Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Performance comparison of prediction filters for respiratory motion tracking in radiotherapy.

PURPOSE: In precision radiotherapy, the intrafractional motion causes substantial uncertainty. Traditionally, the target volume is expanded to cover the tumor in all positions. Alternative approaches are gating and adaptive tracking, which require a time delay as small as possible between the actual tumor motion and the reaction to effectively compensate the motion. Current treatment machines often exhibit large time delays. Prediction filters offer a promising means to mitigate these time delays by predicting the future respiratory motion. METHODS: A total of 18 prediction filters were implemented and their hyperparameters optimized for various time delays and noise levels. A set of 93 traces were standardized to a sampling frequency of 25 Hz and smoothed using the Fourier transform with a 3 Hz cutoff frequency. The hyperparameter optimization was carried out with ten traces, and the optimal hyperparameters were evaluated on the remaining 83 traces. RESULTS: For smooth traces, the wavelet least mean squares prediction filter and the linear filter reached normalized root mean square errors of below 0.05 for time delays of 160 and 480 ms, respectively. For noisy signals, the performance of the prediction filters deteriorated and led to similar results. CONCLUSIONS: Linear methods for prediction filters are sufficient for respiratory motion signals. Reducing the measurement noise generally improves the performance of the prediction filters investigated in this study, even during breathing irregularities.

The ideal couch tracking system-Requirements and evaluation of current systems.

INTRODUCTION: Intrafractional motion can cause substantial uncertainty in precision radiotherapy. Traditionally, the target volume is defined to be sufficiently large to cover the tumor in every position. With the robotic treatment couch, a real-time motion compensation can improve tumor coverage and organ at risk sparing. However, this approach poses additional requirements, which are systematically developed and which allow the ideal robotic couch to be specified. METHODS AND MATERIALS: Data of intrafractional tumor motion were collected and analyzed regarding motion range, frequency, speed, and acceleration. Using this data, ideal couch requirements were formulated. The four robotic couches Protura, Perfect Pitch, RoboCouch, and RPSbase were tested with respect to these requirements. RESULTS: The data collected resulted in maximum speed requirements of 60 mm/s in all directions and maximum accelerations of 80 mm/s2 in the longitudinal, 60 mm/s2 in the lateral, and 30 mm/s2 in the vertical direction. While the two robotic couches RoboCouch and RPSbase completely met the requirements, even these two showed a substantial residual motion (40% of input amplitude), arguably due to their time delays. CONCLUSION: The requirements for the motion compensation by an ideal couch are formulated and found to be feasible for currently available robotic couches. However, the performance these couches can be improved further regarding the position control if the demanded speed and acceleration are taken into account as well.

ELPHA: Dynamically deformable liver phantom for real-time motion-adaptive radiotherapy treatments.

PURPOSE: Real-time motion-adaptive radiotherapy of intrahepatic tumors needs to account for motion and deformations of the liver and the target location within. Phantoms representative of anatomical deformations are required to investigate and improve dynamic treatments. A deformable phantom capable of testing motion detection and motion mitigation techniques is presented here. METHODS: The dynamically dEformable Liver PHAntom (ELPHA) was designed to fulfill three main constraints: First, a reproducibly deformable anatomy is required. Second, the phantom should provide multimodality imaging contrast for motion detection. Third, a time-resolved dosimetry system to measure temporal effects should be provided. An artificial liver with vasculature was casted from soft silicone mixtures. The silicones allow for deformation and radiographic image contrast, while added cellulose provides ultrasonic contrast. An actuator was used for compressing the liver in the inferior direction according to a prescribed respiratory motion trace. Electromagnetic (EM) transponders integrated in ELPHA help provide ground truth motion traces. They were used to quantify the motion reproducibility of the phantom and to validate motion detection based on ultrasound imaging. A two-dimensional ultrasound probe was used to follow the position of the vessels with a template-matching algorithm. This detected vessel motion was compared to the EM transponder signal by calculating the root-mean-square error (RMSE). ELPHA was then used to investigate the dose deposition of dynamic treatment deliveries. Two dosimetry systems, radio-chromic film and plastic scintillation dosimeters (PSD), were integrated in ELPHA. The PSD allow for time-resolved measurement of the delivered dose, which was compared to a time-resolved dose of the treatment planning system. Film and PSD were used to investigate dose delivery to the deforming phantom without motion compensation and with treatment-couch tracking for motion compensation. RESULTS: ELPHA showed densities of 66 and 45 HU in the liver and the surrounding tissues. A high motion reproducibility with a submillimeter RMSE (<0.32 mm) was measured. The motion of the vasculature detected with ultrasound agreed well with the EM transponder position (RMSE < 1 mm). A time-resolved dosimetry system with a 1 Hz time resolution was achieved with the PSD. The agreement of the planned and measured dose to the PSD decreased with increasing motion amplitude: A dosimetric RMSE of 1.2, 2.1, and 2.7 cGy/s was measured for motion amplitudes of 8, 16, and 24 mm, respectively. With couch tracking as motion compensation, these values decreased to 1.1, 1.4, and 1.4 cGy/s. This is closer to the static situation with 0.7 cGy/s. Film measurements showed that couch tracking was able to compensate for motion with a mean target dose within 5% of the static situation (-5% to +1%), which was higher than in the uncompensated cases (-41% to -1%). CONCLUSIONS: ELPHA is a deformable liver phantom with high motion reproducibility. It was demonstrated to be suitable for the verification of motion detection and motion mitigation modalities. Based on the multimodality image contrast, a high accuracy of ultrasound based motion detection was shown. With the time-resolved dosimetry system, ELPHA is suitable for performance assessment of real-time motion-adaptive radiotherapy, as was shown exemplary with couch tracking.

Body motion during dynamic couch tracking with healthy volunteers.

In precision radiotherapy, the intrafractional motion can cause a considerable uncertainty of the location of the tumor to be treated. An established approach is the expansion of the target volume to account for the motion. An alternative approach is couch-tracking, in which the patient is continually moved to compensate the intrafractional motion. However, couch-tracking itself might induce uncertainty of the patient's body position, because the body is non-rigid. One hundred healthy volunteers were positioned supine on a robotic couch. Optical markers were placed on the torso of the volunteers as well as on the couch, and their positions were tracked with an optical surface measurement system. Using these markers, the uncertainty of the body position relative to the couch position was estimated while the couch was static or moving. Over the included 83 healthy volunteers, the median of the uncertainty increased by 0.8 mm (SI), 0.4 mm (LR) and 0.4 mm (AP) when the couch moved. Couch motion was found to increase the uncertainty of the body position relative to the couch. However, this uncertainty is one order of magnitude smaller than the intrafractional tumor motion amplitudes to be compensated. Therefore, even with body motion present, the couch-tracking approach is a viable option. The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal (SNCTP000001878).

Dosimetric influence of pitch in patient positioning for radiotherapy of long treatment volumes; the usefulness of six degree of freedom couch.

OBJECTIVE:: Pitch, the rotation around the transversal axis of the patient during radiotherapy has little impact on the dose distribution of small spherical treatment volumes; however it might affect treatment of long volumes requiring a correction with a six degree of freedom couch. METHODS:: We included 10 patients each with nasopharyngeal carcinoma (NPC) and esophageal cancer, treated with volumetric modulated arc therapy. Pitch was simulated by tilting the planning CT in ventral and dorsal direction by ± 1.5° and ± 3°. Verification plans were calculated on the tilted datasets and were compared to the original plan and the dose constraints of the organs at risk (OAR). RESULTS:: The deviation in dose to the planning target volume is increasing with the degree of pitch with mean changes of up to 2% for NPC and 1% for esophageal cancer. The most affected OAR in NPC patients are brainstem (max. dose +6.0%) and spinal cord (max. dose +10.0%) when tilted by 3° dorsally and lenses (max. dose +3.3%), oral mucosa (mean dose +2.6%) and parotid glands (mean dose +4.3%) when tilted by 3° ventrally. For esophageal cancer patients, there was no significant change in dose to any OAR. Whereas for esophageal cancer, all tilted treatment plans were still clinically acceptable regarding OAR, 5 NPC plans would no longer be acceptable with a pitch of 1.5° ventral (N = 1), 3° ventral (N = 2) and 3° dorsal (N = 2). CONCLUSION:: Planning target volume coverage in both tumor entities was only slightly affected, but pitch errors could be relevant for OAR in NPC patients. ADVANCES IN KNOWLEDGE:: A correction with a six degree of freedom couch is recommended for NPC patients with a pitch mismatch of more than 1.5° to avoid exceeded doses to the OAR.

Unconscious physiological response of healthy volunteers to dynamic respiration-synchronized couch motion.

BACKGROUND: Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient's stress and respiration behavior decreasing the couch-tracking effectiveness. METHODS: In total, 100 volunteers were positioned supine on a robotic couch, which moved dynamically and respiration synchronized. During the measurement, the skin conductivity, the heartrate, and the gaze location were measured indicating the volunteer's stress. Volunteers rated the subjective motion sickness using a questionnaire. The measurement alternated between static and tracking segments (three cycles), each 1 min long. RESULTS: The respiration amplitude showed no significant difference between tracking and static segments, but decreased significantly from the first to the last tracking segment (p < 0.0001). The respiration frequency differed significantly between tracking and static segments (p < 0.0001), but not between the first and the last tracking segment. The physiological parameters and the questionnaire showed mild signals of stress and motion sickness. CONCLUSION: Generally, people tolerated the couch motions. The interaction between couch motion and the patient's breathing pattern should be considered for a clinical implementation. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal ( SNCTP000001878 ) on June 20, 2016.

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

BACKGROUND: Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. METHODS AND MATERIALS: Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. RESULTS: Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. CONCLUSIONS: By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Comparison of multi-leaf collimator tracking and treatment-couch tracking during stereotactic body radiation therapy of prostate cancer.

PURPOSE AND BACKGROUND: Motion mitigation during prostate stereotactic body radiation therapy (SBRT) ensures optimal target coverage while reducing the risk of overdosage of nearby organs. The geometrical and dosimetrical performance of motion mitigation with the multileaf-collimator (MLC tracking) or the treatment couch (couch tracking) were compared. MATERIAL AND METHODS: For ten prostate patients, SBRT treatment plans with integrated boosts were prepared using volumetric modulated arc technique. For the geometrical evaluation, a lead sphere at the beam isocenter was moved according to five prostate motion curves (i) without mitigation, (ii) with MLC tracking or (iii) with couch tracking. During irradiation, MV images were taken and the over-/underexposed areas were evaluated. For the dosimetrical evaluation, the plans were applied to a dosimetric phantom. Dose distributions with and without mitigation were evaluated inside the target structure and organs at risk. RESULTS: The median over-/underexposed area was reduced significantly from 2.02cm2 without mitigation to 1.00cm2 and 0.45cm2 with MLC and couch tracking. Closest dosimetrical agreement to the static references was achieved with couch tracking. CONCLUSIONS: MLC and couch tracking at a conventional linear accelerator significantly improved the accuracy of prostate SBRT in the presence of motion, whereby couch tracking showed slightly better performance than MLC tracking.

ITV, mid-ventilation, gating or couch tracking - A comparison of respiratory motion-management techniques based on 4D dose calculations.

PURPOSE: Respiratory motion-management techniques (MMT) aim to ensure tumor dose coverage while sparing lung tissue. Dynamic treatment-couch tracking of the moving tumor is a promising new MMT and was compared to the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle and the gating approach in a planning study based on 4D dose calculations. METHODS: For twenty patients with lung lesions, planning target volumes (PTV) were adapted to the MMT and stereotactic body radiotherapy treatments were prepared with the 65%-isodose enclosing the PTV. For tracking, three concepts for target volume definition were considered: Including the gross tumor volume of one phase (single-phase tracking), including deformations between phases (multi-phase tracking) and additionally including tracking latencies of a couch tracking system (reliable couch tracking). The accumulated tumor and lung doses were estimated with 4D dose calculations based on 4D-CT datasets and deformable image registration. RESULTS: Single-phase tracking showed the lowest ipsilateral lung Dmean (median: 3.3Gy), followed by multi-phase tracking, gating, reliable couch tracking, MidV and ITV concepts (3.6, 3.8, 4.1, 4.3 and 4.8Gy). The 4D dose calculations showed the MidV and single-phase tracking overestimated the target mean dose (-2.3% and -1.3%), while it was slightly underestimated by the other MMT (<+1%). CONCLUSION: The ITV concept ensures tumor coverage, but exposes the lung tissue to a higher dose. The MidV, gating and tracking concepts were shown to reduce the lung dose. Neglecting non-translational changes of the tumor in the target volume definition for tracking results in a slightly reduced target coverage. The slightly inferior dose coverage for MidV should be considered when applying this technique clinically.

Validation of dynamic treatment-couch tracking for prostate SBRT.

PURPOSE: In stereotactic body radiation therapy (SBRT) of prostatic cancer, a high dose per fraction is applied to the target with steep dose gradients. Intrafractional prostate motion can occur unpredictably during the treatment and lead to target miss. This work investigated the dosimetric benefit of motion compensation with dynamic treatment-couch tracking for prostate SBRT treatments in the presence of prostatic motion. METHODS: Ten SBRT treatment plans for prostate cancer patients with integrated boosts to their index lesion were prepared. The treatment plans were applied with a TrueBeam linear accelerator to a phantom in (a) static reference position, (b) moved with five prostate motion trajectories without any motion compensation, and (c) with real-time compensation using transponder-guided couch tracking. The geometrical position of the electromagnetic transponder was evaluated in the tracked and untracked situation. The dosimetric performance of couch tracking was evaluated, using Gamma agreement indices (GAI) and other dose parameters. These were evaluated within the phantoms biplanar diode array, as well as target- and organ-specific. RESULTS: The root-mean-square error of the motion traces (range: 0.8-4.4 mm) was drastically reduced with couch tracking (0.2-0.4 mm). Residual motion was mainly observed at abrupt direction changes with steep motion gradients. The phantom measurements showed significantly better GAI1%/1mm with tracked (range: 83.4%-100.0%) than with untracked motion (28.9%-99.7%). Also GAI2%/2mm was significantly superior for the tracked (98.4%-100.0%) than the untracked motion (52.3%-100.0%). The organ-specific evaluation showed significantly better target coverage with tracking. The dose to the rectum and bladder showed a dependency on the anterior-posterior motion direction. CONCLUSIONS: Couch tracking clearly improved the dosimetric accuracy of prostate SBRT treatments. The treatment couch was able to compensate the prostatic motion with only some minor residual motion. Therefore, couch tracking combined with electromagnetic position monitoring for prostate SBRT is feasible and improves the accuracy in treatment delivery when prostate motion is present.

Respiratory motion-management in stereotactic body radiation therapy for lung cancer - A dosimetric comparison in an anthropomorphic lung phantom (LuCa).

BACKGROUND AND PURPOSE: The objective of this study was to compare the latest respiratory motion-management strategies, namely the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle, respiratory gating and dynamic couch tracking. MATERIALS AND METHODS: An anthropomorphic, deformable and dynamic lung phantom was used for the dosimetric validation of these techniques. Stereotactic treatments were adapted to match the techniques and five distinct respiration patterns, and delivered to the phantom while radiographic film measurements were taken inside the tumor. To report on tumor coverage, these dose distributions were used to calculate mean doses (Dmean), changes in homogeneity indices (ΔH2-98), gamma agreement, and areas covered by the planned minimum dose (A>Dmin). RESULTS: All techniques achieved good tumor coverage (A>Dmin>99.0%) and minor changes in Dmean (±3.2%). Gating and tracking strategies showed superior results in gamma agreement and ΔH2-98 compared to ITV and MidV concepts, which seem to be more influenced by the interplay and the gradient effect. For lung, heart and spinal cord, significant dose differences between the four techniques were found (p<0.05), with lowest doses for gating and tracking strategies. CONCLUSION: Active motion-management techniques, such as gating or tracking, showed superior tumor dose coverage and better organ dose sparing than the passive techniques based on tumor margins.

Modeling and performance evaluation of a robotic treatment couch for tumor tracking.

Tumor motion during radiation therapy increases the irradiation of healthy tissue. However, this problem may be mitigated by moving the patient via the treatment couch such that the tumor motion relative to the beam is minimized. The treatment couch poses limitations to the potential mitigation, thus the performance of the Protura (CIVCO) treatment couch was characterized and numerically modeled. The unknown parameters were identified using chirp signals and verified with one-dimensional tumor tracking. The Protura tracked chirp signals well up to 0.2 Hz in both longitudinal and vertical directions. If only the vertical or only the longitudinal direction was tracked, the Protura tracked well up to 0.3 Hz. However, there was unintentional yet substantial lateral motion in the former case. And during vertical motion, the extension caused rotation of the Protura around the lateral axis. The numerical model matched the Protura up to 0.3 Hz. Even though the Protura was designed for static positioning, it was able to reduce the tumor motion by 69% (median). The correlation coefficient between the tumor motion reductions of the Protura and the model was 0.99. Therefore, the model allows tumor-tracking results of the Protura to be predicted.

Three-dimensional versus four-dimensional dose calculation for volumetric modulated arc therapy of hypofractionated treatments.

PURPOSE: Respiratory motion is a non-negligible source of uncertainty in radiotherapy. A common approach is to delineate the target volume in all respiratory phases (ITV) and to calculate a treatment plan using the average reconstruction of the four-dimensional computed tomography (4DCT) scans. In this study the extent of the interplay effect caused by interaction between dynamic dose delivery and respiratory tumor motion, as well as other motion effects were investigated. These effects are often ignored when the ITV concept is used. METHODS AND MATERIALS: Nine previously treated patients with in ten abdominal or thoracic cancer lesions (3 liver, 3 adrenal glands and 4 lung lesions) were selected for this planning study. For all patients, phase-sorted respiration-correlated 4DCT scans were taken, and volumetric modulated arc therapy (VMAT) treatments were planned using the ITV concept. Margins from ITV to planning target volume (PTV) of 3-10mm were used. Plans were optimized and dose distributions were calculated on the average reconstruction of the 4DCT. 4D dose distributions were calculated to evaluate motion effects, caused by the interference of dynamic treatment delivery with respiratory tumor motion and inhomogeneously planned target dose. These calculations were performed on the phase-sorted CT series with a respiration-correlated assignment of the treatment plan's monitor units (MU) to the respiration phases of the 4DCT. The 4D dose was accumulated with rigid as well as deformable registrations of the CT series and compared to the original 3D dose distribution. Maximum, minimum and mean doses to ITV and PTV, and maximum or mean doses to organs at risk (OAR), were compared after rigid accumulation. The dose variation in the gross tumor volume (GTV) was compared after deformable registration. RESULTS: Using rigid registrations, variations in the investigated dose parameters between 3D and 4D dose calculations were found to be within -2.1% to 1.4% for all target volumes and within -0.8% to 1.7% in OAR. Using deformable registrations, dose differences in the GTV were below 3.8% for dose accumulation of lung and adrenal gland patients. For liver patients the used deformable registrations were not considered to be robust enough. It was also shown that a major part of the dose differences originates from the Hounsfield unit differences between 3D and 4D calculations, regardless of the interplay effect. CONCLUSION: The evaluated motion effects during VMAT treatments resulted in negligible dose variability. Therefore, the approximation of calculating the dose on the average reconstruction of the 4DCT (3D dose calculation), instead of calculating on the respiration-correlated phase CTs (4D dose calculation) with assignment of the corresponding MUs, gives acceptable results.

Tumor stage, tumor site and HPV dependent correlation of perfusion CT parameters and [18F]-FDG uptake in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: This study investigated whether tumor perfusion, FDG uptake and their correlation depend on tumor stage, site and HPV in head and neck cancer. MATERIAL AND METHODS: 41/55 eligible patients with integrated FDG-PET/perfusion CT from 2 prospective studies were assessed. A GTV(CT) and GTV(PET) were created. Perfusion maps were calculated using singular value decomposition method. Blood volume (BV), blood flow (BF), mean transit time (MTT) and standardized uptake value (SUV) in the tumor were compared to the surrounding tissue using Wilcoxon test and Spearman correlation of perfusion and SUVmean in the tumor was studied (p=0.05). RESULTS: Perfusion parameters were significantly increased in the GTV(CT) of advanced tumors in comparison to the surrounding soft tissue (p<0.01). Oral cavity and oropharyngeal cancer showed a higher BF than laryngeal cancer (p<0.04). No correlation between perfusion and SUVmean was found, however SUVmean correlated significantly with BF for the HPV-positive tumors (r=0.86, p=0.04) and with BV for the oropharyngeal cancer (r=0.63, p=0.05). CONCLUSION: Tumor stage, site and HPV are associated with different perfusion or combined perfusion/SUV signatures. Further studies are needed to investigate if these signatures co-determine clinical outcome.

Clinical evaluation of an anatomy-based patient specific quality assurance system.

The Delta(4DVH) Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta(4DVH) Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta(4DVH) Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta(4DVH) Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta(4DVH) Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta(4PT) QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta(4PT) GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta(4DVH) Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse).

Dosimetric comparison of flattened and unflattened beams for stereotactic ablative radiotherapy of stage I non-small cell lung cancer.

PURPOSE: To compare contribution and accuracy of delivery for two flattening filter free (FFF) beams of the nominal energy 6 and 10 MV and a 6 MV flattened beam for early stage lung cancer. METHODS: For each of 11 patients with stage I nonsmall cell lung cancer three volumetric modulated arc therapy plans were prepared utilizing a 6 MV flattened photon beam (X6FF) and two nonflattened beams of nominal energy 6 and 10 MV (X6FFF, X10FFF). Optimization constraints were set to produce dose distributions that meet the criteria of the RTOG-0915 protocol. The radiation schedule used for plan comparison in all patients was 50 Gy in five fractions. Dosimetric parameters of planning target volume (PTV) and organs-at-risk and delivery times were assessed and compared. All plans were subject to verification using Delta(4) unit (Scandidos, Sweden) and absolutely calibrated gafchromic films in a thorax phantom. RESULTS: All plans had a qualitatively comparable outcome. Obtained dose distributions were conformal (CI < 1.17) and exhibited a steep dose fall-off outside the PTV. The ratio of monitor units for FFF versus FF plans in the authors' study ranged from 0.95 to 1.21 and from 0.93 to 1.25 for X6FFF/X6FF and X10FFF/X6FF comparisons, respectively. The ratio systematically increased with increasing size of the PTV (up to +25% for 150 cm(3) PTV). Yet the integral dose to healthy tissue did not follow this trend. Comparison of cumulative dose volume histograms for a patient's body showed that X6FFF plans exhibit improved conformity and reduced the volume of tissue that received more than 50% of the prescription dose. Parameters related to dose gradient showed statistically significant improvement. CI50%, CI60%, CI80%, and CI100% were on average reduced by 4.6% (p < 0.001), 4.6% (p = 0.002), 3.1% (p = 0.002), and 1.2% (p = 0.039), respectively. Gradient measure was on average reduced by 4.2% (p < 0.001). Due to dose reduction in the surrounding lung tissue, the V20 Gy and V12.5 Gy were reduced by 5.5% (p = 0.002) and 4.5% (p < 0.001). These dosimetric improvements in the fall-off were not observed for the X10FFF plans. Differences in sparing of normal tissues were not found to be statistically significant for either of the two FFF beams. Mean beam-on times were 111 s (2SD = 11 s) for X10FFF, 128 s (2SD = 19 s) for X6FFF, and X6FF plans required on average 269 s (2SD = 71 s). While the mean dose rate was 1555 ± 264 and 1368 ± 63 MU/min, for X10FFF and X6FFF, plans using the conventional X6FF were delivered with the constant maximum dose rate of 600 MU/min. Verification of all plans showed acceptable and comparable results for all plans in homogeneous as well as heterogeneous phantoms. Mean GS (3%, 2 mm) using the Delta(4) phantom were 98.9% (2SD = 3.2%), 99.2% (2SD = 2.3%), and 99.2% (2SD = 2.3%) for X6FFF, X6FF, and X10FFF modalities. Verification using a thorax phantom showed GS > 98% in all cases. CONCLUSIONS: The use of FFF beams for stereotactic radiation therapy of nonsmall cell lung cancer patients yielded dose distributions qualitatively comparable to flattened beams and significantly reduced treatment delivery time. Utilizing the X6FFF beam improved conformity of dose distribution. On the other hand, X10FFF beam offered a slight improvement in treatment efficiency, and lower skin and peripheral dose. All effects were relatively small.

Development and evaluation of a prototype tracking system using the treatment couch.

PURPOSE: Tumor motion increases safety margins around the clinical target volume and leads to an increased dose to the surrounding healthy tissue. The authors have developed and evaluated a one-dimensional treatment couch tracking system to counter steer respiratory tumor motion. Three different motion detection sensors with different lag times were evaluated. METHODS: The couch tracking system consists of a motion detection sensor, which can be the topometrical system Topos (Cyber Technologies, Germany), the respiratory gating system RPM (Varian Medical Systems) or a laser triangulation system (Micro Epsilon), and the Protura treatment couch (Civco Medical Systems). The control of the treatment couch was implemented in the block diagram environment Simulink (MathWorks). To achieve real time performance, the Simulink models were executed on a real time engine, provided by Real-Time Windows Target (MathWorks). A proportional-integral control system was implemented. The lag time of the couch tracking system using the three different motion detection sensors was measured. The geometrical accuracy of the system was evaluated by measuring the mean absolute deviation from the reference (static position) during motion tracking. This deviation was compared to the mean absolute deviation without tracking and a reduction factor was defined. A hexapod system was moving according to seven respiration patterns previously acquired with the RPM system as well as according to a sin(6) function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion. RESULTS: A prototype system for treatment couch tracking of respiratory motion was developed. The laser based tracking system with a small lag time of 57 ms reduced the residual motion by a factor of 11.9 ± 5.5 (mean value ± standard deviation). An increase in delay time from 57 to 130 ms (RPM based system) resulted in a reduction by a factor of 4.7 ± 2.6. The Topos based tracking system with the largest lag time of 300 ms achieved a mean reduction by a factor of 3.4 ± 2.3. The increase in the penumbra of a profile (1 × 1 cm(2)) for a motion of 6 mm was 1.4 mm. With tracking applied there was no increase in the penumbra. CONCLUSIONS: Couch tracking with the Protura treatment couch is achievable. To reliably track all possible respiration patterns without prediction filters a short lag time below 100 ms is needed. More scientific work is necessary to extend our prototype to tracking of internal motion.

TOPOS: a new topometric patient positioning and tracking system for radiation therapy based on structured white light.

PURPOSE: A patient positioning system for radiation therapy based on structured white light and using off-the-shelf hardware components for flexibility and cost-effectiveness has been developed in house. Increased accuracy, patient comfort, abandonment of any skin marks, accelerated workflow, objective reading/recording, better usability and robust sensor design, compared to other positioning approaches, were the main goals of this work. Another aim was the application of a 6 degrees of freedom tracking system working without dose deposition. METHODS: Two optical sensors are the main parts of the TOPOS® system (Topometrical Positioning, cyberTECHNOLOGIES, Germany). The components: cameras, projectors, and computers are commercial off-the-shelf products, allowing for low production costs. The black/white cameras of the prototype are capable of taking up to 240 frames per second (resolution: 640 × 488 pixels). The projector has a resolution of 1024 × 768 and a refresh rate of 120 Hz. The patient's body surface is measured continuously and registered to a reference surface, providing a transformation to superimpose the patient's surface to the reference (planning CT) surface as best as possible. The execution of the calculated transformation provides the correct patient position before the treatment starts. Due to the high-speed acquisition of the surfaces, a surveillance of the patient's (respiration) motion during treatment is also accomplished. The accuracy of the system was determined using a male mannequin. Two treatment sites were evaluated: one simulating a head and neck treatment and the other simulating a thoracic wall treatment. The mannequin was moved to predefined positions, and shift vectors given by the surface registration were evaluated. Additionally manual positioning using a color-coding system was evaluated. RESULTS: Two prototypes have been developed, each allowing a continuous high density scan of a 500 × 500 × 400 mm(3) (L × W × D) large volume with a refresh rate of 10 Hz (extendible to 20 Hz for a single sensor system). Surface and position correction display, as well as respiratory motion, is shown in real-time (delay < 200 ms) using present graphical hardware acceleration. For an intuitive view of the patient's misalignment, a fast surface registration algorithm has been developed and tested and a real-time color-coding technique is proposed and verified that allows the user to easily verify the position of the patient. Using first the surface registration and then the color coding the best results were obtained: for the head and neck case, the mean difference between the actual zero position and the final match was 0.1 ± 0.4, -0.2 ± 0.7, and -0.1 ± 0.3 mm in vertical, longitudinal, and lateral direction. For the thoracic case, the mean differences were 0.3 ± 0.5, -0.6 ± 1.9, 0.0 ± 0.4 mm. CONCLUSIONS: The presented system copes with the increasing demand for more accurate patient positioning due to more precise irradiation technologies and minimizes the preparation times for correct patient alignment, therefore optimizing the treatment workflow. Moreover, TOPOS is a versatile and cost effective image guided radiation therapy device. It allows an objective rating of the patient's position before and during the irradiation and could also be used for respiratory gating or tracking.

Clinical application of flattening filter free beams for extracranial stereotactic radiotherapy.

PURPOSE: To investigate the clinical application of flattening filter free (FFF) beams at maximum dose rate for stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Patients with tumors in the lung or abdomen were subjected to SBRT using 6 MV FFF or 10 MV FFF beams. For each patient, three plans were calculated using 6 MV flattened, 6 MV FFF, and 10 MV FFF beams. Treatment times were recorded and analyzed, and tumor displacements were assessed by pre- and post-treatment cone beam computed tomography (CBCT). RESULTS: Altogether, 26 patients (16 lung, 10 abdominal tumors) were treated. The average dose rate per patient ranged from 442 to 1860 MU/min. Beam-on time was on average 1.6 min (1SD=0.6 min), with the total treatment times recorded at 18.5 min (1SD=3.5 min). The time advantage of using FFF beams was dose-dependent and started at 4 Gy for 6 MV FFF and at 10 Gy for 10 MV FFF beams. The average of the tumor displacements during treatment was 2.0mm (1SD = 1.0mm). CONCLUSIONS: SBRT using FFF beams is time efficient and associated with excellent patient stability. According to Van Herk's formula, ITV-PTV margins of 6mm are sufficient in our patient cohort. Further studies are necessary to assess clinical outcome and toxicity.