Commissioning and initial stereotactic ablative radiotherapy experience with Vero.

The purpose of this study is to describe the comprehensive commissioning process and initial clinical performance of the Vero linear accelerator, a new radiotherapy device recently installed at UT Southwestern Medical Center specifically developed for delivery of image-guided stereotactic ablative radiotherapy (SABR). The Vero system utilizes a ring gantry to integrate a beam delivery platform with image guidance systems. The ring is capable of rotating ± 60° about the vertical axis to facilitate noncoplanar beam arrangements ideal for SABR delivery. The beam delivery platform consists of a 6 MV C-band linac with a 60 leaf MLC projecting a maximum field size of 15 × 15 cm² at isocenter. The Vero planning and delivery systems support a range of treatment techniques, including fixed beam conformal, dynamic conformal arcs, fixed gantry IMRT in either SMLC (step-and-shoot) or DMLC (dynamic) delivery, and hybrid arcs, which combines dynamic conformal arcs and fixed beam IMRT delivery. The accelerator and treatment head are mounted on a gimbal mechanism that allows the linac and MLC to pivot in two dimensions for tumor tracking. Two orthogonal kV imaging subsystems built into the ring facilitate both stereoscopic and volumetric (CBCT) image guidance. The system is also equipped with an always-active electronic portal imaging device (EPID). We present our commissioning process and initial clinical experience focusing on SABR applications with the Vero, including: (1) beam data acquisition; (2) dosimetric commissioning of the treatment planning system, including evaluation of a Monte Carlo algorithm in a specially-designed anthropomorphic thorax phantom; (3) validation using the Radiological Physics Center thorax, head and neck (IMRT), and spine credentialing phantoms; (4) end-to-end evaluation of IGRT localization accuracy; (5) ongoing system performance, including isocenter stability; and (6) clinical SABR applications.

Brachial Plexus Tolerance to Single-Session SABR in a Pig Model.

PURPOSE: The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. METHODS AND MATERIALS: Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. RESULTS: Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. CONCLUSIONS: The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

Effects From Nonuniform Dose Distribution in the Spinal Nerves of Pigs: Analysis of Normal Tissue Complication Probability Models.

PURPOSE: Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig. METHODS AND MATERIALS: Common phenomenological and semimechanistic NTCP models were fit using the maximum likelihood estimate method to dose-response data from spinal nerve irradiation studies in pigs. Statistical analysis was used to compare how well each model fit the data. Model parameters were then applied to a previously published dose distribution used for spinal cord irradiation in rats under the assumption of a similar dose-response. RESULTS: The Lyman-Kutcher-Burman model, relative seriality, and critical volume model fit the spinal nerve data equally well, but the mean dose logistic and relative seriality models gave the best fit after penalizing for the number of model parameters. The minimum dose logistic regression model was the only model showing a lack of fit. When extrapolated to a 0.5-cm simulated square-wave-like dose distribution, the serial behaving models showed negligible increase in dose-response curve. The Lyman-Kutcher-Burman model and relative seriality models showed significant shifting of NTCP curves due to parallel behaving parameters. The critical volume model gave the closest match to the rat data. CONCLUSIONS: Several phenomenological and semimechanistic models were observed to adequately describe the increase in the radiation tolerance of the spinal nerves when changing the irradiated length from 1.5 to 0.5 cm. Contrary to common perception, model parameters suggest parallel behaving tissue architecture. Under the assumption that the spinal nerve response to radiation is similar to that of the spinal cord, only the critical volume model was robust when extrapolating to outcome data from a 0.5-cm square-wave-like dose distribution, as was delivered in rodent spinal cord irradiation research.

Low-cost 3D print-based phantom fabrication to facilitate interstitial prostate brachytherapy training program.

PURPOSE: The purpose of this study was to manufacture a realistic and inexpensive prostate phantom to support training programs for ultrasound-based interstitial prostate brachytherapy. METHODS AND MATERIALS: Five phantom material combinations were tested and evaluated for material characteristics; Ecoflex 00-30 silicone, emulsion silicone with 20% or 50% mineral oil, and regular or supersoft polyvinyl chloride (PVC). A prostate phantom which includes an anatomic simulated prostate, urethra, seminal vesicles, rectum, and normal surrounding tissue was created with 3D-printed molds using 20% emulsion silicone and regular and supersoft PVC materials based on speed of sound testing. Needle artifact retention was evaluated at weekly intervals. RESULTS: Speed of sound testing demonstrated PVC to have the closest ultrasound characteristics of the materials tested to that of soft tissue. Several molds were created with 3D-printed PLA directly or cast on 3D-printed PLA with high heat resistant silicone. The prostate phantom fabrication workflow was developed, including a method to produce dummy seeds for low-dose-rate brachytherapy practice. A complete phantom may be fabricated in 1.5-2 h, and the material cost for each phantom was approximated at $23.98. CONCLUSIONS: A low-cost and reusable phantom was developed based on 3D-printed molds for casting. The proposed educational prostate phantom is an ideal cost-effective platform to develop and build confidence in fundamental brachytherapy procedural skills in addition to actual patient caseloads.

Existence of a Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy.

PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed. RESULTS: Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal. CONCLUSIONS: A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model.

Spinal Nerve Tolerance to Single-Session Stereotactic Ablative Radiation Therapy.

PURPOSE: This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. METHODS AND MATERIALS: Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. RESULTS: Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. CONCLUSIONS: The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.

Quality assurance of immobilization and target localization systems for frameless stereotactic cranial and extracranial hypofractionated radiotherapy.

The success of stereotactic radiosurgery has stimulated significant interest in the application of such an approach for the treatment of extracranial tumors. The potential benefits of reduced healthcare costs and improved patient outcomes that could be realized in a high-precision, hypofractionated treatment paradigm are numerous. Image-guidance technologies are eliminating the historic requirement for rigid head fixation and will also accelerate the clinical implementation of the approach in extracranial sites. An essential prerequisite of "frameless" stereotactic systems is that they provide localization accuracy consistent with the safe delivery of a therapeutic radiation dose given in one or few fractions. In this report, we reviewed the technologies for frameless localization of cranial and extracranial targets with emphasis on the quality assurance aspects.

A method for evaluating quality assurance needs in radiation therapy.

The increasing complexity of modern radiation therapy planning and delivery techniques challenges traditional prescriptive quality control and quality assurance programs that ensure safety and reliability of treatment planning and delivery systems under all clinical scenarios. Until now quality management (QM) guidelines published by concerned organizations (e.g., American Association of Physicists in Medicine [AAPM], European Society for Therapeutic Radiology and Oncology [ESTRO], International Atomic Energy Agency [IAEA]) have focused on monitoring functional performance of radiotherapy equipment by measurable parameters, with tolerances set at strict but achievable values. In the modern environment, however, the number and sophistication of possible tests and measurements have increased dramatically. There is a need to prioritize QM activities in a way that will strike a balance between being reasonably achievable and optimally beneficial to patients. A systematic understanding of possible errors over the course of a radiation therapy treatment and the potential clinical impact of each is needed to direct limited resources in such a way to produce maximal benefit to the quality of patient care. Task Group 100 of the AAPM has taken a broad view of these issues and is developing a framework for designing QM activities, and hence allocating resources, based on estimates of clinical outcome, risk assessment, and failure modes. The report will provide guidelines on risk assessment approaches with emphasis on failure mode and effect analysis (FMEA) and an achievable QM program based on risk analysis. Examples of FMEA to intensity-modulated radiation therapy and high-dose-rate brachytherapy are presented. Recommendations on how to apply this new approach to individual clinics and further research and development will also be discussed.

Use of the BrainLAB ExacTrac X-Ray 6D system in image-guided radiotherapy.

The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patient's skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery.

Emphasis on Repair, Not Just Avoidance of Injury, Facilitates Prudent Stereotactic Ablative Radiotherapy.

Stereotactic ablative radiotherapy (SAbR) is a potent, hypofractionated treatment against cancer which puts adjacent normal tissue in potential peril. Accurate delineation of normal tissue injury risks from SAbR has been challenging, and lack of clear understanding of SAbR tolerance continues to limit its potential. In this review, we contend that SAbR effects on normal tissue could be akin to a surgical "wound," and that adequate wound repair of organs at risk is an essential component of effective SAbR therapy. To mitigate risks of clinical relevance from an SAbR wound, in addition to the traditional views on architectural organization and functional organization of an organ at risk, one should also consider the organ's predominant wound healing tendencies. We also propose that avoidance of SAbR injury to organs at risk must involve careful thought to minimize risk factors that could further impair wound healing. It is imperative that efforts aimed at determining appropriate dose constraints based on predicted SAbR wound injury repair mechanisms for a particular organ to be studied as a critically important step to furthering our understanding of SAbR-related normal tissue tolerances. This can be best achieved through thoughtful design of prospective phase I dose-escalation studies.

Technical Note: System for evaluating local hypothermia as a radioprotector of the rectum in a small animal model.

PURPOSE: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) treatments. This work describes the development of a system to evaluate local hypothermia for a radioprotective effect of the rat rectum during a large dose of radiation relevant to prostate SBRT. This includes the evaluation of a 3D-printed small animal rectal cooling device and the integration with a small animal irradiator. METHODS: A 3-cm long, dual-lumen rectal temperature control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA was capable of recirculating flow in a device small enough for insertion into the rat rectum, with a metal support rod for strength as well as visibility during radiation treatment planning. The outer walls of the RTCA comprised of thin heat shrink plastic, achieving efficient heat transfer into adjacent tissues. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within the rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. Integration with an image-guided small animal irradiator and associated treatment planning system included evaluation for imaging artifacts and effect of brass tubing on dose calculation. RESULTS: The rectal temperature adjacent to the cooling device decreased from body temperature to 15°C within 10-20 min from device insertion and was maintained at 15 ± 3°C during active cooling for the evaluated time of one hour. MR thermometry revealed a steep temperature gradient with increasing distance from the cooling device with the desired temperature range maintained within the surrounding few millimeters. CONCLUSIONS: A 3D-printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in the rat rectum. The RTCA was simply integrated with an image-guided small animal irradiator and Monte Carlo-based treatment planning system to facilitate an in vivo investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation.

Local Hypothermia as a Radioprotector of the Rectal Wall During Prostate Stereotactic Body Radiation Therapy.

PURPOSE: To compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model. METHODS AND MATERIALS: A 1.9-cm length of rectum was irradiated with a single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo-based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1-cm-diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy up to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180 to 186 days. Histologic scoring was performed on all study rats. RESULTS: Probit analysis showed a dose associated with a 50% incidence of rectal obstruction of 24.6 Gy and 40.8 Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the posttreatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated. CONCLUSIONS: A significant radioprotective effect was observed using local hypothermia during a single large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomic and physiologic similarities to humans is suggested.

Image-guided radiotherapy using a mobile kilovoltage x-ray device.

A mobile isocentric C-arm kilovoltage imager has been evaluated as a potential tool for image-guided radiotherapy. The C-arm is equipped with an amorphous silicon flat panel for high-quality image acquisition. Additionally, the device is capable of cone beam computed tomography (CT) and volumetric reconstruction. This is achieved through the application of a modified Feldkamp algorithm with acquisition over a 180 degrees scan arc. The number of projections can be varied from 100 to 1000, resulting in a reconstructed volume 20 cm in diameter by 15-cm long. While acquisition time depends upon number of projections, acceptable quality images can be obtained in less than 60 seconds. Image resolution and contrast of cone-beam phantom images have been compared with images from a conventional CT scanner. The system has a spatial resolution of > or = 10 lp/cm and resolution is approximately equal in all 3 dimensions. Conversely, subject contrast is poorer than conventional CT, compromised by the increased scatter and underlying noise inherent in cone beam reconstruction, as well as the absence of filtering prior to reconstruction. The mobility of the C-arm makes it necessary to determine the C-arm position relative to the linear accelerator isocenter. Two solutions have been investigated: (1) the use of fiducial markers, embedded in the linac couch, that can subsequently be registered in the image sets; and (2), a navigation approach for infrared tracking of the C-arm relative to the linac isocenter. Observed accuracy in phantom positioning ranged from 1.0 to 1.5 mm using the navigation approach and 1.5 to 2.5 mm using the fiducial-based approach. As part of this work, the impact of respiratory motion on cone-beam image quality was evaluated, and a scheme for retrospective gating was devised. Results demonstrated that kilovoltage cone beam CT provides spatial integrity and resolution comparable to conventional CT. Cone-beam CT studies of patients undergoing radiotherapy have demonstrated acceptable soft tissue contrast, allowing assessment of daily changes in target anatomy. Of the 2 approaches developed to register images to the linac isocenter, the navigation method demonstrated superior accuracy for daily patient positioning relative to the fiducial-based method. Finally, significant image degradation due to respiratory motion was observed. It was demonstrated that this could be improved by correlating the acquisition of individual 2D projections with respiration for retrospective reconstruction of phase-based volumetric datasets.

Targeting accuracy of an image guided gating system for stereotactic body radiotherapy.

Recently, a commercial system capable of x-ray image guided patient positioning and respiratory gated delivery has become available. Here we describe the operational principles of this system and investigate its geometric targeting accuracy under controlled conditions. The system tracks breathing via infrared (IR) detection of reflective markers located on the patient's abdomen. Localization kilovoltage (kV) x-rays are triggered from within the gated delivery window portion of the breathing trace and after positioning, the tumour will cross the linac isocentre during gated delivery. We tested geometric accuracy of this system by localizing and delivering gated fields to a moving phantom. Effects of phantom speed, gating window location, timing errors and phantom rotations on positioning and gating accuracy were investigated. The system delivered gated fields to both a moving and static phantom with equal accuracy. The position of the gating window affects accuracy only to the extent that an asymmetric breathing motion could affect dose distribution within its boundaries. Positioning errors were found to be less then 0.5 +/- 0.2 mm for phantom rotations up to 5 degrees. We found and corrected a synchronization error caused by a faulty x-ray duration setting and detected a 60 +/- 20 ms time delay in our linear accelerator.

Investigations of a minimally invasive method for treatment of spinal malignancies with LINAC stereotactic radiation therapy: accuracy and animal studies.

PURPOSE: A new method for stereotactic irradiation of spinal malignancies is presented, with evaluations of the theoretic and practical limitations of localization accuracy and the implementation of the method in swine. MATERIALS AND METHODS: In a percutaneous procedure, a minimum of three small (1.7-mm-diameter) titanium markers are permanently affixed to a vertebra. Markers are localized on biplanar radiographs while isocenter positions are determined on CT. An external fiducial frame defines a three-dimensional coordinate system through the patient. Radiographs coupled with a rigid body rotation algorithm account for daily differences in patient position. Phantom studies were used to verify theoretic uncertainty calculations from a simulation program. A swine model was used to evaluate the difficulty and duration of the implant technique, the suitability of the vertebral process as an implant site, vertebral motion due to normal respiration, and the ability to target one vertebra with markers in an adjacent vertebra. RESULTS: Theoretic accuracy studies confirmed that localization accuracy is a function of marker separation. Phantom studies involving 296 measurements showed that individual implants could be localized within +/-0.25 mm. The largest targeting error observed in 3,600 measurements of 100 implant configurations was 1.17 mm. The implant procedure took 5-10 minutes per site. No significant migration of implants was observed up to 35 days postimplantation, and respiratory motion had no detectable influence on vertebral position. Adjacent vertebrae may be useful for targeting one another with a small sacrifice in localization accuracy. CONCLUSIONS: The use of implanted markers for localization of spinal malignancies has potential for applications in stereotactic radiotherapy. Phantom measurements suggest that localization accuracy similar to intracranial stereotactic radiotherapy techniques is achievable. Swine studies suggest that the implant technique is expedient and feasible for tumor targeting purposes.

Spinal cord tolerance to single-session uniform irradiation in pigs: implications for a dose-volume effect.

BACKGROUND AND PURPOSE: This study was performed to test the hypothesis that spinal cord radiosensitivity is significantly modified by uniform versus laterally non-uniform dose distributions. MATERIALS AND METHODS: A uniform dose distribution was delivered to a 4.5-7.0 cm length of cervical spinal cord in 22 mature Yucatan minipigs for comparison with a companion study in which a laterally non-uniform dose was given [1]. Pigs were allocated into four dose groups with mean maximum spinal cord doses of 17.5 ± 0.1 Gy (n=7), 19.5 ± 0.2 Gy (n=6), 22.0 ± 0.1 Gy (n=5), and 24.1 ± 0.2 Gy (n=4). The study endpoint was motor neurologic deficit determined by a change in gait within one year. Spinal cord sections were stained with a Luxol fast blue/periodic acid Schiff combination. RESULTS: Dose-response curves for uniform versus non-uniform spinal cord irradiation were nearly identical with ED(50)'s (95% confidence interval) of 20.2 Gy (19.1-25.8) and 20.0 Gy (18.3-21.7), respectively. No neurologic change was observed for either dose distribution when the maximum spinal cord dose was ≤ 17.8 Gy while all animals experienced deficits at doses ≥ 21.8 Gy. CONCLUSION: No dose-volume effect was observed in pigs for the dose distributions studied and the endpoint of motor neurologic deficit; however, partial spinal cord irradiation resulted in less debilitating neurologic morbidity and histopathology.

Paralysis following stereotactic spinal irradiation in pigs suggests a tolerance constraint for single-session irradiation of the spinal nerve.

BACKGROUND AND PURPOSE: Paralysis observed during a study of vertebral bone tolerance to single-session irradiation led to further study of the dose-related incidence of motor peripheral neuropathy. MATERIALS AND METHODS: During a bone tolerance study, cervical spinal nerves of 15 minipigs received bilateral irradiation to levels C5-C8 distributed into three dose groups with mean maximum spinal nerve doses of 16.9 ± 0.3 Gy (n=5), 18.7 ± 0.5 Gy (n=5), and 24.3 ± 0.8 Gy (n=5). Changes developing in the gait of the group of pigs receiving a mean maximum dose of 24.3 Gy after 10-15 weeks led to the irradiation of two additional animals. They received mean maximum dose of 24.9 ± 0.2 Gy (n=2), targeted to the left spinal nerves of C5-C8. The followup period was one year. Histologic sections from spinal cords and available spinal nerves were evaluated. MR imaging was performed on pigs in the 24.9 Gy group. RESULTS: No pig that received a maximum spinal nerve point dose ≤19.0 Gy experienced a change in gait while all pigs that received ≥24.1 Gy experienced paralysis. Extensive degeneration and fibrosis were observed in irradiated spinal nerves of the 24.9 Gy animals. All spinal cord sections were normal. Irradiated spinal nerve regions showed increased thickness and hypointensity on MR imaging. CONCLUSION: The single-session tolerance dose of the cervical spinal nerves lies between 19.0 and 24.1 Gy for this model.

Spinal cord tolerance to reirradiation with single-fraction radiosurgery: a swine model.

PURPOSE: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. METHODS AND MATERIALS: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 ± 0.1 Gy (n = 2), 17.1 ± 0.3 Gy (n = 3), 19.0 ± 0.1 Gy (n = 5), 21.2 ± 0.1 Gy (n = 5), 23.4 ± 0.2 Gy (n = 5), and 25.4 ± 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving ≥10 Gy for the same groups were 34% ± 1%, 40% ± 1%, 46% ± 3%, 52% ± 1%, 56 ± 3%, and 57% ± 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. RESULTS: A steep dose-response curve was observed with a 50% incidence of paralysis (ED(50)) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. CONCLUSION: Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.

Quality and safety in stereotactic radiosurgery and stereotactic body radiation therapy: can more be done?

Stereotactic radiosurgery (SRS) has been an effective modality for the treatment of benign and malignant cranial disease for 50 years. Increasingly, the stereotactic approach, ablative doses of radiation delivered in a highly focused manner to a target of interest, is being applied in a number of extracranial disease sites. Stereotactic body radiation therapy (SBRT) holds significant potential for improving tumor control rates across a range of locations and histologies. Both SRS and SBRT require specialized technology, meticulous procedures, and dedicated personnel. Several recent high-profile medical radiation events have generated considerable attention within the media, and serve to remind the profession that close attention to ongoing quality improvement is a fundamental responsibility. The purpose of this manuscript is to provide some recommendations for SRS / SBRT processes and procedures that may be beneficial in understanding and reducing risks inherent to the modalities.

Spinal cord tolerance in the age of spinal radiosurgery: lessons from preclinical studies.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat has demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.