NCTN Assessment on Current Applications of Radiomics in Oncology.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

BACKGROUND: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). METHODS: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DISCUSSION: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

PET-based Treatment Response Assessment for Neoadjuvant Chemoradiation in Pancreatic Adenocarcinoma: An Exploratory Study.

PURPOSE: Performance of anatomical metrics of Response Evaluation Criteria in Solid Tumors (RECIST1.1) versus Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST1.0) for neoadjuvant chemoradiation (nCR) of pancreatic adenocarcinoma was evaluated based on the pathological treatment response (PTR) data. METHODS AND MATERIALS: The pre- and post-nCR CT and PET data for 14 patients with resectable or borderline resectable pancreatic head adenocarcinoma treated with nCR followed by surgery were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade 0, 1, 2 or 3 (G0, G1, G2 or G3) for complete, moderate, minimal and poor responses, respectively. Maximum standardized uptake value (SUVmax) was defined using body-weight (SUVbw). PERCIST1.0 was defined using lean-body mass normalized SUV (SUVlb or SUL). RECIST1.1 was defined by contouring the whole pancreas head on the CT image. Pre- and post-SUL-peak and SUVmax, RECIST1.1 and PETRECIST1.0 were correlated with PTR using Pearson's correlation coefficient test. RESULTS: The average mean and SD in SUL-peak for all patients analyzed were lower in post-nCR (3.63±1.06) compared to those at pre-nCR (4.29±0.89). Using PERCIST1.0, 62% of patients showed stable metabolic disease (SMD), 23% partial metabolic response (PMR), and 15% progressive metabolic disease (PMD). Using RECIST1.1, 85% of patients showed stable disease (SD), 8% partial response (PR), and 7% progressive diseases (PD). A poor insignificant correlation was established between PRT and PERECIST1.0 (r=0.121), whereas no correlation was seen with RECIST1.1. CONCLUSIONS: PERCIST1.0 appears to increase the chance of detecting patients with progressive disease compared to the conventional anatomical-based assessment of RECIST1.1. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select patients that are most suitable for therapeutic intensification.

Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization.

This article reviews key imaging modalities for lung cancer patients treated with radiation therapy (RT) and considers their actual or potential contributions to critical decision-making. An international group of researchers with expertise in imaging in lung cancer patients treated with RT considered the relevant literature on modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These perspectives were coordinated to summarize the current status of imaging in lung cancer and flag developments with future implications. Although there are no useful randomized trials of different imaging modalities in lung cancer, multiple prospective studies indicate that management decisions are frequently impacted by the use of complementary imaging modalities, leading both to more appropriate treatments and better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT which is widely accepted to be the standard imaging modality for staging of lung cancer patients, for selection for potentially curative RT and for treatment planning. PET is also more accurate than CT for predicting survival after RT. PET imaging during RT is also correlated with survival and makes response-adapted therapies possible. PET tracers other than FDG have potential for imaging important biological process in tumors, including hypoxia and proliferation. MRI has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly developing technology with great potential for online monitoring and modification of treatment. The role of imaging in RT-treated lung cancer patients is evolving rapidly and will allow increasing personalization of therapy according to the biology of both the tumor and dose limiting normal tissues.

Assessment of treatment response during chemoradiation therapy for pancreatic cancer based on quantitative radiomic analysis of daily CTs: An exploratory study.

PURPOSE: In an effort for early assessment of treatment response, we investigate radiation induced changes in quantitative CT features of tumor during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. METHODS: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. On each daily CT, the pancreatic head, the spinal cord and the aorta were delineated and the histograms of CT number (CTN) in these contours were extracted. Eight histogram-based radiomic metrics including the mean CTN (MCTN), peak position, volume, standard deviation (SD), skewness, kurtosis, energy and entropy were calculated for each fraction. Paired t-test was used to check the significance of the change of specific metric at specific time. GEE model was used to test the association between changes of metrics over time for different pathology responses. RESULTS: In general, CTN histogram in the pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the 1st to the 26th fraction in MCTN ranged from -15.8 to 3.9 HU with an average of -4.7 HU (p<0.001). Meanwhile the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less peaked). The changes of MCTN, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response is associated with the changes of MCTN, SD, and skewness. In cases of good response, patients tend to have large reductions in MCTN and skewness, and large increases in SD and kurtosis. CONCLUSIONS: Significant changes in CT radiomic features, such as the MCTN, skewness, and kurtosis in tumor were observed during the course of CRT for pancreas cancer based on quantitative analysis of daily CTs. These changes may be potentially used for early assessment of treatment response and stratification for therapeutic intensification.

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

PURPOSE: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. METHODS AND MATERIALS: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. RESULTS: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R2 > 0.99) and correlates weakly with the change in GTV (R2 = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. CONCLUSION: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.

Clinical experience with planning, quality assurance, and delivery of burst-mode modulated arc therapy.

"Burst-mode" modulated arc therapy (hereafter referred to as "mARC") is a form of volumetric-modulated arc therapy characterized by variable gantry rotation speed, static MLCs while the radiation beam is on, and MLC repositioning while the beam is off. We present our clinical experience with the planning techniques and plan quality assurance measurements of mARC delivery. Clinical mARC plans for five representative cases (prostate, low-dose-rate brain, brain with partial-arc vertex fields, pancreas, and liver SBRT) were generated using a Monte Carlo-based treatment planning system. A conventional-dose-rate flat 6 MV and a high-dose-rate non-flat 7 MV beam are available for planning and delivery. mARC plans for intact-prostate cases can typically be created using one 360° arc, and treatment times per fraction seldom exceed 6 min using the flat beam; using the nonflat beam results in slightly higher MU per fraction, but also in delivery times less than 4 min and with reduced mean dose to distal organs at risk. mARC also has utility in low-dose-rate brain irradiation; mARC fields can be designed which deliver a uniform 20 cGy dose to the PTV in approximately 3-minute intervals, making it a viable alternative to conventional 3D CRT. For brain cases using noncoplanar arcs, delivery time is approximately six min using the nonflat beam. For pancreas cases using the nonflat beam, two overlapping 360° arcs are required, and delivery times are approximately 10 min. For liver SBRT, the time to deliver 800 cGy per frac-tion is at least 12 min. Plan QA measurements indicate that the mARC delivery is consistent with the plan calculation for all cases. mARC has been incorporated into routine practice within our clinic; currently, on average approximately 15 patients per day are treated using mARC; and with the exception of LDR brain cases, all are treated using the nonflat beam.

Assessment and management of interfractional variations in daily diagnostic-quality-CT guided prostate-bed irradiation after prostatectomy.

PURPOSE: To quantify interfractional anatomic variations and limitations of the current practice of image-guided radiation therapy (IGRT) for prostate-bed patients and to study dosimetric benefits of an online adaptive replanning scheme that addresses the interfractional variations. METHODS: Contours for the targets and organs at risk (OARs) from daily diagnostic-quality CTs acquired with in-room CT (CTVision, Siemens) were generated by populating the planning contours using an autosegmentation tool based on deformable registration (ABAS, Elekta) with manual editing for ten prostate-bed patients treated with postoperative daily CT-guided IMRT. Dice similarity coefficient (DSC) obtained by maximizing the overlap of contours for a structure between the daily and plan contours was used to quantify the organ deformation between the plan and daily CTs. Three interfractional-variation-correction schemes, the current standard practice of IGRT repositioning, a previously developed online adaptive RT (ART), and the full reoptimization, were applied to these daily CTs and a number of dose-volume quantities for the targets and organs at risk were compared for their effectiveness to account for the interfractional variations. RESULTS: Large interfractional organ deformations in prostate-bed irradiation were seen. The mean DSCs for CTV, rectum, and bladder were 86.6 ± 5.1% (range from 61% to 97%), 77.3% ± 7.4% (range from 55% to 90%), and 75.4% ± 11.2% (range from 46% to 96%), respectively. The fractional and cumulative dose-volume quantities for CTV and PTV: V100 (volume received at least 100% prescription dose), and rectum and bladder: V45Gy and V60Gy (volume received at least 45 or 60 Gy), were compared for the repositioning, adaptive, reoptimization, and original plans. The fractional and cumulative dosimetric results were nearly the same. The average cumulative CTV V100 were 88.0%, 98.4%, 99.2%, and 99.3% for the IGRT, ART, reoptimization, and original plans, respectively. The corresponding rectal V45Gy (V60Gy) were 58.7% (27.3%), 48.1% (20.7%), 43.8% (16.1%), and 44.9% (16.8%). The results for bladder were comparable among three schemes. Paired two-tailed Wilcoxon signed-rank tests were performed and it was found that ART and reoptimization provide better target coverage and better OAR sparing, especially rectum sparing. CONCLUSIONS: The interfractional organ motions and deformations during prostate-bed irradiation are significant. The online adaptive replanning scheme is capable of effectively addressing the large organ deformation, resulting in cumulative doses equivalent to those originally planned.

Assessment of interfraction patient setup for head-and-neck cancer intensity modulated radiation therapy using multiple computed tomography-based image guidance.

PURPOSE: Various image guidance systems are commonly used in conjunction with intensity modulated radiation therapy (IMRT) in head-and-neck cancer irradiation. The purpose of this study was to assess interfraction patient setup variations for 3 computed tomography (CT)-based on-board image guided radiation therapy (IGRT) modalities. METHODS AND MATERIALS: A total of 3302 CT scans for 117 patients, including 53 patients receiving megavoltage cone-beam CT (MVCBCT), 29 receiving kilovoltage cone-beam CT (KVCBCT), and 35 receiving megavoltage fan-beam CT (MVFBCT), were retrospectively analyzed. The daily variations in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) dimensions were measured. The clinical target volume-to-planned target volume (CTV-to-PTV) margins were calculated using 2.5Σ + 0.7 σ, where Σ and σ were systematic and random positioning errors, respectively. Various patient characteristics for the MVCBCT group, including weight, weight loss, tumor location, and initial body mass index, were analyzed to determine their possible correlation with daily patient setup. RESULTS: The average interfraction displacements (± standard deviation) in the ML, CC, and AP directions were 0.5 ± 1.5, -0.3 ± 2.0, and 0.3 ± 1.7 mm (KVCBCT); 0.2 ± 1.9, -0.2 ± 2.4, and 0.0 ± 1.7 mm (MVFBCT); and 0.0 ± 1.8, 0.5 ± 1.7, and 0.8 ± 3.0 mm (MVCBCT). The day-to-day random errors for KVCBCT, MVFBCT, and MVCBCT were 1.4-1.6, 1.7, and 2.0-2.1 mm. The interobserver variations were 0.8, 1.1, and 0.7 mm (MVCBCT); 0.5, 0.4, and 0.8 mm (MVFBCT); and 0.5, 0.4, and 0.6 mm (KVCBCT) in the ML, CC, and AP directions, respectively. The maximal calculated uniform CTV-to-PTV margins were 5.6, 6.9, and 8.9 mm for KVCBCT, MVFBCT, and MVCBCT, respectively. For the evaluated patient characteristics, the calculated margins for different patient parameters appeared to differ; analysis of variance (ANOVA) and/or t test analysis found no statistically significant setup difference in any direction. CONCLUSIONS: Daily random setup errors and CTV-to-PTV margins for treatment of head-and-neck cancer were affected by imaging quality. Our data indicated that larger margins were associated with MVFBCT and MVCBCT, compared with smaller margins for KVCBCT. IGRT modalities with better image quality are encouraged in clinical practice.

Internal margin assessment using cine MRI analysis of deglutition in head and neck cancer radiotherapy.

PURPOSE: Intensity-modulated radiation therapy (IMRT) is a promising treatment modality for patients with head and neck cancer (HNC). The dose distributions from IMRT are static and, thus, are unable to account for variations and/or uncertainties in the relationship between the patient (region being treated) and the beam. Organ motion comprises one such source of this uncertainty, introduced by physiological variation in the position, size, and shape of organs during treatment. In the head and neck, the predominant source of this variation arises from deglutition (swallowing). The purpose of this study was to investigate whether cinematographic MRI (cine MRI) could be used to determine asymmetric (nonuniform) internal margin (IM) components of tumor planning target volumes based on the actual deglutition-induced tumor displacement. METHODS: Five head and neck cancer patients were set up in treatment position on a 3 T MRI scanner. Two time series of single-slice, sagittal, cine images were acquired using a 2D FLASH sequence. The first time series was a 12.8 min scan designed to capture the frequency and duration of deglutition in the treatment position. The second time series was a short, 15 s scan designed to capture the displacement of deglutition in the treatment position. Deglutition frequency and mean swallow duration were estimated from the long time series acquisition. Swallowing and resting (nonswallowing) events were identified on the short time series acquisition and displacement was estimated based on contours of gross tumor volume (GTV) generated at each time point of a particular event. A simple linear relationship was derived to estimate 1D asymmetric IMs in the presence of resting- and deglutition-induced displacement. RESULTS: Deglutition was nonperiodic, with frequency and duration ranging from 2.89-24.18 mHz and from 3.86 to 6.10 s, respectively. The deglutition frequency and mean duration were found to vary among patients. Deglutition-induced maximal GTV displacements ranged from 0.00 to 28.36 mm with mean and standard deviation of 4.72 +/- 3.18, 3.70 +/- 2.81, 2.75 +/- 5.24, and 10.40 +/- 10.76 mm in the A, P, I, and S directions, respectively. Resting-induced maximal GTV displacement ranged from 0.00 to 5.59 mm with mean and standard deviation of 3.01 +/- 1.80, 1.25 +/- 1.10, 3.23 +/- 2.20, and 2.47 +/- 1.11 mm in the A, P, I, and S directions, respectively. For both resting and swallowing states, displacement along the S-I direction dominated displacement along the A-P direction. The calculated IMs were dependent on deglutition frequency, ranging from 3.28-4.37 mm for the lowest deglutition frequency patient to 3.76-6.43 mm for the highest deglutition frequency patient. A statistically significant difference was detected between IMs calculated for P and S directions (p = 0.0018). CONCLUSIONS: Cine MRI is able to capture tumor motion during deglutition. Swallowing events can be demarcated by MR signal intensity changes caused by anatomy containing fully relaxed spins that move medially into the imaging plane during deglutition. Deglutition is nonperiodic and results in dynamic changes in the tumor position. Deglutition-induced displacements are larger and more variable than resting displacements. The nonzero mean maximum resting displacement indicates that some tumor motion occurs even when the patient is not swallowing. Asymmetric IMs, derived from deglutition frequency, duration, and directional displacement, should be employed to account for tumor motion in HNC RT.

Dynamic MRI analysis of tumor and organ motion during rest and deglutition and margin assessment for radiotherapy of head-and-neck cancer.

PURPOSE: To quantify swallowing frequency and tumor and normal structure displacements during deglutition using dynamic magnetic resonance imaging (MRI) and to determine planning target volume (PTV) margins to account for resting and deglutition-induced displacements in patients with head-and-neck cancer (HNC). METHODS AND MATERIALS: Twenty-two patients with HNC were imaged in the treatment position using dynamic MRI. Sagittal images were acquired. Two-dimensional displacement was analyzed using contours of normal structures and GTV drawn for one swallowing event. Deglutition-induced displacements were quantified based on position change during deglutition relative to preswallow structure location for anterior (A), posterior (P), superior (S), and inferior (I) directions. Additional long-time MRI series were obtained from a subset of 11 patients while they were resting in order to determine swallowing frequency and duration. PTV margins to account for setup error, frequency and duration of deglutition, and resting and deglutition-induced GTV motion were calculated. RESULTS: Mean maximum resting displacements ranged from 1.5 to 3.1 mm for combined GTV subsites. Mean maximum swallowing GTV displacement for combined subsites ranged from 4.0 to 11.6 mm. Swallowing was nonperiodic, with a frequency ranging from 0 to 19 swallows over 12.8 min and mean swallow duration of 3.5 s. Based on the average swallowing characteristics in this cohort, the average PTV margins to account for setup error and tumor motion are estimated to be 4.7 mm anteriorly, 4.2 mm posteriorly, 4.7 mm inferiorly, and 6.0 mm superiorly. CONCLUSIONS: The measurable mean maximum resting displacement for the GTV indicates that tumor motion occurs even when the patient is not swallowing. Nonuniform margins should be used as a standard PTV margin that accounts for setup error and tumor motion in radiotherapy of HNC unless adaptive radiotherapy with respect to intrafraction tumor motion is performed. The PTV margin can be individualized to a single patient's swallowing characteristics or calculated as an average based on the swallowing data from the cohort.

Report of AAPM Therapy Physics Committee Task Group 74: in-air output ratio, Sc, for megavoltage photon beams.

The concept of in-air output ratio (Sc) was introduced to characterize how the incident photon fluence per monitor unit (or unit time for a Co-60 unit) varies with collimator settings. However, there has been much confusion regarding the measurement technique to be used that has prevented the accurate and consistent determination of Sc. The main thrust of the report is to devise a theoretical and measurement formalism that ensures interinstitutional consistency of Sc. The in-air output ratio, Sc, is defined as the ratio of primary collision water kerma in free-space, Kp, per monitor unit between an arbitrary collimator setting and the reference collimator setting at the same location. Miniphantoms with sufficient lateral and longitudinal thicknesses to eliminate electron contamination and maintain transient electron equilibrium are recommended for the measurement of Sc. The authors present a correction formalism to extrapolate the correct Sc from the measured values using high-Z miniphantom. Miniphantoms made of high-Z material are used to measure Sc for small fields (e.g., IMRT or stereotactic radiosurgery). This report presents a review of the components of Sc, including headscatter, source-obscuring, and monitor-backscattering effects. A review of calculation methods (Monte Carlo and empirical) used to calculate Sc for arbitrary shaped fields is presented. The authors discussed the use of Sc in photon dose calculation algorithms, in particular, monitor unit calculation. Finally, a summary of Sc data (from RPC and other institutions) is included for QA purposes.

A Monte-Carlo derived dual-source model for helical tomotherapy treatment planning.

Full Monte Carlo radiation transport simulations of accelerator heads are impractical for routine treatment planning because of the excessive computational burden and memory requirements. To improve the accuracy and efficiency of treatment plans for helical tomotherapy, we have developed a dual-source model to characterize the radiation emitted from the head of a commercial helical tomotherapy accelerator. Percentage depth dose (PDD) and beam profiles computed using the dual-source model with the EGS/BEAMnrc Monte Carlo package agree within 2% of measurements for a wide range of field sizes, which suggests that the proposed dual-source model provides an adequate representation of the tomotherapy head for dose calculations in routine treatment planning.

Improving patient-specific dosimetry for intravascular brachytherapy.

PURPOSE: Accurate patient-specific dosimetry in intravascular brachytherapy (IVBT) is generally difficult due to the extremely high-dose gradient, complexity of treatment device, and patient-specific geometry (e.g., calcification, stent, curvature, movement of target). The purpose of this study is to analyze quantitatively and systematically the dose effects of calcification, stent, guidewire, and source curvature on clinical dosimetry in an IVBT procedure, and propose a method that can be used to assess these effects in routine clinical practice. METHODS AND MATERIALS: Monte Carlo techniques were used to calculate 3-D dose distribution in both homogeneous and inhomogeneous media for three most commonly used IVBT sources: (90)Sr beta (Novoste), (192)Ir gamma (Cordis/Best), and (32)P beta (Guidant). Dosimetric perturbations in the presence of metallic stents, calcified plaques, metallic guide wires, and source curvature were studied for situations commonly encountered in the clinic. The importance of each of these perturbations and their practical influence on patient-specific dosimetry were analyzed. Factors (plaque, stent, guidewire, and curvature) that may be used to correct/reduce these perturbations were introduced to prevent dosimetric cold spots during IVBT. Practical methods of using these correction factors are proposed. RESULTS: Dose perturbations are significant due to the presence of source curvature, metallic stents, calcified plaques, and metallic guide wires, especially for beta sources. These perturbations can be as high as 30% under normal clinical conditions, although they can be much higher in extreme situations. Empirical relationships of plaque factor with the thickness of calcified plaque, stent factor with stent metallic surface area, guidewire with guidewire thickness, and curvature factor with the bending angle are derived. These relationships are found to be useful in improving clinical dose accuracy in IVBT treatment planning or dose evaluation after treatment. CONCLUSIONS: Significant dose perturbations due to the presence of source curvature, metallic stents, calcified plaques, and guide wires have been found in IVBT for in-stent restenosis. Because it has been reported that, with the current prescriptions for IVBT, higher doses consistently improve treatment outcomes, the empirical method derived from this work can be used to assess cold spots dosimetrically, thus improving patient-specific dosimetry for IVBT.

Dose perturbations due to contrast medium and air in mammosite treatment: an experimental and Monte Carlo study.

In the management of early breast cancer, a partial breast irradiation technique called MammoSite (Proxima Therapeutic Inc., Alpharetta, GA) has been advocated in recent years. In MammoSite, a balloon implanted at the surgical cavity during tumor excision is filled with a radio-opaque solution, and radiation is delivered via a high dose rate brachytherapy source situated at the center of the balloon. Frequently air may be introduced during placement of the balloon and/or injection of the contrast solution into the balloon. The purpose of this work is to quantify as well as to understand dose perturbations due to the presence of a high-Z contrast medium and/or an air bubble with measurements and Monte Carlo calculations. In addition, the measured dose distribution is compared with that obtained from a commercial treatment planning system (Nucletron PLATO system). For a balloon diameter of 42 mm, the dose variation as a function of distance from the balloon surface is measured for various concentrations of a radio-opaque solution (in the range 5%-25% by volume) with a small volume parallel plate ion chamber and a micro-diode detector placed perpendicular to the balloon axis. Monte Carlo simulations are performed to provide a basic understanding of the interaction mechanism and the magnitude of dose perturbation at the interface near balloon surface. Our results show that the radio-opaque concentration produces dose perturbation up to 6%. The dose perturbation occurs mostly within the distances <1 mm from the balloon surface. The Plato system that does not include heterogeneity correction may be sufficient for dose planning at distances > or = 10 mm from the balloon surface for the iodine concentrations used in the MammoSite procedures. The dose enhancement effect near the balloon surface (<1 mm) due to the higher iodine concentration is not correctly predicted by the Plato system. The dose near the balloon surface may be increased by 0.5% per cm3 of air. Monte Carlo simulation suggests that the interface effect (enhanced dose near surface) is primarily due to Compton electrons of short range (<0.5 mm). For more accurate dosimetry in MammoSite delivery, the dose perturbation due to the presence of a radio-opaque contrast medium and air bubbles should be considered in a brachytherapy planning system.

A technique to sharpen the beam penumbra for Gamma Knife radiosurgery.

In stereotactic radiosurgery, a narrow beam penumbra is often desired for producing steep dose fall-off between the target volume and adjacent critical structures. Due to limited source sizes and the scattering effects, the physical penumbra of the Gamma Knife (GK) is often restricted to a width of 1-2 mm. In this work, we developed a technique to further reduce the beam penumbra and improve the dose profile for the Gamma Knife delivery. Under this technique, a conic filter is inserted into an individual plug collimator of a GK helmet to flatten the beam profile. Monte Carlo calculations were carried out to simulate the GK geometry of the individual plug collimator and to optimize the physical shapes of the filters. The calculations were performed for a series of filter shapes with different collimator sizes. Our results show that a proper filter significantly reduces the single GK beam penumbra width (defined as the distance from the 90% to 50% isodose lines) by 30-60%. The beam intensity is reduced by about 20-50% when the filter is used. A treatment plan was developed for a trigeminal neuralgia case by commissioning the filtered beam profile for Leksell Gamma Plan (version 5.31). Compared with the conventional treatment plan, a significant improvement was found on the critical structure sparing and on the target dose uniformity. In conclusion, the proposed technique is feasible and effective in sharpening the beam penumbra for Gamma Knife beam profiles.

Dose effects of stents in intravascular brachytherapy for in-stent restenosis: a Monte Carlo calculation.

PURPOSE: Intravascular brachytherapy (IVBT) has been recognized as a preferred treatment for coronary in-stent restenosis (ISR) in routine practice. Stents made of high-Z materials will inevitably perturb the dose distribution of IVBT. In this work, we have conducted a systematic study on these dose perturbations for three commercially available IVBT sources. METHODS AND MATERIALS: The EGSnrc Monte Carlo codes were used to calculate the dose distributions for the 90Sr, 32P, and 192Ir IVBT sources with and without a metallic stent in place. The ring stent type made of different material and with different strut size, metallic surface area (MSA), and radius was studied. RESULTS: Calculations show that dose enhancement of 5% to 20% occurs inside stent in the region close to the stent struts (luminal side) for all three sources. In the region outside stent (adventitial side), dose reduction of 5% to 20% is observed for a beta source, whereas the dose effect is negligible for the gamma source. For a given stent design, the tantalum stent yields a larger dose effect than other stents made of steel, Ti, Ni, or nitinol. It is found that the dose effect significantly depends on strut thickness, and it is strongly correlated to MSA. The MSA may be used to characterize the dose effect of a stent. Sample empiric equations to relate the dose perturbations to MSA for a given source, a stent material, and a strut thickness were derived. CONCLUSIONS: The dose perturbations due to the presence of metallic stents were found to be significant in IVBT for ISR. The dose effects of a stent can be estimated from its MSA based on derived empiric equations. The data presented are practically useful to consider the dose effects of stents in dose evaluation/treatment planning for using IVBT to treat ISR.

Monte Carlo dose characterization of a new 90Sr/90Y source with balloon for intravascular brachytherapy.

Beta emitting source wires or seeds have been adopted in clinical practice of intravascular brachytherapy for coronary vessels. Due to the limitation of penetration depth, this type of source is normally not applicable to treat vessels with large diameter, e.g., peripheral vessel. In the effort to extend application of its beta source for peripheral vessels, Novoste has recently developed a new catheter-based system, the Corona 90Sr/90Y system. It is a source train of 6 cm length and is jacketed by a balloon. The existence of the balloon increases the penetration of the beta particles and maintains the source within a location away from the vessel wall. Using the EGSnrc Monte Carlo system, we have calculated the two-dimensional (2-D) dose rate distribution of the Corona system in water for a balloon diameter of 5 mm. The dose rates on the transverse axis obtained in this study are in good agreement with calibration results of the National Institute of Standards and Technology for the same system for balloon diameters of 5 and 8 mm. Features of the 2-D dose field were studied in detail. The dose parameters based on AAPM TG-60 protocol were derived. For a balloon diameter of 5 mm, the dose rate at the reference point (defined as r0 = 4.5 mm, 2 mm from the balloon surface) is found to be 0.01028 Gy min(-1) mCi(-1). A new formalism for a better characterization of this long source is presented. Calculations were also performed for other balloon diameters. The dosimetry for this source is compared with a 192Ir source, commonly used for peripheral arteries. In conclusion, we have performed a detailed dosimetric characterization for a new beta source for peripheral vessels. Our study shows that, from dosimetric point of view, the Corona system can be used for the treatment of an artery with a large diameter, e.g., peripheral vessel.

IVBTMC, a Monte Carlo dose calculation tool for intravascular brachytherapy.

A new Monte Carlo code (IVBTMC) is developed for accurate dose calculations in intravascular brachytherapy (IVBT). IVBTMC calculates the dose distribution of a brachytherapy source with arbitrary size and curvature in a general three-dimensional heterogeneous medium. Both beta and gamma sources are considered. IVBTMC is based on a modified version of the EGSNRC code. A voxel-based geometry is used to describe the target medium incorporating heterogeneities with arbitrary composition and shape. The source term is modeled using appropriate phase-space data. The phase-space data are calculated for three widely used sources (32P, 90Sr/90Y, and 192Ir). To speed up dose calculations for gamma sources, a special version of IVBTMC based on the kerma approximation is developed. The accuracy of the phase-space data model is verified and IVBTMC is validated against other Monte Carlo codes and against reported measurements using radio-chromic films. To illustrate the IVBTMC capabilities, a variety of examples are treated. 32P, 90Sr/90Y, and 192Ir sources with different lengths and degrees of curvature are considered. Calcified plaques with regular and irregular shapes are modeled. The dose distributions are calculated with a spatial resolution ranging between 0.1 and 0.5 mm. They are presented in terms of isodose contour plots. The dosimetric effects of the source curvature and/or the presence of calcified plaques are discussed. In conclusion, IVBTMC has the capability to perform high-precision IVBT dose calculations taking into account the realistic configurations of both the source and the target medium.