A REVIEW OF TREATMENT PLANNING AND DOSE CALCULATION IN VETERINARY RADIATION ONCOLOGY

Because radiation cell killing follows Poisson statistics, radiation dose response curves for tumors and normal tissue response are sigmoidal in shape. This shape implies that small errors in delivery of radiation dose can result in large changes in the probability of normal tissue necrosis or tumor control. Thus it is important for veterinarians involved with radiation oncology to be familiar with the basic aspects of radiation physics and dose calculation as they relate to radiation therapy. In this paper, we present a review of pertinent physics and treatment planning relative to orthovoltage and cobalt irradiation. The usefulness of radiation treatment planning computers is emphasized for improving the radiation oncologist's knowledge of dose distribution and selection of the optimum treatment plan.     

Clinical and imaging findings,treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi‐center study

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow‐up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44–424 days and mean 95% CI for stereotactic radiation therapy dogs was 260–518 days).     

BONE SARCOMA FOLLOWING ORTHOVOLTAGE RADIOTHERAPY IN TWO DOGS

In two dogs that received orthovoltage radiotherapy, osteosarcoma developed in irradiated bone 38 and 77 months after treatment. Irridiated bone in one dog was presumably normal prior to radiotherapy; irradiated bone in the other was infiltrated by an acanthomatous epulis. Both osteosarcomas were probably radiation induced. Radiation-induced bone sarcoma is an important, but uncommon, complication of radiaotherapy.     

Equine external beam radiation therapy: Techniques and challenges

Radiation therapy is becoming increasingly more available and in demand for small animal veterinary cases. Although there is a demand for radiation therapy in large animal cases, there are certain limitations of external beam radiation therapy for horses that restrict treatment options. Currently, there are only five veterinary teaching hospitals in the United States where external beam radiation therapy can be performed on horses and other large animals. This is in contrast to the roughly 80 facilities, both academic and private, available for small animals. The goal of this commentary is to give a brief overview of external beam radiation therapy and highlight the steps involved, and the technical difficulties faced, while treating horses with external beam radiation therapy.     

RADIATION THERAPY COMMUNICATION—REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY

A 5‐year‐old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT.     

Correlations between acute radiation scores and pain scores in canine radiation patients with cancer of the forelimb

Objective To determine whether there is a correlation between skin acute radiation score (ARS) and pain scores and to determine if skin ARSs can be used to predict future pain scores and increased need for analgesia in dogs undergoing radiation therapy for cancer of the forelimb. Study design Prospective observational study. Animals Seven middle‐aged dogs of various breeds with cancer of the forelimb. Methods Each neoplasm was surgically removed and a histologic diagnosis was obtained. Curative intent radiation therapy was initiated 2½–4½ weeks after surgery. Curative intent radiation therapy was delivered as prescribed. Two trained observers scored the dogs using a visual analog pain scale (VAS), Glasgow composite measure of pain scale, short form (GCMPS) and skin ARS prior to each day’s therapy. Daily scores were averaged and scatter plots were developed. Generalized estimating equation regressions were used to calculate standard error, 95% confidence interval, and p‐values for each relationship. Confidence and prediction bands were plotted. Results A statistically significant correlation between skin ARS and VAS and GCMPS pain scores was identified indicating that as the skin ARS increased so did the pain scores. A general correlation between VAS and GCMPS scores was observed. Early (fraction days 1–6) GCMPS scores were significantly influenced by anxiety behavior unrelated to pain. Skin ARS was found to predict precisely current and future presence of pain, but could only predict a range of potential future pain scores based on the pain management approach in use during this study. Conclusions Skin ARS can provide valuable information for initiating preemptive analgesia and intensifying pain management during curative intent radiation therapy. Daily pain scoring with an acceptable pain scale should be used in conjunction with the skin ARS to improve patient pain management. Clinical relevance Pain is an anticipated consequence of curative intent radiation therapy. Understanding the correlation between pain and skin ARS may facilitate more effective pain management.     

USE OF PORTAL RADIOGRAPHY TO INCREASE ACCURACY OF DOSE DELIVERY IN RADIATION THERAPY

Port films were acquired for all radiation therapy patients (n = 132) treated over a thirteen month period to 1] assist in initial treatment field set-up on Day 1, 2] for quality assurance with a second port film taken on Day 7 of radiation therapy, and 3] as a means to document the radiation treatment field as a part of the patients permanent medical record. Port films were used for both patients treated with a definitive course of radiation (n = 97 patients), and those treated palliatively (n = 35 patients). The portal radiographs were valuable in terms of the initial set-up, and to correct for any positioning or other errors at the time of the one week recheck. Changes were made, based on the initial port film on Day 1, in 53% and 57% of treatment fields for palliative and definitive radiation patients, respectively. The changes made in both definitively and palliatively irradiated patients were usually in field position, an increase in field size to include all of the tumor, or a decrease in field size to spare normal tissue. Fewer changes were necessary based on the Day 7 recheck port films, but these day-7 rechecks are recommended for quality control. Based on the high frequency of changes introduced because of the initial port film findings, it is recommended that port films be incorporated on a routine basis in veterinary radiation therapy.     

A SURVEY OF VETERINARY RADIATION FACILITIES IN THE UNITED STATES DURING 2001

A survey of veterinary radiation therapy facilities in the United States was done in 2001 to determine the type of equipment available, radiation protocols used, case load, tumor types irradiated, as well as other details of the practice of radiation oncology. A total of 42 sites were identified and included 17 (40%) academic institutions, and 25 (60%) private practice external beam radiation facilities. The overall response rate was 79% (33/42 responded). Based on this survey there is substantial variation between facilities in all aspects ranging from equipment and personnel to radiation protocols and caseloads. American College of Veterinary Radiology boarded radiation oncologists direct 76% of the radiation facilities at academic institutions and 60% of the private practice facilities. Three facilities had orthovoltage radiation units only, and 30 facilities had mega-voltage equipment: cobalt 60 or linear accelerator. A total of 18 facilities had linear accelerators with three of these off site at a human radiation facility. Patient load information was available from 31 sites (74% of the radiation facilities in the United States), and based on the responses 2790 dogs and 1081 cats were irradiated in 2001. Canine mast cell tumors were the most frequently irradiated tumor. This represents the first survey of veterinary radiation facilities in the United States and provides information on the specialty of veterinary radiation oncology.     

TDP辐射对艾维茵商品代肉仔鸡生长增重影响

为探讨特定电磁波谱辐射器（TDP辐射器）辐射对肉仔鸡增重的影响，进行了本试验。结果表明：连续照射组雏鸡只均增重比对照组多62g，试验组总增重高3100g；分周照射组雏鸡只均增重比对照组多43g，总增重高2150g。试验Ⅰ、Ⅱ组只均盈利分别比对照组高1．28元、0．54元，饲料报酬：Ⅰ组为1．85、Ⅱ组为1．85、Ⅲ组为1．92。     

Analysis of radiosensitivity of cancer stem‐like cells derived from canine cancer cell lines

Cancer stem‐like cells (CSCs) are self‐renewing cells comprising a small subpopulation in tumours, and generate differentiated progeny through asymmetric division. It has been shown that CSCs are resistant to ionizing radiation, and this feature could be one of the mechanisms of tumour recurrence after radiation therapy. Much attention has been focused on to target CSCs; however, difficult of isolating CSCs and lack of knowledge on their radiosensitivity have limited this kind of research in veterinary medicine. In the present study, sphere‐forming cells (SC), cultured using sphere formation method, were isolated from four type of canine tumour cell lines and evaluated if they have CSCs‐like properties by expression of CSCs markers (real‐time polymerase chain reaction) and capacity of tumorigenesis (xenograft transplantation in nude mice), and were assessed radiosensitivity (clonogenic survival assay) and DNA repair kinetics (immunofluorescence staining for p53‐binding protein 1) after X‐ray irradiation in comparison with the corresponding normal adherent culture cells (AC). All SCs were isolated using sphere formation and showed high gene expression of CD133 and tumorigenic ability as compared with AC. All SCs were significantly resistant against X‐ray irradiation as compared with AC. In addition, the amount of DNA double‐strand breaks after X‐ray irradiation were significantly lower in SC compared with the corresponding AC. These results indicate that SC isolated through sphere formation possess CSCs‐like characteristics and CSCs are important factor that affect radiosensitivity in canine tumours. In addition, radioresistance of CSCs may depend on reaction of DNA double‐strand break after X‐ray exposure.     

A complication probability study for a definitive‐intent,moderately hypofractionated image‐guided intensity‐modulated radiotherapy protocol for anal sac adenocarcinoma in dogs

Previous trials showed the importance of administering radiation therapy (RT) with small doses per fraction in canine pelvic tumours to maintain acceptable toxicity levels. With increased accuracy/precision of RT, namely intensity‐modulated RT (IMRT), this approach might be challenged. Theoretical toxicity calculations for a new definitive‐intent moderately hypofractionated RT protocol for canine anal sac adenocarcinomas (ASAC) were performed, focussing on the risk of toxicity in pelvic organs at risk (OAR). Computed tomography datasets of 18 dogs with stage 3b ASAC were included. Re‐planning with margins for daily image‐guidance/IMRT was performed and a new protocol isoeffective to previously described definitive‐intent protocols was computed. Dose‐volume information were derived from individual plans and used for normal tissue complication probability (NTCP) computations. A 12 × 3.8 Gy protocol was computed for risk estimation. Tumour volumes ranged from 27.9 to 820.4 cm³ (mean 221.3 cm³ ± 188.9). For late rectal toxicity/bleeding ≥grade 2, median risk probability was 2.3% inter quartile range (IQR: 5.9; 95% confidence interval (CI): 1.2, 8.4) (rho = 0.436) and 3.4% (IQR: 0.96; 95%CI: 3.1, 4.0) (rho = 0.565), respectively. Median late toxicities in urinary bladder, kidneys and small bowel were <1%, except in one kidney. Myelopathy/myelonecrosis had a median risk probability of 4.1% (IQR: 23.5; 95%CI: 2.1, 25.2) (rho = 0.366) and 5.6% (IQR: 13.5; 95%CI: 3.1, 14.1) (rho = 0.363), respectively. However, graded risk showed a probability estimate for late spinal cord toxicity of ≥5% in 8/18 patients. The daily‐imaging IMRT 12 × 3.8 Gy protocol for canine ASAC seems tolerable for most cases, even in advanced disease. Theoretical dose computations serve as estimate, but are safe measures before implementing new protocols into clinical use.     

DOSIMETRIC CONSEQUENCES OF USING CONTRAST‐ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY‐MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING

Potential benefits of planning radiation therapy on a contrast‐enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity‐modulated stereotactic body radiotherapy (IM‐SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross‐sectional study. All IM‐SBRT plans were constructed on a pre‐ or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM‐SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre‐ and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM‐SBRT for tumors near “reservoirs” for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM‐SBRT treatment planning.     

USE OF A PETROLEUM-BASED BOLUS FOR PHOTON RADIATION THERAPY OF DISTAL EXTREMITIES IN DOGS

While skin sparing is an advantage of megavoltage beams, in certain clinical situations the planning target volume includes the skin surface and a skin sparing effect is not desirable. A tissue equivalent material, termed build up bolus, is used in these situations to provide adequate absorbed dose at the surface of the skin. However, an irregular patient contour can lead to air gaps between the build up bolus and the skin surface, which may result in variability in radiation dose across the target volume. The shape of the canine distal hind extremity is irregular, and commercially available bolus materials do not conform well to this region. The purpose of this study was to assess the dose homogeneity achieved using a petroleum-based bolus material, in combination with a commercially available sheet bolus, for radiation treatment of the canine tarsus. Repeated setups were performed to mimic daily treatment setups in the clinic setting, and computed tomographic scans were performed after each setup. Dose distribution achieved with a cobalt therapy machine and a 6 MV linear accelerator was assessed using three-dimensional treatment planning software. The dose to the clinical target volume fell within 95% and 107% of the prescribed dose for both treatment machines, which is considered clinically acceptable by the authors. This petroleum-based bolus is equivalent to water in its photon attenuation, conforms well to an irregular patient contour, and retains its shape after positioning. Applications to other anatomical sites could be considered.     

RADIATION EXPOSURE DURING EQUINE RADIOGRAPHY

All personnel present in the X-ray examination room during equine radiography were monitored using low energy direct reading ionization chambers (pockets dosimeters) worn outside the lead apron at neck level. The individuals' task and dosimeter readings were recorded after each examination. Average doses ranged from 0 to 6 mrad per study. The greatest exposures were associated with radiography of the shoulder and averaged less than 4 mrad. The individual extending the horse's limb was at greatest risk although the individual holding the horse's halter and the one making the X-ray exposure received similar exposures.
A survey of the overhead tube assembly used for some of the X-ray examinations also was performed. Meter readings obtained indicated an asymetric dose distribution around the tube assembly, with the highest dose occurring on the side to which the exposure cord was attached.
Although the exposures observed were within acceptable limits for occupational workers, we have altered our protocol and no longer radiograph the equine shoulder unless the horse is anesthetized. Continued use of the pocket dosimeters and maintenance of a case record of radiation exposure appears to make the technologists more aware of radiation hazards.     

Retrospective analysis of nonradiation complications in dogs undergoing radiation therapy

Dogs receiving radiation can develop complications unrelated to the radiation treatment. No study to date has described these complications in clinical patients undergoing multiple radiation therapy treatments. The purpose of this retrospective case‐control study was to characterize the incidence and type of complications that occur in these dogs. A secondary goal was to evaluate whether patient and treatment characteristics could be identified to predict the risk of these complications. Medical records of 268 dogs receiving at least one radiation treatment at a single institution, between September, 2004 and June, 2007 were reviewed. Age, breed, gender, body weight, tumor type, tumor location, number of treatments, pre‐treatment blood work abnormalities, and whether chemotherapy, glucocorticoids, or nonsteroidal anti‐inflammatory drugs were given were collected. Number, type, and severity of nonradiation complications were recorded. Complications attributed to the tumor or to the radiation were excluded. Statistical analyses were performed to determine whether demographic and clinical characteristics were associated with development of a complication. General anesthesia was used for all treatments. Complications occurred in 101 (37%) cases including diarrhea, vomiting, cough, and loss of appetite, which were typically mild. Seventeen dogs (6%) developed severe complications. Eight dogs (3%) died from their complication. Dogs that developed complications were younger, received more treatments, had leukocytosis, received glucocorticoids, and were less likely to have thrombocytopenia. On multivariate analysis, number of treatments and leukocytosis were significantly associated with complications. Findings indicate that nonradiation complications are common in dogs receiving radiotherapy under general anesthesia. In this population, complications were usually mild or self‐limiting.     

ANCILLARY EQUIPMENT TO INCREASE QUALITY AND REDUCE RADIATION EXPOSURE IN THE EQUINE NUCLEAR MEDICINE LABORATORY

The construction of ancillary equipment used to improve image quality and reduce personnel radiation exposure in the equine nuclear medicine laboratory is illustrated. The devices include a self supporting lead sheet for shielding the distal limb or limb pair, a hanging lead sheet for shielding the proximal limb, a lead square for shielding the urinary bladder or jugular catheter, a restraining board for acquiring a palmar view of the foot, a head support to stabilize the head for imaging and a head support for stabilizing the neck for imaging. The restraining board and head supports decrease patient motion, improve image quality, and decrease the number of repeat acquisitions so that the time to perform the complete study is shortened. The self supporting shielding device allows the handlers to increase their distance from the horse which enhances radiation safety.     

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999–2013)

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252–448 days). Median progression free survival was 289 days (range: 224–469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC.