Nadine Linthout

Innovations in image-guided radiotherapy

The limited ability to control for the location of a tumour compromises the accuracy with which radiation can be delivered to tumour-bearing tissue. The resultant requirement for larger treatment volumes to accommodate target uncertainty restricts the radiation dose because more surrounding normal tissue is exposed. With image-guided radiotherapy (IGRT) these volumes can be optimized and tumoricidal doses can be delivered, achieving maximal tumour control with minimal complications. Moreover, with the ability of high-precision dose delivery and real-time knowledge of the target volume location, IGRT has initiated the exploration of new indications for radiotherapy, some of which were previously considered infeasible.

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.

Prospective, Risk-Adapted Strategy of Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer: Results of a Phase II Trial

PURPOSE Validation of a prospective, risk-adapted strategy for early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Patients with a T1-3N0M0 (American Joint Committee on Cancer 6th edition) NSCLC were accrued. Using the Radiation Therapy Oncology Group definition, patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for centrally located lesions. The primary endpoint was toxicity, graded according to the Radiation Therapy Oncology Group acute and late morbidity scoring system, and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Secondary endpoints were local control and survival. RESULTS A total of 40 patients were included, 17 with a centrally located lesion. The lung toxicity-free survival estimate at 2 years was 74% and was related to the location (central vs. peripheral) and the size of the target volume. No dose volumetric parameters could predict the occurrence of lung toxicity. One patient died because of treatment-related toxicity. The 1-year and 2-year local progression-free survival estimates were 97% and 84%, respectively, and were related to stage (T1 vs. T2) related (p = 0.006). Local failure was not more frequent for patients treated in four fractions. The 1-year local progression-free survival estimate dropped below 80% for lesions with a diameter of more than 4 cm. CONCLUSION The proposed risk-adapted strategy for both centrally and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates. The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design.

Initial experience with intensity-modulated conformal radiation therapy for treatment of the head and neck region

PURPOSE The efficacy of a conventional, noninvasive fixation technique in combination with a commercially available system for conformal radiotherapy by intensity modulation of the treatment beam has been studied. METHODS AND MATERIALS A slice-by-slice arc-rotation approach was used to deliver a conformal dose to the target and patient fixation was performed by means of thermoplastic casts. Eleven patients have been treated, of which 9 were for tumors of the head and neck region and 2 were for intracranial lesions. A procedure for target localization and verification of patient positioning suitable for this particular treatment technique has been developed based on the superposition of digitized portals with plots generated from the treatment-planning system. A dosimetric verification of the treatment procedure was performed with an anthropomorphic phantom: both absolute dose measurements (alanine and thermoluminescent detectors) and relative dose distribution measurements (film dosimetry) have been applied. The dose delivered outside the target has also been investigated. RESULTS The dose verification with the anthropomorphic phantom yielded a ratio between measured and predicted dose values of 1.0 for different treatment schedules and the calculated dose distribution agreed with the measured dose distribution. Day-to-day variations in patient setup of 0.3 cm (translations) and 2.0 degrees (rotations) were considered acceptable for this particular patient population, whereas the verification protocol allowed detection of 0.1 cm translational errors and 1.0 rotational errors. CONCLUSIONS The noninvasive fixation technique in combination with an adapted verification protocol proved to be acceptable for conformal treatment of the head and neck region. Dose measurements, in turn, confirmed the predicted dose values to the target and organs at risk within uncertainty. Daily monitoring becomes mandatory if an accuracy superior to 0.1 cm and 1.0 degree is required for patient setup.

Six dimensional analysis with daily stereoscopic x-ray imaging of intrafraction patient motion in head and neck treatments using five points fixation masks.

The safety margins used to define the Planning Target Volume (PTV) should reflect the accuracy of the target localization during treatment that comprises both the reproducibility of the patient positioning and the positional uncertainty of the target, so both the inter- and intrafraction motion of the target. Our first aim in this study was to determine the intrafraction motion of patients immobilized with a five-point thermoplastic mask for head and neck treatments. The five-point masks have the advantage that the patients shoulders as well as the cranial part of the patients head is covered with the thermoplastic material that improves the overall immobilization of the head and neck region of the patient. Thirteen patients were consecutively assigned to use a five-point thermoplastic mask. The patients were positioned by tracking of infrared markers (IR) fixed to the immobilization device and stereoscopic x-ray images were used for daily on-line setup verification. Repositioning was carried out prior to treatment as needed; rotations were not corrected. Movements during treatment were monitored by real-time IR tracking. Intrafraction motion and rotation was supplementary assessed by a six-degree-of-freedom (6-D) fusion of x-ray images, taken before and after all 385 treatments, with DRR images generated from the planning CT data. The latter evaluates the movement of the patient within the thermoplastic mask independent from the mask movement, where IR tracking evaluates the movement of the mask caused by patient movement in the mask. These two movements are not necessarily equal to each other. The maximum intrafraction movement detected by IR tracking showed a shift [mean (SD; range)] of -0.1(0.7; 6.0), 0.1(0.6; 3.6), -0.2(0.8;5.5) mm in the vertical, longitudinal, and lateral direction, respectively, and rotations of 0.0(0.2; 1.6), 0.0(0.2; 1.7) and 0.2(0.2; 2.4) degrees about the vertical, longitudinal, and lateral axis, respectively. The standard deviations and ranges found with the 6-D fusion demonstrate intrafraction patient displacements of -0.5(1.2; 7.4), 0.3(0.7; 5.3), 0.0(0.7; 5.7) mm in the vertical, longitudinal, and lateral direction, respectively, and rotations of -0.1(0.6; 4.1), 0.1(0.7; 8.3) and -0.2(0.8; 8.2) degrees about the vertical, longitudinal, and lateral axis, respectively. The 6-D fusions are considerably larger (p < 0.05) than detected by IR tracking. This indicates that the external marker tracking underestimates the magnitude of the actual intrafraction motion and rotation of the patient. The intrafraction motion detected for the patients immobilized with a conventional thermoplastic mask was relatively large. The feasibility to reduce this intrafraction movement by the application of alternative five-point thermoplastic mask types was evaluated as a second aim of this study. The preliminary results showed a clear reduction in the range, being an indication for the random movements, of both the intrafraction shift and rotation for both alternative mask types. The 6-D fusion is found a useful tool for a fast evaluation of the actual patients intrafraction shift and rotation and shows the latter is not negligible and needs to be taken into account additional to the initial setup accuracy when determining the PTV margin.

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.

Assessment of Intrafractional Movement and Internal Motion in Radiotherapy of Rectal Cancer Using Megavoltage Computed Tomography

PURPOSE The aim of this study was to provide estimates of setup and internal margins of patients treated for rectal carcinoma using helical tomotherapy and to assess possible margin adaptations. Using helical tomotherapy, highly conformal dose distributions can be created, and the integrated megavoltage computed tomography (MVCT) modality allows very precise daily patient positioning. In clinical protocols, however, margins originating from traditional setup procedures are still being applied. This work investigates whether this modality can aid in redefining treatment margins. METHODS AND MATERIALS Ten patients who were treated with tomotherapy underwent MVCT scanning before and after 10 treatments. Using automatic registration the necessary setup margin was investigated by means of bony landmarks. Internal margins were assessed by delineating and describing the mesorectal movement. RESULTS Based on bony landmarks, movement of patients during treatments was limited to 2.45 mm, 1.99 mm, and 1.09 mm in the lateral, longitudinal, and vertical direction, respectively. Systematic errors were limited to <1 mm. Measured movement of the mesorectal space was -1.6 mm (+/- 4.2 mm) and 0.1 mm (+/- 4.0 mm) for left and right lateral direction. In the antero-posterior direction, mean shifts were -2 mm (+/- 6.8 mm) and -0.4 mm (+/- 3.8 mm). Mean shifts in the cranio-caudal direction were respectively -3.2 mm (+/- 5.6 mm) and -3.2 mm (+/- 6.8 mm). CONCLUSIONS The use of the integrated MVCT on the tomotherapy system can minimize the setup margin for rectal cancer, and can also be used to adequately describe the internal margin allowing for direct treatment margin adaptation.

Single Fraction Versus Fractionated Linac-Based Stereotactic Radiotherapy for Vestibular Schwannoma: A Single-Institution Experience

PURPOSE To evaluate and compare outcomes for patients with vestibular schwannoma (VS) treated in a single institution with linac-based stereotactic radiosurgery (SRS) or by fractionated stereotactic radiotherapy (SRT). METHODS AND MATERIALS One hundred and nineteen patients (SRS = 78, SRT = 41) were treated. For both SRS and SRT, beam shaping is performed by a mini-multileaf collimator. For SRS, a median single dose of 12.5 Gy (range, 11-14 Gy), prescribed to the 80% isodose line encompassing the target, was applied. Of the 42 SRT treatments, 32 treatments consisted of 10 fractions of 3-4 Gy, and 10 patients received 25 sessions of 2 Gy, prescribed to the 100% with the 95% isodose line encompassing the planning target volume. Mean largest tumor diameter was 16.6 mm in the SRS and 24.6 mm in the SRT group. Local tumor control, cranial nerve toxicity, and preservation of useful hearing were recorded. Any new treatment-induced cranial nerve neuropathy was scored as a complication. RESULTS Median follow-up was 62 months (range, 6-136 months), 5 patients progressed, resulting in an overall 5-year local tumor control of 95%. The overall 5-year facial nerve preservation probability was 88% and facial nerve neuropathy was statistically significantly higher after SRS, after prior surgery, for larger tumors, and in Koos Grade ≥3. The overall 5-year trigeminal nerve preservation probability was 96%, not significantly influenced by any of the risk factors. The overall 4-year probability of preservation of useful hearing (Gardner-Robertson score 1 or 2) was 68%, not significantly different between SRS or SRT (59% vs. 82%, p = 0.089, log rank). CONCLUSION Linac-based RT results in good local control and acceptable clinical outcome in small to medium-sized vestibular schwannomas (VSs). Radiosurgery for large VSs (Koos Grade ≥3) remains a challenge because of increased facial nerve neuropathy.

Treatment delivery time optimization of respiratory gated radiation therapy by application of audio-visual feedback

PURPOSE The feasibility to use visually guided voluntary breath-hold with and without audio assistance to reduce the total treatment time was evaluated. MATERIALS AND METHODS Patients referred for gated SBRT received hypofractionation schedules for lung or liver treatments. The patients were treated with the Novalis system (BrainLAB AG, Feldkirchen, Germany) and IGRT was performed with ExacTrac5.0/NovalisBody allowing gated irradiation. Video glasses, used for visual feedback to guide voluntary breath-hold, allowed additional audio assistance during treatment. The technique was applied for 25 patients of whom 9 were treated in free breathing, 7 had only visual feedback and another 9 had both audio and visual feedback. RESULTS The delivery time of gated treatment during free breathing had an average value of 1.7 min/100 MU (SD 0.6 min/100 MU). The introduction of visual feedback reduced the average delivery time to 1.4 min/100 MU (SD 0.4 min/100 MU). The treatments with additional audio assistance indicated a significant reduction (p=0.004) of the average delivery time to 0.9 min/100 MU (SD 0.2 min/100 MU). CONCLUSION The introduction of visually guided voluntary breath-hold with audio assistance led to treatment times for gated radiation therapy approaching conformal beam delivery times, which made gated treatments applicable in conventional treatment time slots.

An overview of volumetric imaging technologies and their quality assurance for IGRT

Image-guided radiation therapy (IGRT) aims at frequent imaging in the treatment room during a course of radiotherapy, with decisions made on the basis of this information. The concept is not new, but recent developments and clinical implementations of IGRT drastically improved the quality of radiotherapy and broadened its possibilities as well as its indications. In general IGRT solutions can be classified in planar imaging, volumetric imaging using ionising radiation (kV- and MV- based CT) or non-radiographic techniques. This review will focus on volumetric imaging techniques applying ionising radiation with some comments on Quality Assurance (QA) specific for clinical implementation. By far the most important advantage of volumetric IGRT solutions is the ability to visualize soft tissue prior to treatment and defining the spatial relationship between target and organs at risk. A major challenge is imaging during treatment delivery. As some of these IGRT systems consist of peripheral equipment and others present fully integrated solutions, the QA requirements will differ considerably. It should be noted for instance that some systems correct for mechanical instabilities in the image reconstruction process whereas others aim at optimal mechanical stability, and the coincidence of imaging and treatment isocentre needs special attention. Some of the solutions that will be covered in detail are: (a) A dedicated CT-scanner inside the treatment room. (b) Peripheral systems mounted to the gantry of the treatment machine to acquire cone beam volumetric CT data (CBCT). Both kV-based solutions and MV-based solutions using EPIDs will be covered. (c) Integrated systems designed for both IGRT and treatment delivery. This overview will explain some of the technical features and clinical implementations of these technologies as well as providing an insight in the limitations and QA procedures required for each specific solution.