B. Tagaste

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation

OBJECTIVES To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. MATERIALS AND METHODS One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. RESULTS All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT (P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT (P = 0.001) and higher PSA (P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. CONCLUSIONS The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.

Commissioning and Quality Assurance of an Integrated System for Patient Positioning and Setup Verification in Particle Therapy

In an increasing number of clinical indications, radiotherapy with accelerated particles shows relevant advantages when compared with high energy X-ray irradiation. However, due to the finite range of ions, particle therapy can be severely compromised by setup errors and geometric uncertainties. The purpose of this work is to describe the commissioning and the design of the quality assurance procedures for patient positioning and setup verification systems at the Italian National Center for Oncological Hadrontherapy (CNAO). The accuracy of systems installed in CNAO and devoted to patient positioning and setup verification have been assessed using a laser tracking device. The accuracy in calibration and image based setup verification relying on in room X-ray imaging system was also quantified. Quality assurance tests to check the integration among all patient setup systems were designed, and records of daily QA tests since the start of clinical operation (2011) are presented. The overall accuracy of the patient positioning system and the patient verification system motion was proved to be below 0.5 mm under all the examined conditions, with median values below the 0.3 mm threshold. Image based registration in phantom studies exhibited sub-millimetric accuracy in setup verification at both cranial and extra-cranial sites. The calibration residuals of the OTS were found consistent with the expectations, with peak values below 0.3 mm. Quality assurance tests, daily performed before clinical operation, confirm adequate integration and sub-millimetric setup accuracy. Robotic patient positioning was successfully integrated with optical tracking and stereoscopic X-ray verification for patient setup in particle therapy. Sub-millimetric setup accuracy was achieved and consistently verified in daily clinical operation.

Automated Fiducial Localization in CT Images Based on Surface Processing and Geometrical Prior Knowledge for Radiotherapy Applications

We propose a novel method for radio-opaque external marker localization in CT scans for infrared (IR) patient set-up in radiotherapy. Efforts were focused on the quantification of uncertainties in marker localization in the CT dataset as a function of algorithm performance. We implemented a 3-D approach to fiducial localization based on surface extraction and marker recognition according to geometrical prior knowledge. The algorithm parameters were optimized on a clinical CT dataset coming from 35 cranial and extra-cranial patients; the localization accuracy was benchmarked at variable image resolution versus laser tracker measurements. The applicability of conventional IR optical tracking systems for localizing external surrogates in daily patient set-up procedures was also investigated in 121 proton therapy treatment sessions. Our study shows that the implemented algorithm features surrogates localization with uncertainties lower than 0.3 mm and with a true positive rate of 90.1%, being this latter mainly influenced by fiducial homogeneity in the CT images. The reported clinical validation in proton therapy confirmed the submillimetric accuracy and the expected algorithm sensitivity. Geometrical prior knowledge allows judging the reliability of the extracted fiducial coordinates, ensuring the highest accuracy in patient set-up.

Deep inspiration breath‐hold technique guided by an opto‐electronic system for extracranial stereotactic treatments

The purpose of this work was to evaluate the intrapatient tumor position reproducibility in a deep inspiration breath‐hold (DIBH) technique based on two infrared optical tracking systems, ExacTrac and ELITETM, in stereotactic treatment of lung and liver lesions. After a feasibility study, the technique was applied to 15 patients. Each patient, provided with a real‐time visual feedback of external optical marker displacements, underwent a full DIBH, a free‐breathing (FB), and three consecutive DIBH CT‐scans centered on the lesion to evaluate the tumor position reproducibility. The mean reproducibility of tumor position during repeated DIBH was 0.5±0.3mm in laterolateral (LL), 1.0±0.9mm in anteroposterior (AP), and 1.4±0.9mm in craniocaudal (CC) direction for lung lesions, and 1.0±0.6mm in LL, 1.1±0.5mm in AP, and 1.2±0.4mm in CC direction for liver lesions. Intra‐and interbreath‐hold reproducibility during treatment, as determined by optical markers displacements, was below 1 mm and 3 mm, respectively, in all directions for all patients. Optically‐guided DIBH technique provides a simple noninvasive method to minimize breathing motion for collaborative patients. For each patient, it is important to ensure that the tumor position is reproducible with respect to the external markers configuration. PACS numbers: 87.53.Ly, 87.55.km

Robust frameless stereotactic localization in extra-cranial radiotherapy.

In the field of extra-cranial radiotherapy, several inaccuracies can make the application of frameless stereotactic localization techniques error-prone. When optical tracking systems based on surface fiducials are used, inter- and intra-fractional uncertainties in marker three-dimensional (3D) detection may lead to inexact tumor position estimation, resulting in erroneous patient setup. This is due to the fact that external fiducials misdetection results in deformation effects that are poorly handled in a rigid-body approach. In this work, the performance of two frameless stereotactic localization algorithms for 3D tumor position reconstruction in extra-cranial radiotherapy has been specifically tested. Two strategies, unweighted versus weighted, for stereotactic tumor localization were examined by exploiting data coming from 46 patients treated for extra-cranial lesions. Measured isocenter displacements and rotations were combined to define isocentric procedures, featuring 6 degrees of freedom, for correcting patient alignment (isocentric positioning correction). The sensitivity of the algorithms to uncertainties in the 3D localization of fiducials was investigated by means of 184 numerical simulations. The performance of the implemented isocentric positioning correction was compared to conventional point-based registration. The isocentric positioning correction algorithm was tested on a clinical dataset of inter-fractional and intra-fractional setup errors, which was collected by means of an optical tracker on the same group of patients. The weighted strategy exhibited a lower sensitivity to fiducial localization errors in simulated misalignments than those of the unweighted strategy. Isocenter 3D displacements provided by the weighted strategy were consistently smaller than those featured by the unweighted strategy. The peak decrease in median and quartile values of isocenter 3D displacements were 1.4 and 2.7 mm, respectively. Concerning clinical data, the weighted strategy isocentric positioning correction provided the reduction of fiducial registration errors, featuring up to 61.7% decrease in median values (versus 46.8% for the unweighted strategy) of initial displacements. The weighted strategy proved high performance in minimizing the effects of fiducial localization errors, showing a great potential in improving patient setup. The clinical data analysis revealed that the application of a robust reconstruction algorithm may provide high-quality results in patient setup verification, by properly managing external fiducials localization errors.

A comparative study between the imaging system and the optical tracking system in proton therapy at CNAO

The synergy between in-room imaging and optical tracking, in co-operation with highly accurate robotic patient handling represents a concept for patient-set-up which has been implemented at CNAO (Centro Nazionale di Adroterapia Oncologica). In-room imaging is based on a double oblique X-ray projection system; optical tracking consists of the detection of the position of spherical markers placed directly on the patients skin or on the immobilization devices. These markers are used as external fiducials during patient positioning and dose delivery. This study reports the results of a comparative analysis between in-room imaging and optical tracking data for patient positioning within the framework of high-precision particle therapy. Differences between the optical tracking system (OTS) and the imaging system (IS) were on average within the expected localization accuracy. On the first 633 fractions for head and neck (H&N) set-up procedures, the corrections applied by the IS, after patient positioning using the OTS only, were for the mostly sub-millimetric regarding the translations (0.4±1.1 mm) and sub-gradual regarding the rotations (0.0°±0.8°). On the first 236 fractions for pelvis localizations the amplitude of the corrections applied by the IS after preliminary optical set-up correction were moderately higher and more dispersed (translations: 1.3±2.9 mm, rotations 0.1±0.9°). Although the indication of the OTS cannot replace information provided by in-room imaging devices and 2D-3D image registration, the reported data show that OTS preliminary correction might greatly support image-based patient set-up refinement and also provide a secondary, independent verification system for patient positioning.

Optical eye tracking system for real-time noninvasive tumor localization in external beam radiotherapy

PURPOSE External beam radiotherapy currently represents an important therapeutic strategy for the treatment of intraocular tumors. Accurate target localization and efficient compensation of involuntary eye movements are crucial to avoid deviations in dose distribution with respect to the treatment plan. This paper describes an eye tracking system (ETS) based on noninvasive infrared video imaging. The system was designed for capturing the tridimensional (3D) ocular motion and provides an on-line estimation of intraocular lesions position based on a priori knowledge coming from volumetric imaging. METHODS Eye tracking is performed by localizing cornea and pupil centers on stereo images captured by two calibrated video cameras, exploiting eye reflections produced by infrared illumination. Additionally, torsional eye movements are detected by template matching in the iris region of eye images. This information allows estimating the 3D position and orientation of the eye by means of an eye local reference system. By combining ETS measurements with volumetric imaging for treatment planning [computed tomography (CT) and magnetic resonance (MR)], one is able to map the position of the lesion to be treated in local eye coordinates, thus enabling real-time tumor referencing during treatment setup and irradiation. Experimental tests on an eye phantom and seven healthy subjects were performed to assess ETS tracking accuracy. RESULTS Measurements on phantom showed an overall median accuracy within 0.16 mm and 0.40° for translations and rotations, respectively. Torsional movements were affected by 0.28° median uncertainty. On healthy subjects, the gaze direction error ranged between 0.19° and 0.82° at a median working distance of 29 cm. The median processing time of the eye tracking algorithm was 18.60 ms, thus allowing eye monitoring up to 50 Hz. CONCLUSIONS A noninvasive ETS prototype was designed to perform real-time target localization and eye movement monitoring during ocular radiotherapy treatments. The device aims at improving state-of-the-art invasive procedures based on surgical implantation of radiopaque clips and repeated acquisition of X-ray images, with expected positive effects on treatment quality and patient outcome.

Comparison Between Infrared Optical and Stereoscopic X-Ray Technologies for Patient Setup in Image Guided Stereotactic Radiotherapy

PURPOSE To compare infrared (IR) optical vs. stereoscopic X-ray technologies for patient setup in image-guided stereotactic radiotherapy. METHODS AND MATERIALS Retrospective data analysis of 233 fractions in 127 patients treated with hypofractionated stereotactic radiotherapy was performed. Patient setup at the linear accelerator was carried out by means of combined IR optical localization and stereoscopic X-ray image fusion in 6 degrees of freedom (6D). Data were analyzed to evaluate the geometric and dosimetric discrepancy between the two patient setup strategies. RESULTS Differences between IR optical localization and 6D X-ray image fusion parameters were on average within the expected localization accuracy, as limited by CT image resolution (3 mm). A disagreement between the two systems below 1 mm in all directions was measured in patients treated for cranial tumors. In extracranial sites, larger discrepancies and higher variability were observed as a function of the initial patient alignment. The compensation of IR-detected rotational errors resulted in a significantly improved agreement with 6D X-ray image fusion. On the basis of the bony anatomy registrations, the measured differences were found not to be sensitive to patient breathing. The related dosimetric analysis showed that IR-based patient setup caused limited variations in three cases, with 7% maximum dose reduction in the clinical target volume and no dose increase in organs at risk. CONCLUSIONS In conclusion, patient setup driven by IR external surrogates localization in 6D featured comparable accuracy with respect to procedures based on stereoscopic X-ray imaging.

Genetic evolutionary taboo search for optimal marker placement in infrared patient setup

In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

Image guided particle therapy in CNAO room 2: implementation and clinical validation.

In this contribution we describe the implementation of a novel solution for image guided particle therapy, designed to ensure the maximal accuracy in patient setup. The presented system is installed in the central treatment room at Centro Nazionale di Adroterapia Oncologica (CNAO, Italy), featuring two fixed beam lines (horizontal and vertical) for proton and carbon ion therapy. Treatment geometry verification is based on robotic in-room imaging acquisitions, allowing for 2D/3D registration from double planar kV-images or 3D/3D alignment from cone beam image reconstruction. The calculated six degrees-of-freedom correction vector is transferred to the robotic patient positioning system, thus yielding automated setup error compensation. Sub-millimetre scale residual errors were measured in absolute positioning of rigid phantoms, in agreement with optical- and laser-based assessment. Sub-millimetre and sub-degree positioning accuracy was achieved when simulating setup errors with anthropomorphic head, thorax and pelvis phantoms. The in-house design and development allowed a high level of system customization, capable of replicating the clinical performance of commercially available products, as reported with preliminary clinical results in 10 patients.