Effect of breathing motion in radiotherapy of breast cancer: 4D dose calculation and motion tracking via EPID.

PURPOSE: To evaluate the influence of breathing motion in postoperative whole-breast radiotherapy. PATIENTS AND METHODS: For ten patients with left-sided breast cancer, radiotherapy treatment plans were generated based on conventional three-dimensional computed tomography (3D CT) studies: two techniques (segmented and wedge-based tangential fields) were compared. The influence of breathing motion on the dose to the target and organs at risk (OARs) was evaluated with four-dimensional (4D) dose calculation based on respiration-correlated CTs. Reproducibility of breathing motion was evaluated with electronic portal images (EPID) acquired in cine mode during treatment. RESULTS: Differences in dose distributions were small between segmented and wedge techniques based on 3D studies. Because of small motion amplitude of the chest in the 4D CT studies (1.8 mm +/- 0.9 mm), target coverage was reduced by < 5% due to breathing motion. Differences between 3D and 4D dose calculation were similar for segmented and wedge techniques. Blurring of the dose distribution in 4D dose calculation resulted in lower doses to the OARs. Analysis of EPID movies proved good reproducibility of breathing motion observed in the 4D CT study. CONCLUSION: Breathing motion was of minor relevance in postoperative radiotherapy treatment of breast cancer for both segmented and wedge tangential field techniques.

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.

Tumor tracking and motion compensation with an adaptive tumor tracking system (ATTS): system description and prototype testing.

A novel system for real-time tumor tracking and motion compensation with a robotic HexaPOD treatment couch is described. The approach is based on continuous tracking of the tumor motion in portal images without implanted fiducial markers, using the therapeutic megavoltage beam, and tracking of abdominal breathing motion with optical markers. Based on the two independently acquired data sets the table movements for motion compensation are calculated. The principle of operation of the entire prototype system is detailed first. In the second part the performance of the HexaPOD couch was investigated with a robotic four-dimensional-phantom capable of simulating real patient tumor trajectories in three-dimensional space. The performance and limitations of the HexaPOD table and the control system were characterized in terms of its dynamic behavior. The maximum speed and acceleration of the HexaPOD were 8 mm/s and 34.5 mm/s2 in the lateral direction, and 9.5 mm/s and 29.5 mm/s2 in longitudinal and anterior-posterior direction, respectively. Base line drifts of the mean tumor position of realistic lung tumor trajectories could be fully compensated. For continuous tumor tracking and motion compensation a reduction of tumor motion up to 68% of the original amplitude was achieved. In conclusion, this study demonstrated that it is technically feasible to compensate breathing induced tumor motion in the lung with the adaptive tumor tracking system.

Is a single respiratory correlated 4D-CT study sufficient for evaluation of breathing motion?

PURPOSE: Respiratory correlated computed tomography has been shown to be effective for evaluation of breathing-induced motion of pulmonary tumors. This study investigated whether a single four-dimensional CT study (4D-CT) is representative and sufficient for treatment planning in stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Four repeated helical 4D-CT studies were acquired every 10 min for 10 patients with 14 pulmonary metastases. Patients remained immobilized in a stereotactic body frame (SBF) for 30 min; abdominal compression was applied to seven patients. Using amplitude based sorting, eight phases equally distributed over the breathing cycle were reconstructed for each 4D-CT study. Tumor position was defined in a total of 406 CT series and variability of breathing motion and mean tumor position were evaluated. RESULTS: Peak-to-peak tumor motion was 9.9 mm +/- 6.8 mm (mean +/- standard deviation) and 9.0 mm +/- 7.4 mm at time point 0 min (t(0)) and t(30), respectively. In one patient with poor pulmonary function, continuous increase of breathing motion from 17.4 mm at t(0) to 28.3 mm at t(30) was seen. In five and two lesions, respectively, a drift of the mean tumor position greater than 3 mm and 5 mm was observed. A borderline significance was calculated for larger tumor position variability in midventilation phases compared with peak-ventilation phases of the breathing cycle (p = 0.08). CONCLUSION: Treatment planning based on a single 4D-CT study is reliable for the majority of patients. Increased intrafractional uncertainties were seen for patients with poor pulmonary function and with tumors located in the lower lobe.

Four-dimensional treatment planning for stereotactic body radiotherapy.

PURPOSE: To investigate the influence of tumor motion on the calculation of four-dimensional (4D) dose distributions of the gross tumor volume (GTV) in pulmonary stereotactic body radiotherapy. METHODS AND MATERIALS: For 7 patients with eight pulmonary tumors, a respiratory-correlated 4D-computed tomography study was acquired. The internal target volume was the sum of all tumor positions in the planning 4D-computed tomography study, and a 5-mm margin was used for generation of the planning target volume. Three-dimensional (3D) treatment plans were generated with a dose prescription of 3 x 12.5 Gy to the planning target volume enclosing the 65% and 80% isodose. After model-based nonrigid image registration, the 4D dose distributions were calculated. RESULTS: No significant difference was found in the dose to the GTV with the tumor in the end-exhalation, end-inhalation, or mid-ventilation phase of the breathing cycle. The high-dose region was confined to the solid tumor, and lower doses were delivered to the surrounding pulmonary tissue of lower density. This nonstatic, variant dose distribution increased the 4D dose to the GTV by 6.2%, on average, compared with calculations using on a static dose distribution during the breathing cycle. The 4D accumulation resulted in a biologic effective dose (BED) of 143 +/- 8 Gy and 106 +/- 4 Gy to the GTV in the plan-65% and plan-80%, respectively. The dose to the ipsilateral lung was not different between the 3D and 4D dose calculations or between plan-65% and plan-80%. CONCLUSIONS: In this study, the dose to the GTV was not decreased or blurred in the 4D plan compared with the 3D plan. The 3D doses to the GTV, internal target volume, and dose at the isocenter were good approximations of the 4D dose calculations. The 3D dose at the planning target volume margin underestimated the 4D dose significantly.

Reliability of the bony anatomy in image-guided stereotactic radiotherapy of brain metastases.

PURPOSE: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). METHODS AND MATERIALS: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. RESULTS: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean +/- SD) was 4.0 +/- 2.1 mm and 3.5 +/- 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r >/= 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 +/- 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. CONCLUSION: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT.

Positioning accuracy of cone-beam computed tomography in combination with a HexaPOD robot treatment table.

PURPOSE: To scrutinize the positioning accuracy and reproducibility of a commercial hexapod robot treatment table (HRTT) in combination with a commercial cone-beam computed tomography system for image-guided radiotherapy (IGRT). METHODS AND MATERIALS: The mechanical stability of the X-ray volume imaging (XVI) system was tested in terms of reproducibility and with a focus on the moveable parts, i.e., the influence of kV panel and the source arm on the reproducibility and accuracy of both bone and gray value registration using a head-and-neck phantom. In consecutive measurements the accuracy of the HRTT for translational, rotational, and a combination of translational and rotational corrections was investigated. The operational range of the HRTT was also determined and analyzed. RESULTS: The system performance of the XVI system alone was very stable with mean translational and rotational errors of below 0.2 mm and below 0.2 degrees , respectively. The mean positioning accuracy of the HRTT in combination with the XVI system summarized over all measurements was below 0.3 mm and below 0.3 degrees for translational and rotational corrections, respectively. The gray value match was more accurate than the bone match. CONCLUSION: The XVI image acquisition and registration procedure were highly reproducible. Both translational and rotational positioning errors can be corrected very precisely with the HRTT. The HRTT is therefore well suited to complement cone-beam computed tomography to take full advantage of position correction in six degrees of freedom for IGRT. The combination of XVI and the HRTT has the potential to improve the accuracy of high-precision treatments.

Precision required for dose-escalated treatment of spinal metastases and implications for image-guided radiation therapy (IGRT).

INTRODUCTION: To evaluate the precision required in dose-escalated IMRT treatment of spinal metastases and paraspinal tumors. METHODS: In IMRT treatment plans of nine patients with spinal metastases (n=7) and paraspinal tumors (n=2) translational patient positioning errors (0-10mm) and rotational errors (0-7.5 degrees ) were simulated. The dose to the spinal cord (D5(spine)) resulting from these simulations was evaluated and NTCP for spinal cord necrosis was calculated. All patient set-up errors observed during treatment were simulated and the influence on D5(spine) was investigated. RESULTS: To keep the dose distribution to the spinal cord within +/-5% (+/-10%) of the prescribed dose, maximum tolerable errors of 1mm (2mm) in the transversal plane, 4mm (7mm) in superior-inferior direction and maximum rotations of 3.5 degrees (5 degrees ) were calculated on average. The translational and rotational component of clinically observed set-up errors increased D5(spine) by 23+/-14% and 3+/-2% on average, respectively. CONCLUSION: Steep dose gradients of IMRT planning require very high precision. In selected patients correction of both translational and rotational errors may be beneficial.

Intra-fractional uncertainties in cone-beam CT based image-guided radiotherapy (IGRT) of pulmonary tumors.

PURPOSE: Intra-fractional variability of tumor position and breathing motion was evaluated in cone-beam CT (CB-CT) based image-guided radiotherapy (IGRT) of pulmonary tumors. MATERIALS AND METHODS: Twenty-four patients (27 lesions: prim. NSCLC n=6; metastases n=21) were treated with stereotactic body radiotherapy (SBRT) (one to eight fractions). Prior to every treatment fraction (n=66) and immediately after treatment a CB-CT was acquired. Patient motion, absolute drift and drift of the tumor relative to the bony anatomy were measured. Tumor motion was investigated based on the density distribution in the CB-CT. RESULTS: Absolute intra-fractional drift (3D vector) of the tumor position was 2.8 mm+/-1.6 mm (mean +/- SD), maximum 7.2 mm. Poor correlation between patient motion and absolute tumor drift was observed. Changes of the tumor position due to patient motion and due to drifts independently from the bony anatomy were of similar magnitude with 2.1 mm +/- 1.4 mm and 2.3 mm +/- 1.6 mm, respectively. No systematic increase or decrease of breathing motion was seen. The intra-fractional change of breathing motion was more than 2 mm and 3 mm in 39% and 16%, respectively. CONCLUSION: Intra-fractional tumor position and breathing motion were stable. In IGRT of pulmonary tumors we suggest an ITV-to-PTV margin of 5 mm to compensate intra-fractional changes.

Influence of retrospective sorting on image quality in respiratory correlated computed tomography.

PURPOSE: To evaluate the influence of retrospective sorting on image quality in four-dimensional respiratory correlated CT. MATERIALS AND METHODS: Twelve patients with intrapulmonary tumors were examined using a 24-slice CT-scanner in helical mode. Images were reconstructed after retrospective sorting based on five algorithms: amplitude-based sorting with definition of peak-exhalation and peak-inhalation separately/locally for all breathing cycles (LAS) and globally for the time of image acquisition (GAS). Drifts of the breathing signal were corrected in dc-GAS. In phase-based (PS) and cycle-based (CS) algorithm the projections were sorted relative to time. Motion artifacts were scored by a radiologist. The tumor volumes were measured using automatic image segmentation. RESULTS: Averaged over all breathing phases, LAS and PS achieved significantly improved image quality and lowest tumor volume variability compared to GAS, dc-GAS and CS. Imaging redundancy of 5s was not sufficient for GAS and dc-GAS: missing corresponding amplitude positions in one or several breathing cycles resulted in incomplete reconstruction of peak-ventilation images in 11/12 and 10/12 patients with GAS and dc-GAS, respectively. Limiting the analysis to mid-ventilation phases showed GAS and dc-GAS as the most reliable algorithms. CONCLUSIONS: LAS and PS are suggested as a compromise between image quality and radiation dose.

Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma cells.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) overexpression has been linked to tumor progression and poor prognosis. We investigated whether targeting of HIF-1 using chetomin, a disrupter of the interaction of HIF-1 with the transcriptional coactivator p300, influences the radiosensitivity of hypoxic HT 1080 human fibrosarcoma cells. METHODS: Optimal dose of chetomin was determined by EGFP-HRE gene reporter assay in stably transfected HT 1080 cells. Cells were assayed for expression of the hypoxia-inducible genes carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) by RT-PCR and for clonogenic survival after irradiation with 2, 5 or 10 Gy, under normoxic or hypoxic (0.1% O2, 12 h) conditions in the presence or absence of chetomin (150 nM, 12 h, pre-treatment of 4 h). RESULTS: Chetomin treatment significantly reduced CA9 and VEGF mRNA expression in hypoxic cells to 44.4 +/- 7.2% and 39.6 +/- 16.0%, respectively, of untreated hypoxic controls. Chetomin clearly reduced the modified oxygen enhancement ratio (OER') compared to untreated cells, from 2.02 to 1.27, from 1.86 to 1.22 and from 1.49 to 1.06 at the 50%, 37% and 10% clonogenic survival levels, respectively. CONCLUSION: HIF-1 inhibition by chetomin effectively reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro.

Magnitude and clinical relevance of translational and rotational patient setup errors: a cone-beam CT study.

PURPOSE: To establish volume imaging using an on-board cone-beam CT (CB-CT) scanner for evaluation of three-dimensional patient setup errors. METHODS AND MATERIALS: The data from 24 patients were included in this study, and the setup errors using 209 CB-CT studies and 148 electronic portal images were analyzed and compared. The effect of rotational errors alone, translational errors alone, and combined rotational and translational errors on target coverage and sparing of organs at risk was investigated. RESULTS: Translational setup errors using the CB-CT scanner and an electronic portal imaging device differed <1 mm in 70.7% and <2 mm in 93.2% of the measurements. Rotational errors >2 degrees were recorded in 3.7% of pelvic tumors, 26.4% of thoracic tumors, and 12.4% of head-and-neck tumors; the corresponding maximal rotational errors were 5 degrees , 8 degrees , and 6 degrees . No correlation between the magnitude of translational and rotational setup errors was observed. For patients with elongated target volumes and sharp dose gradients to adjacent organs at risk, both translational and rotational errors resulted in considerably decreased target coverage and highly increased doses to the organs at risk compared with the initial treatment plan. CONCLUSIONS: The CB-CT scanner has been successfully established for the evaluation of patient setup errors, and its feasibility in day-to-day clinical practice has been demonstrated. Our results have indicated that rotational errors are of clinical significance for selected patients receiving high-precision radiotherapy.

Adverse effect of a distended rectum in intensity-modulated radiotherapy (IMRT) treatment planning of prostate cancer.

BACKGROUND AND PURPOSE: The retrospective planning study for intensity-modulated radiotherapy (IMRT) of prostate cancer evaluated whether proximal rectum and supra-anal rectum/anal canal should be delineated as separated organs-at-risk (OARs) to achieve optimal dose distributions to the anorectal region. PATIENTS AND METHODS: For 10 patients with localized prostate cancer IMRT plans were generated with the rectum and anal canal as separated OARs (Rec-sep) and as one single OAR (Rec-tot). Two different treatment planning systems (TPS) were utilized. Influence on dose distributions to target and OARs was analyzed. RESULTS: Results from both TPS showed significantly increased doses to the distal rectum/anal canal for plans Rec-tot compared with Rec-sep in case of a distended rectum in the planning CT study: doses were increased by up to mean 31% (P = 0.02) and 18% (P = 0.03), respectively, in both TPS. For the patient with the largest rectum, the maximum dose increase was 61%. No significant differences in doses to target, bladder, femoral head and proximal rectum were seen. CONCLUSIONS: For patients with a distended rectum in the planning CT, delineation of separated OARs for proximal rectum and distal rectum/anal canal resulted in superior dose distributions to the anorectal region and therefore, we recommend this as standard procedure for IMRT planning of prostate cancer.

Tracking moving objects with megavoltage portal imaging: a feasibility study.

Four different algorithms were investigated with the aim to determine their suitability to track an object in conventional megavoltage portal images. The algorithms considered were the mean of the sum of squared differences (MSSD), mutual information (MI), the correlation ratio (CR), and the correlation coefficient (CC). Simulation studies were carried out with various image series containing a rigid object of interest that was moved along a predefined trajectory. For each of the series the signal-to-noise ratio (SNR) was varied to compare the performance of the algorithms under noisy conditions. For a poor SNR of -6 dB the mean tracking error was 2.4, 6.5, 39.0, and 17.2 pixels for MSSD, CC, CR and MI, respectively, with a standard deviation of 1.9, 12.9, 19.5, and 7.5 pixels, respectively. The size of a pixel was 0.5 mm. These results improved to 1.1, 1.3, 1.3, and 2.0 pixels, respectively, with a standard deviation of 0.6, 0.8, 0.8, and 2.1 pixels, respectively, when a mean filter was applied to the images prior to tracking. The implementation of MSSD into existing in-house software demonstrated that, depending on the search range, it was possible to process between 2 and 15 images/s, making this approach capable of real-time applications. In conclusion, the best geometric tracking accuracy overall was obtained with MSSD, followed by CC, CR, and MI. The simplest and best algorithm, both in terms of geometric accuracy as well as computational cost, was the MSSD algorithm and was therefore the method of choice.

Dose-response in stereotactic irradiation of lung tumors.

The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1-8 fractions with different fraction doses was used. After a median follow-up of 14 months (2-85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94Gy at the isocenter and 50Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control.

Fast image acquisition and processing on a TV camera-based portal imaging system.

The present paper describes the fast acquisition and processing of portal images directly from a TV camera-based portal imaging device (Siemens Beamview Plus). This approach employs not only hard- and software included in the standard package installed by the manufacturer (in particular the frame grabber card and the Matrox Intellicam interpreter software), but also a software tool developed in-house for further processing and analysis of the images. The technical details are presented, including the source code for the Matrox interpreter script that enables the image capturing process. With this method it is possible to obtain raw images directly from the frame grabber card at an acquisition rate of 15 images per second. The original configuration by the manufacturer allows the acquisition of only a few images over the course of a treatment session. The approach has a wide range of applications, such as quality assurance (QA) of the radiation beam, real-time imaging, real-time verification of intensity-modulated radiation therapy (IMRT) fields, and generation of movies of the radiation field (fluoroscopy mode).

Cell type-specific association of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein accumulation and radiobiologic tumor hypoxia.

PURPOSE: The transcription factor subunit hypoxia-inducible factor-1 alpha (HIF-1 alpha) is currently discussed as a potential endogenous marker of tumor hypoxia to select patients for modified treatment. Despite an association of immunohistochemical HIF-1 alpha overexpression and poor prognosis after radiotherapy in many tumor entities, the reported pattern of HIF-1 alpha staining was often not consistent with tumor hypoxia. To explain this discrepancy, we studied the in vitro conditions under which HIF-1 alpha protein accumulates. METHODS AND MATERIALS: FaDu human pharyngeal carcinoma and HT 1080 human fibrosarcoma cells were treated with different schedules of in vitro hypoxia at 5%, 1%, and 0.1% O(2) and reoxygenation. HIF-1 alpha protein levels were determined in nuclear extracts. Cellular radiation sensitivity was assessed by clonogenic survival assay after single-dose irradiation at the above oxygen concentrations. RESULTS: In both cell lines, weak HIF-1 alpha expression was observed at 20% O(2) and after 10 min of hypoxia. Increased HIF-1 alpha protein levels were observed at 1 h of hypoxia, remained stable over 24 h, and decreased to baseline within 15 min of reoxygenation. HIF-1 alpha protein at 5% O(2) was half-maximal in FaDu but indistinguishable from 0.1% O(2) in HT 1080. A good correlation of HIF-1 alpha protein level and hypoxic radiation resistance, with equal ranking of data points by both assays, was observed in FaDu cells but not in HT 1080 cells. CONCLUSIONS: The ability of HIF-1 alpha to indicate radiobiologically relevant levels of tumor hypoxia seems to be cell type specific. This finding may explain the inconsistent results regarding the pattern of HIF-1 alpha expression in tumor sections.

Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer.

BACKGROUND: To evaluate the influence of total dose and tumor volume on local control and survival in primary radiotherapy of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: We retrospectively analyzed the clinical course and CT-derived pre- and post-therapeutic tumor volume data of 135 patients with NSCLC undergoing primary radiotherapy at our department between 1989 and 1996. Among these, a total of 192 spatially separated tumor volumes (135 primary tumors, 1 additional intrapulmonary tumor, and 56 involved lymph nodes) were available for analysis. In all patients, treatment was planned using CT-based three-dimensional treatment planning. The dose to each tumor volume was derived from the individual dose plans. Mean total dose was 59.9 Gy (range: 30-80 Gy). All but 3 patients were followed until death. For local control analysis, each tumor was analyzed separately, and its remission status was determined in serial follow-up CT scans. A total of 784 CT scans were analyzed. Actuarial local control analysis was performed for the 192 separated tumor volumes, and survival analysis was performed for the 135 patients. Tumor control probability was calculated using a Poisson statistical model. RESULTS: Overall 1- and 2-year local control rate was 50% and 37%, respectively. The 2-year local control rate for tumors <50 ccm, 50-200 ccm, and >200 ccm was 51%, 22%, and 10%, respectively (p = 0.02). The 2-year local control rate for dose levels < or = 60 Gy and >60 Gy was 28% and 43% (p < 0.001). For the subgroup of 147 tumors smaller than 100 ccm, the local control rate increased up to 70% (1 year) and 51% (2 years) with doses of more than 60 Gy. For tumors larger than 100 ccm, no dose effect was seen. Only 2 of 45 tumors >100 ccm were controlled more than 2 years. Multivariate analysis revealed tumor volume, total dose, histopathologic type, and grading as significant and independent prognostic factors for local control. The number of delay days by split course (if used) and application of chemotherapy was not found to influence local control. Overall 1- and 2-year survival rate was 42% and 13%. Total radiation dose, chemotherapy, and T and N stage---but not tumor volume---were found to be independent and significant prognostic factors for survival in multivariate analysis. CONCLUSION: Tumor volume is an important predictor of local control in NSCLC. We found a clear dose effect for local control and survival in NSCLC. Long-term local control for a significant proportion of patients seems possible for small tumors only (<100 ccm, i.e., maximum diameter 6 cm) with doses of 70 Gy and more. Tumors of > or = 100 ccm are unlikely to be controlled long term by conventional doses up to 70 Gy. These results support dose escalation in patients with NSCLC.

A table top suited for CT and radiotherapy.

A radiotherapy table top was to be designed and manufactured, suitable for computer tomography in the same room. The aim was a distortion of the dose distribution by the table top of not more than 4% in small subunits of the target volume (TV) and less than 2% for the mean dose in the TV. Only negligible artifacts in the CT slices should occur in order to assure the exact relocalization of the TV. The table top manufactured of carbon fiber reinforced plastic was constructed by means of finite-element-algorithms. The trapezoidal shaped sandwich plate is supported with tapered beams. The small side of the table can penetrate a 60 cm CT-gantry. When turned, the table top allows large ap-pa opposed fields without irradiating through the beams. Transmission measurements were performed with an ionization chamber under different irradiation angles to determine the influence of the beams and the covering plate. Additionally, a portal imaging device (PID) was used for comparison. It was found that the deflection and torsion of the carbon fiber table top was smaller than for the original. The transmission of the sandwich plate was 97.5% (18 MV) and 96.5% (6 MV photons) respectively. If the irradiation of the beam walls can not be avoided the transmission is not in a critical range. The CT-slices show only minor artifacts along the side walls of the beams. The localization of the tumor or the TV is not restricted.

Suitability of markerless EPID tracking for tumor position verification in gated radiotherapy.

PURPOSE: To maximize the benefits of respiratory gated radiotherapy (RGRT) of lung tumors real-time verification of the tumor position is required. This work investigates the feasibility of markerless tracking of lung tumors during beam-on time in electronic portal imaging device (EPID) images of the MV therapeutic beam. METHODS: EPID movies were acquired at ∼2 fps for seven lung cancer patients with tumor peak-to-peak motion ranges between 7.8 and 17.9 mm (mean: 13.7 mm) undergoing stereotactic body radiotherapy. The external breathing motion of the abdomen was synchronously measured. Both datasets were retrospectively analyzed in PortalTrack, an in-house developed tracking software. The authors define a three-step procedure to run the simulations: (1) gating window definition, (2) gated-beam delivery simulation, and (3) tumor tracking. First, an amplitude threshold level was set on the external signal, defining the onset of beam-on/-off signals. This information was then mapped onto a sequence of EPID images to generate stamps of beam-on/-hold periods throughout the EPID movies in PortalTrack, by obscuring the frames corresponding to beam-off times. Last, tumor motion in the superior-inferior direction was determined on portal images by the tracking algorithm during beam-on time. The residual motion inside the gating window as well as target coverage (TC) and the marginal target displacement (MTD) were used as measures to quantify tumor position variability. RESULTS: Tumor position monitoring and estimation from beam's-eye-view images during RGRT was possible in 67% of the analyzed beams. For a reference gating window of 5 mm, deviations ranging from 2% to 86% (35% on average) were recorded between the reference and measured residual motion. TC (range: 62%-93%; mean: 77%) losses were correlated with false positives incidence rates resulting mostly from intra-/inter-beam baseline drifts, as well as sudden cycle-to-cycle fluctuations in exhale positions. Both phenomena can lead to considerable deviations (with MTD values up to a maximum of 7.8 mm) from the intended tumor position, and in turn may result in a marginal miss. The difference between tumor traces determined within the gating window against ground truth trajectory maps was 1.1 ± 0.7 mm on average (range: 0.4-2.3 mm). CONCLUSIONS: In this retrospective analysis of motion data, it is demonstrated that the system is capable of determining tumor positions in the plane perpendicular to the beam direction without the aid of fiducial markers, and may hence be suitable as an online verification tool in RGRT. It may be possible to use the tracking information to enable on-the-fly corrections to intra-/inter-beam variations by adapting the gating window by means of a robotic couch.