A compact and lightweight small animal PET with uniform high-resolution for onboard PET/CT image-guided preclinical radiation oncology research.

OBJECTIVE: In contrast to clinical radiation therapy (RT) that ubiquitously uses PET/CT image to accurately guide RT, all current commercial animal irradiators can only provide CT image-guided preclinical RT that severely limits their capability for preclinical and compatibility for translational radiation oncology research. To address this problem, we have developed a compact and lightweight PET with uniform, high spatial resolution that is suited to be installed inside an existing animal irradiator for potential onboard PET/CT image-guided preclinical RT research. APPROACH: The design focused on the balance of achieving sufficient imaging performance for practical preclinical RT guidance with constrained size and weight. The detector head consists of a ring of 12 detector panels in a dodecagon configuration and 12 front-end electronics boards that are closely attached to the detector panels. The overall size and weight of the detector head are 33.0 cm diameter, 11.0 cm axial length and ∼6.5 kg weight that can be installed inside an existing irradiator. Each detector panel has a 30 × 30 array of 1 × 1 × 20 mm3LYSO scintillators with depth-of-interaction (DOI) measurement. The front-end electronics boards process and convert detected signals to digital signals and transfer them to system electronics and data acquisition located outside the irradiator through low-voltage-differential-signaling cables. MAIN RESULTS: The typical energy, DOI and coincidence timing resolutions are around 22.1%, 3.1 mm, and 1.92 ns. The imaging field-of-view (FOV) is 8.0 cm diameter and 3.5 cm axial length. The performance evaluations show a 1.8% sensitivity at the center FOV, uniform ∼1.1 mm resolution within 6 cm diameter FOV, and all rods of 1.0 mm diameter can be clearly resolved from the image of an ultra-micro hot-rods phantom. SIGNIFICANCE: Overall, this compact and lightweight PET has demonstrated its designed capability and performance sufficient for providing onboard functional/biological/molecular image to guide the preclinical RT research.

Patterns of local residual disease and local failure after intensity modulated/image guided radiation therapy for sinonasal tumors in dogs.

BACKGROUND: Most dogs with sinonasal tumors (SNT) treated with radiation therapy (RT) died because of local disease progression. HYPOTHESIS/OBJECTIVES: Our hypothesis is that the majority of local failure and residual disease would occur within the radiation field. ANIMALS: Twenty-two dogs with SNT treated with RT. METHODS: Retrospective cohort study. INCLUSION CRITERIA: dogs with SNT receiving 10 daily fractions of 4.2 Gy with intensity modulated radiation therapy (IMRT)/image guided radiation therapy (IGRT) and follow-up cone beam computed tomography (CBCT). Each CBCT was registered with the original radiation planning CT and the gross tumor volume (GTV) contoured. The GTV was classified as residual (GTVr) or a failure (GTVf). The dose statistic for each GTV was calculated with the original IMRT plan. For GTVf, failures were classified as "in-field," "marginal," or "out-field" if at least 95, 20-95, or less than 20% of the volume of failure was within 95% (D95) of the total prescription dose, respectively. RESULTS: There were 52 follow-up CBCT/CTs. Overall there was a GTVr for 20 dogs and GTVf for 16 dogs. The majority of GTVr volume was within the original GTV. GTVf analysis showed that 75% (12/16) were "in-field," 19% (3/16) were "marginal" and 6% (1/16) were "out-field." CONCLUSION AND CLINICAL IMPORTANCE: In-field failures are the main pattern for local recurrence, and there is evidence of radioresistant subvolumes within the GTV.

Estimation of planning organ at risk volumes for ocular structures in dogs undergoing three-dimensional image-guided periocular radiotherapy with rigid bite block immobilization.

Planning organ at risk volume (PRV) estimates have been reported as methods for sparing organs at risk (OARs) during radiation therapy, especially for hypofractioned and/or dose-escalated protocols. The objectives of this retrospective, analytical, observational study were to evaluate peri-ocular OAR shifts and derive PRVs in a sample of dogs undergoing radiation therapy for periocular tumors. Inclusion criteria were as follows: dogs irradiated for periocular tumors, with 3D-image-guidance and at least four cone-beam CTs (CBCTs) used for position verification, and positioning in a rigid bite block immobilization device. Peri-ocular OARs were contoured on each CBCT and the systematic and random error of the shifts in relation to the planning CT position computed. The formula 1.3×Σ+0.5xσ was used to generate a PRV of each OAR in the dorsoventral, mediolateral, and craniocaudal axis. A total of 30 dogs were sampled, with 450 OARs contoured, and 2145 shifts assessed. The PRV expansion was qualitatively different for each organ (1-4 mm for the dorsoventral and 1-2 mm for the mediolateral and craniocaudal axes). Maximal PRV expansion was ≤4 mm and directional for the majority; most pronounced for corneas and retinas. Findings from the current study may help improve awareness of and minimization of radiation dose in peri-ocular OARs for future canine patients. Because some OARs were difficult to visualize on CBCTs and/ or to delineate on the planning CT, authors recommend that PRV estimates be institution-specific and applied with caution.

Residual setup error in the canine intracranial region after megavoltage, kilovoltage, or cone-beam computed tomographic image guidance for radiation therapy.

Sources of residual setup error after image guidance include image localization accuracy, errors associated with image registration, and inability of some treatment couches to correct submillimeter translational errors and/or pitch and roll errors. The purpose of this experimental study was to measure setup error after image-guided correction of the canine intracranial region, using a four degrees-of-freedom couch capable of 1 mm translational moves. Six cadaver dogs were positioned 45 times as for clinical treatment using a vacuum deformable body cushion, a customizable head cushion, a thermoplastic mask and an indexed maxillary plate with a dental mould. The location of five fiducial markers in the skull bones was compared between the reference position and after megavoltage (MV), kilovoltage (kV) and cone-beam computed tomography (CBCT)-guided correction using orthogonal kV images. The mean three-dimensional distance vectors (3DDV) after MV, kV and CBCT-guided correction were 1.7, 1.5 and 2.2 mm, respectively. All values were significantly different (P < .01). The 95th percentiles of the 3DDV after online MV, kV and CBCT-guided correction were 2.8, 2.6 and 3.6 mm, respectively. Residual setup error in the clinical scenario examined was on the order of millimetres and should be considered when choosing PTV margins for image-guided radiation therapy of the canine intracranial region.

Potential for BioXmark liquid fiducial marker to improve identification of superficial component of canine oral tumors for computer-based radiation therapy planning.

The objective of this study was to evaluate a novel liquid fiducial marker, BioXmark, to improve identification of the superficial component of oral tumors in dogs with computed tomography imaging. Liquid fiducial marker was injected in 6 patients at the visible and palpable extent of each tumor. Gross tumor volumes with and without BioXmark were compared in terms of volume and conformity using a Paddick conformity index, Dice similarity coefficient, and gross tumor volumes mismatch analysis. All patients showed an increase in gross tumor volumes defined by BioXmark compared with the conventionally identified post-contrast gross tumor volumes contours. Volumetric conformity and gross tumor volumes mismatch analysis of the superficial component of gross tumor volumes resulted in a median conformity index of 0.61 and median Dice similarity coefficient of 0.76. The superficial gross tumor volumes showed a median increase of 47% when BioXmark was used. This study demonstrated a potential utility to combining liquid fiducial markers to post-contrast computed tomography images for improved oral tumor localization and gross tumor volumes contouring for radiation therapy planning.

Potentiel du marqueur de repère liquide BioXmark à améliorer l'identification d'éléments superficiels de tumeurs orales canines pour la planification de radiothérapie assistée par ordinateur. L'objectif de la présente étude était d'évaluer un nouveau marqueur de repère liquide, BioXmark, à améliorer l'identification des éléments superficiels des tumeurs orales canines par tomodensitométrie. Le marqueur de repère liquide fut injecté à six patients à la limite visible et palpable de chaque tumeur. Les volumes bruts des tumeurs avec et sans BioXmark furent comparés en termes de volume et de conformité en utilisant l'index de conformité de Paddick, le coefficient de similarité de Dice, et une analyse de disparité des volumes bruts des tumeurs. Tous les patients montrèrent une augmentation des volumes bruts des tumeurs déterminés par BioXmark comparativement aux volumes bruts des tumeurs déterminés par la méthode conventionnelle d'identification des contours post-contrastes. La conformité volumétrique et l'analyse de disparité des volumes bruts des tumeurs du composant superficiel des volumes bruts des tumeurs a résulté en un index de conformité médian de 0,61 et un coefficient de similarité de Dice médian de 0,76. Les volumes bruts superficiels des tumeurs montraient une augmentation médiane de 47 % lorsque le BioXmark était utilisé. La présente étude a démontré une utilité potentielle à combiner des marqueurs de repère liquides aux images de tomodensitométrie post-contraste pour améliorer la localisation de tumeurs orales et la détermination des volumes bruts des tumeurs pour la planification de la radiothérapie.(Traduit par Dr Serge Messier).

An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms.

METHODS:: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro-CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro-CBCT-based radiation-delivery plans were evaluated based on their dose-volume histogram metrics of tumor and organs at risk to select the optimal treatment plan. RESULTS:: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT-based volume quantification strongly correlated with BLI-integrated intensity. Parallel-opposed single angle beam plans through a single lung are preferred for smaller tumors, whereas for larger tumors, plans that spread the radiation dose across healthy tissues are favored. CONCLUSIONS:: Closely mimicking a clinical setting for lung cancer with highly advanced preclinical radiation treatment planning is possible in mice developing orthotopic lung tumors. ADVANCES IN KNOWLEDGE:: BLI and CBCT imaging of orthotopic lung tumors provide complementary information in a temporal manner. The optimal radiotherapy plan is tumor volume-dependent.

Quantifying the setup uncertainty of a stereotactic murine micro-image guided radiation therapy system.

OBJECTIVE:: Investigate the reproducibility of murine cranial positioning using solely a stereotactic stage, and quantify the potential improvements from the on-board image guidance of the X-RAD SmART irradiator. METHODS:: For intermouse reproducibility, athymic nude mice (N = 5, ×4 groups) were cranially fixed on a stereotactic stage. Each mouse was imaged via cone-beam CT (CBCT). A virtual isocenter target was placed in the brain, the stage shifted to that target, and the couch positions recorded. The mouse was removed from the stage and this process repeated twice (N=60 measurements). The first acquired CBCT coordinates (within each group of five mice) were used to define "stereotactic couch coordinates." CBCT shifts were calculated to quantify the accuracy of setup based on couch coordinates alone. For intramouse reproducibility, C57BL/6 mice (N=4) were imaged daily for 7 days. Each mouse had individual stereotactic coordinates defined from their first day of CBCT localization, and positional shifts required on the six subsequent days of imaging were quantified (N = 24 measurements). RESULTS:: The mean vector shift between stereotactic setup and CBCT alignment for inter and intramouse analysis was 0.78 ± 0.27 mm and 0.82 ± 0.34 mm, respectively. CONCLUSION:: Cranial irradiation that can permit positional uncertainties on the order of a millimeter can rely solely on stereotactic coordinates derived from a single daily CBCT. Irradiations of subregions requiring submillimeter accuracy require daily image guidance for each mouse. ADVANCES IN KNOWLEDGE:: This is the first investigation of stereotactic reproducibility using the X-RAD SmART and it suggests a method for increased efficiency in high-throughput experiments.

The potential impact of ultrathin filter design on dosimetry and relative biological effectiveness in modern image-guided small animal irradiators.

OBJECTIVE:: Modern image-guided small animal irradiators like the Xstrahl Small Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15 mm Cu filters, which compared with more heavily filtrated traditional cabinet-style biological irradiators, produce X-ray spectra weighted toward lower energies, impacting the dosimetric properties and the relative biological effectiveness (RBE). This study quantifies the effect of ultrathin filter design on relative depth dose profiles, absolute dose output, and RBE using Monte Carlo techniques. METHODS:: The percent depth-dose and absolute dose output are calculated using kVDoseCalc and EGSnrc, respectively, while a tally based on the induction of double-strand breaks as a function of electron spectra invoked in PENELOPE is used to estimate the RBE. RESULTS:: The RBE increases by >2.4% in the ultrathin filter design compared to a traditional irradiator. Furthermore, minute variations in filter thickness have notable effects on the dosimetric properties of the X-ray beam, increasing the percent depth dose (at 2 cm in water) by + 0.4%/0.01 mm Cu and decreasing absolute dose (at 2 cm depth in water) by -1.8%/0.01 mm Cu for the SARRP. CONCLUSIONS:: These results show that modern image-guided irradiators are quite sensitive to small manufacturing variations in filter thickness, and show a small change in RBE compared to traditional X-ray irradiators. ADVANCES IN KNOWLEDGE:: We quantify the consequences of ultrathin filter design in modern image-guided biological irradiators on relative and absolute dose, and RBE. Our results show these to be small, but not insignificant, suggesting laboratories transitioning between irradiators should carefully design their radiobiological experiments.

Implementation and evaluation of respiratory gating in small animal radiotherapy.

Major advance was done in preclinical radiotherapy thanks to the development of image guided micro-irradiator. Nevertheless, some applications still can benefit of improvements, such as the irradiation of mobile tumors. This preclinical radiotherapy case presents increased difficulties compared to clinical practice because of the waveform of small animals breathing cycle, its frequency and amplitude. To answer this issue, we developed a specific beam shutter and implemented respiratory gating on the X-RAD 225Cx preclinical irradiator. In the first step of this study, the shutter was accurately characterized. Opening and closing speed of 1.28 and 0.33 mm ms-1 were respectively measured, and a transmission of 0.7% of the beam was measured with the shutter fully closed. Beam-on times were also determined for various gating parameters and highlighted a difference of 57 ms between the beam delivery duration and the gate width. This discrepancy was compensated during the respiratory monitoring adjustment. In a second step, a respiratory protocol was evaluated with two vertical beams of 2.5 and 5 mm diameters, for motion amplitudes ranging from 0.5 to 4 mm. This evaluation demonstrated the effectiveness of our set up to perform motion compensation for amplitude as small as 0.5 mm despite a dose gradient of 1.47 cGy mm-1 observed with the 5 mm irradiation field, due to the shutter opening and closing durations. We also investigated the efficiency of a scintillating fiber dosimeter, adapted to small beams and providing real-time dose rate measurements. This detector showed very good performances to detect motion in small irradiation fields and would be very suitable to monitor the number of delivered gates until the planned delivered dose is achieved. This study presented a new respiratory gating set up and showed that very efficient motion compensation could be achieved in small animal radiotherapy.

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.

PURPOSE: To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. METHODS AND MATERIALS: A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. RESULTS: The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. CONCLUSIONS: It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics.

Novel technique for high-precision stereotactic irradiation of mouse brains.

BACKGROUND AND PURPOSE: Small animal irradiation systems were developed for preclinical evaluation of tumor therapy closely resembling the clinical situation. Mostly only clinical LINACs are available, so protocols for small animal partial body irradiation using a conventional clinical system are essential. This study defines a protocol for conformal brain tumor irradiations in mice. MATERIALS AND METHODS: CT and MRI images were used to demarcate the target volume and organs at risk. Three 6 MV photon beams were planned for a total dose of 10 fractions of 1.8 Gy. The mouse position in a dedicated applicator was verified by an X­ray patient positioning system before each irradiation. Dosimetric verifications (using ionization chambers and films) were performed. Irradiation-induced DNA damage was analyzed to verify the treatment effects on the cellular level. RESULTS: The defined treatment protocol and the applied fractionation scheme were feasible. The in-house developed applicator was suitable for individual positioning at submillimeter accuracy of anesthetized mice during irradiation, altogether performed in less than 10 min. All mice tolerated the treatment well. Measured dose values perfectly matched the nominal values from treatment planning. Cellular response was restricted to the target volume. CONCLUSION: Clinical LINAC-based irradiations of mice offer the potential to treat orthotopic tumors conformably. Especially with respect to lateral penumbra, dedicated small animal irradiation systems exceed the clinical LINAC solution.

Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia.

The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy(®) in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted.

Radiothérapie stéréotactique guidée par imagerie chez 4 chiens atteints de néoplasie intracrâniale. Cette étude avait pour objectif de décrire l'utilisation et les effets secondaires d'un nouveau protocole de radiothérapie stéréotactique utilisant la TomoTherapyMD chez 4 chiens atteints de néoplasie intracrâniale extra-axiale primaire confirmée ou suspectée. Trois fractions de 8 Gy ont été prescrites. Des effets secondaires aigus ont été observés chez 1 chien; aucun effet tardif n'a été observé.(Traduit par Isabelle Vallières).

INVITED REVIEW--IMAGE REGISTRATION IN VETERINARY RADIATION ONCOLOGY: INDICATIONS, IMPLICATIONS, AND FUTURE ADVANCES.

The field of veterinary radiation therapy (RT) has gained substantial momentum in recent decades with significant advances in conformal treatment planning, image-guided radiation therapy (IGRT), and intensity-modulated (IMRT) techniques. At the root of these advancements lie improvements in tumor imaging, image alignment (registration), target volume delineation, and identification of critical structures. Image registration has been widely used to combine information from multimodality images such as computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) to improve the accuracy of radiation delivery and reliably identify tumor-bearing areas. Many different techniques have been applied in image registration. This review provides an overview of medical image registration in RT and its applications in veterinary oncology. A summary of the most commonly used approaches in human and veterinary medicine is presented along with their current use in IGRT and adaptive radiation therapy (ART). It is important to realize that registration does not guarantee that target volumes, such as the gross tumor volume (GTV), are correctly identified on the image being registered, as limitations unique to registration algorithms exist. Research involving novel registration frameworks for automatic segmentation of tumor volumes is ongoing and comparative oncology programs offer a unique opportunity to test the efficacy of proposed algorithms.

RETROSPECTIVE EVALUATION OF INTERFRACTION URETERAL MOVEMENT IN DOGS UNDERGOING RADIATION THERAPY TO ELUCIDATE APPROPRIATE SETUP MARGINS.

Radiation-induced ureteral damage can result in serious complications (i.e., hydronephrosis). Also, ureters can be included in planning target volume (PTV) such as ureteral invasion of urinary bladder carcinoma. Therefore, knowing the interfractional movement of the ureters is critical for creation of appropriate planning organs at risk (pOAR) and PTV. This retrospective and descriptive study of 17 dogs with genitourinary carcinomas that underwent intensity-modulated, image-guided radiation therapy (IM-IGRT) was conducted to describe the movement and calculate suggested pOAR/PTV expansions at three locations (at the levels of third lumbar vertebra, immediately cranial to vesicoureteral junction [VUJ], and midway between those two) and from two perspectives: during a course of (1) IM-IGRT, where position verification is performed using soft tissue registration when the dogs underwent clinical IM-IGRT; (2) radiation therapy whereby position verification is performed using planar radiography with a corresponding bony registration. This registration was performed by fusing the radiation planning computed tomography (CT) and cone-beam CTs using bony landmarks. With soft tissue registration, findings supported the use of larger pOAR expansion (0.7-1.8 cm) for the mid region of the ureters compared to the areas near VUJ (0.7-1.1 cm). With bony registration, findings supported the use of larger pOAR/PTV expansions (1.6-1.7 cm) for dorsal direction bilaterally at areas near VUJ compared to those with soft tissue registration (0.9-1.0 cm). The results of this study should help radiation oncologists use appropriate ureter expansions for specific patient orientations and positioning verification methods.

Comparison of adaptive radiotherapy techniques for external radiation therapy of canine bladder cancer.

Daily bladder variations make it difficult to utilize standard radiotherapy as a primary treatment option for muscle-invasive bladder cancer. Our purpose was to develop a model comparing dose distributions of image-guided and adaptive radiotherapy (ART) techniques for canine bladder cancer. Images were obtained retrospectively from cone-beam computed tomography (CBCT) scans used for daily positioning of four dogs undergoing fractionated image-guided radiotherapy (IGRT). Four different treatment plans were modeled for each dog, and dosimetric data were compared. Two plans were developed using planning target volumes based on planning computed tomography (CT) bladder volume. These plans then used bony anatomy or soft tissue anatomy for daily positioning and dosimetric modeling. The third plan type was a hybrid IGRT and ART technique utilizing a library of premade anisotropic planning target volumes using bladder wall motion data and selection of a "plan-of-the-day" determined from positioning CBCT bladder volumes. The fourth plan was an ART technique that constructed a new planning target volume each day based on daily bladder volume as determined by pretreatment CBCT. Dose volume histograms were generated for each plan type and dose distribution for the bladder and rectum were compared between plan types. Irradiated rectal volume decreased and irradiated bladder volume increased as plan conformality increased. ART provided the greatest rectal sparing, with lowest irradiated rectal volume (P < 0.001), and largest bladder volume receiving 95% of the prescription dose (P < 0.001). In our model, adaptive radiotherapy techniques for canine bladder cancer showed significant reduction in rectal volume irradiated when compared to nonadaptive techniques, while maintaining appropriate bladder coverage.

Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors.

An image-guided robotic stereotactic radiosurgery (SRS) system can be used to deliver curative-intent radiation in either single fraction or hypofractionated doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT), either with or without adjunctive treatment, were retrospectively analyzed for survival and prognostic factors. Median survival time (MST) was evaluated using Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size, prescribed radiation dose, and heterogeneity index were analyzed for prognostic significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy) fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant prognostic factors were identified. Acute side effects were rare and mild. Late side effects included one dog with an oronasal fistula and six dogs with seizures. In three of six dogs, seizures were a presenting complaint prior to SBRT. The cause of seizures in the remaining three dogs could not be definitively determined due to lack of follow-up computed tomography (CT) imaging. The seizures could have been related to either progression of disease or late radiation effect. Results indicate that image-guided robotic SBRT, either with or without adjunctive therapy, for canine nonlymphomatous nasal tumors provides comparable survival times (STs) to daily fractionated megavoltage radiation with fewer required fractions and fewer acute side effects.

Helical tomotherapy setup variations in canine nasal tumor patients immobilized with a bite block.

The purpose of our study was to compare setup variation in four degrees of freedom (vertical, longitudinal, lateral, and roll) between canine nasal tumor patients immobilized with a mattress and bite block, versus a mattress alone. Our secondary aim was to define a clinical target volume (CTV) to planning target volume (PTV) expansion margin based on our mean systematic error values associated with nasal tumor patients immobilized by a mattress and bite block. We evaluated six parameters for setup corrections: systematic error, random error, patient-patient variation in systematic errors, the magnitude of patient-specific random errors (root mean square [RMS]), distance error, and the variation of setup corrections from zero shift. The variations in all parameters were statistically smaller in the group immobilized by a mattress and bite block. The mean setup corrections in the mattress and bite block group ranged from 0.91 mm to 1.59 mm for the translational errors and 0.5°. Although most veterinary radiation facilities do not have access to Image-guided radiotherapy (IGRT), we identified a need for more rigid fixation, established the value of adding IGRT to veterinary radiation therapy, and define the CTV-PTV setup error margin for canine nasal tumor patients immobilized in a mattress and bite block.

Intensity-modulated and image-guided radiation therapy for treatment of genitourinary carcinomas in dogs.

BACKGROUND: External beam radiation therapy can be used to treat pelvic tumors in dogs, but its utility is limited by lack of efficacy data and associated late complications. HYPOTHESIS/OBJECTIVES: The objective of this study was to assess local tumor control, overall survival, and toxicosis after intensity-modulated and image-guided radiation therapy (IM/IGRT) for treatment of genitourinary carcinomas (CGUC) in dogs. ANIMALS: 21 client-owned dogs. METHODS: A retrospective study was performed. Medical records of dogs for which there was intent to treat with a course of definitive-intent IM/IGRT for CGUC between 2008 and 2011 were reviewed. Descriptive and actuarial statistics comprised the data analysis. RESULTS: Primary tumors were located in the prostate (10), urinary bladder (9), or urethra (2). The total radiation dose ranged from 54-58 Gy, delivered in 20 daily fractions. Grade 1 and 2 acute gastrointestinal toxicoses developed in 33 and 5% of dogs, respectively. Grade 1 and 2 acute genitourinary and grade 1 acute integumentary toxicoses were documented in 5, 5, and 20% of dogs, respectively. Four dogs experienced late grade 3 gastrointestinal or genitourinary toxicosis. The subjective response rate was 60%. The median event-free survival was 317 days; the overall median survival time was 654 days. Neither local tumor control nor overall survival was statistically dependent upon location of the primary tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: IM/IGRT is generally well-tolerated and provides an effective option for locoregional control of CGUC. As compared with previous reports in the veterinary literature, inclusion of IM/IGRT in multimodal treatment protocols for CGUC can result in superior survival times; controlled prospective evaluation is warranted.