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Purpose Carbon ion radiotherapy (CIRT) is sensitive to anatomical density variations. We examined the dosimetric effect of variable intestinal filling condition during CIRT to ten sacral chordoma patients. Methods For each patient, eight virtual computed tomography scans (vCTs) were generated by varying the density distribution within the rectum and the sigmoid in the planning computed tomography (pCT) with a density override approach mimicking a heterogeneous combination of gas and feces. Totally full and empty intestinal preparations were modelled. In addition, five different intestinal filling conditions were modelled by a mixed density pattern derived from two combined and weighted Gaussian distributions simulating gas and feces respectively. Finally, a patient-specific mixing proportion was estimated by evaluating the daily amount of gas detected in the cone beam computed tomography (CBCT). Dose distribution was recalculated on each vCT and dose volume histograms (DVHs) were examined. Results No target coverage degradation was observed at different vCTs. Rectum and sigma dose degradation ranged respectively between: [-6.7; 21.6]GyE and [-0.7; 15.4]GyE for D50%; [-377.4; 1197.9] and [-95.2; 1027.5] for AUC; [-1.2; 10.7]GyE and [-2.6; 21.5]GyE for D1%. Conclusions Variation of intestinal density can greatly influence the penetration depth of charged particle and might compromise dose distribution. In particular cases, with large clinical target volume in very close proximity to rectum and sigmoid colon, it is appropriate to evaluate the amount of gas present in the daily CBCT images even if it is totally included in the reference planning structures.

Ocular proton therapy (OPT) is acknowledged as a therapeutic option for the treatment of ocular melanomas. OPT clinical workflow is deeply based on x-ray image guidance procedures, both for treatment planning and patient setup verification purposes. An optimized eye orientation relative to the proton beam axis is determined during treatment planning and it is reproduced during treatment by focusing the patient gaze on a fixation light conveniently positioned in space. Treatment geometry verification is routinely performed through stereoscopic radiographic images while real time patient gaze reproducibility is qualitatively monitored by visual control of eye surface images acquired by dedicated optical cameras. We described an approach to quantitatively evaluate the stability of patients’ gaze direction over an OPT treatment course at the National Centre of Oncological Hadrontherapy (Centro Nazionale di Adroterapia Oncologica, CNAO, Pavia, Italy).

An Eye Tracking System (ETS) is used at CNAO for providing a stable and reproducible ocular proton therapy (OPT) set-up, featuring a fixation light (FL) and monitoring stereo-cameras embedded in a rigid case. The aim of this work is to propose an ETS set-up simulation algorithm, that automatically provides the FL positioning in space, according to patient-specific gaze direction and avoiding interferences with patient, beam and collimator. Two configurations are provided: one in the CT room for acquiring images required for treatment planning with the patient lying on a couch, and one related to the treatment room with the patient sitting in front of the beam. Algorithm validation was performed reproducing ETS simulation (CT) and treatment (room) set-up for 30 patients previously treated at CNAO. The positioning accuracy of the device was quantified through a set of 14 control points applied to the ETS case and localizable both in the CT volume and in room X-ray images. Differences between the position of ETS reference points estimated by the algorithm and those measured by imaging systems are reported. The corresponding gaze direction deviation is on average 0.2° polar and 0.3° azimuth for positioning in CT room and 0.1° polar and 0.4° azimuth in the treatment room. The simulation algorithm was embedded in a clinically usable software application, which we assessed as capable of ensuring ETS positioning with an average accuracy of 2 mm in CT room and 1.5 mm in treatment room, corresponding to gaze direction deviations consistently lower than 1°.

Objective: Accurate patient positioning is crucial in particle therapy due to the geometrical selectivity of particles. We report and discuss the National Center for Oncological Hadrontherapy (CNAO) experience in positioning accuracy and stability achieved with solid thermoplastic masks fixed on index base plates and assessed by daily orthogonal X-ray imaging. Methods: Positioning data were retrospectively collected (between 2012 and 2018) and grouped according to the treated anatomical site. 19696 fractions of 1325 patients were evaluated. The study was designed to assess: (i) the number of fractions in which a single correction vector was applied(SCV); (ii) the number of fractions in which further setup verification was performed (SV); (iii) the number of fractions in which SV lead to an additional correction within (MCV5min) 5 minutes from the first setup correction; (iv) the systematic (Σ) and random (σ) error components of the correction vectors applied. Results: A SCV was applied in 71.5% of fractions, otherwise SV was required. In 30.6% of fractions with SV, patient position was not further revised. In the remaining fractions, MCV5min were applied mainly in extracranial and cranial sites respectively. Interfraction Σ was ≤ 1.7 mm/0.7° and σ was ≤ 1.2 mm/0.6° in cranial sites while in extracranial sites Σ was ≤ 5.5 mm/0.9° and σ was ≤4.4 mm/0.9°. Setup residuals were submillimetric in all sites. In cranial patients, maximum intrafractional Σ was 0.8 mm/0.4°. Conclusion: This report extensively quantifies inter- and intrafraction setup accuracy on an institutional basis and confirms the need of image guidance to fully benefit from the geometrical selectivity of particles. Advances in knowledge: The reported analysis provides a board institutional data set on the evaluation of patient immobilization and bony anatomy alignment for several particle therapy clinical indications.

Particle therapy (PT) has shown positive therapeutic results in local control of locally advanced pancreatic lesions. PT effectiveness is highly influenced by target localization accuracy both in space, since the pancreas is located in proximity to radiosensitive vital organs, and in time as it is subject to substantial breathing‐related motion. The purpose of this preliminary study was to quantify pancreas range of motion under typical PT treatment conditions. Three common immobilization devices (vacuum cushion, thermoplastic mask, and compressor belt) were evaluated on five male patients in prone and supine positions. Retrospective four‐dimensional magnetic resonance imaging data were reconstructed for each condition and the pancreas was manually segmented on each of six breathing phases. A k‐means algorithm was then applied on the manually segmented map in order to obtain clusters representative of the three pancreas segments: head, body, and tail. Centers of mass (COM) for the pancreas and its segments were computed, as well as their displacements with respect to a reference breathing phase (beginning exhalation). The median three‐dimensional COM displacements were in the range of 3 mm. Latero–lateral and superior–inferior directions had a higher range of motion than the anterior–posterior direction. Motion analysis of the pancreas segments showed slightly lower COM displacements for the head cluster compared to the tail cluster, especially in prone position. Statistically significant differences were found within patients among the investigated setups. Hence a patient‐specific approach, rather than a general strategy, is suggested to define the optimal treatment setup in the frame of a millimeter positioning accuracy. PACS number(s): 87.55.‐x, 87.57.nm, 87.61

Purpose At Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) ocular proton therapy (OPT) is delivered using a non-dedicated beamline. This paper describes the novel clinical workflow as well as technologies and methods adopted to achieve accurate target positioning and verification during ocular proton therapy at CNAO. Method The OPT clinical protocol at CNAO prescribes a treatment simulation and a delivery phase, performed in the CT and treatment rooms, respectively. The patient gaze direction is controlled and monitored during the entire workflow by means of an eye tracking system (ETS) featuring two optical cameras and an embedded fixation diode light. Thus, the accurate alignment of the fixation light provided to the patient to the prescribed gazed direction is required for an effective treatment. As such, a technological platform based on active robotic manipulators and IR optical tracking-based guidance was developed and tested. The effectiveness of patient positioning strategies was evaluated on a clinical dataset comprising twenty patients treated at CNAO. Results According to experimental testing, the developed technologies guarantee uncertainties lower than one degree in gaze direction definition by means of ETS-guided positioning. Patient positioning and monitoring strategies during treatment effectively mitigated set-up uncertainties and exhibited sub-millimetric accuracy in radiopaque markers alignment. Conclusion Ocular proton therapy is currently delivered at CNAO with a non-dedicated beamline. The technologies developed for patient positioning and motion monitoring have proven to be compliant with the high geometrical accuracy required for the treatment of intraocular tumors.

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 subjectsmore » 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.« less

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.

The Italian National Centre for Oncological Hadrontherapy (Centro Nazionale di Adroterapia Oncologica, CNAO), equipped with a proton and ion synchrotron, started clinical activity in September 2011. The clinical and technical characteristics of the first ten proton beam radiotherapy treatments are reported. Ten patients, six males and four females (age range 27–73 years, median 55.5), were treated with proton beam radiotherapy. After one to two surgical procedures, seven patients received a histological diagnosis of chordoma (of the skull base in three cases, the cervical spine in one case and the sacrum in three cases) and three of low-grade chondrosarcoma (skull base). Prescribed doses were 74 GyE for chordoma and 70 GyE for chondrosarcoma at 2 GyE/fraction delivered 5 days per week. Treatment was well tolerated without toxicity-related interruptions. The maximal acute toxicity was grade 2, with oropharyngeal mucositis, nausea and vomiting for the skull base tumours, and grade 2 dermatitis for the sacral tumours. After 6–12 months of follow-up, no patient developed tumour progression. The analysis of the first ten patients treated with proton therapy at CNAO showed that this treatment was feasible and safe. Currently, patient accrual into these as well as other approved protocols is continuing, and a longer follow-up period is needed to assess tumour control and late toxicity.

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.

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.

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 trackermore » 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.« less

Aims and Background This study evaluates 3 different imaging modalities—ultrasound (US), stereoscopic X-ray imaging of implanted markers (Visicoils) (X-ray), and kV cone-beam computed tomography (CBCT)—to assess interfraction and intrafraction localization error during conformal radiation therapy of prostate cancer. Methods and Study Design The study population consisted of 186 consecutive prostate cancer patients treated with an image-guided radiotherapy (IGRT) hypofractionated protocol using 3 techniques: 32 with X-ray, 30 with CBCT, and 124 with US. Treatment dose of 70.2 Gy was delivered in 26 fractions with a conformal dynamic arcs technique. Interfraction prostate localization errors were determined for the 3 techniques. Moreover, interfraction and intrafraction prostate motion in terms of translations and rotations, as well as residual errors, were determined with X-ray. Results The systematic and random components of the prostate localization errors were as follows: ( 1 ) with X-ray 3.0 ± 3.4, 2.3 ± 2.7, 1.8 ± 2.3 mm in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions and 1.8° ± 1.2°, 2.3° ± 1.5°, 2.7° ± 3.1°, for the yaw, roll, and pitch rotations; ( 2 ) with CBCT3.5 ± 4.2, 3.3 ± 3.3, 2.5 ± 3.1 mm in AP, SI, and LR directions; ( 3 ) with US 3.7 ± 4.7, 3.4 ± 4.3, 2.3 ± 3.5 mm in AP, SI, and LR directions. Residual errors with X-ray were less than 1 mm in all directions. Intrafraction prostate motion of less than 0.5 mm in LR and of the order of 1 mm in AP and SI directions was found. This led to a significant reduction of the margins, potentially important for dose escalation studies. Conclusions Daily on-line IGRT with stereoscopic X-ray imaging allowed a consistent PTV margin reduction considering residual interfraction prostate localization error and intrafraction motion. X-ray offers the best compromise among accuracy, reliability, dose to the patient, and time investment for daily IGRT treatment of prostate.

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.

La Fondazione CNAO ha tra i suoi scopi anche lo svolgimento di attività di ricerca. Il centro CNAO è stato concepito sin dall'inizio con tre sale di trattamento, espandibili fino a cinque, ed una 'sala sperimentale' nella quale le attività di ricerca possano venire svolte senza intralciare e senza essere intralciate dalla attività clinica.Tale sala sperimentale deve essere progettata per essere 'multi-uso', cioè tale da poter venire utilizzata per attività di ricerca nei campi più disparati e non specializzata in un tipo di attività particolare. Possibili argomenti di ricerca sono radiobiologia, sviluppo di monitor di fascio, sviluppo di dosimetri, studi di radiation hardness e molti altri ancora.Lo studio di tale facility ed in particolare lo studio degli aspetti tecnici legati all'ampliamento del complesso dell'acceleratore è stato portato avanti congiuntamente da CNAO e INFN, nell'ambito dell'accordo quadro approvato nel 2009 e del nuovo accordo quadro stipulato nel 2013. Per meglio identificare le necessità dei possibili utenti è stato svolto un sondaggio i cui risultati sono stati considerati nella definizione delle specifiche funzionali della linea e della sala sperimentale. Tale sondaggio è illustrato più avanti in questo documento. In questo documento viene descritto il progetto della sala sperimentale e delle linee di alta e di bassa energie coinvolte. Nella prima parte del documento viene data una descrizione generale del progetto, mentre i dettagli sono generalmente riportati nelle appendici e nei documenti allegati.

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 patient's 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 (HN) 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.

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

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 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.

To quantify the advantages of a 6 degrees of freedom (dof) versus the conventional 3- or 4-dof correction modality for stereotactic body radiation therapy (SBRT) treatments. Eighty-five patients were fitted with 5-7 infra-red passive markers for optical localization. Data, acquired during the treatment, were analyzed retrospectively to simulate and evaluate the best approach for correcting patient misalignments. After the implementation of each correction, the new position of the target (tumor's center of mass) was estimated by means of a dedicated stereotactic algorithm. The Euclidean distance between the corrected and the planned location of target point was calculated and compared to the initial mismatching. Initial and after correction median+/-quartile displacements affecting external control points were 3.74+/-2.55 mm (initial), 2.45+/-0.91 mm (3-dof), 2.37+/-0.95 mm (4-dof), and 2.03+/-1.47 mm (6-dof). The benefit of a six-parameter adjustment was particularly evident when evaluating the results relative to the target position before and after the re-alignment. In this context, the Euclidean distance between the planned and the current target point turned to 0.82+/-1.12 mm (median+/-quartile values) after the roto-translation versus the initial displacement of 2.98+/-2.32 mm. No statistical improvements were found after 3- and 4-dof correction (2.73+/-1.22 mm and 2.60+/-1.31 mm, respectively). Angular errors were 0.09+/-0.93 degrees (mean+/-std). Pitch rotation in abdomen site showed the most relevant deviation, being -0.46+/-1.27 degrees with a peak value of 5.46 degrees . Translational misalignments were -0.68+/-2.60 mm (mean+/-std) with the maximum value of 12 mm along the cranio-caudal direction. We conclude that positioning system platforms featuring 6-dof are preferred for high precision radiation therapy. Data are in line with previous results relative to other sites and represent a relevant record in the framework of SBRT.

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.

Purpose: To investigate size and frequency of interfractional patient setup variability in hypofractionated stereotactic extracranial radiotherapy. Methods and Materials: Infrared optical 3D tracking of surface markers was applied to quantify setup variability on 51 patients. Isocenter position repeatability was assessed by means of frameless anatomic calibration and was compared with portal image evaluation. Specific data analysis allowed for compensation of patients' breathing movements and for separation of the effects of operator-dependent misalignments and respiration-induced displacements. Effects of patient position (supine vs. prone) and treatment table configuration were investigated. Results: Patient positioning assisted by the optical tracking device allowed reducing displacements of surface control points within the 3-mm range. Errors in isocenter localization were in the range of a few millimeters. This was in agreement with the portal image evaluation. Breathing motion introduced appreciable errors, which increased control points and isocenter 3D variability. This effect was significantly higher than those related to other investigated factors. Conclusions: The role of infrared optical tracking devices for patient positioning is assessed on a large patient population. Their use in the frame of high-precision radiotherapy is emphasized by the application of related methodologies for breathing phase detection and frameless isocenter localization.

Purpose: To investigate intrafraction setup variability in high precision stereotactic body radiotherapy(SBRT) by means of integrated infra‐red optical localization and stereoscopic kV X‐ray imaging.Method and Materials: We analyzed data coming from 24 patients treated with SBRT. Patient setup was realized through the ExacTrac X‐ray 6D system (BrainLAB, Germany), consisting of 2 infra‐red TV cameras for external fiducial localization and 2 couples of X‐ray source‐detectors for image registration. Before irradiation, patients were pre‐aligned relying on optical marker localization. Subsequently, patient position was refined through the automatic matching of X‐ray images to digitally reconstructedradiographs(DRR, 3 mm CT slice thickeness), providing 6 corrective parameters that were automatically applied using a robotic couch. The 3D position of the external configuration of control points was detected and stored before (PREmk) and after (POSTmk) the irradiation fraction. A final set of stereoscopic images was acquired and registered to DRR at the end of the treatment, relying on bony anatomy, thus obtaining 6 verification parameters (VP_post). Patient intrafraction motion was evaluated by comparing PREmk with POSTmk (optical measurement). Moreover VP_post parameters were applied to POSTmk thus defining a new configuration of control points (POSTmk‐Xray) that was compared to PREmk (X‐ray measurement). Results: According to the optical measurement, intrafraction motion measured on external fiducials was 0.61±0.53 mm (median±quartile). The X‐ray measurement overestimated intrafraction motion up to 2.05±1.8 mm. The latero‐lateral direction resulted more sensitive to residual errors in X‐ray measurement (0.34±2.88 mm, mean±std). Conclusion: Intrafraction motion, as monitored by the optical system, is not significant. When relying on X‐ray imaging registration, larger motion may be measured because of inherent limitations in DRR cranio‐caudal resolution and digital X‐ray image noise. Such results lead to further questions in assessing the accuracy of X‐ray based setup when integration with optical patient localization is not taken into account.

Purpose: To develop the methods of a novel approach for optimal marker placement in infrared patient positioning. Method and Materials: A nondeterministic optimization technique (Genetic Evolutionary Taboo Search, GETS), combining genetic algorithms and taboo search, was implemented. A population‐based evolution is generated, where adaptive memory features guide the evolutionary process to thoroughly explore the solution space. Preset taboo solutions are introduced to reject marker configurations resulting collinear from the point of view of infrared cameras. The GETS algorithm was tested on 10 prostate patients: treatment planningCT scans were segmented to provide 3‐D representation of PTV (prostate + seminal vesicles), OARs (bladder and rectum) and skin surface model. Segmented data were fed to the GETS algorithm to obtain optimized configurations of markers, minimizing the target registration error (TRE), to be compared to a random configuration. The changes in the optimal marker configuration when OARs are included within the target were also investigated. Results: The GETS algorithm yielded a significant improvement in TRE values: optimal configurations ensured a 26.5% mean TRE decrease. Common features in the optimal marker configurations were found for the 10 patients group, being optimized solutions symmetrically distributed, with markers mostly placed on lateral sides. Optimal marker configurations when OARs were included within the target resulted in a similar spatial distribution, if compared to the PTV‐only condition. The implemented memory‐based design resulted in improved gene expression over the evolution process, with respect to memoryless genetic algorithms. Conclusion: The GETS algorithm revealed high performance in solving the optimal marker placement problem, leading to improved marker configuration for stereophotogrammetric patient positioning in radiotherapy. Memory features ensured enhanced capabilities in exploring the solution space, if compared to conventional genetic optimization. The application of the new algorithm to a 10 patient group provided practical indications toward better marker placement for prostate cases.