Characterizing spatial differences between SPECT-ventilation and SPECT-perfusion in patients with lung cancer undergoing radiotherapy.

This study investigates agreement between ventilation and perfusion for lung cancer patients undergoing radiotherapy. Ventilation-perfusion scans of nineteen patients with stage III lung cancer from a prospective protocol were compared using voxel-wise Spearman correlation-coefficients. The presented results show in about 25% of patients, ventilation and perfusion exhibit lower agreement.

Integration of automation into an existing clinical workflow to improve efficiency and reduce errors in the manual treatment planning process for total body irradiation (TBI).

PURPOSE: To identify causes of error, and present the concept of an automated technique that improves efficiency and helps to reduce transcription and manual data entry errors in the treatment planning of total body irradiation (TBI). METHODS: Analysis of incidents submitted to incident learning system (ILS) was performed to identify potential avenues for improvement by implementation of automation of the manual treatment planning process for total body irradiation (TBI). Following this analysis, it became obvious that while the individual components of the TBI treatment planning process were well implemented, the manual 'bridging' of the components (transcribing data, manual data entry etc.) were leading to high potential for error. A C#-based plug-in treatment planning script was developed to remove the manual parts of the treatment planning workflow that were contributing to increased risk. RESULTS: Here we present an example of the implementation of "Glue" programming, combining treatment planning C# scripts with existing spreadsheet calculation worksheets. Prior to the implementation of automation, 35 incident reports related to the TBI treatment process were submitted to the ILS over a 6-year period, with an average of 1.4 ± 1.7 reports submitted per quarter. While no incidents reached patients, reports ranged from minor documentation issues to potential for mistreatment if not caught before delivery. Since the implementation of automated treatment planning and documentation, treatment planning time per patient, including documentation, has been reduced; from an average of 45 min pre-automation to <20 min post-automation. CONCLUSIONS: Manual treatment planning techniques may be well validated, but they are time-intensive and have potential for error. Often the barrier to automating these techniques becomes the time required to "re-code" existing solutions in unfamiliar computer languages. We present the workflow here as a proof of concept that automation may help to improve clinical efficiency and safety for special procedures.

Evaluating Positron Emission Tomography-Based Functional Imaging Changes in the Heart After Chemo-Radiation for Patients With Lung Cancer.

PURPOSE: Studies have noted a link between radiation dose to the heart and overall survival (OS) for patients with lung cancer treated with chemoradiation. The purpose of this study was to characterize pre- to posttreatment cardiac metabolic changes using fluorodeoxyglucose/positron emission tomography (FDG-PET) images and to evaluate whether changes in cardiac metabolism predict for OS. METHODS AND MATERIALS: Thirty-nine patients enrolled in a functional avoidance prospective study who had undergone pre- and postchemoradiation FDG-PET imaging were evaluated. For each patient, the pretreatment and posttreatment PET/CTs were rigidly registered to the planning CT, dose, and structure set. PET-based metabolic dose-response was assessed by comparing pretreatment to posttreatment mean standardized uptake values (SUVmean) in the heart as a function of dose-bin. OS analysis was performed by comparing SUVmean changes for patients who were alive or had died at last follow-up and by using a multivariate model to assess whether pre- to posttreatment SUVmean changes were a predictor of OS. RESULTS: The dose-response curve revealed increasing changes in SUV as a function of cardiac dose with an average SUVmean increase of 1.7% per 10 Gy. Patients were followed for a median of 437 days (range, 201-1131 days). SUVmean change was significantly predictive of OS on multivariate analysis with a hazard ratio of 0.541 (95% confidence intervals, 0.312-0.937). Patients alive at follow-up had an average increase of 17.2% in cardiac SUVmean while patients that died had an average decrease in SUVmean decrease of 13.5% (P = .048). CONCLUSIONS: Our data demonstrated that posttreatment SUV changes in the heart were significant indicators of dose-response and predictors of OS. The present work is hypothesis generating and must be validated in an independent cohort. If validated, our data show the potential for cardiac metabolic changes to be an early predictor for clinical outcomes.

Electromagnetic wave propagation in a fast pulse line ion accelerator.

PURPOSE: The pulse line ion accelerator (PLIA) is a low-cost accelerator concept originally designed to accelerate heavy ions. Our group has been investigating the use of PLIA to accelerate light ions and believe a multi-stage PLIA could be useful for short half-life PET isotope production. The goal of this work was to develop a single prototype fast PLIA structure and demonstrate electromagnetic wave propagation using a high-voltage pulser. MATERIALS AND METHODS: A 1.6 m fast PLIA structure (wave speed > 107  m/s) was constructed along with a high-voltage, sinusoidal pulse generator. The latter uses capacitive voltage doubling and spark gap switching. A step-up transformer couples voltage from the pulser to the PLIA coil. Voltage measurements on the coil were made in air using a high-voltage resistive probe, while capacitive probes placed along the length of the PLIA were used to measure wave propagation with the PLIA structure filled with transformer oil. RESULTS: Voltage measurements acquired on the primary and secondary coils of the transformer coupler in air demonstrated a peak-to-peak voltage step-up of 4.2 relative to the pulser DC charging voltage. The maximum voltage time-rate-of-change on the PLIA coil was 0.76 × 1013  V/s. Capacitive probe measurements indicated voltage oscillations on the PLIA coil with half-period equal to 43 ± 0.9 ns and wave speed (with oil) of 1.2 × 107  m/s. Average and peak accelerating gradients were conservatively estimated to be 0.44 and 0.60 MV/m, respectively, with a charging voltage of 55 kV. Wave propagation was demonstrated at these gradients without flashover at a vacuum pressure of 9 × 10-6  Torr. Submerging the pulser in oil would allow for charging voltages up to 150 kV and produce accelerating gradients >1.2 MV/m. CONCLUSIONS: Use of a multi-stage, fast PLIA for light ion acceleration could provide a low-cost complement to cyclotrons for the production of short half-life isotopes used for PET imaging, including carbon-11, nitrogen-13, oxygen-15, and fluorine-18.

Design considerations for a pulse line ion accelerator (PLIA)-based PET isotope generator.

PURPOSE: Positron emission tomography (PET) imaging remains limited due to the cost associated with on-site production of short half-life, positron-emitting isotopes. In this work, we examine the use of a pulse line ion accelerator (PLIA) to accelerate protons for single-dose PET isotope production. METHODS: Time-domain electromagnetic field and particle-in-cell (PIC) simulations were performed for a 1.5-m PLIA structure modeled in CST Microwave Studio and Particle Studio software. Scaled measurements from a kV ramp-pulse generator were incorporated into the simulations to accelerate a 1 A, 50 ns proton beam injected with initial kinetic energy of 100 keV. A uniform, 3 T, solenoidal magnetic field was used to provide external beam focusing. Electromagnetic fields and particle phase space were recorded with ns resolution for subsequent analysis. RESULTS: Applying a scaled 100 kV, 20 ns ramped voltage pulse to the PLIA input resulted in a travelling electric field wave inside the structure with accelerating gradient of 2.4 MV/m. The observed wave speed was 1.2 × 107 m/s and is in good agreement with theoretical predictions. Phase space monitors showed both acceleration and bunching of the proton beam, with a maximum kinetic energy of 2.5 MeV, observed at the exit of the single PLIA stage. Evaluation of beam position monitors at different locations in the accelerator showed bunch compression and minimal beam divergence, illustrating that the 3 T field is adequate to contain the beam over the length of the PLIA structure. CONCLUSION: Simulations performed in this work demonstrate the feasibility of using a PLIA structure to accelerate protons with MV/m level gradients. Combining several PLIA stages in series could allow for a low-cost accelerator suitable for dose-on-demand PET isotope production.

A Multi-institution, Retrospective Analysis of Cervix Intracavitary Brachytherapy Treatments. Part 1: Is EQD2 Good Enough for Reporting Radiobiological Effects?

PURPOSE: When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices-T&O and tandem and ring (T&R)-and different styles; and (3) the same site using T&O and T&R with the same style. METHODS AND MATERIALS: EUBED and gBEUD were calculated for 260 fractions from 3 institutions using BED(α/ß = 10 Gy). EUBED uses an extra parameter α with smaller values associated with radioresistant tumors. Similarly, gBEUD uses a, which places variable emphasis on hot/cold spots. Distributions were compared using the Kolmogorov-Smirnoff test at 5% significance. RESULTS: For the 2 sites using T&O, the distribution of EUBED-BED(D90) was not different for values of α = 0.5 to 0.3 Gy-1 but was statistically different for values of α = 0.15 to 0.05 Gy-1 (P=.01, .002). The mean percentage differences between EUBED and BED(D90) ranged from 20% to 100% for α = 0.5 Gy-1 to 0.05 Gy-1. Using gBEUD-BED(D90), the P values indicate the distributions to be similar for a = -10 but to be significantly different for other values of a (-5, -1, 1). Between sites and at the same site using T&O versus T&R, the distributions were statistically different with EUBED/gBEUD irrespective of parameter values at which these quantities were computed. These differences indicate that EUBED/gBEUD capture differences between the techniques and applicators that are not detected by the BED(D90). CONCLUSIONS: BED(D90) is unable to distinguish between plans created by different devices or optimized differently. EUBED/gBEUD distinguish between dose distributions created by different devices and styles of implant and planning. This discrepancy is particularly important with the increased use of magnetic resonance imaging and hybrid devices, whereby one has the ability to create dose distributions that are significant departures from the classic pear.

A complete 4DCT-ventilation functional avoidance virtual trial: Developing strategies for prospective clinical trials.

INTRODUCTION: 4DCT-ventilation is an exciting new imaging modality that uses 4DCT data to calculate lung-function maps. Because 4DCTs are acquired as standard of care for lung cancer patients undergoing radiotherapy, 4DCT-ventiltation provides functional information at no extra dosimetric or monetary cost to the patient. The development of clinical trials is underway to use 4DCT-ventilation imaging to spare functional lung in patients undergoing radiotherapy. The purpose of this work was to perform a virtual trial using retrospective data to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial. METHODS: The study included 96 stage III lung cancer patients. A 4DCT-ventilation map was calculated using the patient's 4DCT-imaging, deformable registration, and a density-change-based algorithm. Clinical trial inclusion assessment used quantitative and qualitative metrics based on the patient's spatial ventilation profile. Clinical and functional plans were generated for 25 patients. The functional plan aimed to reduce dose to functional lung while meeting standard target and critical structure constraints. Standard and dose-function metrics were compared between the clinical and functional plans. RESULTS: Our data showed that 69% and 59% of stage III patients have regional variability in function based on qualitative and quantitative metrics, respectively. Functional planning demonstrated an average reduction of 2.8 Gy (maximum 8.2 Gy) in the mean dose to functional lung. CONCLUSIONS: Our work demonstrated that 60-70% of stage III patients would be eligible for functional planning and that a typical functional lung mean dose reduction of 2.8 Gy can be expected relative to standard clinical plans. These findings provide salient data for the development of functional clinical trials.

Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy.

PURPOSE: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. METHODS AND MATERIALS: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change-based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. RESULTS: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. CONCLUSION: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.

Lung deformations and radiation-induced regional lung collapse in patients treated with stereotactic body radiation therapy.

PURPOSE: To differentiate radiation-induced fibrosis from regional lung collapse outside of the high dose region in patients treated with stereotactic body radiation therapy (SBRT) for lung tumors. METHODS: Lung deformation maps were computed from pre-treatment and post-treatment computed tomography (CT) scans using a point-to-point translation method. Fifty anatomical landmarks inside the lung (vessel or airway branches) were matched on planning and follow-up scans for the computation process. Two methods using the deformation maps were developed to differentiate regional lung collapse from fibrosis: vector field and Jacobian methods. A total of 40 planning and follow-ups CT scans were analyzed for 20 lung SBRT patients. RESULTS: Regional lung collapse was detected in 15 patients (75%) using the vector field method, in ten patients (50%) using the Jacobian method, and in 12 patients (60%) by radiologists. In terms of sensitivity and specificity the Jacobian method performed better. Only weak correlations were observed between the dose to the proximal airways and the occurrence of regional lung collapse. CONCLUSIONS: The authors presented and evaluated two novel methods using anatomical lung deformations to investigate lung collapse and fibrosis caused by SBRT treatment. Differentiation of these distinct physiological mechanisms beyond what is usually labeled "fibrosis" is necessary for accurate modeling of lung SBRT-induced injuries. With the help of better models, it becomes possible to expand the therapeutic benefits of SBRT to a larger population of lung patients with large or centrally located tumors that were previously considered ineligible.

Clinical validation of 4-dimensional computed tomography ventilation with pulmonary function test data.

PURPOSE: A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. METHODS AND MATERIALS: Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change-based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. RESULTS: Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. CONCLUSIONS: Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.

Comparison of radiation-induced normal lung tissue density changes for patients from multiple institutions receiving conventional or hypofractionated treatments.

PURPOSE: To quantitatively assess changes in computed tomography (CT)-defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT). METHODS AND MATERIALS: The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times. RESULTS: For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD50) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons). CONCLUSION: Compared with conventional fractionation, hypofractionation has a lower TD50 and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation.

Spatial and dose-response analysis of fibrotic lung changes after stereotactic body radiation therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is becoming the standard of care for early stage nonoperable lung cancers. Accurate dose-response modeling is challenging for SBRT because of the decreased number of clinical toxicity events. As a surrogate for a clinical toxicity endpoint, studies have proposed to use radiographic changes in follow up computed tomography (CT) scans to evaluate lung SBRT normal tissue effects. The purpose of the current study was to use local fibrotic lung regions to spatially and dosimetrically evaluate lung changes in patients that underwent SBRT. METHODS: Forty seven SBRT patients treated at our institution from 2003 to 2009 were used for the current study. Our patient cohort had a total of 148 follow up CT scans ranging from 3 to 48 months post-therapy. Post-treatment scans were binned into intervals of 3, 6, 12, 18, 24, 30, and 36 months after the completion of treatment. Deformable image registration was used to align the follow up CT scans with the pretreatment CT and dose distribution. Areas of visible fibrotic changes were contoured. The centroid of each gross tumor volume (GTV) and contoured fibrosis volume was calculated and the fibrosis volume location and movement (magnitude and direction) relative to the GTV and 30 Gy isodose centroid were analyzed. To perform a dose-response analysis, each voxel in the fibrosis volume was sorted into 10 Gy dose bins and the average CT number value for each dose bin was calculated. Dose-response curves were generated by plotting the CT number as a function of dose bin and time posttherapy. RESULTS: Both fibrosis and GTV centroids were concentrated in the upper third of the lung. The average radial movement of fibrosis centroids relative to the GTV centroids was 2.6 cm with movement greater than 5 cm occurring in 11% of patients. Evaluating dose-response curves revealed an overall trend of increasing CT number as a function of dose. The authors observed a CT number plateau at doses ranging from 30 to 50 Gy for the 3, 6, and 12 months posttherapy time points. There was no evident plateau for the dose-response curves generated using data from the 18, 24, 30, and 36 months posttherapy time points. CONCLUSIONS: Regions of local fibrotic lung changes in patients that underwent SBRT were evaluated spatially and dosimetrically. The authors found that the average fibrosis movement was 2.6 cm with movement greater than 5 cm possible. Evaluating dose-response curves revealed an overall trend of increasing CT number as a function of dose. Furthermore, our dose-response data also suggest that one of the possible explanations of the CT number plateau effect may be the time posttherapy of the acquired data. Understanding normal tissue dose-response is important for reducing toxicity after SBRT, especially in cases where larger tumors are treated. The methods presented in the current work build on prior quantitative studies and further enhance the understanding of normal lung dose-response after SBRT.

Dosimetric and deformation effects of image-guided interventions during stereotactic body radiation therapy of the prostate using an endorectal balloon.

PURPOSE: During stereotactic body radiation therapy (SBRT) for the treatment of prostate cancer, an inflatable endorectal balloon (ERB) may be used to reduce motion of the target and reduce the dose to the posterior rectal wall. This work assessed the dosimetric impact of manual interventions on ERB position in patients receiving prostate SBRT and investigated the impact of ERB interventions on prostate shape. METHODS: The data of seven consecutive patients receiving SBRT for the treatment of clinical stage T1cN0M0 prostate cancer enrolled in a multi-institutional, IRB-approved trial were analyzed. The SBRT dose was 50 Gy in five fractions to a planning target volume (PTV) that included the prostate (implanted with three fiducial markers) with a 3-5 mm margin. All plans were based on simulation images that included an ERB inflated with 60 cm(3) of air. Daily kilovoltage cone-beam computed tomography (CBCT) imaging was performed to localize the PTV, and an automated fusion with the planning images yielded displacements required for PTV relocalization. When the ERB volume and/or position were judged to yield inaccurate repositioning, manual adjustment (ERB reinflation and/or repositioning) was performed. Based on all 59 CBCT image sets acquired, a deformable registration algorithm was used to determine the dose received by, displacement of, and deformation of the prostate, bladder (BLA), and anterior rectal wall (ARW). This dose tracking methodology was applied to images taken before and after manual adjustment of the ERB (intervention), and the delivered dose was compared to that which would have been delivered in the absence of intervention. RESULTS: Interventions occurred in 24 out of 35 (69%) of the treated fractions. The direct effect of these interventions was an increase in the prostate radiation dose that included 95% of the PTV (D95) from 9.6 ± 1.0 to 10.0 ± 0.2 Gy (p = 0.06) and an increase in prostate coverage from 94.0% ± 8.5% to 97.8% ± 1.9% (p = 0.03). Additionally, ERB interventions reduced prostate deformation in the anterior-posterior (AP) direction, reduced errors in the sagittal rotation of the prostate, and increased the similarity in shape of the prostate to the radiotherapy plan (increased Dice coefficient from 0.76 ± 0.06 to 0.80 ± 0.04, p = 0.01). Postintervention decreases in prostate volume receiving less than the prescribed dose and decreases in the voxel-wise displacement of the prostate, bladder, and anterior rectal wall were observed, which resulted in improved dose-volume histogram (DVH) characteristics. CONCLUSIONS: Image-guided interventions in ERB volume and/or position during prostate SBRT were necessary to ensure the delivery of the dose distribution as planned. ERB interventions resulted in reductions in prostate deformations that would have prevented accurate localization of patient anatomy.

Normal liver tissue density dose response in patients treated with stereotactic body radiation therapy for liver metastases.

PURPOSE: To evaluate the temporal dose response of normal liver tissue for patients with liver metastases treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Ninety-nine noncontrast follow-up computed tomography (CT) scans of 34 patients who received SBRT between 2004 and 2011 were retrospectively analyzed at a median of 8 months post-SBRT (range, 0.7-36 months). SBRT-induced normal liver tissue density changes in follow-up CT scans were evaluated at 2, 6, 10, 15, and 27 months. The dose distributions from planning CTs were mapped to follow-up CTs to relate the mean Hounsfield unit change (ΔHU) to dose received over the range 0-55 Gy in 3-5 fractions. An absolute density change of 7 HU was considered a significant radiographic change in normal liver tissue. RESULTS: Increasing radiation dose was linearly correlated with lower post-SBRT liver tissue density (slope, -0.65 ΔHU/5 Gy). The threshold for significant change (-7 ΔHU) was observed in the range of 30-35 Gy. This effect did not vary significantly over the time intervals evaluated. CONCLUSIONS: SBRT induces a dose-dependent and relatively time-independent hypodense radiation reaction within normal liver tissue that is characterized by a decrease of >7 HU in liver density for doses >30-35 Gy.

Regional normal lung tissue density changes in patients treated with stereotactic body radiation therapy for lung tumors.

PURPOSE: To describe regional lung tissue density changes in normal lung tissue of patients with primary and metastatic lung tumors who received stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: A total of 179 post-SBRT follow-up computed tomography (CT) scans of 62 patients who received SBRT between 2003 and 2009 were studied. Median prescription dose was 54 Gy (range, 30-60 Gy) in 3 to 5 fractions. SBRT-induced lung density changes on post-SBRT follow-up CT were evaluated at approximately 3, 6, 12, 18, 24, and 30 months after treatment. Dose-response curves (DRC) were generated for SBRT-induced lung damage by averaging CT number (HU) changes for regions of the lungs receiving the same dose at 5-Gy intervals. RESULTS: For all follow-up interval periods, CT numbers linearly increased with dose until 35 Gy and were constant thereafter. For 3, 18, 24, and 30 months, the rate of relative electron density increase with dose was approximately 0.24% per Gy. At 6 months, the rate was also similar below 20 Gy but then rose to 0.6% per Gy above this threshold. After 6 months, DRCs were mostly time-independent. When split between patients treated with 3 fractions of 12 to 20 Gy (median, 20 Gy; average tumor volume, 12±16 cm3) and with >3 fractions of 6 to 12.5 Gy (median, 9 Gy; average tumor volume, 30±40 cm3), DRCs differed significantly. In both cases, CT changes at 3, 18, 24, and 30 months were identical to those of the population DRC; however, patients who received >3 fractions showed 6-month CT changes that were more than twice those for the group that received 3 fractions. CONCLUSIONS: This analysis of SBRT-induced normal lung density changes indicates that lung normal tissue has more pronounced self-limited acute effects than late effects. Differences in acute CT changes following treatments in 3 fractions were considerably less than for treatments in >3 fractions.

Fluorodeoxyglucose positron emission tomography response and normal tissue regeneration after stereotactic body radiotherapy to liver metastases.

PURPOSE: To characterize changes in standardized uptake value (SUV) in positron emission tomography (PET) scans and determine the pace of normal tissue regeneration after stereotactic body radiation therapy (SBRT) for solid tumor liver metastases. METHODS AND MATERIALS: We reviewed records of patients with liver metastases treated with SBRT to ≥40 Gy in 3-5 fractions. Evaluable patients had pretreatment PET and ≥1 post-treatment PET. Each PET/CT scan was fused to the planning computed tomography (CT) scan. The maximum SUV (SUV(max)) for each lesion and the total liver volume were measured on each PET/CT scan. Maximum SUV levels before and after SBRT were recorded. RESULTS: Twenty-seven patients with 35 treated liver lesions were studied. The median follow-up was 15.7 months (range, 1.5-38.4 mo), with 5 PET scans per patient (range, 2-14). Exponential decay curve fitting (r=0.97) showed that SUV(max) declined to a plateau of 3.1 for controlled lesions at 5 months after SBRT. The estimated SUV(max) decay half-time was 2.0 months. The SUV(max) in controlled lesions fluctuated up to 4.2 during follow-up and later declined; this level is close to 2 standard deviations above the mean normal liver SUV(max) (4.01). A failure cutoff of SUV(max) ≥6 is twice the calculated plateau SUV(max) of controlled lesions. Parenchymal liver volume decreased by 20% at 3-6 months and regenerated to a new baseline level approximately 10% below the pretreatment level at 12 months. CONCLUSIONS: Maximum SUV decreases over the first months after SBRT to plateau at 3.1, similar to the median SUV(max) of normal livers. Transient moderate increases in SUV(max) may be observed after SBRT. We propose a cutoff SUV(max) ≥6, twice the baseline normal liver SUV(max), to score local failure by PET criteria. Post-SBRT values between 4 and 6 would be suspicious for local tumor persistence or recurrence. The volume of normal liver reached nadir 3-6 months after SBRT and regenerated within the next 6 months.

Biological-based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy.

PURPOSE: To describe biological-based optimization and Monte Carlo (MC) dose calculation-based treatment planning for volumetric modulated arc therapy (VMAT) delivery of stereotactic body radiation therapy (SBRT) in lung, liver, and prostate patients. METHODS: Optimization strategies and VMAT planning parameters using a biological-based optimization MC planning system were analyzed for 24 SBRT patients. Patients received a median dose of 45 Gy [range, 34-54 Gy] for lung tumors in 1-5 fxs and a median dose of 52 Gy [range, 48-60 Gy] for liver tumors in 3-6 fxs. Prostate patients received a fractional dose of 10 Gy in 5 fxs. Biological-cost functions were used for plan optimization, and its dosimetric quality was evaluated using the conformity index (CI), the conformation number (CN), the ratio of the volume receiving 50% of the prescription dose over the planning target volume (Rx/PTV50). The quality and efficiency of the delivery were assessed according to measured quality assurance (QA) passing rates and delivery times. For each disease site, one patient was replanned using physical cost function and compared to the corresponding biological plan. RESULTS: Median CI, CN, and Rx/PTV50 for all 24 patients were 1.13 (1.02-1.28), 0.79 (0.70-0.88), and 5.3 (3.1-10.8), respectively. The median delivery rate for all patients was 410 MU/min with a maximum possible rate of 480 MU/min (85%). Median QA passing rate was 96.7%, and it did not significantly vary with the tumor site. CONCLUSIONS: VMAT delivery of SBRT plans optimized using biological-motivated cost-functions result in highly conformal dose distributions. Plans offer shorter treatment-time benefits and provide efficient dose delivery without compromising the plan conformity for tumors in the prostate, lung, and liver, thereby improving patient comfort and clinical throughput. The short delivery times minimize the risk of patient setup and intrafraction motion errors often associated with long SBRT treatment delivery times.

Dosimetric effect of online image-guided anatomical interventions for postprostatectomy cancer patients.

PURPOSE: To assess daily variations in delivered doses in postprostatectomy patients, using kilovoltage cone-beam CT (CBCT) datasets acquired before and after interventions to correct for observed distortions in volume/shape of rectum and bladder. METHODS AND MATERIALS: Seventeen consecutive patients treated with intensity-modulated radiotherapy to the prostate bed were studied. For patients with large anatomical variations, quantified by either a rectal wall displacement of >5 mm or bladder volume change of >50% on the CBCT compared with the planning CT, an intervention was performed to adjust the rectum and/or bladder filling. Cumulative doses over the pre- and post-intervention fractions were calculated by tracking the position of the planning CT voxels on different CBCTs using a deformable surface-mapping algorithm. Dose and displacements vectors were projected on two-dimensional maps, the minimal dose received by the highest 95% of the planing target volume (PTV D95) and the highest 10% of the rectum volume (D10) as well as the bladder volume receiving >2 Gy (V2) were evaluated. RESULTS: Of 544 fractions, 96 required intervention. Median (range) number of interventions per patient was 5 (2-12). Compared with the planning values, the mean (SD) pre- vs. postintervention value for PTV D95 was -2% (2%) vs. -1% (2%) (p < 0.12), for rectum D10 was -1% (4%) vs. +1% (4%) (p < 0.24), and for bladder V2 was +6% vs. +20% (p < 0.84). CONCLUSIONS: Interventions to reduce treatment volume deformations due to bladder and rectum fillings are not necessary when patients receive daily accurate CBCT localization, and the frequency of those potential interventions is low. However, for hypofractionated treatments, the relative frequency can significantly increase, and interventions can become more dosimetrically beneficial.

Impact of anatomical interventions on the localization of post-prostatectomy cancer patients.

PURPOSE: Anatomical deformations of prostate-bed, rectum, and bladder can compromise the targeting accuracy in post-prostatectomy cancer patients. In this work, the impact of anatomical interventions on the localization data from post-prostatectomy patients who received image-guided IMRT was analyzed. METHODS: Patients were localized daily with online kilovoltage cone-beam computed tomography (kV-CBCT). The target and the organs at risk (OARs) positional and volumetric changes were evaluated and couch shifts were applied. For patients with large target or OAR volumetric changes, quantified by either a rectal or bladder wall displacement of >5 mm on the CBCT sagittal images compared to the planning CT, repeated localization CBCT scans were performed following an interventional procedure. The procedure involves insertion of a catheter to deflate the rectum, evacuation of stools, and/or adjustment of bladder filling. The required shifts were then evaluated, and the IMRT treatment was subsequently delivered after proper patient positioning. The pre- and post-intervention shifts were compared in the lateral [left-right (LR)], longitudinal [superior-inferior (SI)], and vertical [anterior-posterior (AP)] directions. The percentage of shifts larger than 5 mm in all directions was also compared. Clinical target volume to planning target volume (CTV-to-PTV) expansion margins were estimated based on the pre- and post-intervention localization data. RESULTS: Intervention was performed on all patients (n=17) treated between October 2008 and March 2009. The number of interventions ranged from 2 to 12 with a median number of 5, resulting in a total of 96 pairs of pre- and post-intervention shifts. The mean value (sigma) and standard deviation (sigma) of the shifts from pre- versus post-intervention data were LR, 0.0 +/- 3.0 mm vs. 0.5 +/- 2.8 mm; SI, 0.2 +/- 3.1 mm vs. -1.0 +/- 2.1 mm; and AP, -2.6 +/- 5.8 mm vs. 1.7 +/- 3.9 mm. The mean 3D shift distance was 7.0 +/- 3.1 mm vs. 5.0 +/- 2.6 mm. The percentage of pre-intervention shifts larger than 5 mm were 7%, 7%, and 45% in the LR, SI, and AP directions, respectively, compared to 8%, 4%, and 21% for post-intervention. Localization data from pre- and post-intervention procedures suggest that treatments that do not include intervention to correct for rectum/bladder anatomical variations require an additional 3.3 mm CTV-to-PTV margin. CONCLUSIONS: Anatomical interventions reduced the localization errors arising from large volume and shape changes in the rectum and/or bladder compared to treatments without interventions.

Atom Michelson interferometer on a chip using a Bose-Einstein condensate.

An atom Michelson interferometer is implemented on an "atom chip." The chip uses lithographically patterned conductors and external magnetic fields to produce and guide a Bose-Einstein condensate. Splitting, reflecting, and recombining of condensate atoms are achieved by a standing-wave light field having a wave vector aligned along the atom waveguide. A differential phase shift between the two arms of the interferometer is introduced by either a magnetic-field gradient or with an initial condensate velocity. Interference contrast is still observable at 20% with an atom propagation time of 10 ms.