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.

Accuracy of real-time couch tracking during 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, and volumetric modulated arc therapy for prostate cancer.

PURPOSE: To evaluate the accuracy of real-time couch tracking for prostate cancer. METHODS AND MATERIALS: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). RESULTS: Motion of the prostate was largest in the anterior-posterior direction, with systematic (∑) and random (σ) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%±19.8% of treatment time. Real-time tracking reduced prostate motion to ∑=0.01 mm and σ = 0.55 mm in the anterior-posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%±4.6% and 99.7%±0.4% of the time, respectively. Without real-time tracking, pass rates based on a γ index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. CONCLUSIONS: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

Dosimetric consequences of translational and rotational errors in frame-less image-guided radiosurgery.

BACKGROUND: To investigate geometric and dosimetric accuracy of frame-less image-guided radiosurgery (IG-RS) for brain metastases. METHODS AND MATERIALS: Single fraction IG-RS was practiced in 72 patients with 98 brain metastases. Patient positioning and immobilization used either double- (n = 71) or single-layer (n = 27) thermoplastic masks. Pre-treatment set-up errors (n = 98) were evaluated with cone-beam CT (CBCT) based image-guidance (IG) and were corrected in six degrees of freedom without an action level. CBCT imaging after treatment measured intra-fractional errors (n = 64). Pre- and post-treatment errors were simulated in the treatment planning system and target coverage and dose conformity were evaluated. Three scenarios of 0 mm, 1 mm and 2 mm GTV-to-PTV (gross tumor volume, planning target volume) safety margins (SM) were simulated. RESULTS: Errors prior to IG were 3.9 mm ± 1.7 mm (3D vector) and the maximum rotational error was 1.7° ± 0.8° on average. The post-treatment 3D error was 0.9 mm ± 0.6 mm. No differences between double- and single-layer masks were observed. Intra-fractional errors were significantly correlated with the total treatment time with 0.7 mm ± 0.5 mm and 1.2 mm ± 0.7 mm for treatment times ≤23 minutes and >23 minutes (p<0.01), respectively. Simulation of RS without image-guidance reduced target coverage and conformity to 75% ± 19% and 60% ± 25% of planned values. Each 3D set-up error of 1 mm decreased target coverage and dose conformity by 6% and 10% on average, respectively, with a large inter-patient variability. Pre-treatment correction of translations only but not rotations did not affect target coverage and conformity. Post-treatment errors reduced target coverage by >5% in 14% of the patients. A 1 mm safety margin fully compensated intra-fractional patient motion. CONCLUSIONS: IG-RS with online correction of translational errors achieves high geometric and dosimetric accuracy. Intra-fractional errors decrease target coverage and conformity unless compensated with appropriate safety margins.

Control of a HexaPOD treatment couch for robot-assisted radiotherapy.

Moving tumors, for example in the vicinity of the lungs, pose a challenging problem in radiotherapy, as healthy tissue should not be irradiated. Apart from gating approaches, one standard method is to irradiate the complete volume within which a tumor moves plus a safety margin containing a considerable volume of healthy tissue. This work deals with a system for tumor motion compensation using the HexaPOD® robotic treatment couch (Medical Intelligence GmbH, Schwabmünchen, Germany). The HexaPOD, carrying the patient during treatment, is instructed to perform translational movements such that the tumor motion, from the beams-eye view of the linear accelerator, is eliminated. The dynamics of the HexaPOD are characterized by time delays, saturations, and other non-linearities that make the design of control a challenging task. The focus of this work lies on two control methods for the HexaPOD that can be used for reference tracking. The first method uses a model predictive controller based on a model gained through system identification methods, and the second method uses a position control scheme useful for reference tracking. We compared the tracking performance of both methods in various experiments with real hardware using ideal reference trajectories, prerecorded patient trajectories, and human volunteers whose breathing motion was compensated by the system.

Potential of adaptive radiotherapy to escalate the radiation dose in combined radiochemotherapy for locally advanced non-small cell lung cancer.

PURPOSE: To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. METHODS AND MATERIALS: In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n=1) or radiochemotherapy (n=12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan_3D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan_4D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. RESULTS: A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49%±15% after six weeks of treatment. No systematic differences between Plan_3D and Plan_4D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0%±4.4%, 5.6%±2.9% and 7.9%±4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy±0.8 Gy to 73.6 Gy±3.8 Gy. CONCLUSIONS: Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy.

PURPOSE: To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n=21) or pulmonary metastases (n=54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n=29) or three fractions of 12.5 Gy to 65% (n=40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/ß ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ≥ grade II SWOG were fitted using NTCP models. RESULTS: Eleven patients developed RP grade II. With an average MLD of 10.3±5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5±4.3 Gy and 9.9±5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V(2.5)-V(50)) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses. CONCLUSIONS: The MLD and V(2.5)-V(50) of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.

Feasibility study for markerless tracking of lung tumors in stereotactic body radiotherapy.

PURPOSE: To evaluate the feasibility and accuracy of a method for markerless tracking of lung tumors in electronic portal imaging device (EPID) movies and to analyze intra- and interfractional variations in tumor motion. METHODS AND MATERIALS: EPID movies were acquired during stereotactic body radiotherapy (SBRT) given to 40 patients with 49 pulmonary targets and retrospectively analyzed. Tumor visibility and tracking accuracy were determined by three observers. Tumor motion of 30 targets was analyzed in detail via four-dimensional computed tomography (4DCT) and EPID in the superior-inferior direction for intra- and interfractional variations. RESULTS: Tumor visibility was sufficient for markerless tracking in 47% of the EPID movies. Tumor size and visibility in the DRR were correlated with visibility in the EPID images. The difference between automatic and manual tracking was a maximum of 2 mm for 98.3% in the x direction and 89.4% in the y direction. Motion amplitudes in 4DCT images (range, 0.7-17.9 mm; median, 4.9 mm) were closely correlated with amplitudes in the EPID movies. Intrafractional and interfractional variability of tumor motion amplitude were of similar magnitude: 1 mm on average to a maximum of 4 mm. A change in moving average of more than ±1 mm, ±2 mm, and ±4 mm were observed in 47.1%, 17.1%, and 4.5% of treatment time for all trajectories, respectively. Mean tumor velocity was 3.4 mm/sec, to a maximum 61 mm/sec. CONCLUSIONS: Tracking of pulmonary tumors in EPID images without implanted markers was feasible in 47% of all treatment beams. 4DCT is representative of the evaluation of mean breathing motion on average, but larger deviations occurred in target motion between treatment planning and delivery effort a monitoring during delivery.

Influence of continuous table motion on patient breathing patterns.

PURPOSE: To investigate the influence of continuous table motion on patient breathing patterns for compensation of moving targets by a robotic treatment couch. METHODS AND MATERIALS: Fifteen volunteers were placed on a robotic treatment couch, and the couch was moved on different breathing-correlated and -uncorrelated trajectories. External abdominal breathing motion of the patients was measured using an infrared camera system. The influence of table motion on breathing range and pattern was analyzed. RESULTS: Continuous table motion was tolerated well by all test persons. Volunteers reacted differently to table motion. Four test persons showed no change of breathing range and pattern. Increased irregular breathing was observed in 4 patients; however, irregularity was not correlated with table motion. Only 4 test persons showed an increase in mean breathing amplitude of more than 2mm during motion of the couch. The mean cycle period decreased by more than 1 s for 2 test persons only. No abrupt changes in amplitude or cycle period could be observed. CONCLUSIONS: The observed small changes in breathing patterns support the application of motion compensation by a robotic treatment couch.

Stereotactic body radiotherapy for local boost irradiation in unfavourable locally recurrent gynaecological cancer.

PURPOSE: To evaluate outcome of radiotherapy for locally recurrent cervical and endometrial cancer. MATERIALS AND METHODS: Nineteen patients were treated for a locally recurrent cervical (n=12) or endometrial (n=7) cancer median 26 months after initial surgery (n=18) or radiotherapy (n=1). The whole pelvis was irradiated with 50Gy conventionally fractionated radiotherapy (n=16). Because of large size of the recurrent cancer (median 4.5 cm) and peripheral location (n=12), stereotactic body radiotherapy (SBRT; median 3 fractions of 5Gy to 65%) was used for local dose escalation instead of (n=16) or combined with (n=3) vaginal brachytherapy. RESULTS: After median follow-up of 22 months, 3-year overall survival was 34% with systemic progression the leading cause of death (7/10). Median time to systemic progression was 16 months. Three local recurrences resulted in a local control rate of 81% at 3 years. No correlation between survival, systemic or local control and any patient or treatment characteristic was observed. The rate of late toxicity>grade II was 25% at 3 years: two patients developed a grade IV intestino-vaginal fistula and one patient suffered from a grade IV small bowel ileus. CONCLUSION: Image-guided SBRT for local dose escalation resulted in high rates of local control but was associated with significant late toxicity.

Evolution of surface-based deformable image registration for adaptive radiotherapy of non-small cell lung cancer (NSCLC).

BACKGROUND: To evaluate the performance of surface-based deformable image registration (DR) for adaptive radiotherapy of non-small cell lung cancer (NSCLC). METHODS: Based on 13 patients with locally advanced NSCLC, CT images acquired at treatment planning, midway and the end of the radio- (n = 1) or radiochemotherapy (n = 12) course were used for evaluation of DR. All CT images were manually [gross tumor volume (GTV)] and automatically [organs-at-risk (OAR) lung, spinal cord, vertebral spine, trachea, aorta, outline] segmented. Contours were transformed into 3D meshes using the Pinnacle treatment planning system and corresponding mesh points defined control points for DR with interpolation within the structures. Using these deformation maps, follow-up CT images were transformed into the planning images and compared with the original planning CT images. RESULTS: A progressive tumor shrinkage was observed with median GTV volumes of 170 cm(3) (range 42 cm(3) - 353 cm(3)), 124 cm(3) (19 cm(3) - 325 cm(3)) and 100 cm(3) (10 cm(3) - 270 cm(3)) at treatment planning, mid-way and at the end of treatment. Without DR, correlation coefficients (CC) were 0.76 +/- 0.11 and 0.74 +/- 0.10 for comparison of the planning CT and the CT images acquired mid-way and at the end of treatment, respectively; DR significantly improved the CC to 0.88 +/- 0.03 and 0.86 +/- 0.05 (p = 0.001), respectively. With manual landmark registration as reference, DR reduced uncertainties on the GTV surface from 11.8 mm +/- 5.1 mm to 2.9 mm +/- 1.2 mm. Regarding the carina and intrapulmonary vessel bifurcations, DR reduced uncertainties by about 40% with residual errors of 4 mm to 6 mm on average. Severe deformation artefacts were observed in patients with resolving atelectasis and pleural effusion, in one patient, where the tumor was located around large bronchi and separate segmentation of the GTV and OARs was not possible, and in one patient, where no clear shrinkage but more a decay of the tumor was observed. DISCUSSION: The surface-based DR performed accurately for the majority of the patients with locally advanced NSCLC. However, morphological response patterns were identified, where results of the surface-based DR are uncertain.

Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes?

PURPOSE: To compare step-and-shoot intensity-modulated radiotherapy (ss-IMRT) with volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes with a simultaneous integrated boost (SIB). MATERIALS AND METHODS: This retrospective planning study was based on 20 patients composed of prostate cancer (n=5), postoperative (n=5) or primary (n=5) radiotherapy for pharyngeal cancer and for cancer of the paranasal sinuses (n=5); a SIB with two or three dose levels was planned in all patients. For each patient, one ss-IMRT plan with direct-machine-parameter optimization (DMPO) and VMAT plans with one to three arcs (SmartArc technique) were generated in the Pinnacle planning system. RESULTS: Single arc VMAT improved target coverage and dose homogeneity in radiotherapy for prostate cancer. Two and three VMAT arcs were required to achieve equivalent results compared to ss-IMRT in postoperative and primary radiotherapy for pharyngeal cancer, respectively. In radiotherapy for cancer of the paranasal sinuses, multiarc VMAT resulted in increased spread of low doses to the lenses and decreased target coverage in the region between the orbits. CONCLUSIONS: The complexity of the target volume determined whether single arc VMAT was equivalent to ss-IMRT. Multiple arc VMAT improved results compared to single arc VMAT at cost of increased delivery times, increased monitor unites and increased spread of low doses.

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.

Mid-ventilation concept for mobile pulmonary tumors: internal tumor trajectory versus selective reconstruction of four-dimensional computed tomography frames based on external breathing motion.

PURPOSE: To evaluate the accuracy of direct reconstruction of mid-ventilation and peak-phase four-dimensional (4D) computed tomography (CT) frames based on the external breathing signal. METHODS AND MATERIALS: For 11 patients with 15 pulmonary targets, a respiration-correlated CT study (4D CT) was acquired for treatment planning. After retrospective time-based sorting of raw projection data and reconstruction of eight CT frames equally distributed over the breathing cycle, mean tumor position (P(mean)), mid-ventilation frame, and breathing motion were evaluated based on the internal tumor trajectory. Analysis of the external breathing signal (pressure sensor around abdomen) with amplitude-based sorting of projections was performed for direct reconstruction of the mid-ventilation frame and frames at peak phases of the breathing cycle. RESULTS: On the basis of the eight 4D CT frames equally spaced in time, tumor motion was largest in the craniocaudal direction, with 12 +/- 7 mm on average. Tumor motion between the two frames reconstructed at peak phases was not different in the craniocaudal and anterior-posterior directions but was systematically smaller in the left-right direction by 1 mm on average. The 3-dimensional distance between P(mean) and the tumor position in the mid-ventilation frame based on the internal tumor trajectory was 1.2 +/- 1 mm. Reconstruction of the mid-ventilation frame at the mean amplitude position of the external breathing signal resulted in tumor positions 2.0 +/- 1.1 mm distant from P(mean). Breathing-induced motion artifacts in mid-ventilation frames caused negligible changes in tumor volume and shape. CONCLUSIONS: Direct reconstruction of the mid-ventilation frame and frames at peak phases based on the external breathing signal was reliable. This makes the reconstruction of only three 4D CT frames sufficient for application of the mid-ventilation technique in clinical practice.

Clinical outcome of dose-escalated image-guided radiotherapy for spinal metastases.

PURPOSE: To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. METHODS AND MATERIALS: A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy(10) (range, 55-86) in a median of 20 fractions (range, 3-34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. RESULTS: After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. CONCLUSION: Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.

Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: importance of baseline symptoms and of prostate-V150.

BACKGROUND AND PURPOSE: Detailed knowledge of quality of life (QoL) after permanent I-125 brachytherapy may aid in counselling patients with early-stage prostate cancer. MATERIALS AND METHODS: Seventy-four consecutive patients with low-risk prostate cancer were asked to complete the EORTC QLQ-C30 questionnaire with the prostate-specific PR25 module before implant, four weeks and one year after implant (response rates 97%, 88% and 89%, respectively). Implant characteristics were correlated with QoL scores. RESULTS: Global QoL was stable from pre-treatment to one year after implant and similar to age-adjusted scores of healthy controls. Significant changes versus baseline in QLQ-C30 domains were worsened social function at four weeks, increased constipation at four weeks and at one year and improved emotional function at one year. PR25 urinary symptoms were significantly increased at four weeks and, despite some improvement, at one year; bowel symptoms were slightly increased. Both types of symptoms were most strongly related with pre-treatment symptom scores. Prostate-V150 was the only implant parameter significantly associated with both urinary and bowel symptoms at four weeks and one year. CONCLUSIONS: Limiting the high-dose subvolume in the prostate may be beneficial to reduce urinary and bowel symptoms but the major determinant of symptoms after I-125 implant is the baseline symptom level.

Dose-response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: relevance of 4D dose calculation.

PURPOSE: To evaluate outcome after image-guided stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) and pulmonary metastases. METHODS AND MATERIALS: A total of 124 patients with 159 pulmonary lesions (metastases n = 118; NSCLC, n = 41; Stage IA, n = 13; Stage IB, n = 19; T3N0, n = 9) were treated with SBRT. Patients were treated with hypofractionated schemata (one to eight fractions of 6-26 Gy); biologic effective doses (BED) to the clinical target volume (CTV) were calculated based on four-dimensional (4D) dose calculation. The position of the pulmonary target was verified using volume imaging before all treatments. RESULTS: With mean/median follow-up of 18/14 months, actuarial local control was 83% at 36 months with no difference between NSCLC and metastases. The dose to the CTV based on 4D dose calculation was closely correlated with local control: local control rates were 89% and 62% at 36 months for >100 Gy and <100 Gy BED (p = 0.0001), respectively. Actuarial freedom from regional and systemic progression was 34% at 36 months for primary NSCLC group; crude rate of regional failure was 15%. Three-year overall survival was 37% for primary NSCLC and 16% for metastases; no dose-response relationship for survival was observed. Exacerbation of comorbidities was the most frequent cause of death for primary NSCLC. CONCLUSIONS: Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates. This cutoff dose is not specific to the treatment technique and protocol of our study and may serve as a general recommendation.

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy.

PURPOSE: To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. RESULTS: Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4mm and 6mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively. CONCLUSION: Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.

Influence of increased target dose inhomogeneity on margins for breathing motion compensation in conformal stereotactic body radiotherapy.

BACKGROUND: Breathing motion should be considered for stereotactic body radiotherapy (SBRT) of lung tumors. Four-dimensional computer tomography (4D-CT) offers detailed information of tumor motion. The aim of this work is to evaluate the influence of inhomogeneous dose distributions in the presence of breathing induced target motion and to calculate margins for motion compensation. METHODS: Based on 4D-CT examinations, the probability density function of pulmonary tumors was generated for ten patients. The time-accumulated dose to the tumor was calculated using one-dimensional (1D) convolution simulations of a 'static' dose distribution and target probability density function (PDF). In analogy to stereotactic body radiotherapy (SBRT), different degrees of dose inhomogeneity were allowed in the target volume: minimum doses of 100% were prescribed to the edge of the target and maximum doses varied between 102% (P102) and 150% (P150). The dose loss due to breathing motion was quantified and margins were added until this loss was completely compensated. RESULTS: With the time-weighted mean tumor position as the isocentre, a close correlation with a quadratic relationship between the standard deviation of the PDF and the margin size was observed. Increased dose inhomogeneity in the target volume required smaller margins for motion compensation: margins of 2.5 mm, 2.4 mm and 1.3 mm were sufficient for compensation of 11.5 mm motion range and standard deviation of 3.9 mm in P105, P125 and P150, respectively. This effect of smaller margins for increased dose inhomogeneity was observed for all patients. Optimal sparing of the organ-at-risk surrounding the target was achieved for dose prescriptions P105 to P118. The internal target volume concept over-compensated breathing motion with higher than planned doses to the target and increased doses to the surrounding normal tissue. CONCLUSION: Treatment planning with inhomogeneous dose distributions in the target volume required smaller margins for compensation of breathing induced target motion with the consequence of lower doses to the surrounding organs-at-risk.

Investigation of the usability of conebeam CT data sets for dose calculation.

BACKGROUND: To investigate the feasibility and accuracy of dose calculation in cone beam CT (CBCT) data sets. METHODS: Kilovoltage CBCT images were acquired with the Elekta XVI system, CT studies generated with a conventional multi-slice CT scanner (Siemens Somatom Sensation Open) served as reference images. Material specific volumes of interest (VOI) were defined for commercial CT Phantoms (CATPhan and Gammex RMI) and CT values were evaluated in CT and CBCT images. For CBCT imaging, the influence of image acquisition parameters such as tube voltage, with or without filter (F1 or F0) and collimation on the CT values was investigated. CBCT images of 33 patients (pelvis n = 11, thorax n = 11, head n = 11) were compared with corresponding planning CT studies. Dose distributions for three different treatment plans were calculated in CT and CBCT images and differences were evaluated. Four different correction strategies to match CT values (HU) and density (D) in CBCT images were analysed: standard CT HU-D table without adjustment for CBCT; phantom based HU-D tables; patient group based HU-D tables (pelvis, thorax, head); and patient specific HU-D tables. RESULTS: CT values in the CBCT images of the CATPhan were highly variable depending on the image acquisition parameters: a mean difference of 564 HU +/- 377 HU was calculated between CT values determined from the planning CT and CBCT images. Hence, two protocols were selected for CBCT imaging in the further part of the study and HU-D tables were always specific for these protocols (pelvis and thorax with M20F1 filter, 120 kV; head S10F0 no filter, 100 kV). For dose calculation in real patient CBCT images, the largest differences between CT and CBCT were observed for the standard CT HU-D table: differences were 8.0% +/- 5.7%, 10.9% +/- 6.8% and 14.5% +/- 10.4% respectively for pelvis, thorax and head patients using clinical treatment plans. The use of patient and group based HU-D tables resulted in small dose differences between planning CT and CBCT: 0.9% +/- 0.9%, 1.8% +/- 1.6%, 1.5% +/- 2.5% for pelvis, thorax and head patients, respectively. The application of the phantom based HU-D table was acceptable for the head patients but larger deviations were determined for the pelvis and thorax patient populations. CONCLUSION: The generation of three HU-D tables specific for the anatomical regions pelvis, thorax and head and specific for the corresponding CBCT image acquisition parameters resulted in accurate dose calculation in CBCT images. Once these HU-D tables are created, direct dose calculation on CBCT datasets is possible without the need of a reference CT images for pixel value calibration.

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.