients, the ITV encompassing visible tumors in all sets of gated-CT and regular spiral CT images seemed to be consistent with the target volume determined from PET images. PTV expanded from the ITV with a setup uncertainty margin had less volume than PTVs from spiral CT images with a 10-mm generalized margin or an individualized margin determined at fluoroscopy., Conclusions: A technique of determining the ITV using gated-CT images was developed and was clinically implemented successfully for fractionated stereotactic lung radiotherapy.

The purpose of the present study was to compare a new internal mammary irradiation technique with traditional techniques for locally advanced breast cancers in terms of sparing ipsilateral lung and heart and reducing the "cold" and "hot spots"in breast tissue. The new technique uses wide tangential fields for the first eight fractions of treatment. A medial internal mammary field (IMF) of electrons matched with narrowed tangential fields is used for the remaining fractions. Intensity-modulated radiation therapy (IMRT) by means of segmented multileaf collimation (SMLC) is used in the narrowed tangential fields to improve the match between the electron and the photon fields. Treatment planning was performed to compare this technique to a wide-tangential-only technique and to a traditional oblique IMF technique for three patients with differing habitus. Film dosimetry was performed in a solid water phantom to confirm the planning results. For all three patients, the mean doses of the ipsilateral lung and the heart were significantly reduced with the new technique. The lung and the heart volumes were remarkably reduced at lowdose levels (< or =12 Gy) compared to the traditional IMF technique, and significantly reduced at all dose levels compared to the wide tangential technique. The new technique also reduced the "cold" and "hot spots" along the match plane between the IMF and the tangential fields compared to the traditional IMF technique. In conclusion, the new IMF technique shows dosimetric improvement compared to the traditional IMF technique in terms of the critical organ sparing and target dose uniformity.

A time delay in a respiratory gating system could cause an unexpected phase mismatch for synchronized gating radiotherapy. This study presents a method of identifying and measuring the time delay in a gating system. Various port films were taken for a motion phantom at different gating window levels with a very narrow window size. The time delay for the gating system was determined by comparing the motion curve (the position of a moving object versus the gating time) measured in the port films to the motion curve determined by the video cameras. The measured time delay for a linac-based gating system was 0.17+/-0.03 s. This time delay could induce target missing if it was not properly taken into account for the synchronized gating radiotherapy. Measurement/verification of the time delay should be considered as an important part of the accepting/commissioning test before the clinical use of the gating system.

This paper systematically studied the dosimetric difference between a 3 mm micro multileaf collimator (MLC), a 5 mm MLC, and a 10 mm MLC for stereotactic radiosurgery using the Brainscan treatment planning system. Thirty-four cases treated with the dynamic conformal arcs technique and 20 cases treated with the intensity modulated radiosurgery/fractionated radiotherapy (IMRS/ IMRT) technique were retrospectively studied. The conformity index, the percentage target coverage, and the dose-volume histogram (DVH) for organs-at-risk (OARs) were used for dosimetric analysis and comparison for different treatment techniques, target volumes, and treatment sites. For the dynamic conformal arcs technique, there were statistically significant differences in the conformity indices between different leaf-width MLCs. The ratio of the conformity indices between different MLCs depended on the target volume. The average conformity index ratios between the 5 mm MLC and the 3 mm MLC were 1.37+/-0.09, 1.12+/-0.04, 1.08+/-0.02 and 1.04+/-0.01, respectively, for patients with the target volume (V) in groups: (1) V< 1 cm3, (2) 1 cm3 < V< 8 cm3, (3) 8 cm3 < V< 27 cm3, and (4) V> 27 CC. The average conformity index ratios between the 10 and 3 mm MLCs were 2.00+/-0.33, 1.45+/-0.09, 1.28+/-0.09, and 1.18+/-0.05 for patients in these four volume groups, respectively. No statistically significant difference was found for the target coverage among different MLCs. For the IMRS/IMRT technique, the average conformity index and target coverage ratios were 1.01+/-0.05 and 1.00+/-0.02, respectively, between the 5 and 3 mm MLCs, and were 1.04+/-0.07 and 0.97+/-0.02, respectively, between the 10 and 3 mm MLCs. The 3 mm MLC showed slightly better overall OAR DVHs than the 5 and 10 mm MLCs, especially for the cranial site with small-volume OARs defined. The results suggest that for the dynamic conformal arcs technique, the narrower leaf-width MLC provides better dose conformity than the wider leaf-width MLCs. This advantage decreases when the target volume increases. For the IMRS/IMRT technique, the narrower leaf-width MLC could have better sparing of small OARs than the wider leaf-width MLC.

The purpose of this study is to develop a simple independent dose calculation method to verify treatment plans for Leksell Gamma Knife radiosurgery. Our approach uses the total integral dose within the skull as an end point for comparison. The total integral dose is computed using a spreadsheet and is compared to that obtained from Leksell GammaPlan. It is calculated as the sum of the integral doses of 201 beams, each passing through a cylindrical volume. The average length of the cylinders is estimated from the Skull-Scaler measurement data taken before treatment. Correction factors are applied to the length of the cylinder depending on the location of a shot in the skull. The radius of the cylinder corresponds to the collimator aperture of the helmet, with a correction factor for the beam penumbra and scattering. We have tested our simple spreadsheet program using treatment plans of 40 patients treated with Gamma Knife in our center. These patients differ in geometry, size, lesion locations, collimator helmet, and treatment complexities. Results show that differences between our calculations and treatment planning results are typically within +/-3%, with a maximum difference of +/-3.8%. We demonstrate that our spreadsheet program is a convenient and effective independent method to verify treatment planning irradiation times prior to implementation of Gamma Knife radiosurgery.

Techniques to treat breast cancer inclusive of the internal mammary lymph node chain (IMC) vary. This study compared a presently accepted technique implemented at the Radiation Oncology Department at Barnes-Jewish Hospital/Washington University School of Medicine (BJ/WU) to a proposed technique for irradiation of breast tissue and the IMC. The present technique consists of parallel-opposed breast tangential beams in combination with photon and electron IMC fields angled along the chest wall. The proposed method involves a wide medial tangent field covering the IMC, with an angled electron IMC field for a portion of the treatment regimen and an opposed lateral breast-only tangent. This technique uses a multileaf collimation (MLC) reduction to treat the IMC aspect following the wide medial tangent, to supplement the IMC to a tumorcidal dose. These techniques were compared by reviewing isodoses with subsequent isodensity confirmation. Computerized tomography imaging sets of patients with various body types (chest wall, small and large breasts) for left-sided tumors were planned using a three-dimensional treatment planning system (FOCUS, Computerized Medical Systems). The plans were evaluated by comparing irradiated heart and lung volumes and the respective dose distribution at the IMC field/medial tangent junction. Specific treatment aids and photon/electron energies were employed to produce desirable isodose distributions, with a dose prescription of 4680-cGy total dose. The efficiency of the radiation treatments itself was also evaluated. The proposed technique decreases treatment time by eliminating an additional IMC field that involves repositioning and placement of a block. Phantom-based film isodensity measurements were evaluated to validate the calculated dosimetry for these techniques.