Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part II: Offline and online plan adaption for interfractional changes.

PURPOSE: The POP-ART RT study aims to determine to what extent and how intrafractional real-time respiratory motion management (RRMM), and plan adaptation for interfractional anatomical changes (ART) are used in clinical practice and to understand barriers to implementation. Here we report on part II: ART using more than one plan per target per treatment course. MATERIALS AND METHODS: A questionnaire on the current practice of ART, wishes for expansion or implementation, and barriers to implementation was distributed worldwide. Four types of ART were discriminated: daily online replanning, online plan library, protocolled offline replanning (all three based on a protocol), and ad-hoc offline replanning. RESULTS: The questionnaire was completed by 177 centres from 40 countries. ART was used by 61% of respondents (31% with protocol) for a median (range) of 3 (1-8) tumour sites. CBCT/MVCT was the main imaging modality except for online daily replanning (11 users) where 10 users used MR. Two thirds of respondents wished to implement ART for a new tumour site; 40% of these had plans to do it in the next 2 years. Human/material resources and technical limitations were the main barriers to further use and implementation. CONCLUSIONS: ART was used for a broad range of tumour sites, mainly with ad-hoc offline replanning and for a median of 3 tumour sites. There was a large interest in implementing ART for more tumour sites, mainly limited by human/material resources and technical limitations. Daily online replanning was primarily performed on MR-linacs.

Improving the intra-fraction update efficiency of a correlation model used for internal motion estimation during real-time tumor tracking for SBRT patients: fast update or no update?

BACKGROUND AND PURPOSE: For tumor tracking, a correlation model is used to estimate internal tumor position based on external surrogate motion. When patients experience an internal/external surrogate drift, an update of the correlation model is required to continue tumor tracking. In this study, the accuracy of the internal tumor position estimation for both the clinical available update at discrete points in time (rebuild) and an in-house developed non-clinical online update approach was investigated. METHODS: A dynamic phantom with superimposed baseline drifts and 14 SBRT patients, treated with real-time tumor tracking (RTTT) on the Vero system, were retrospectively simulated for three update scenarios, respectively no update, clinical rebuild and 0.5 Hz automated online update of the correlation model. By comparing the target positions based on 0.5 Hz verification X-ray images with the estimated internal tumor positions regarding all three update scenarios, 95th percentile modeling errors (ME95), incidences of full geometrical coverage of the CTV by a 5 mm extended PTV (P5mm) and population-based PTV margins were calculated. Further, the treatment time reduction was estimated when switching from the clinical rebuild approach to the online correlation model update. RESULTS: For dynamic phantom motion with baseline drifts up to 0.4 mm/min, a 0.5 Hz intra-fraction update showed a similar accuracy in terms of ME95 and P5 mm compared to clinical rebuild. For SBRT patients treated on Vero with RTTT, accuracy was improved by 0.5 Hz online update compared to the clinical rebuild protocol, yielding smaller PTV margins (from 3.2 mm to 2.7 mm), reduced ME95,3D (from 4.1 mm to 3.4 mm) and an increased 5th percentile P5 mm (from 90.7% to 96.1%) for the entire patient group. Further, 80% of treatment sessions were reduced in time with on average 5.5 ± 4.1(1 SD)min. CONCLUSION: With a fast (0.5 Hz) automated online update of the correlation model, an efficient RTTT workflow with improved geometrical accuracy was obtained.

Impact of inadequate respiratory motion management in SBRT for oligometastatic colorectal cancer.

PURPOSE: Stereotactic body radiotherapy (SBRT) in oligometastatic colorectal cancer (CRC) resulted in a disappointing 1-year local control rate of 54% in our experience. We aimed to determine the root cause(s). METHODS: 47 oligometastatic CRC patients were treated with SBRT by helical tomotherapy to a dose of 40 or 50Gy in 10 fractions, without specific respiratory motion management and PTV-margins of 10-10-12mm in all patients. The local recurrences (LRs) were delineated on diagnostic PET-CT scans and co-registered with initial planning CTs. LRs were classified as in-field or marginal with respect to the initial dose distribution, and predictors for LR were determined. RESULTS: Out of 105 irradiated metastases, LR modeling yielded 15 in-field and 15 marginal failures. Metastases in moving organs (liver and lung) exhibited a local control of 53% at 1-year (95% confidence interval (CI): 38-67%), compared to 79% for lymph nodes (95% CI: 32-95%). The first group exhibited a sixfold increased risk compared to the latter on multivariate analysis (p=0.01). CONCLUSIONS: The nature and locations of LR indicated that dose prescription and methodology were both inadequate for liver and lung metastases. This study demonstrates the need for individual respiratory motion management and a biological effective dose of >75Gy.

Treating patients with real-time tumor tracking using the Vero gimbaled linac system: implementation and first review.

PURPOSE: To report on the first clinical application of a real-time tumor tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for treatment of moving tumors. METHODS AND MATERIALS: A first group of 10 SBRT patients diagnosed with NSCLC or oligometastatic disease in lung or liver was treated with the RTTT technique. The PTV volumes and OAR exposure were benchmarked against the widely used ITV approach. Based on data acquired during execution of RTTT treatments, a first review was performed of the process. RESULTS: The 35% PTV volume reduction with RTTT of the studied single lesions SBRT irradiations of small target volumes is expected to result in a small (<1%) reduction of lung or liver NTCP. A GTV-PTV margin of 5.0mm was applied for treatment planning of RTTT. From patient data on residual geometric uncertainties, a CTV-PTV margin of 3.2mm was calculated. Reduction of the GTV-PTV margin below 5.0mm without better understanding of biological definition of tumor boundaries was discouraged. Total treatment times were reduced to 34.4 min on average. CONCLUSION: A considerable PTV volume reduction was achieved applying RTTT and time efficiency for respiratory correlated SBRT was reestablished with Vero RTTT.

A complementary dual-modality verification for tumor tracking on a gimbaled linac system.

BACKGROUND AND PURPOSE: For dynamic tracking of moving tumors, robust intra-fraction verification was required, to assure that tumor motion was properly managed during the course of radiotherapy. A dual-modality verification system, consisting of an on-board orthogonal kV and planar MV imaging device, was validated and applied retrospectively to patient data. METHODS AND MATERIALS: Real-time tumor tracking (RTTT) was managed by applying PAN and TILT angular corrections to the therapeutic beam using a gimbaled linac. In this study, orthogonal X-ray imaging and MV EPID fluoroscopy was acquired simultaneously. The tracking beam position was derived from respectively real-time gimbals log files and the detected field outline on EPID. For both imaging modalities, the moving target was localized by detection of an implanted fiducial. The dual-modality tracking verification was validated against a high-precision optical camera in phantom experiments and applied to clinical tracking data from a liver and two lung cancer patients. RESULTS: Both verification modalities showed a high accuracy (<0.3mm) during validation on phantom. Marker detection on EPID was influenced by low image contrast. For the clinical cases, gimbaled tracking showed a 90th percentile error (E90) of 3.45 (liver), 2.44 (lung A) and 3.40 mm (lung B) based on EPID fluoroscopy and good agreement with XR-log file data by an E90 of 3.13, 1.92 and 3.33 mm, respectively, during beam on. CONCLUSION: Dual-modality verification was successfully implemented, offering the possibility of detailed reporting on RTTT performance.

Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: a patient simulation study.

PURPOSE: To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. METHODS AND MATERIALS: The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. RESULTS: The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. CONCLUSION: The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems.

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of arteriovenous malformations and acoustic neuromas.

PURPOSE: We investigated the influence of beam modulation on treatment planning by comparing four available stereotactic radiosurgery (SRS) modalities: Gamma-Knife-Perfexion, Novalis-Tx Dynamic-Conformal-Arc (DCA) and Dynamic-Multileaf-Collimation-Intensity-Modulated-radiotherapy (DMLC-IMRT), and Cyberknife. MATERIAL AND METHODS: Patients with arteriovenous malformation (n = 10) or acoustic neuromas (n = 5) were planned with different treatment modalities. Paddick conformity index (CI), dose heterogeneity (DH), gradient index (GI) and beam-on time were used as dosimetric indices. RESULTS: Gamma-Knife-Perfexion can achieve high degree of conformity (CI = 0.77 ± 0.04) with limited low-doses (GI = 2.59 ± 0.10) surrounding the inhomogeneous dose distribution (D(H) = 0.84 ± 0.05) at the cost of treatment time (68.1 min ± 27.5). Novalis-Tx-DCA improved this inhomogeneity (D(H) = 0.30 ± 0.03) and treatment time (16.8 min ± 2.2) at the cost of conformity (CI = 0.66 ± 0.04) and Novalis-TX-DMLC-IMRT improved the DCA CI (CI = 0.68 ± 0.04) and inhomogeneity (D(H) = 0.18 ± 0.05) at the cost of low-doses (GI = 3.94 ± 0.92) and treatment time (21.7 min ± 3.4) (p<0.01). Cyberknife achieved comparable conformity (CI = 0.77 ± 0.06) at the cost of low-doses (GI = 3.48 ± 0.47) surrounding the homogeneous (D(H) = 0.22 ± 0.02) dose distribution and treatment time (28.4min±8.1) (p<0.01). CONCLUSIONS: Gamma-Knife-Perfexion will comply with all SRS constraints (high conformity while minimizing low-dose spread). Multiple focal entries (Gamma-Knife-Perfexion and Cyberknife) will achieve better conformity than High-Definition-MLC of Novalis-Tx at the cost of treatment time. Non-isocentric beams (Cyberknife) or IMRT-beams (Novalis-Tx-DMLC-IMRT) will spread more low-dose than multiple isocenters (Gamma-Knife-Perfexion) or dynamic arcs (Novalis-Tx-DCA). Inverse planning and modulated fluences (Novalis-Tx-DMLC-IMRT and CyberKnife) will deliver the most homogeneous treatment. Furthermore, Linac-based systems (Novalis and Cyberknife) can perform image verification at the time of treatment delivery.

Implementation of HybridArc treatment technique in preoperative radiotherapy of rectal cancer: dose patterns in target lesions and organs at risk as compared to helical Tomotherapy and RapidArc.

PURPOSE: HybridArc is a novel treatment technique blending aperture-enhanced optimized arcs with discrete IMRT-elements, allowing selection of arcs with a set of static IMRT-beams. This study compared this new technique to helical Tomotherapy, and RapidArc, in preoperative radiotherapy of rectal cancer. MATERIAL AND METHODS: Twelve rectal cancer patients treated consecutively with Tomotherapy Hi-Art II system were simulated with HybridArc and RapidArc. Treatment plans were designed to deliver homogeneous dose of 46.0Gy to mesorectum and draining lymph nodes, with a simultaneous-integrated-boost to the primary tumor up to a total dose of 55.2Gy. Planning objectives were 95% of prescribed dose to 95% of PTVs, while minimizing the volume of small bowel receiving more than 15Gy (V15) and the mean bladder dose. Dose gradient towards simultaneous-integrated-boost (GI), calculated by dividing the volume receiving more then 52.4Gy (95% of PTV55.2Gy)to the volume of PTV55.2Gy, was kept below 1.5. Mean beam-on time and amount of MUs were also analyzed. RESULTS: PTV swere adequately covered by all plans. Significant advantage was found for Tomotherapy in sparing small bowel (V15 = 112.7cm(3)SD73.4cm(3)) compared to RapidArc (133.4cm(3)SD75.3cm(3)) and HybridArc (143.7cm(3)SD74.4cm(3)) (p < 0.01). The mean bladder dose was better with RapidArc (20.6GySD2.2Gy) compared to HybridArc (24.2Gy SD4.3Gy) and Tomotherapy (23.0GySD4.7Gy) (p < 0.01). The mean beam-on time was significantly lower (p < 0.01) for HybridArc (2.7min SD0.8) and RapidArc (2.5min SD0.5) compared to Tomotherapy (11.0min SD0.7). The total amount of MUs was significantly (p < 0.01) lower for RapidArc (547SD44)compared to HybridArc (949 SD153). CONCLUSIONS: HybridArc is a feasible solution for preoperative RT with a simultaneous-integrated-boost in rectal cancer patients. It achieved similar PTV coverage with significant lower beam-on time, but less efficient in sparing small bowel and bladder compared to Tomotherapy and RapidArc. The added value of HybridArc is that the treatment modality can be implemented on every LINAC equipped with Dynamic-Conform-Arc and IMRT treatment techniques, while maintaining the same QA-schemes.

Computer-aided analysis of star shot films for high-accuracy radiation therapy treatment units.

As mechanical stability of radiation therapy treatment devices has gone beyond sub-millimeter levels, there is a rising demand for simple yet highly accurate measurement techniques to support the routine quality control of these devices. A combination of using high-resolution radiosensitive film and computer-aided analysis could provide an answer. One generally known technique is the acquisition of star shot films to determine the mechanical stability of rotations of gantries and the therapeutic beam. With computer-aided analysis, mechanical performance can be quantified as a radiation isocenter radius size. In this work, computer-aided analysis of star shot film is further refined by applying an analytical solution for the smallest intersecting circle problem, in contrast to the gradient optimization approaches used until today. An algorithm is presented and subjected to a performance test using two different types of radiosensitive film, the Kodak EDR2 radiographic film and the ISP EBT2 radiochromic film. Artificial star shots with a priori known radiation isocenter size are used to determine the systematic errors introduced by the digitization of the film and the computer analysis. The estimated uncertainty on the isocenter size measurement with the presented technique was 0.04 mm (2σ) and 0.06 mm (2σ) for radiographic and radiochromic films, respectively. As an application of the technique, a study was conducted to compare the mechanical stability of O-ring gantry systems with C-arm-based gantries. In total ten systems of five different institutions were included in this study and star shots were acquired for gantry, collimator, ring, couch rotations and gantry wobble. It was not possible to draw general conclusions about differences in mechanical performance between O-ring and C-arm gantry systems, mainly due to differences in the beam-MLC alignment procedure accuracy. Nevertheless, the best performing O-ring system in this study, a BrainLab/MHI Vero system, and the best performing C-arm system, a Varian Truebeam system, showed comparable mechanical performance: gantry isocenter radius of 0.12 and 0.09 mm, respectively, ring/couch rotation of below 0.10 mm for both systems and a wobble of 0.06 and 0.18 mm, respectively. The methodology described in this work can be used to monitor mechanical performance constancy of high-accuracy treatment devices, with means available in a clinical radiation therapy environment.

Clinical evaluation of a robotic 6-degree of freedom treatment couch for frameless radiosurgery.

PURPOSE: To evaluate the added value of 6-degree of freedom (DOF) patient positioning with a robotic couch compared with 4DOF positioning for intracranial lesions and to estimate the immobilization characteristics of the BrainLAB frameless mask (BrainLAB AG, Feldkirchen, Germany), more specifically, the setup errors and intrafraction motion. METHODS AND MATERIALS: We enrolled 40 patients with 66 brain metastases treated with frameless stereotactic radiosurgery and a 6DOF robotic couch. Patient positioning was performed with the BrainLAB ExacTrac stereoscopic X-ray system. Positioning results were collected before and after treatment to assess patient setup error and intrafraction motion. Existing treatment planning data were loaded and simulated for 4DOF positioning and compared with the 6DOF positioning. The clinical relevance was analyzed by means of the Paddick conformity index and the ratio of prescribed isodose volume covered with 4DOF to that obtained with the 6DOF positioning. RESULTS: The mean three-dimensional setup error before 6DOF correction was 1.91 mm (SD, 1.25 mm). The rotational errors were larger in the longitudinal (mean, 0.23°; SD, 0.82°) direction compared with the lateral (mean, -0.09°; SD, 0.72°) and vertical (mean, -0.10°; SD, 1.03°) directions (p < 0.05). The mean three-dimensional intrafraction shift was 0.58 mm (SD, 0.42 mm). The mean intrafractional rotational errors were comparable for the vertical, longitudinal, and lateral directions: 0.01° (SD, 0.35°), 0.03° (SD, 0.31°), and -0.03° (SD, 0.33°), respectively. The mean conformity index decreased from 0.68 (SD, 0.08) (6DOF) to 0.59 (SD, 0.12) (4DOF) (p < 0.05). A loss of prescribed isodose coverage of 5% (SD, 0.08) was found with the 4DOF positioning (p < 0.05). Half a degree for longitudinal and lateral rotations can be identified as a threshold for coverage loss. CONCLUSIONS: With a mask immobilization, patient setup error and intrafraction motions need to be evaluated and corrected for. The 6DOF patient positioning with a 6DOF robotic couch to correct translational and rotational setup errors improves target positioning with respect to treatment isocenter, which is in direct relation with the clinical outcome, compared with the 4DOF positioning.

Setup accuracy of the Novalis ExacTrac 6DOF system for frameless radiosurgery.

PURPOSE: Stereotactic radiosurgery using frame-based positioning is a well-established technique for the treatment of benign and malignant lesions. By contrast, a new trend toward frameless systems using image-guided positioning techniques is gaining mainstream acceptance. This study was designed to measure the detection and positioning accuracy of the ExacTrac/Novalis Body (ET/NB) for rotations and to compare the accuracy of the frameless with the frame-based radiosurgery technique. METHODS AND MATERIALS: A program was developed in house to rotate reference computed tomography images. The angles measured by the system were compared with the known rotations. The accuracy of ET/NB was evaluated with a head phantom with seven lead beads inserted, mounted on a treatment couch equipped with a robotic tilt module, and was measured with a digital water level and portal films. Multiple hidden target tests (HTT) were performed to measure the overall accuracy of the different positioning techniques for radiosurgery (i.e., frameless and frame-based with relocatable mask or invasive ring, respectively). RESULTS: The ET/NB system can detect rotational setup errors with an average accuracy of 0.09° (standard deviation [SD] 0.06°), 0.02° (SD 0.07°), and 0.06° (SD 0.14°) for longitudinal, lateral, and vertical rotations, respectively. The average positioning accuracy was 0.06° (SD 0.04°), 0.08° (SD 0.06°), and 0.08° (SD 0.07°) for longitudinal, lateral and vertical rotations, respectively. The results of the HTT showed an overall three-dimensional accuracy of 0.76 mm (SD 0.46 mm) for the frameless technique, 0.87 mm (SD 0.44 mm) for the relocatable mask, and 1.19 mm (SD 0.45 mm) for the frame-based technique. CONCLUSIONS: The study showed high detection accuracy and a subdegree positioning accuracy. On the basis of phantom studies, the frameless technique showed comparable accuracy to the frame-based approach.

Geometric accuracy of a novel gimbals based radiation therapy tumor tracking system.

PURPOSE: VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking. MATERIALS AND METHODS: To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured. RESULTS: The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E(90%)<0.82 mm and similar performance for pan/tilt. Systematic tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E(90%) of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt. CONCLUSIONS: In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy.

Daily megavoltage computed tomography in lung cancer radiotherapy: correlation between volumetric changes and local outcome.

PURPOSE: To assess the predictive or comparative value of volumetric changes, measured on daily megavoltage computed tomography during radiotherapy for lung cancer. PATIENTS AND METHODS: We included 80 patients with locally advanced non-small-cell lung cancer treated with image-guided intensity-modulated radiotherapy. The radiotherapy was combined with concurrent chemotherapy, combined with induction chemotherapy, or given as primary treatment. Patients entered two parallel studies with moderately hypofractionated radiotherapy. Tumor volume contouring was done on the daily acquired images. A regression coefficient was derived from the volumetric changes on megavoltage computed tomography, and its predictive value was validated. Logarithmic or polynomial fits were applied to the intratreatment changes to compare the different treatment schedules radiobiologically. RESULTS: Regardless of the treatment type, a high regression coefficient during radiotherapy predicted for a significantly prolonged cause-specific local progression free-survival (p = 0.05). Significant differences were found in the response during radiotherapy. The significant difference in volumetric treatment response between radiotherapy with concurrent chemotherapy and radiotherapy plus induction chemotherapy translated to a superior long-term local progression-free survival for concurrent chemotherapy (p = 0.03). An enhancement ratio of 1.3 was measured for the used platinum/taxane doublet in comparison with radiotherapy alone. CONCLUSION: Contouring on daily megavoltage computed tomography images during radiotherapy enabled us to predict the efficacy of a given treatment. The significant differences in volumetric response between treatment strategies makes it a possible tool for future schedule comparison.

The effect of tomotherapy imaging beam output instabilities on dose calculation.

A radiotherapy treatment plan is based on an anatomical 'snapshot' of the patient acquired during the preparation stage using a kVCT (kilovolt computed tomography) scanner. Anatomical changes will occur during the treatment course, in some cases requiring a new treatment plan to deliver the prescribed dose. With the introduction of 3D volumetric on-board imaging devices, it became feasible to use the produced images for dose recalculation. However, the use of these on-board imaging devices in clinical routine for the calculation of dose depends on the stability of the images. In this study the validation of tomotherapy MVCT (megavolt computed tomography) produced images, for the purpose of dose recalculation by the Planned Adaptive software, has been performed. To investigate the validity of MVCT images for dose calculation, a treatment plan was created based on kVCT-acquired images of a solid water phantom. During a period of 4 months, MVCT images of the phantom have been acquired and were used by the planned adaptive software to recalculate the initial kVCT-based dose on the MVCT images. The influence of the adapted IVDTs (image value-to-density tables) has been investigated as well as the effect of image acquisition with or without preceding airscan. Output fluctuations and/or instabilities of the imaging beam result in MV images of different quality yielding different results when used for dose calculation. It was shown that the output of the imaging beam is not stable, leading to differences of nearly 3% between the original kV-based dose and the recalculated MV-based dose, for solid water only. MVCT images can be used for dose calculation purposes bearing in mind that the output beam is liable to fluctuations. The acquisition of an IVDT together with the MVCT image set, that is going to be used for dose calculation, is highly recommended.

Volumetric imaging by megavoltage computed tomography for assessment of internal organ motion during radiotherapy for cervical cancer.

PURPOSE: To assess the internal organ motion of the cervix and uterus by megavoltage computed tomography (MVCT) during intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten patients with Stage IIB-IVA cervical cancer underwent daily MVCT imaging. Internal organ motion was evaluated on 150 pretreatment MVCT images by measuring shifts in their boundaries between the MVCT and kilovoltage (kV) planning CT scan in the anterior, posterior, left and right lateral, and superior and inferior direction. Additional intrafractional patient movement was evaluated on 50 posttreatment MVCT images. RESULTS: Measured cervical motion (mean +/- SD) was 0.4 +/- 10.1 mm in the anterior, -3.0 +/- 6.9 mm in the posterior direction, -3.5 +/- 4.9 mm in the left and 0.2 +/- 4.5 mm in the right lateral direction, 2.2 +/- 8.0 mm in the superior and 0.5 +/- 5.0 mm in the inferior direction. Compared to the cervix, larger uterine motion was observed. Patient movement during treatment was limited to 1.1 +/- 1.3 mm, -0.3 +/- 1.6 mm, and 0.2 +/- 2.3 mm in anteroposterior, laterolateral and superoinferior direction respectively. CONCLUSIONS: MVCT imaging can be used to study patient setup accuracy and cervical and uterine motion during IMRT. This data may be used to refine treatment margins.

Toxicity and outcome results of a class solution with moderately hypofractionated radiotherapy in inoperable Stage III non-small cell lung cancer using helical tomotherapy.

PURPOSE: To prospectively assess the feasibility, toxicity, and local control of a class solution protocol of moderately hypofractionated tomotherapy in Stage III, inoperable, locally advanced non-small-cell lung cancer patients. METHODS AND MATERIALS: Eligible patients were treated according to a uniform class solution (70.5 Gy in 30 fractions) with fixed constraints and priorities using helical tomotherapy. Toxicity monitoring was performed using the Radiation Therapy Oncology Group criteria and the National Cancer Institute Common Terminology Criteria and Adverse Events (CTCAE) version 3.0. Pulmonary function tests were performed at the start and repeated at 3 months after treatment. RESULTS: Our class solution resulted in a deliverable plan in all 40 consecutive patients. Acute Grade 3 lung toxicity was seen in 10% of patients. Two patients died during acute follow-up with pulmonary toxicity. Correlations were found between changes in pulmonary function test results and mean lung dose or the lung volume receiving 20 Gy (V(20)). The correlation was strongest for lung diffusion capacity for carbon monoxide. A V(20) of >27% and >32% were predictive for Grades 2 and 3 acute lung toxicity respectively (p < 0.05). Late Grade 3 toxicity was exclusively pulmonary, with an incidence of 16%. Overall Grade 3 lung toxicity correlated with a mean lung dose of >18 Gy and a median lung dose of >5 Gy (p < 0.05). Median survival was 17 months, and the 1-year and 2-year local progression-free survivals were 66% and 50%, respectively. CONCLUSION: The current class solution using moderately hypofractionated helical tomotherapy in patients with locally advanced non-small-cell lung cancer is feasible. Toxicity was acceptable and in line with other reports on intensity-modulated radiotherapy. The local progression-free survival was encouraging considering the unselected population.

An in-house developed resettable MOSFET dosimeter for radiotherapy.

The purpose of this note is to report the feasibility and clinical validation of an in-house developed MOSFET dosimetry system and describe an integrated non-destructive reset procedure. Off-the-shelf MOSFETs are connected to a common PC using an 18 bit/analogue-input and 16 bit/output data acquisition card. A reading algorithm was developed defining the zero-temperature-coefficient point (ZTC) to determine the threshold voltage. A wireless interface was established for ease of use. The reset procedure consists of an internal circuit generating a local heating induced by an electrical current. Sensitivity has been investigated as a function of bias voltage (0-9 V) to the gate. Dosimetric properties have been evaluated for 6 MV and 15 MV clinical photon beams and in vivo benchmarking was performed against thermoluminescence dosimeters (TLD) for conventional treatments (two groups of ten patients for each energy) and total body irradiation (TBI). MOSFETS were pre-irradiated with 20 Gy. Sensitivity of 0.08 mV cGy(-1) can be obtained for 200 cGy irradiations at 5 V bias voltage. Ten consecutive measurements at 200 cGy yield a SD of 2.08 cGy (1.05%). Increasing the dose in steps from 5 cGy to 1000 cGy yields a 1.00 Pearson correlation coefficient and agreement within 2.0%. Dose rate dependence (160-800 cGy min(-1)) was within 2.5%, temperature dependence within 2.0% (25-37 degrees C). A strong angular dependence has been observed for gantry incidences exceeding +/-30 degrees C. Dose response is stable up to 50 Gy (saturation occurs at approximately 90 Gy), which is used as threshold dose before resetting the MOSFET. An average measured-over-calculated dose ratio within 1.05 (SD: 0.04) has been obtained in vivo. TBI midplane-dose assessed by entrance and exit dose measurements agreed within 1.9% with ionization chamber in phantom, and within 1.0% with TLD in vivo. An in-house developed resettable MOSFET-based dosimetry system is proposed. The system has been validated and is currently used for in vivo entrance dose measurement in clinical routine for simple (open field) treatment configurations.

Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy.

BACKGROUND: The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system). METHODS: This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity. RESULTS: Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade > or =3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images. CONCLUSIONS: The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction.

A diagnostic tool for basic daily quality assurance of a Tomotherapy Hi*Art machine.

To investigate and evaluate the use of an in-house developed diagnostic software tool using the imaging detector data for a quick daily quality assurance check of the output (dose) and lateral profile (cone) of a tomotherapy Hi*Art system. The Hi*Art treatment system is a radiation therapy machine for delivering intensity modulated radiation therapy (IMRT) in a helical fashion with an integrated CT scanner used for improved patient positioning before treatment. Since the system was developed specifically for IMRT, flat fields can be obtained by modulating the beam and therefore the flattening filter could be omitted. Because of this, the field has a cone-like profile in both lateral and transversal directions. Patients are treated in a helical fashion with a tight pitch and a constant gantry rotation speed, while modulation is performed by a binary MLC. Consequently dose output per time-unit (dose rate) as well as the shape of the cone-profile are very important for correct patient treatment and should be closely monitored. However, using the company-provided initial tools and conventional dosimetry, this can be a time consuming daily procedure. The aim of this work is to develop a fast, automated method of quality assurance based on the detector signal. A software tool called "tomocheck" running on the operation station has been developed to evaluate the output (dose rate) and the lateral cone profile (energy) of the Hi*Art system, comparing actual output and cone profile with a reference (previously approved against ionization chamber measurements). This is done by using the data of the 640 on-board detector array that are directly retrieved and processed after a specific QA procedure. The detector file consists of the CT detector data and the three monitoring dose chamber readings over a time period of 200 sec. To evaluate the method, the system was benchmarked against ionization chamber measurements and classical IMRT QA methods. Action levels (final status "NOT ACCEPTED") for dose ratio as well as the cone ratio are set to +/- 2%. The QA tool was introduced for daily QA in May 2007. For the following 24 months, a total of 931 morning checks was made on both tomotherapy machines. In 42 cases the check status was "NOT ACCEPTED". In 34 cases the dose ratio (DR) was out of tolerance. The corrected cone ratio (CCR) was outside of specification tolerance in 8 cases. The tomocheck data was related to the ionization chamber measurements for the IMRT plan indicating a close relationship between the CCR and the off-axis measurements. Average dose ratio against the mean value of the on- and off-axis IC measurement indicates that this parameter is a good interpretation of the dose output. This tool makes it possible to perform an easy-to-use and fast basic daily quality assurance check featuring an output as well as an energy evaluation. Ideally this tool should offer also the combined dosimetry check of jaw width, couch speed, leaf latency, output, leaf/gantry synchrony, and lasers. This will be investigated in the future.

Dosimetric assessment of static and helical TomoTherapy in the clinical implementation of breast cancer treatments.

BACKGROUND AND PURPOSE: Investigation of the use of TomoTherapy and TomoDirect versus conventional radiotherapy for the treatment of post-operative breast carcinoma. This study concentrates on the evaluation of the planning protocol for the TomoTherapy and TomoDirect TPS, dose verification and the implementation of in vivo dosimetry. MATERIALS AND METHODS: Eight patients with different breast cancer indications (left/right tumor, axillary nodes involvement (N+)/no nodes (N0), tumorectomy/mastectomy) were enrolled. TomoTherapy, TomoDirect and conventional plans were generated for prone and supine positions leading to six or seven plans per patient. Dose prescription was 42Gy in 15 fractions over 3weeks. Dose verification of a TomoTherapy plan is performed using TLDs and EDR2 film inside a home-made wax breast phantom fixed on a rando-alderson phantom. In vivo dosimetry was performed with TLDs. RESULTS: It is possible to create clinically acceptable plans with TomoTherapy and TomoDirect. TLD calibration protocol with a water equivalent phantom is accurate. TLD verification with the phantom shows measured over calculated ratios within 2.2% (PTV). An overresponse of the TLDs was observed in the low dose regions (<0.1Gy). The film measurements show good agreement for high and low dose regions inside the phantom. A sharp gradient can be created to the thoracic wall. In vivo dosimetry with TLDs was clinically feasible. CONCLUSIONS: The TomoTherapy and TomoDirect modalities can deliver dose distributions which the radiotherapist judges to be equal to or better than conventional treatment of breast carcinoma according to the organ to be protected.