A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer.

PURPOSE: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. METHODS: Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. RESULTS: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction, seven required a single correction, one required two corrections, and one required three corrections. Mean residual GTV deviation (3D distance) following GTV-based systematic correction (mean ± 1 standard deviation 4.8 ± 1.5 mm) is significantly lower than for systematic skeletal-based (6.5 ± 2.9 mm, p = 0.015), and weekly skeletal-based correction (7.2 ± 3.0 mm, p = 0.001), but is not significantly lower than daily skeletal-based correction (5.4 ± 2.6 mm, p = 0.34). In two cases, first-day CBCT images reveal tumor changes-one showing tumor growth, the other showing large tumor displacement-that are not readily observed in radiographs. Differences in computed GTV deviations between respiration-correlated and respiration-averaged images are 0.2 ± 1.8 mm in the superior-inferior direction and are of similar magnitude in the other directions. CONCLUSIONS: An off-line protocol to correct GTV-based systematic error in locally advanced lung tumor cases can be effective at reducing tumor deviations, although the findings need confirmation with larger patient statistics. In some cases, a single cone-beam CT can be useful for assessing tumor changes early in treatment, if more than a few days elapse between simulation and the start of treatment. Tumor deviations measured with respiration-averaged CT and CBCT images are consistent with those measured with respiration-correlated images; the respiration-averaged method is more easily implemented in the clinic.

Evaluation of deformable image registration and a motion model in CT images with limited features.

Deformable image registration (DIR) is increasingly used in radiotherapy applications and provides the basis for a previously described model of patient-specific respiratory motion. We examine the accuracy of a DIR algorithm and a motion model with respiration-correlated CT (RCCT) images of software phantom with known displacement fields, physical deformable abdominal phantom with implanted fiducials in the liver and small liver structures in patient images. The motion model is derived from a principal component analysis that relates volumetric deformations with the motion of the diaphragm or fiducials in the RCCT. Patient data analysis compares DIR with rigid registration as ground truth: the mean ± standard deviation 3D discrepancy of liver structure centroid positions is 2.0 ± 2.2 mm. DIR discrepancy in the software phantom is 3.8 ± 2.0 mm in lung and 3.7 ± 1.8 mm in abdomen; discrepancies near the chest wall are larger than indicated by image feature matching. Marker's 3D discrepancy in the physical phantom is 3.6 ± 2.8 mm. The results indicate that visible features in the images are important for guiding the DIR algorithm. Motion model accuracy is comparable to DIR, indicating that two principal components are sufficient to describe DIR-derived deformation in these datasets.

Phase and amplitude binning for 4D-CT imaging.

We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis.

Evaluation of an automated deformable image matching method for quantifying lung motion in respiration-correlated CT images.

We have evaluated an automated registration procedure for predicting tumor and lung deformation based on CT images of the thorax obtained at different respiration phases. The method uses a viscous fluid model of tissue deformation to map voxels from one CT dataset to another. To validate the deformable matching algorithm we used a respiration-correlated CT protocol to acquire images at different phases of the respiratory cycle for six patients with nonsmall cell lung carcinoma. The position and shape of the deformable gross tumor volumes (GTV) at the end-inhale (EI) phase predicted by the algorithm was compared to those drawn by four observers. To minimize interobserver differences, all observers used the contours drawn by a single observer at end-exhale (EE) phase as a guideline to outline GTV contours at EI. The differences between model-predicted and observer-drawn GTV surfaces at EI, as well as differences between structures delineated by observers at EI (interobserver variations) were evaluated using a contour comparison algorithm written for this purpose, which determined the distance between the two surfaces along different directions. The mean and 90% confidence interval for model-predicted versus observer-drawn GTV surface differences over all patients and all directions were 2.6 and 5.1 mm, respectively, whereas the mean and 90% confidence interval for interobserver differences were 2.1 and 3.7 mm. We have also evaluated the algorithm's ability to predict normal tissue deformations by examining the three-dimensional (3-D) vector displacement of 41 landmarks placed by each observer at bronchial and vascular branch points in the lung between the EE and EI image sets (mean and 90% confidence interval displacements of 11.7 and 25.1 mm, respectively). The mean and 90% confidence interval discrepancy between model-predicted and observer-determined landmark displacements over all patients were 2.9 and 7.3 mm, whereas interobserver discrepancies were 2.8 and 6.0 mm. Paired t tests indicate no significant statistical differences between model predicted and observer drawn structures. We conclude that the accuracy of the algorithm to map lung anatomy in CT images at different respiratory phases is comparable to the variability in manual delineation. This method has therefore the potential for predicting and quantifying respiration-induced tumor motion in the lung.

Quantitation of respiratory motion during 4D-PET/CT acquisition.

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

Four-dimensional (4D) PET/CT imaging of the thorax.

We have reported in our previous studies on the methodology, and feasibility of 4D-PET (Gated PET) acquisition, to reduce respiratory motion artifact in PET imaging of the thorax. In this study, we expand our investigation to address the problem of respiration motion in PET/CT imaging. The respiratory motion of four lung cancer patients were monitored by tracking external markers placed on the thorax. A 4D-CT acquisition was performed using a "step-and-shoot" technique, in which computed tomography (CT) projection data were acquired over a complete respiratory cycle at each couch position. The period of each CT acquisition segment was time stamped with an "x-ray ON" signal, which was recorded by the tracking system. 4D-CT data were then sorted into 10 groups, according to their corresponding phase of the breathing cycle. 4D-PET data were acquired in the gated mode, where each breathing cycle was divided into ten 0.5 s bins. For both CT and PET acquisitions, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to respiratory phase. The effect of 4D acquisition on improving the co-registration of PET and CT images, reducing motion smearing, and consequently increase the quantitation of the SUV, were investigated. Also, quantitation of the tumor motions in PET, and CT, were studied and compared. 4D-PET with matching phase 4D-CTAC showed an improved accuracy in PET-CT image co-registration of up to 41%, compared to measurements from 4D-PET with clinical-CTAC. Gating PET data in correlation with respiratory motion reduced motion-induced smearing, thereby decreasing the observed tumor volume, by as much as 43%. 4D-PET lesions volumes showed a maximum deviation of 19% between clinical CT and phase- matched 4D-CT attenuation corrected PET images. In CT, 4D acquisition resulted in increasing the tumor volume in two patients by up to 79%, and decreasing it in the other two by up to 35%. Consequently, these corrections have yielded an increase in the measured SUV by up to 16% over the clinical measured SUV, and 36% over SUV's measured in 4D-PET with clinical-CT Attenuation Correction (CTAC) SUV's. Quantitation of the maximum tumor motion amplitude, using 4D-PET and 4D-CT, showed up to 30% discrepancy between the two modalities. We have shown that 4D PET/CT is clinically a feasible method, to correct for respiratory motion artifacts in PET/CT imaging of the thorax. 4D PET/CT acquisition can reduce smearing, improve the accuracy in PET-CT co-registration, and increase the measured SUV. This should result in an improved tumor assessment for patients with lung malignancies.

Respiration-correlated spiral CT: a method of measuring respiratory-induced anatomic motion for radiation treatment planning.

We describe a method for generating CT images at multiple respiratory phases with a single spiral CT scan, referred to as respiratory-correlated spiral CT (RCCT). RCCT relies on a respiration wave form supplied by an external patient monitor. During acquisition this wave form is recorded along with the initiation time of the CT scan, so as to "time stamp" each reconstructed slice with the phase of the respiratory cycle. By selecting the appropriate slices, a full CT image set is generated at several phases, typically 7-11 per cycle. The CT parameters are chosen to optimize the temporal resolution while minimizing the spatial gap between slices at successive respiratory cycles. Using a pitch of 0.5, a gantry rotation period of 1.5 s, and a 180 degrees reconstruction algorithm results in approximately 5 mm slice spacing at a given phase for typical respiration periods, and a respiratory motion within each slice that is acceptably small, particularly near end expiration or end inspiration where gated radiotherapy is to occur. We have performed validation measurements on a phantom with a moving sphere designed to simulate respiration-induced tumor motion. RCCT scans of the phantom at respiratory periods of 4, 5, and 6 s show good agreement of the sphere's motion with that observed under fluoroscopic imaging. The positional deviations in the sphere's centroid between RCCT and fluoroscopy are 1.1+/-0.9 mm in the transaxial direction (average over all scans at all phases +/-1 s.d.) and 1.2+/-1.0 mm in the longitudinal direction. Reconstructed volumes match those expected on the basis of stationary-phantom scans to within 5% in all cases. The surface distortions of the reconstructed sphere, as quantified by deviations from a mathematical reference sphere, are similar to those from a stationary phantom scan and are correlated with the speed of the phantom. A RCCT scan of the phantom undergoing irregular motion, demonstrates that successful reconstruction can be achieved even with irregular respiration. Limitations from x-ray tube heating in our current CT unit restrict the length of the scan region to 9 cm for the RCCT settings used, though this will not be a limitation for a multislice scanner. RCCT offers an alternative to the current method of respiration-triggered axial scans. Multiple phases of respiration are imaged with RCCT in approximately the same scanning time required to image a single phase with a triggered axial scan. RCCT scans can be used in connection with respiratory-gated treatment to identify the patient-specific phase of minimum tumor motion, determine residual tumor motion within the gate interval, and compare treatment plans at different phases.

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer.

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Evaluation of respiratory movement during gated radiotherapy using film and electronic portal imaging.

PURPOSE: To evaluate the effectiveness of a commercial system(1) in reducing respiration-induced treatment uncertainty by gating the radiation delivery. METHODS AND MATERIALS: The gating system considered here measures respiration from the position of a reflective marker on the patient's chest. Respiration-triggered planning CT scans were obtained for 8 patients (4 lung, 4 liver) at the intended phase of respiration (6 at end expiration and 2 at end inspiration). In addition, fluoroscopic movies were recorded simultaneously with the respiratory waveform. During the treatment sessions, gated localization films were used to measure the position of the diaphragm relative to the vertebral bodies, which was compared to the reference digitally reconstructed radiograph derived from the respiration-triggered planning CT. Variability was quantified by the standard deviation about the mean position. We also assessed the interfraction variability of soft tissue structures during gated treatment in 2 patients using an amorphous silicon electronic portal imaging device. RESULTS: The gated localization films revealed an interfraction patient-averaged diaphragm variability of 2.8 +/- 1.0 mm (error bars indicate standard deviation in the patient population). The fluoroscopic data yielded a patient-averaged intrafraction diaphragm variability of 2.6 +/- 1.7 mm. With no gating, this intrafraction excursion became 6.9 +/- 2.1 mm. In gated localization films, the patient-averaged mean displacement of the diaphragm from the planning position was 0.0 +/- 3.9 mm. However, in 4 of the 8 patients, the mean (over localization films) displacement was >4 mm, indicating a systematic displacement in treatment position from the planned one. The position of soft tissue features observed in portal images during gated treatments over several fractions showed a mean variability between 2.6 and 5.7 mm. The intrafraction variability, however, was between 0.6 and 1.4 mm, indicating that most of the variability was due to patient setup errors rather than to respiratory motion. CONCLUSIONS: The gating system evaluated here reduces the intra- and interfraction variability of anatomy due to respiratory motion. However, systematic displacements were observed in some cases between the location of an anatomic feature at simulation and its location during treatment. Frequent monitoring is advisable with film or portal imaging.

Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system.

We report on initial patient studies to evaluate the performance of a commercial respiratory gating radiotherapy system. The system uses a breathing monitor, consisting of a video camera and passive infrared reflective markers placed on the patient's thorax, to synchronize radiation from a linear accelerator with the patient's breathing cycle. Six patients receiving treatment for lung cancer participated in a study of system characteristics during treatment simulation with fluoroscopy. Breathing synchronized fluoroscopy was performed initially without instruction, followed by fluoroscopy with recorded verbal instruction (i.e., when to inhale and exhale) with the tempo matched to the patient's normal breathing period. Patients tended to inhale more consistently when given instruction, as assessed by an external marker movement. This resulted in smaller variation in expiration and inspiration marker positions relative to total excursion, thereby permitting more precise gating tolerances at those parts of the breathing cycle. Breathing instruction also reduced the fraction of session times having irregular breathing as measured by the system software, thereby potentially increasing the accelerator duty factor and decreasing treatment times. Fluoroscopy studies showed external monitor movement to correlate well with that of the diaphragm in four patients, whereas time delays of up to 0.7 s in diaphragm movement were observed in two patients with impaired lung function. From fluoroscopic observations, average patient diaphragm excursion was reduced from 1.4 cm (range 0.7-2.1 cm) without gating and without breathing instruction, to 0.3 cm (range 0.2-0.5 cm) with instruction and with gating tolerances set for treatment at expiration for 25% of the breathing cycle. Patients expressed no difficulty with following instruction for the duration of a session. We conclude that the external monitor accurately predicts internal respiratory motion in most cases; however, it may be important to check with fluoroscopy for possible time delays in patients with impaired lung function. Furthermore, we observe that verbal instruction can improve breathing regularity, thus improving the performance of gated treatments with this system.

An iterative EPID calibration procedure for dosimetric verification that considers the EPID scattering factor.

There has been an increasing interest in the application of electronic portal imaging devices (EPIDs) to dosimetric verification, particularly for intensity modulated radiotherapy. Although not water equivalent, the phantom scatter factor of an EPID, Spe, is generally assumed to be that of a full phantom, Sp, a slab phantom, Sps, or a mini phantom. This assumption may introduce errors in absolute dosimetry using EPIDs. A calibration procedure that iteratively updates Spe and the calibration curve (pixel value to dose rate) is presented. The EPID (Varian Portal Vision) is irradiated using a 20 x 20 cm2 field with different beam intensities. The initial guess of dose rates in the EPID is calculated from ionization chamber measurements in air, multiplied by Sp or Sps. The calibration curve is obtained by fitting EPID readings from pixels near the beam central axis and dose rates in EPID to a quadratic equation. The Spe is obtained from EPID measurements in 10 X 10 cm2 and 20 x 20 cm2 field and from the calibration curve, and is in turn used to adjust the dose rate measurements and hence the calibration curve. The above procedure is repeated until it converges. The final calibration curve is used to convert portal dose to dose in the slab phantom, using the calibrated Spe, or assuming Spe = Sp or Spe=Sps . The converted doses are then compared with the dose measured using an ionization chamber. We also apply this procedure to off-axis points and study its dependence on the energy spectrum. The hypothesis testing results (on the 95% significance level) indicate that systematic errors are introduced when assuming Spe = Sp or Spe=Sps and the dose calculated using Spe is more consistent with ionization chamber measurements. Differences between Spe and Sps are as large as 2% for large field sizes. The measured relative dose profile at dmax using the EPID agrees well with the measured profile at dmax of the isocentric plane using film in a polystyrene phantom with full buildup and full backup, for open and wedged fields, and for a broad range of field sizes of interest. The dependence of the EPID response on the energy spectrum is removed once the calibration is performed under the same conditions as the actual measurements.

Relative profile and dose verification of intensity-modulated radiation therapy.

PURPOSE: To develop a quality assurance (QA) procedure to assess the intensity profile and dosimetry for intensity-modulated (IM) treatment fields using electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: A series of rapidly acquired (approximately 1/sec) portal images are summed and converted to dose. For relative intensity QA, the intended profile is subtracted point-by-point from the measured profile forming a series of error values. The standard deviation, sigma, of the errors, a measure of the goodness of the match, is minimized by applying a normalization and uniform scatter subtraction from the measured profile. For dose verification (dose to isocenter), an empirically determined phantom-correction factor is added to incorporate the effect of patient presence on EPID readings. Seventy prostate treatment fields were used in a phantom study to verify these approaches. Sensitivity was studied by creating artificial mismatches. RESULTS: The average sigma for relative profile verification is 3.3% (percentage of average intended intensity) whereas artificial mismatches resulted in sigma values from 5% to 27%. The average isocentric dose calculated from EPID readings is 1.001 relative to the planned dose with a standard deviation of 0.018. CONCLUSIONS: An EPID can be used for profile verification and absolute isocentric dose measurement for IM fields.

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation.

PURPOSE/OBJECTIVE: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Quantification and predictors of prostate position variability in 50 patients evaluated with multiple CT scans during conformal radiotherapy.

PURPOSE: To determine the extent and predictors for prostatic motion in a large number of patients evaluated with multiple CT scans during radiotherapy, and evaluate the implications of these data on the design of appropriate treatment margins for patients receiving high-dose three-dimensional conformal radiotherapy. MATERIALS AND METHODS: Fifty patients underwent four serial computerized tomography (CT) scans, consisting of an initial planning scan and subsequent scans at the beginning, middle, and end of the treatment course. Each scan was performed with the patient in the prone treatment position within an immobilization device used during therapy. Contours of the prostate and seminal vesicles were drawn on the axial CT slices of each scan, and the scans were matched by alignment of the pelvic bones with a chamfer matching algorithm. Using the contour information, distributions of the displacement of the organ center of mass and organ border from the planning position were determined separately for the prostate and seminal vesicles in each of the three principle directions: anterior-posterior (AP), superior-inferior (SI) and left-right (LR). Each distribution was fitted to a normal (Gaussian) distribution to determine confidence limits in the center of mass and border displacements and thereby evaluate for the optimal margins needed to contain target motion. RESULTS: The most common directions of displacement of the prostate center of mass (COM) were in the AP and SI directions and were significantly larger than any LR movement. The mean prostate COM displacement (+/- 1 standard deviation, SD) for the entire population was -1.2 +/- 2.9 mm, -0.5 +/- 3.3 mm and -0.6 +/- 0.8 mm in the, AP and SI and LR directions respectively (negative values indicate posterior, inferior or left displacement). The mean (+/- 1 SD) seminal vesicle COM displacement for the entire population was - 1.4 +/- 4.9 mm, 1.3 +/- 5.5 mm and -0.8 +/- 3.1 mm in the AP and SI and LR directions, respectively. The data indicate a tendency for the population towards posterior displacements of the prostate from the planning position and both posterior and superior displacements of the seminal vesicles. AP movement of both the prostate and seminal vesicles were correlated with changes in rectal volume (P = 0.0014 and < 0.0001, respectively) more than with changes in bladder volume (P = 0.030 for seminal vesicles and 0.19 for prostate). A logistic regression analysis identified the combination of rectal volume > 60 cm3 and bladder volumes > 40 cm3 as the only predictor of large ( > 3 mm) systematic deviations for the prostate and seminal vesicles (P = 0.05) defined for each patient as the difference between organ position in the planning scan and mean position as calculated from the three subsequent scans. CONCLUSIONS: Prostatic displacement during a course of radiotherapy is more pronounced among patients with initial planning scans with large rectal and bladder volumes. Such patients may require more generous margins around the CTV to assure its enclosure within the prescription dose region. Identification and correction of patients with large systematic errors will minimize the extent of the margin required and decrease the volume of normal tissue exposed to higher radiation doses.

Computerized design of target margins for treatment uncertainties in conformal radiotherapy.

PURPOSE: We describe a computerized method of determining target margins for beam aperture design in conformal radiotherapy plans. MATERIALS AND METHODS: The method uses previously measured data from a population of patients to simulate setup error and organ motion in the patient currently being planned. Starting with a clinical target volume (CTV) and nontarget organs from the patient's planning CT scan, the simulation is repeated many times to produce a spatial probability distribution for each organ in the treatment machine coordinate system. This is used to determine a prescribed dose volume (PDV), defined as the volume to receive the prescribed dose, which encompasses the CTV while restricting the volume of nontarget organs within it, according to planner-specified values. The PDV is used to design beam apertures using a conventional margin for beam penumbra. RESULTS: The method is applied to 6-field prostate conformal treatment plans, in which the PDV encloses the prostate and seminal vesicles while limiting the enclosed rectal wall volume. The effect of organ motion is assessed by applying the plans on subsequent CT scans of the same patients, calculating probabilities for tumor control (TCP) and normal tissue complication (NTCP), and comparing with plans designed from a physician-drawn planning target volume (PTV). Although prostate TCP and rectal wall NTCP are found to be similar in the two sets of plans, TCP for the seminal vesicles is significantly higher in the PDV-based plans. CONCLUSIONS: The method can improve the dose conformality of treatment plans by incorporating population-based measurements of treatment uncertainties and consideration of nontarget tissues in the design of nonuniform target margins.

Variation in prostate position quantitation and implications for three-dimensional conformal treatment planning.

PURPOSE: This study describes and quantitates the motion, i.e., variation in position, of the prostate within the pelvis and its effect on target and normal organ dose. METHODS AND MATERIALS: The motion of the planning target volume (PTV) borders and center of mass was studied in 13 patients with carcinoma of the prostate through the use of superimposed serial computerized tomography (CT) scans. Changes in bladder and rectal volumes were measured and their relationship to displacements of the PTV position were noted. The effects of this motion on target and normal organ doses were measured. RESULTS: A variability in the position of the PTV is seen over time, which is related to changes in bladder and rectal volumes. The one standard deviation displacements of the PTV center of mass with respect to the planning scan center of mass position were 0.12, 0.40, and 0.31 cm in the lateral, anterior-posterior, and superior-inferior directions, respectively. Movement was significantly larger in the superior part of the PTV above the base of the bladder than in the inferior part. Movement of the borders of the PTV outward from the patient axis; hence, toward the edges of the treatment field, was also examined. Outward displacements of the anterior target border below the base of the bladder were less than 0.3 cm in 90% of the cases, and 1.4 cm above the bladder base. For the posterior wall these displacements were less than 0.7 cm and 1.1 cm, respectively, whereas the lateral border displacements were less than 0.3 cm throughout (90% confidence limits). These displacements would cause a median of 6% of the PTV to receive less than 95% of the planned dose for any given treatment day in these patients; the effect on rectal and bladder wall doses was greater and true doses may not be measurable through the use of only one treatment planning CT scan. CONCLUSIONS: The prostate is not a static organ, but rather has some limited motion in the pelvis secondary to bladder and rectal volume changes. This motion has been quantified for a group of patients, and may provide a guide to further studies on the placement of field borders.

Measurement of patient positioning errors in three-dimensional conformal radiotherapy of the prostate.

PURPOSE/OBJECTIVE: To determine the spatial distribution of setup errors for patients treated with six-field, three-dimensional (3D) conformal radiation therapy for prostate cancer. METHODS AND MATERIALS: Port films for 50 patients were analyzed retrospectively. The port films were digitized and compared, using image registration software, to simulator films (representing the ideal treatment position). Patient positioning uncertainty for a given setup was determined using port films from three projections, two obliques, and one lateral. A total of 1239 port films and 300 simulator films were analyzed for the study. Patient position was analyzed for out-of-plane rotations and time trends over the course of treatment. RESULTS: The distribution of systematic setup errors for the 50 patients, defined as the mean patient displacement for the treatment course, had a mean and standard deviation (SD) of (-0.1 +/- 1.9) mm, (0.4 +/- 1.4) mm, and (-0.3 +/- 1.3) mm in the mediolateral (ML), superior-inferior (SI) and anterior-posterior (AP) directions, and (-0.1 +/- 0.2) for rotational errors. The distribution of random setup errors about the mean approximated a normal distribution and the standard deviations for the population of patients in the ML, SI, and AP directions, were 2.0 mm, 1.7 mm, and 1.9 mm, respectively. The distribution of out-of-plane rotations had 1 SD of 0.9 degrees and 0.6 degrees about the SI and AP axes. Ten of the 50 patients demonstrated a statistically significant time trend in their setup position resulting in shifts ranging from 2 to 7 mm. CONCLUSIONS: The setup verification protocol appears to minimize systematic setup errors to a level that approaches the sensitivity of the image registration technique. The random day to day fluctuations, represented by the average values of the standard deviations, are minor in comparison to the currently used margins, which further emphasizes the effectiveness of this protocol in conjunction with the use of the immobilization device.

A method of incorporating organ motion uncertainties into three-dimensional conformal treatment plans.

PURPOSE: We describe a method of incorporating organ motion into three-dimensional (3D) conformal treatment plans, which predicts the effect of organ motion on the calculated dose to both the clinical target volume (CTV) and nontarget organs. METHODS AND MATERIALS: The method is based on measurements of organ motion by means of multiple computed tomography (CT) scans from a group of "reference" patients, in which the data consist of previously drawn contours of the target and nontarget organs. A computer program records the differences in contour position and shape that occur between scans in the reference data, and according to those differences adjusts the contours and dose calculation points of a "study" patient currently being planned, thus simulating organ motion. Dose-volume histograms (DVHs) are accumulated, and the process is repeated over the set of reference patient scans, resulting in a set of treatment plans that are ranked according to a dose-based endpoint. Two plans are selected corresponding to specified lower and upper confidence limits in the endpoint, and the DVHs from these plans are displayed for comparison with the DVHs from the nominal plan in the absence of motion. RESULTS: As an example of the method's use, it is applied to a 6-field conformal treatment plan for prostate cancer. Confidence limit DVHs of the CTV and rectal wall (in which the plans were ranked by probabilities for tumor control and normal tissue complication, respectively) are presented and compared to those from the nominal plan. CONCLUSION: The method provides a means of estimating the uncertainty in dose delivered by a treatment plan when organ motion is present. It is generally applicable to any treatment site for which data in the form of multiple CT scans are available, and can be extended to include other treatment uncertainties such as variation in patient positioning.

The effects of out-of-plane rotations on two dimensional portal image registration in conformal radiotherapy of the prostate.

PURPOSE: Rotations of the patient out of the image plane can significantly degrade the accuracy of two-dimensional (2D) image registration. This study determines the magnitude of the geometric errors introduced by 2D image registration as a result of out-of-plane rotations, and analyzes the dosimetric effects of these errors. METHODS AND MATERIALS: The magnitude of the errors introduced by 2D registration were determined by comparing orthogonal view portal images of a rotated phantom to simulator reference images of the same phantom without rotation. Dosimetric effects were calculated for three-dimensional (3D) conformal prostate treatments by applying the registration errors to patient treatment plans. The calculations were performed using a modified version of the dose calculation software used in our Cancer Center for 3D treatment planning based on computed tomography (CT). A method to detect out-of-plane rotations, specific to pelvic treatments, is introduced that uses the relative displacement of the centers of gravity of the acetabula in lateral images. RESULTS: The inherent uncertainty in the registration algorithm was 0.6 +/- 0.5 mm in translation and 0.7 +/- 0.8 degree in rotation within the image plane. For a 2 degrees out-of-plane rotation, the errors increase to 2.3 +/- 1.0 mm and 1.2 +/- 1.1 degrees. In some clinically realizable treatment scenarios it was observed that the errors introduced by the registration procedure could result in an overdosing of the rectal wall. The method to detect out-of-plane rotations was found to have an accuracy of better than 1 degree for rotations of less than 10 degrees. CONCLUSIONS: The errors introduced to the patient position by 2D image registration have dosimetrically significant consequences for out-of-plane rotations of 2 degrees or more. However, when used in conjunction with the method to detect out-of-plane rotations, 2D registration software was found to cause insignificant dose errors and, thus, become a more reliable and accurate clinical tool.

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron.

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.