VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies.

In the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse "hotel", designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the "hotel" and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use.

IRIDIUM 192 (192-Ir) HIGH DOSE RATE BRACHYTHERAPY IN A CENTRAL BEARDED DRAGON (POGONA VITTICEPS) WITH ROSTRAL SQUAMOUS CELL CARCINOMA.

A 0.5-kg, 9-yr-old, male central bearded dragon (Pogona vitticeps) presented with a proliferative mass (0.4 × 0.2 inches) on the left rostral aspect of the lower lip. Physical examination, blood work, and whole-body radiography did not reveal any other abnormalities. Histopathology confirmed squamous cell carcinoma. Considering the small size of the tumor, absence of deep tissue infiltration, and its radioresponsive characteristics, iridium 192 high dose rate brachytherapy was attempted. The dragon initially received three doses of 4 Gy/site at days 0, 7, and 17. Recurrence developed 3 mo later. Three more fractions of 6 Gy/site at days 0, 7, and 14 were delivered according to the same procedure. A second recurrence appeared after 2 mo. Surgical excision was then performed, followed by four fractions of 6 Gy/site on the surgical site at 2-wk intervals. Sixteen months posttreatment, no recurrence of the mass was observed.

Treatment of feline injection-site sarcoma with surgery and iridium-192 brachytherapy: retrospective evaluation of 22 cats.

OBJECTIVES: The aim of this retrospective descriptive study was to determine the effectiveness of using iridium implants in addition to surgery in cats with feline injection-site sarcomas (FISSs) in terms of time to progression and disease-specific survival and to identify prognostic factors for patient outcome. METHODS: Medical records of cats presented at our institution with FISS were reviewed. Inclusion criteria included histologic diagnosis of a tumor type associated with post-injection neoplastic development, tumor located at a site associated with vaccination, no other therapies prior to the administration of brachytherapy with the exception of surgery and adequate follow-up data. RESULTS: Twenty-two cats with FISS were treated with surgery and brachytherapy delivered by postoperative iridium-192 interstitial implants. Radiation doses ranged from 4000 to 6000 cGy (median dose 5079.55 cGy), with most doses delivered over 7 days. The median number of surgeries prior to brachytherapy was one (range 1-4). The complications associated with postoperative brachytherapy were typically mild, although four cats developed more severe complications. The median time to progression for all cats was 619 days and disease-specific survival time for all cats was 1242 days. The 1 and 2 year tumor-free rates in these cats were 63.6% and 40.9%, respectively. The local failure rate was 54.5% and the distant failure rate was 13.6% due to lung metastasis. There was a significant difference in time to progression of cats that had a single surgery performed prior to brachytherapy and those that had multiple surgeries (undefined vs 310 days; P = 0.01). There were no other statistically significant identified prognostic factors. CONCLUSIONS AND RELEVANCE: These data suggest that the addition of brachytherapy postoperatively in cats with FISS was well tolerated and is comparable to other forms of adjuvant therapy.

Behavioural and cardiovascular effects of medetomidine constant rate infusion compared with detomidine for standing sedation in horses.

OBJECTIVE: To compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy. STUDY DESIGN: Randomized, controlled, crossover, blinded clinical trial. ANIMALS: A total of 50 horses with owner consent, excluding stallions. METHODS: Each horse was sedated with intravenous acepromazine (0.02 mg kg-1), followed by an α2-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg-1) 5 minutes later. A CRI of the same α2-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 µg kg-1; CRI, 6 µg kg-1 hour-1) or medetomidine (bolus dose, 5 µg kg-1; CRI, 3.5 µg kg-1 hour-1). If sedation was inadequate, a quarter of the initial bolus of the α2-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance. RESULTS: Total treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.

Prognostic factors for cats with squamous cell carcinoma of the nasal planum following high-dose rate brachytherapy.

OBJECTIVES: The aim of the study was to investigate retrospectively the prognostic impact of variables such as sex, neuter status, breed, age, number of lesions, location and size of the tumour, tumour extension beyond the nasal planum, ulceration and lymph node status, among others, in a population of cats treated with high-dose rate brachytherapy. METHODS: This study reviews the outcome of 58 cats with cytologically and/or histologically confirmed squamous cell carcinoma of the nasal planum, treated at the Clinic Alliance (Bordeaux, France) with high-dose rate brachytherapy from 2010-2016. The total radiation dose delivered was 30 Gy, administered in two different schedules: five fractions of 6 Gy for a period of 4 days (Tuesday-Friday) or four fractions of 7.5 Gy for a period of 3 days (Tuesday- Thursday). Data were collected from cats' clinical records. RESULTS: Complete response was achieved in 72% (n = 36) of the cats, partial response in 24% (n = 13) and 2% (n = 1) did not respond. Median progression-free survival and overall survival times were 316 and 835 days, respectively. CONCLUSIONS AND RELEVANCE: Results indicated that sex (P = 0.045), extension of the tumour from the nasal planum to the upper lip (P = 0.015), tumour size (P = 0.015; P = 0.001), the existence of a previous treatment (P = 0.043) and the tumour response to high-dose rate brachytherapy (P = 0.038; P <0.001) are prognostic factors for cats with squamous cell carcinoma of the nasal planum following high-dose rate brachytherapy.

Intratumoral injection of radioactive holmium ( 166 Ho) microspheres for treatment of oral squamous cell carcinoma in cats.

BACKGROUND & AIMS: A "microbrachytherapy" was developed as treatment option for inoperable tumours by direct intratumoral injection of radioactive holmium-166 ( 166 Ho) microspheres (MS). 166 Ho emits ß-radiation which potentially enables a high, ablative, radioactive-absorbed dose on the tumour tissue while sparing surrounding tissues. MATERIALS & METHODS: Safety and efficacy of 166 Ho microbrachytherapy were evaluated in a prospective cohort study of 13 cats with inoperable oral squamous cell carcinoma without evidence of distant metastasis. RESULTS: Local response rate was 55%, including complete response or partial response (downstaging) enabling subsequent marginal resection. Median survival time was 113 days overall, and 296 days for patients with local response. Side effects were minimal. Tumour volume was a significant predictor of response. DISCUSSION: Response rate may be further improved by optimizing the intratumoral spatial distribution of 166 Ho MS. CONCLUSION: 166 Ho microbrachytherapy has potential as a minimally invasive, single procedure radio-ablation treatment of unresectable tumours with minimal morbidity.

Use of an electronic brachytherapy surface applicator to treat an epiglottal fibrosarcoma in a dog.

Presented is the case of an epiglottal fibrosarcoma in a dog. The location of the mass resulted in challenges in the delivery of adequate dose to the tumor, and herein we describe the treatment using an electronic brachytherapy source. The treatment consisted of four Gy fractions, twice daily for a total of 10 fractions (40 Gy total). Visual reevaluation two weeks after treatment supported adequate spatial dose delivery, and the patient was reportedly improved six weeks after treatment. We demonstrate that plesiotherapy using an electronic brachytherapy device is feasible and may be useful in the treatment of carefully selected veterinary tumors.

Design and characterization of an economical (192)Ir hemi-brain small animal irradiator.

PURPOSE: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. MATERIALS AND METHODS: A high dose rate (HDR) (192)Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements. RESULTS: The tungsten collimator provided a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. CONCLUSIONS: Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients.

Use of Ir192 interstitial brachytherapy for an equine malignant dermal schwannoma.

A 10-year-old Hanoverian mare was evaluated for a right buccal swelling that recurred 3 months following surgical resection. Ultrasonographic examination showed a broadly pedunculated subcutaneous mass at the level of 106-109 and 406-409 cheek teeth associated with an erosive mucosal lesion on the inside of the cheek. Histological examination of a biopsy specimen revealed a well-demarcated, malignant, dermal schwannoma. Following subcutaneous placement of platinum coated Ir192 wires under general anaesthesia, low-dose radiation of 5 gray per day was delivered for 14 days. Short-term complications included loss of patency of the right nasolacrimal duct, erythema, dermatitis, leukotrichia and left-sided deviation of the muzzle. Ten months later, there has been no tumour recurrence. Findings suggest that the use of interstitial brachytherapy should be considered for a malignant, dermal schwannoma that has recurred or is not amenable to surgery.

Combined keratectomy, strontium-90 irradiation and permanent bulbar conjunctival grafts for corneolimbal squamous cell carcinomas in horses (1990-2002): 38 horses.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of postoperative beta-irradiation with strontium-90 as an adjunctive treatment to superficial keratectomy and permanent bulbar conjunctival graft for removal of equine corneolimbal squamous cell carcinoma (SCC), in decreasing recurrence rate. STUDY: The retrospective case study included 38 horses diagnosed and treated for SCC of the eye that involved the limbus and/or cornea. The patients were treated between 1990 and 2002, with strontium-90 irradiation immediately after corneal and conjunctival graft surgery. Recurrence was defined as the postoperative and postirradiation regrowth of SCC in the same site and globe that was previously treated. RESULTS: The Appaloosa was the most commonly represented breed and horses that had more than one base coat color represented the majority of the cases (53%). The coat colors of white, chestnut/sorrel and gray were the most commonly represented colors of the horses treated. Eight horses (21%) could not be assessed for tumor recurrence due to lack of two or more post-treatment examinations, and another horse was enucleated 6 days postoperatively due to progressive corneal ulceration. Twenty-four horses (63% of the entire study population; 83% of the followed cases) had a mean +/- SD of 1754 +/- 1319 days without tumor recurrence, ranging from 14 days to 5110 days. Five horses (13% of the entire study population; 17% of the assessed horses) had tumor recurrence at a mean +/- SD of 449 +/- 339 days with a range of 29 days to 900 days. For the five recurrences, treatment included local excision (n = 1), enucleation (n = 2), and additional strontium-90 therapy (n = 3). CONCLUSIONS: The combination of superficial keratectomy, beta-irradiation and permanent bulbar conjunctival grafts for limbal, corneal or corneolimbal SCC in horses is effective in at least 83% of the horses. Recurrence occurred in about 17% of the horses. Multiple biannual re-examinations are recommended to observe for tumor recurrence.

Treatment of periocular and non-ocular sarcoids in 18 horses by interstitial brachytherapy with iridium-192.

Treatment of the equine sarcoid has posed a significant challenge to clinicians for years and many different methods have been tried with varying success, including ionising radiation. The aim of this study was to review the efficacy of iridium-192 interstitial brachytherapy for the treatment of eight periocular sarcoids and 15 non-ocular sarcoids on 18 horses. All the periocular sarcoids and 13 of the 15 non-ocular sarcoids were treated successfully.

Iridium-192 interstitial brachytherapy as adjunctive treatment for canine cutaneous mast cell tumors.

Eleven dogs with cutaneous mast cell tumors (MCTs) were treated with surgery and iridium-192 ((192)Ir) interstitial brachytherapy. Minimum tumor doses ranged from 47.2 to 63.3 Gy. Treated tumors were classified as grade II (n=7) or III (n=4). Five dogs had recurrences with a median progression-free interval of 1391 days, and six dogs had no recurrence at a median follow-up time of 942 days. Acute adverse effects were well tolerated, and late effects were mild. One dog developed a second tumor of a different cell type in the radiation treatment field.

Radioactive gold-198 seeds for the treatment of squamous cell carcinoma in the eyelid of a cat.

A 19-year-old, speyed, domestic short-hair cat was presented with an eyelid tumour of 3 months duration. Ophthalmic examination revealed a large, raised, ulcerated and bleeding mass affecting the left lower eyelid. The mass was 12 mm x 10 mm in size, extended to the medial canthus and had eroded 10 mm of eyelid margin. Mandibular lymph nodes were not palpably enlarged. A diagnosis of squamous cell carcinoma was confirmed by histologic examination. Due to involvement of more than half the lower eyelid, it was decided that treatment with radioactive gold-198 seeds was appropriate. Nine radioactive gold-198 seeds were implanted, delivering a minimum tumour dose of 65 Gy. Three weeks postoperatively the mass had resolved, with only a small scab remaining. After a further 3 weeks, there was no evidence of the eyelid tumour. Although approximately 7 mm of eyelid margin was absent, this did not cause any clinical signs other than mild conjunctivitis. There was no evidence of the tumour 10 months postoperatively, when the cat was euthanased for unrelated disease.

Radiation therapy in the horse.

This article covers the principles and applications of radiation therapy in horses. The goal in treating tumors by irradiation is tumor control with minimum treatment complications. Various treatment techniques are available to achieve this goal. The prognosis depends on many factors such as the extent and location of the tumor, tumor type and tumor cell proliferation. Radiation therapy is a very effective treatment modality for equine tumors but logistical reasons limit its impact in equine oncology.

Interstitial implant brachytherapy in small animals.

This article presents highlights of the physics, implantation technique, and clinical application of iridium-192 interstitial implant brachytherapy. Some of the physical differences between iridium-192 brachytherapy and cobalt-60 teletherapy are compared.

Iridium-192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses.

One hundred and fifteen horses with periocular tumours were treated with iridium-192 interstitial brachytherapy. Tumours included squamous cell carcinomas (n = 52) and sarcoids (n = 63). All horses were scheduled to receive 60 Gy (minimal tumour dose) given at a low dose rate (0.034 +/- 0.010 Gy/h). The mean and median follow-up times to last contact or death were 24 and 16 months, respectively. Chronic radiation reactions included palpebral fibrosis (10.4%), cataract (7.8%), keratitis and corneal ulceration (6.9%). Cosmetic changes included permanent epilation (21.7%) and hair dyspigmentation (78.3%). The one year progression-free survival (PFS) rates for sarcoids and carcinomas were 86.6% and 81.8% and the 5 year PFS rates were 74.0% and 63.5%, respectively. The horse age and sex, histopathological type, anatomical subsite and classification (WHO T1-3) were included in the analysis of prognostic factors. The only significant prognostic factor that independently affected PFS time was the WHO T-classification (P = 0.009, relative risk = 0.85). When compared to horses with T1 lesions, horses with T2 and T3 lesions had 1.8-fold and 3.4-fold increased risks, respectively, for tumour recurrence (relative excess risk). The one year PFS rates for T1, T2 and T3 lesions were 95.2%, 89.5% and 66.2%, respectively. The 5 year PFS rates were 72.2%, 74.0% and 53.1%, respectively. The results of this study indicate that irradiation is an effective treatment option for horses with T1-2 lesions and should be part of a combined treatment modality for horses with T3 lesions.

192iridium brachytherapy, using an intracavitary afterload device, for treatment of intranasal neoplasms in dogs.

After surgical removal of a primary intranasal neoplasm, an implant device, designed to deliver 192iridium (192Ir) brachytherapy, was positioned in the nasal cavity of 8 dogs. Ribbons containing 192Ir seeds were placed in the device, using an afterloading technique. Dosimetry, to a dose of 7,000 to 10,000 centiGray (cGy), was calculated to encompass the site previously occupied by the tumor and a 1-cm margin of surrounding normal tissue. The quantity of 192Ir implanted varied between 16.69 and 100.80 mg of radium equivalent. The duration of implantation ranged from 90 to 168 hours. All dogs tolerated the implant well, but had a mucoid nasal discharge after radiotherapy. The implant device allowed rapid application and removal of the radioactive ribbons. Mean (+/- SD) radiation exposure to each radiotherapist during seed loading and unloading was 14.4 (+/- 5.3) and 4.5 (+/- 0.9) mrem, respectively. A uniform dose distribution around the intranasal implant device was achieved; however, dogs that received doses in excess of 9,400 cGy at the dorsolateral surface of the nose and/or hard palate had bone and soft tissue necrosis between 70 and 120 days after treatment. One dog was euthanatized 50 days after treatment because of metastatic disease, and 2 dogs were euthanatized because of local tumor recurrence at 125 and 212 days. Death, considered unrelated to treatment, occurred in 1 dog that was euthanatized 27 days after treatment and in 3 dogs that died 30, 93, and 456 days after treatment. Necropsy was performed on 3 of these dogs and evidence of intranasal neoplasia was not observed. One dog remained disease-free at 587 days after treatment.