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.

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening-a prospective vaginal length and dose correlation.

PURPOSE: Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). MATERIALS AND METHODS: Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. RESULTS: The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. CONCLUSION: Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

Bony structure enhanced synthetic CT generation using Dixon sequences for pelvis MR-only radiotherapy.

BACKGROUND: MRI-only radiotherapy planning (MROP) is beneficial to patients by avoiding MRI/CT registration errors, simplifying the radiation treatment simulation workflow and reducing exposure to ionizing radiation. MRI is the primary imaging modality for soft tissue delineation. Treatment planning CTs (i.e., CT simulation scan) are redundant if a synthetic CT (sCT) can be generated from the MRI to provide the patient positioning and electron density information. Unsupervised deep learning (DL) models like CycleGAN are widely used in MR-to-sCT conversion, when paired patient CT and MR image datasets are not available for model training. However, compared to supervised DL models, they cannot guarantee anatomic consistency, especially around bone. PURPOSE: The purpose of this work was to improve the sCT accuracy generated from MRI around bone for MROP. METHODS: To generate more reliable bony structures on sCT images, we proposed to add bony structure constraints in the unsupervised CycleGAN model's loss function and leverage Dixon constructed fat and in-phase (IP) MR images. Dixon images provide better bone contrast than T2-weighted images as inputs to a modified multi-channel CycleGAN. A private dataset with a total of 31 prostate cancer patients were used for training (20) and testing (11). RESULTS: We compared model performance with and without bony structure constraints using single- and multi-channel inputs. Among all the models, multi-channel CycleGAN with bony structure constraints had the lowest mean absolute error, both inside the bone and whole body (50.7 and 145.2 HU). This approach also resulted in the highest Dice similarity coefficient (0.88) of all bony structures compared with the planning CT. CONCLUSION: Modified multi-channel CycleGAN with bony structure constraints, taking Dixon-constructed fat and IP images as inputs, can generate clinically suitable sCT images in both bone and soft tissue. The generated sCT images have the potential to be used for accurate dose calculation and patient positioning in MROP radiation therapy.

Change in image-guided planning strategies over time impacts oncologic and survival outcomes for intracavitary cervical cancer brachytherapy.

PURPOSE: Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional nonvolumetric (NV) dosimetry system to three-dimensional computed tomography (CT) and/or magnetic resonance imaging (MRI)-based planning techniques. The purpose of this study is to retrospectively evaluate the relative improvements in image-guided planning strategies over time with regards to dosimetry, survival, and toxicity. METHODS AND MATERIALS: A single site retrospective review of 95 locally advanced cervical cancer patients treated with concurrent chemoradiation and high dose rate BT from 2009 to 2016 were divided into three BT planning groups: point-A based NV dosimetry using CT imaging (n = 37), CT-based volumetric dosimetry (n = 33), and MRI-based volumetric dosimetry (n = 25). Overall survival (OS), progression free survival (PFS), and pelvic control (PC) at 5 years were plotted using Kaplan-Meier curves. Univariate and multivariate (MVA) cox proportional-hazards models calculated hazard-ratios (HZ). Finally, acute and late grade 3-4 toxicities were compared between the cohorts. RESULTS: Both MRI and CT had significantly less D2cc to bowel (p < 0.001) and sigmoid (p < 0.001) compared to NV-based planning. On MVA, age (<60 vs. ≥60 years) was significant for worse 5-year OS (HZ: 2.48) and PC (HZ: 5.25). MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and PC (HZ: 0.16). There was no significant difference in grade ≥3 toxicities between the cohorts. CONCLUSIONS: CT and MRI-based 3D planning had significantly less D2cc to bowel and sigmoid. MRI-based planning had significant improvement in 5-year OS, PFS, and LC compared to NV on MVA.

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.

Initial application of a geometric QA tool for integrated MV and kV imaging systems on three image guided radiotherapy systems.

PURPOSE: Several linacs with integrated kilovoltage (kV) imaging have been developed for delivery of image guided radiation therapy (IGRT). High geometric accuracy and coincidence of kV imaging systems and megavoltage (MV) beam delivery are essential for successful image guidance. A geometric QA tool has been adapted for routine QA for evaluating and characterizing the geometric accuracy of kV and MV cone-beam imaging systems. The purpose of this work is to demonstrate the application of methodology to routine QA across three IGRT-dedicated linac platforms. METHODS: It has been applied to a Varian Trilogy (Varian Medical Systems, Palo Alto, CA), an Elekta SynergyS (Elekta, Stockholm, Sweden), and a Brainlab Vero (Brainlab AG, Feldkirchen, Germany). Both the Trilogy and SynergyS linacs are equipped with a retractable kV x-ray tube and a flat panel detector. The Vero utilizes a rotating, rigid ring structure integrating a MV x-ray head mounted on orthogonal gimbals, an electronic portal imaging device (EPID), two kV x-ray tubes, and two fixed flat panel detectors. This dual kV imaging system provides orthogonal radiographs, CBCT images, and real-time fluoroscopic monitoring. Two QA phantoms were built to suit different field sizes. Projection images of a QA phantom were acquired using MV and kV imaging systems at a series of gantry angles. Software developed for this study was used to analyze the projection images and calculate nine geometric parameters for each projection. The Trilogy was characterized five times over one year, while the SynergyS was characterized four times and the Vero once. Over 6500 individual projections were acquired and analyzed. Quantitative geometric parameters of both MV and kV imaging systems, as well as the isocenter consistency of the imaging systems, were successfully evaluated. RESULTS: A geometric tool has been successfully implemented for calibration and QA of integrated kV and MV across a variety of radiotherapy platforms. X-ray source angle deviations up to 0.8 degrees, and detector center offsets up to 3 mm, were observed for three linacs, with the exception of the Vero, for which a significant center offset of one kV detector (prior to machine commissioning) was observed. In contrast, the gimbal-based MV source positioning of the Vero demonstrated differences between observed and expected source positions of less than 0.2 mm, both with and without gimbal rotation. CONCLUSIONS: This initial application of this geometric QA tool shows promise as a universal, independent tool for quantitative evaluation of geometric accuracies of both MV and integrated kV imaging systems across a range of platforms. It provides nine geometric parameters of any imaging system at every gantry angle as well as the isocenter coincidence of the MV and kV image systems.

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.

Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy.

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤70 Gy; SBRT thecal sac EQD22 Dmax ≤25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates.

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.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

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.

Reduced toxicity with equivalent outcomes using three-dimensional volumetric (3DV) image-based versus nonvolumetric point-based (NV) brachytherapy in a cervical cancer population.

PURPOSE: Brachytherapy (BT) techniques have historically used a two-dimensional nonvolumetric (NV) system involving dose prescribed to a point fixed in space. We compared dosimetric, toxicity, and oncologic outcomes for volumetric planning (3DV) versus CT point-based planning. METHODS AND MATERIALS: Patients treated with external beam radiation therapy and high dose rate (HDR) intracavitary BT were included (n = 71). Patients planned with NV BT treated from 2009 to 2011 (n = 37) were compared to patients planned with 3DV BT treated from 2012 to 2014 (n = 34). Investigators delineated volumes for organs at risk clinical target volumes for the 2009-2011 NV cohort. Acute and chronic toxicity data were graded. RESULTS: The mean HDR clinical target volume D90 received in the NV and 3DV cohorts were significantly different (p < 0.001). The mean dose to point A was significantly higher in the NV cohort than in the 3DV cohort (p < 0.001). There were significantly more Grade 3 or higher gastrointestinal toxicities in the NV cohort (p = 0.048). There was a nonsignificant trend toward improved oncologic outcomes for patients undergoing CT-based planning. CONCLUSIONS: 3DV BT allows for a significant reduction of dose to critical structures, resulting in decreased gastrointestinal toxicity, while delivering noninferior doses to the high-risk clinical target volume. Outcomes were improved in the 3D cohort trending toward statistical significance.

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.