Assessment of intrafraction mediastinal and hilar lymph node movement and comparison to lung tumor motion using four-dimensional CT

PURPOSE: To quantify the amount of free-breathing motion measured using Four-dimensional (4D) CT scans of mediastinal and hilar lymph nodes and to compare this motion to the primary lung tumor motion. METHODS AND MATERIALS: Twenty patients with primary lung cancer, radiographically positive lymph nodes, and prior 4D CT scans were retrospectively analyzed. The 4D CT data sets were divided into four respiratory phases, and the primary tumor and radiographically positive nodes were contoured. Geometric and volumetric analysis was performed to analyze the motion of the primary tumors and the lymph nodes. RESULTS: The mean lymph node motion was 2.6 mm in the mediolateral direction, 2.5 mm in the anterior-posterior direction, and 5.2 mm in the cranial-caudal direction with a maximum of 14.4 mm. All lymph nodes were found to move inferiorly during inspiration, with 12.5% of nodes moving more than 1 cm. Lymph nodes located below the carina showed significantly more motion than those above the carina (p = 0.01). In comparing the primary tumor motion to the lymph node motion, no correlation was identified. CONCLUSIONS: Four-dimensional CT scans can be used to measure the motion of the primary lung tumor and pathologic lymph nodes encountered during the respiratory cycle. Both the primary lung tumor and the lymph node must to be examined to assess their individual degree of motion. This study demonstrates the need for individualized plans to assess the heterogeneous motion encountered in both primary lung tumors and among lymph node stations.     

Quantification of motion of different thoracic locations using four-dimensional computed tomography: implications for radiotherapy planning

PURPOSE: To assess the respiratory motion of different thoracic nodal locations and its dependence on the presence of enlarged nodes; to assess the respiratory motion of different parenchymal tumor locations; and to determine the appropriate margins to cover the respiratory motion of targets at these locations. METHODS AND MATERIALS: We reviewed the four-dimensional computed tomography scans of 20 patients with thoracic tumors treated at our institution. The motion of four central thoracic locations (aortic arch, carina, and bilateral hila), parenchymal tumor locations (upper vs. lower, and anterior vs. middle vs. posterior thorax), and bilateral diaphragmatic domes was measured. RESULTS: For the central thoracic locations, the largest motion was in the superoinferior (SI) dimension (>5 mm for bilateral hila and carina, but <4 mm for aortic arch). No significant difference was found in the motion of these locations in the absence or presence of enlarged nodes. For parenchymal tumors, upper tumors exhibited smaller SI motion than did lower tumors (3.7 vs. 10.4 mm, p = 0.029). Similarly, anterior tumors exhibited smaller motion than did posterior tumors in both the SI (4.0 vs. 8.0 mm, p = 0.013) and lateral (2.8 vs. 4.6 mm, p = 0.045) directions. The margins that would be needed to encompass the respiratory motion of each of the evaluated locations in 95% of patients were tabulated and range from 3.4 to 37.2 mm, depending on the location and direction. CONCLUSIONS: The results of our study have provided data for appropriate site-specific internal target volume expansion that could be useful in the absence of four-dimensional computed tomography-based treatment planning. However, generalizing the results from a small patient population requires discretion.     

Design of 4D treatment planning target volumes

PURPOSE: When using non-patient-specific treatment planning margins, respiratory motion may lead to geometric miss of the target while unnecessarily irradiating normal tissue. Imaging different respiratory states of a patient allows patient-specific target design. We used four-dimensional computed tomography (4DCT) to characterize tumor motion and create treatment volumes in 10 patients with lung cancer. These were compared with standard treatment volumes. METHODS AND MATERIALS: Four-dimensional CT and free breathing helical CT data of 10 patients were acquired. Gross target volumes (GTV) were delineated on the helical scan as well as on each phase of the 4D data. Composite GTVs were defined on 4DCT. Planning target volumes (PTV) including clinical target volume, internal margin (IM), and setup margin were generated. 4DPTVs with different IMs and standard PTVs were compared by computing centroid positions, volumes, volumetric overlap, and bounding boxes. RESULTS: Four-dimensional PTVs and conventional PTVs differed in volume and centroid positions. Overlap between 4DPTVs generated from two extreme tumor positions only compared with 10 respiratory phases was 93.7%. Comparing PTVs with margins of 15 mm (IM 5 mm) on composite 4D target volumes to PTVs with 20 mm (IM 10 mm) on helical CT data resulted in a decrease in target volume sizes by 23% on average. CONCLUSION: With patient-specific characterization of tumor motion, it should be possible to decrease internal margins. Patient-specific treatment volumes can be generated using extreme tumor positions on 4DCT. To date, more than 150 patients have been treated using 4D target design.     

Comparison of different strategies to use four-dimensional computed tomography in treatment planning for lung cancer patients

PURPOSE: To discuss planning target volumes (PTVs) based on internal target volume (PTVITV), exhale-gated radiotherapy (PTVGating), and a new proposed midposition (PTVMidP; time-weighted mean tumor position) and compare them with the conventional free-breathing CT scan PTV (PTVConv). METHODS AND MATERIALS: Respiratory motion induces systematic and random geometric uncertainties. Their contribution to the clinical target volume (CTV)-to-PTV margins differs for each PTV approach. The uncertainty margins were calculated using a dose-probability-based margin recipe (based on patient statistics). Tumor motion in four-dimensional CT scans was determined using a local rigid registration of the tumor. Geometric uncertainties for interfractional setup errors and tumor baseline variation were included. For PTVGating, the residual motion within a 30% gating (time) window was determined. The concepts were evaluated in terms of required CTV-to-PTV margin and PTV volume for 45 patients. RESULTS: Over the patient group, the PTVITV was on average larger (+6%) and the PTVGating and PTVMidP smaller (-10%) than the PTVConv using an off-line (bony anatomy) setup correction protocol. With an on-line (soft tissue) protocol the differences in PTV compared with PTVConv were +33%, -4%, and 0, respectively. CONCLUSIONS: The internal target volume method resulted in a significantly larger PTV than conventional CT scanning. The exhale-gated and mid-position approaches were comparable in terms of PTV. However, mid-position (or mid-ventilation) is easier to use in the clinic because it only affects the planning part of treatment and not the delivery.     

Locate: An application of computed tomography in radiation therapy treatment planning with emphasis on tumor localization

Computed tomography can provide precise information for radiation therapy treatment planning. However, inaccuracies in radiation field design may occur when the radiation oncologist attempts to transfer information about tumor location from the transverse plane of the CT scan to the longitudinal plane of the simulation film. This report describes a new computer program, LOCATE, which addresses this problem. The program uses operator generated information from the cross sectional CT images to draw an outline of tumor on AP and lateral longitudinal scanned projection radiographs. The resultant images are useful because they are in the same plane as radiographs obtained on a therapy simulator. The impact of LOCATE on radiation treatment planning for 26 patients is discussed along with several cases in which LOCATE was particularly helpful.     

Maximum-intensity volumes for fast contouring of lung tumors including respiratory motion in 4DCT planning

PURPOSE: To assess the accuracy of maximum-intensity volumes (MIV) for fast contouring of lung tumors including respiratory motion. METHODS AND MATERIALS: Four-dimensional computed tomography (4DCT) data of 10 patients were acquired. Maximum-intensity volumes were constructed by assigning the maximum Hounsfield unit in all CT volumes per geometric voxel to a new, synthetic volume. Gross tumor volumes (GTVs) were contoured on all CT volumes, and their union was constructed. The GTV with all its respiratory motion was contoured on the MIV as well. Union GTVs and GTVs including motion were compared visually. Furthermore, planning target volumes (PTVs) were constructed for the union of GTVs and the GTV on MIV. These PTVs were compared by centroid position, volume, geometric extent, and surface distance. RESULTS: Visual comparison of GTVs demonstrated failure of the MIV technique for 5 of 10 patients. For adequate GTV(MIV)s, differences between PTVs were <1.0 mm in centroid position, 5% in volume, +/-5 mm in geometric extent, and +/-0.5 +/- 2.0 mm in surface distance. These values represent the uncertainties for successful MIV contouring. CONCLUSION: Maximum-intensity volumes are a good first estimate for target volume definition including respiratory motion. However, it seems mandatory to validate each individual MIV by overlaying it on a movie loop displaying the 4DCT data and editing it for possible inadequate coverage of GTVs on additional 4DCT motion states.     

Four-dimensional proton treatment planning for lung tumors

PURPOSE: In proton radiotherapy, respiration-induced variations in density lead to changes in radiologic path lengths and will possibly result in geometric misses. We compared different treatment planning strategies for lung tumors that compensate for respiratory motion. METHODS AND MATERIALS: Particle-specific treatment planning margins were applied to standard helical computed tomography (CT) scans as well as to "representative" CT scans. Margins were incorporated beam specific laterally by aperture widening and longitudinally by compensator smearing. Furthermore, treatment plans using full time-resolved 4D-computed tomography data were generated. RESULTS: Four-dimensional treatment planning guaranteed target coverage throughout a respiratory cycle. Use of a standard helical CT data set resulted in underdosing the target volume to 36% of the prescribed dose. For CT data representing average target positions, coverage can be expected but not guaranteed. In comparison to this strategy, 4D planning decreased the mean lung dose by up to 16% and the lung volume receiving 20 Gy (prescribed target dose 72 Gy) by up to 15%. CONCLUSION: When the three planning strategies are compared, only 4D proton treatment planning guarantees delivery of the prescribed dose throughout a respiratory cycle. Furthermore, the 4D planning approach results in equal or reduced dose to critical structures; even the ipsilateral lung is spared.     

Effect of novel amplitude/phase binning algorithm on commercial four-dimensional computed tomography quality

PURPOSE: Respiratory motion is a significant source of anatomic uncertainty in radiotherapy planning and can result in errors of portal size and the subsequent radiation dose. Although four-dimensional computed tomography allows for more accurate analysis of the respiratory cycle, breathing irregularities during data acquisition can cause considerable image distortions. The aim of this study was to examine the effect of respiratory irregularities on four-dimensional computed tomography, and to evaluate a novel image reconstruction algorithm using percentile-based tagging of the respiratory cycle. METHODS AND MATERIALS: Respiratory-correlated helical computed tomography scans were acquired for 11 consecutive patients. The inspiration and expiration data sets were reconstructed using the default phase-based method, as well as a novel respiration percentile-based method with patient-specific metrics to define the ranges of the reconstruction. The image output was analyzed in a blinded fashion for the phase- and percentile-based reconstructions to determine the prevalence and severity of the image artifacts. RESULTS: The percentile-based algorithm resulted in a significant reduction in artifact severity compared with the phase-based algorithm, although the overall artifact prevalence did not differ between the two algorithms. The magnitude of differences in respiratory tag placement between the phase- and percentile-based algorithms correlated with the presence of image artifacts. CONCLUSION: The results of our study have indicated that our novel four-dimensional computed tomography reconstruction method could be useful in detecting clinically relevant image distortions that might otherwise go unnoticed and to reduce the image distortion associated with some respiratory irregularities. Additional work is necessary to assess the clinical impact on areas of possible irregular breathing.     

Determination of respiratory motion for distal esophagus cancer using four-dimensional computed tomography

PURPOSE: To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). METHODS AND MATERIALS: Thirty-one consecutive patients treated for esophagus cancer who received respiratory-gated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. RESULTS: The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y-direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. CONCLUSIONS: Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of +/-1.8 cm would provide tumor motion coverage for 95% of the cases in our study population.     

Image-guided radiotherapy for liver cancer using respiratory-correlated computed tomography and cone-beam computed tomography

PURPOSE: To evaluate a novel four-dimensional (4D) image-guided radiotherapy (IGRT) technique in stereotactic body RT for liver tumors. METHODS AND MATERIALS: For 11 patients with 13 intrahepatic tumors, a respiratory-correlated 4D computed tomography (CT) scan was acquired at treatment planning. The target was defined using CT series reconstructed at end-inhalation and end-exhalation. The liver was delineated on these two CT series and served as a reference for image guidance. A cone-beam CT scan was acquired after patient positioning; the blurred diaphragm dome was interpreted as a probability density function showing the motion range of the liver. Manual contour matching of the liver structures from the planning 4D CT scan with the cone-beam CT scan was performed. Inter- and intrafractional uncertainties of target position and motion range were evaluated, and interobserver variability of the 4D-IGRT technique was tested. RESULTS: The workflow of 4D-IGRT was successfully practiced in all patients. The absolute error in the liver position and error in relation to the bony anatomy was 8 +/- 4 mm and 5 +/- 2 mm (three-dimensional vector), respectively. Margins of 4-6 mm were calculated for compensation of the intrafractional drifts of the liver. The motion range of the diaphragm dome was reproducible within 5 mm for 11 of 13 lesions, and the interobserver variability of the 4D-IGRT technique was small (standard deviation, 1.5 mm). In 4 patients, the position of the intrahepatic lesion was directly verified using a mobile in-room CT scanner after application of intravenous contrast. CONCLUSION: The results of our study have shown that 4D image guidance using liver contour matching between respiratory-correlated CT and cone-beam CT scans increased the accuracy compared with stereotactic positioning and compared with IGRT without consideration of breathing motion.     

Advantages and limitations of computed tomography scans for treatment planning of lung cancer

Forty-five Chest computed tomography (CT) scans performed on patients with lung carcinoma (LC) were evaluated in an attempt to understand the pattern of intrathoracic tumor spread and the advantages and limitations this technique offers for treatment planning when compared to planning done by conventional X rays. The following findings can help treatment planning. (1) When regular X rays do not show tumor location (i.e., hemithorax opacification), CT scan will show it in 68% of patients. If regular X rays show a well localized mass, unsuspected tumor extensions were disclosed in 78 % of these patients. Hence, CT scans should be done in all LC patients prior to treatment planning; (2) Mediastinal masses frequently spread anteriorly toward the sternum and posteriorly around the vertebral bodies toward the cord and costal pleura. This should be considered for radiotherapy boost techniques; (3) Lung masses spread in one third of cases toward the lateral costal pleura. Thus, the usual 1–2cm of safety margin around the LC are not sufficient in some cases; (4) Tumor size can appear much smaller in regular X rays than in CT scans. Hence, CT scans are necessary for accurate staging and evaluation of tumor response. Some CT scan limitations are: (1) Atelectasis blends with tumor in approximately half of the patients, thus obscuring tumor boundaries; (2) CT numbers and contrast enhancement did not help to differentiate between these two structures; and (3) Limited definition of CT scan prevents investigation of suspected microscopic spread around tumor masses.     

The utility of computed tomography in radiation therapy: an estimate of outcome

Several studies have shown that computed tomography (CT) scanning leads to changes in planned therapy for some 40 to 60 % of patients studied. An empirical model has been developed to estimate the improvement in local control and long term survival attributable to CT. The model is based upon an average dose-response relationship for the tumors and involves a technique for estimating the change in tumor control probability when part of the tumor is underdosed. Using this model, it was estimated that, in one series of patients, CT scanning improved the local tumor control probability by an average of 6 %, and improved the chance of 5-year survival by an average of 3.5 %.     

Localization and protection of kidneys in radiation treatment planning using computed tomography

Irradiation treatment portals of the upper abdomen must limit the dose to the kidneys. Sparing one-third of the parenchyma of each kidney will prevent late clinical sequelae. One hundred CT scans of the abdomen were studied to evaluate using the vertebrae as landmark for treatment planning. In lateral fields, using the anterior border of the vertebral column as a landmark for the posterior high isodose line will limit treatment to less than 60% (mean 22%) of a single kidney. Placing the edge of an anterior/posterior field 2 cm lateral to the vertebral column will limit the dose to less than 44% of a single kidney (mean 11%).     

Computed tomography in planning radiation therapy for Bronchogenic Carcinoma

Computerized tomography (CT) was used in the pretreatment evaluation of 23 patients who had bronchogenic carcinoma and applied to planning radiation therapy treatments. It was used to supplement conventional radiologic and clinical methods. Major changes in radiation therapy treatment were based on CT scans in nine patients, either through demonstration of larger or smaller treatment volumes or additional sites of disease, including distant metastasis. In two patients, CT scans falsely indicated absence of metastasis or benign rather than malignant disease. Changes in treatment techniques, e.g. electron beams for superficial lesions, were made based on CT scans in an additional eight patients. Follow-up studies were obtained at three-month intervals; however, CT scans did not distinguish conclusively between tumor recurrence and radiation fibrosis of the lung, although the possible value of contrast material was noted.     

Comparison of radiotherapy treatment plans for left-sided breast cancer patients based on three- and four-dimensional computed tomography imaging

Aims

The target volume for breast radiotherapy after conservative surgery for breast cancer may be affected by breathing motion. We investigated differences between conventional and four-dimensional computed tomography-based treatment planning and whether gating could improve dose volume parameters.

Materials and methods

Ten patients with left-sided breast cancer and surgical clips at the excision site had conventional treatment planning computed tomography and four-dimensional computed tomography. Treatment plans using two tangential beams (6 MV X-rays) were optimised for target coverage and homogeneity using a field in field technique for the three-dimensional scan. This plan was applied directly to four-dimensional datasets representing individual phases of the breathing cycle and combinations thereof (average and maximum intensity projection). Optimised plans were generated for the maximum inhalation scan to study what could potentially be achieved in gated radiotherapy.

Results

Four-dimensional computed tomography with effective doses of around 10 mSv proved to be adequate for treatment planning in all patients. The average motion of the surgical clips was 3.7 mm (range 1.7–6.5 mm), which was similar to the movement of the chest wall. With a margin of 7 mm for the whole breast to planning target volume, conventional three-dimensional computed tomography-based planning was found to adequately cover the target as seen on four-dimensional computed tomography without significant differences in normal tissue sparing. Improved sparing of the heart and lung could only be achieved by reducing the posterior margin of the target volume, which may be justified if four-dimensional computed tomography is used to determine the target and its motion.

Conclusion

No significant benefit has been shown for the use of four-dimensional computed tomography-based planning if motion management is not implemented concurrently with a reduced posterior margin between clinical and planning target volumes.     

Motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes

Background and purpose

To quantify the benefit of motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes generated using 4D-PET, vs. conventional internal target volumes generated using non-respiratory gated PET and 4D-CT scans.

Materials and methods

Five patients with FDG-avid tumors metastatic to 11 hilar or mediastinal lymph nodes were imaged with respiratory-correlated FDG-PET (4D-PET) and 4D-CT. FDG-avid nodes were contoured by a radiation oncologist in two ways. Standard-of-care volumes were contoured using conventional un-gated PET, 4D-CT, and breath-hold CT. A second, motion-specific, set of volumes were contoured using 4D-PET.Contours based on 4D-PET corresponded directly to an internal target volume (ITV_4D), whereas contours based on un-gated PET were expanded by a series of exploratory isotropic margins (from 5 to 13 mm) based on literature recommendations on lymph node motion to form internal target volumes (ITV_3D).

Results

A 13 mm expansion of the un-gated PET nodal volume was needed to cover the ITV_4D for 10 of 11 nodes studied. The ITV_3D based on a 13 mm expansion included on average 45 cm³ of tissue that was not included in the ITV_4D.

Conclusions

Motion-specific lymph-node internal target volumes generated from 4D-PET imaging could be used to improve accuracy and/or reduce normal-tissue irradiation compared to the standard-of-care un-gated PET based internal target volumes.