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.

A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy.

INTRODUCTION: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. METHODS: Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180). RESULTS: With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. CONCLUSIONS: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.

Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer?

INTRODUCTION: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. METHODS: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1-3 cN0 were treated with image-guided SBRT at five international institutions (1998-2010). Sixty-four percent of the tumors were biopsy-proven and 18F-fluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available. RESULTS: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was significantly correlated with overall survival but not cause-specific survival: diffusing capacity for carbon monoxide of 11.2 ml/min/mmHg differentiated between 3-year overall survival of 66% and 42%. Radiation-induced pneumonitis grade ≥II occurred in 7% of patients and was not increased in patients with lower PF. A significant and progressive change of PF was observed after SBRT: PF decreased by 3.6% and 6.8% on average within 6 and 6 to 24 months after SBRT, respectively. Changes of PF after SBRT were significantly correlated with pretreatment PF: PF improved for worst pretreatment PF and the largest loss was observed for best pretreatment PF. CONCLUSIONS: Image-guided SBRT is safe in terms of acute and chronic pulmonary toxicity even for patients with severe pulmonary comorbidities. SBRT should be considered as a curative treatment option for inoperable patients with pretreatment PF as reported in this study.

Adaptive radiotherapy for locally advanced non-small-cell lung cancer does not underdose the microscopic disease and has the potential to increase tumor control.

PURPOSE: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). METHODS AND MATERIALS: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. RESULTS: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% ± 10% to 73% ± 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. CONCLUSIONS: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40% compared with radiotherapy planning without ART.

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.

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.

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.

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.

Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy (IMRT) of prostate cancer.

PURPOSE: To evaluate intra-fractional uncertainties during intensity-modulated radiotherapy (IMRT) of prostate cancer. PATIENTS AND METHODS: During IMRT of 21 consecutive patients, kilovolt (kV) cone-beam computed tomography (CBCT) images were acquired prior to and immediately after treatment: a total of 252 treatment fractions with 504 CBCT studies were basis of this analysis. The prostate position in anterior-posterior (AP) direction was determined using contour matching; patient set-up based on the pelvic bony anatomy was evaluated using automatic image registration. Internal variability of the prostate position was the difference between absolute prostate and patient position errors. Intra-fractional changes of prostate position, patient position, rectal distension in AP direction and bladder volume were analyzed. RESULTS: With a median treatment time of 16 min, intra-fractional drifts of the prostate were >5 mm in 12% of all fractions and a margin of 6 mm was calculated for compensation of this uncertainty. Mobility of the prostate was independent from the bony anatomy with poor correlation between absolute prostate motion and motion of the bony anatomy (R2=0.24). A systematic increase of bladder filling by 41 ccm on average was observed; however, these changes did not influence the prostate position. Small variations of the prostate position occurred independently from intra-fractional changes of the rectal distension; a weak correlation between large internal prostate motion and changes of the rectal volume was observed (R2=0.55). CONCLUSION: Clinically significant intra-fractional changes of the prostate position were observed and margins of 6 mm were calculated for this intra-fractional uncertainty. Repeated or continuous verification of the prostate position may allow further margin reduction.

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.

Nonrigid patient setup errors in the head-and-neck region.

PURPOSE: To investigate the magnitude and clinical relevance of relative motion/nonrigid setup errors in the head-and-neck (H&N) region. MATERIAL AND METHODS: Eleven patients with tumors in the H&N region were immobilized in thermoplastic head masks. Patient positioning was verified using a kilovoltage cone-beam CT (kv CBCT) prior to 100 treatment fractions. Five different regions of interest (ROIs) were selected for automatic image registration of planning CT and verification CBCT: (1) the whole volume covering planning CT and CBCT, (2) the skull, (3) the mandible, (4) C1-C3, and (5) C4-C6. Differences were calculated describing relative motion between the ROIs. RESULTS: The 3-D patient setup error was 3.2 mm +/- 1.7 mm based on registration of the whole volume. No systematic relative motion (group mean errors <0.5 mm and <0.5 degrees ) between planning and treatment for any ROI was observed. Mobility was largest for the skull and the mandible relative to C4-C6 with 3-D displacements of 4.7 mm +/- 2.5 mm and 4.4 mm +/- 2.5 mm. Relative rotations were largest around the left-right axis (nodding) between C1-C3 and C4-C6 with maximum 11 degrees . No time trend of relative motion was observed. Margins for compensation of relative motion ranged between 5 mm and 10 mm. CONCLUSION: The simplification of the patient as a rigid body was shown to result in significant errors due to relative motion in the H&N region. Margins for compensation of relative motion exceeded margins for compensation of patient positioning errors.

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.

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.