Definitive-intent uniform megavoltage fractioned radiotherapy protocol for presumed canine intracranial gliomas: retrospective analysis of survival and prognostic factors in 38 cases (2013-2019).

BACKGROUND: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT's impact on the dogs' clinical signs and Qol were evaluated by the owners. RESULTS: The disease-specific MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2 ± 7.4% and 49.0 ± 9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed. CONCLUSIONS: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life's quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.

Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5-5.5 months (45-165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty-one cats with histologically confirmed oral SCC and T1-3N0M0 were treated with 10 once-daily fractions (Monday-Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow-up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression-free survival (PFS) was 105 days (1 year PFS of 23%), median local progression-free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.

The use of megavoltage radiation therapy in the treatment of thymomas in rabbits: 19 cases.

An overall median survival time (MST) and prognostic factors in rabbits with thymomas treated with megavoltage radiation therapy (RT) were determined in this multi-institutional retrospective case analysis. Medical records for 19 rabbits with suspected or confirmed thymomas treated with RT were evaluated for data including signalment, haematological and serum biochemistry abnormalities, presence of pleural effusion, radiation plan, body weight, total radiation dose and institution administering RT. Statistical significance of these factors related to overall survival was assessed. An overall MST for all 19 rabbits was 313 days; exclusion of 3 rabbits that died acutely during the first 14 days of RT yielded a MST of 727 days. The only factor associated with a significantly decreased survival time was having a body weight lower than mean body weight of 1.57 kg. Radiation treatment-associated complications were infrequent and included radiation-induced myocardial failure, radiation pneumonitis and alopecia.

The electron beam attenuating properties of SuperFlab, Play-Doh, and wet gauze, compared to plastic water.

Bolus material is used commonly with electron treatments. The purpose of this study was to compare the electron beam attenuating properties of SuperFlab, Play-Doh, and wet gauze to that of plastic water, and evaluate their characteristics as bolus materials for electron beam therapy. Electron beams of 5, 6, 7, 8, 10, and 12 MeV were used. Dose reduction from a range of bolus thicknesses from 2 mm to a thickness well beyond the thickness required to reach peak ioization was measured for each of the bolus materials to establish independent isodose curves. Measurements performed at the known water Dmax for all bolus materials indicated similar results for SuperFlab and plastic water with less than 3% difference for most energies. Play-Doh resulted in more attenuation or less dose buildup compared with plastic water, especially at lower energies. The difference was as high as 24.7% for the beam energy of 5 MeV for Play-Doh. Evaluation of the dose build up curves for all materials indicated the peak dose build up for wet gauze and Play-Doh occurred at lesser thicknesses compared to plastic water and SuperFlab, particularly at lower energies. If Play-Doh and wet gauze are to be used for electron bolus materials, dose build up curves should be established for the machine being used and the appropriate thickness of bolus material be chosen based on those curves.

Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E2, thromboxane B2, leukotriene B4, and 11-dehydro thromboxane B2), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P < .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy.

Total skin electron therapy technique for the canine patient.

Cutaneous epitheliotropic T-cell lymphoma in canine patients is a radiation sensitive tumor but total skin electron therapy is used only rarely. Our purpose was to evaluate dose distribution from a total skin electron therapy technique using 6MeV electron beams. The treatment was comprised of 12 fields, with the dog in lateral recumbency in a stride position at an extended distance from the source. Uniformity, flatness and symmetry were determined for each beam. The composite percent depth dose profile for all beams was measured in solid water phantoms and skin dose was determined on a canine cadaver using thermoluminescent dosimeters. The resulting d(max) of the composite beams was 1mm and dose variation over the skin was 6.8%, with the extremities having the most uneven dose distribution. Dimensions of the fields were adequate to obtain an effective treatment profile for the entire thickness of canine epidermis and the technique was feasible for clinical application. Individual tailoring of the protocol to deal with hot and cold spots may be necessary and set up will likely involve a significant time commitment for the therapy team.

Effect of wetness level on the suitability of wet gauze as a substitute for Superflab as a bolus material for use with 6 mv photons.

Despite the availability of commercial tissue equivalent bolus material, wet gauze has an application in radiation therapy to provide superior conformance to irregular contours. Wet gauze bolus has the potential to reduce air gaps between the bolus and surface, which could decrease surface dose if sufficiently large to disrupt electronic equilibrium. Wet gauze bolus is often fabricated and wetness judged qualitatively. We assessed the effect of specific gauze wetness levels, quantified in terms of physical density, at various field sizes with respect to their effectiveness as bolus material compared with Superflab. For large fields, > 7 x 7 cm2 in this study, wet gauze sponges with a physical density of 1.02 g/cm3 performed essentially identical to Superflab; at a smaller field size the wet gauze was slightly less effective, likely due to the heterogeneity of the gauze-water matrix. Gauze that was wetter, with a physical density of 1.2 g/cm3, or less wet, with a physical density of 0.75 g/cm3 was not as effective either due to enhanced photon absorption in the wetter sponges, or less effective establishment of electronic equilibrium in the less wet sponges. The presence of an air gap under Superflab led to reduced surface dose, especially for small fields and large air gaps. Thus, if Superflab use leads to poor contact with the skin, wet gauze having a physical density of 1.02 g/cm3 can be used as a substitute. Judging the water content of wet gauze subjectively is not acceptable as over- or under wetness can lead to decreased effectiveness of the bolus material.

Radiation therapy communication: equine hemangioma.

A 13-month-old Standardbred Colt had a recurrent hemangioma at the level of the coronary band. Multiple excisions had led to a nonhealing skin and hoof defect. Using 14 MV electrons, a total dose of 36 Gy was administered, given as six fractions of 6 Gy twice a week. Wound healing by second intention was achieved over the next 4 months and the colt began race training 6 months after the end of therapy. Twenty months later the colt is sound and there is no evidence of tumor recurrence.

Impact of tissue inhomogeneity on dose distribution in the canine carpal and tarsal regions for cobalt and 6 MV photons.

We quantified the effect of tissue inhomogeneity on dose distribution in a canine distal extremity resulting from treatment with cobalt photons and photons from a 6MV accelerator. Monitor units for a typical distal extremity treatment were calculated by two methods, using equally weighted, parallel-opposed fields. The first method was a computed tomography (CT)-based, computerized treatment plan, calculated without inhomogeneity correction. The second method was a manual point dose calculation to the isocenter. A computerized planning system was then used to assess the dose distribution achieved by these two methods when tissue inhomogeneity was taken into account. For cobalt photons, the median percentage of the planning target volume (PTV) that received < 95% of the prescribed dose was 4.5% for the CT-based treatment plan, and 26.2% for the manually calculated plan. For 6 MV photons, the median percentage of the PTV that received < 95% of the prescribed dose was < 1% for both planning methods. The PTV dose achieved without using inhomogeneity correction for cobalt photons results in potentially significant under dosing of portions of the PTV.

Tolerance doses of cutaneous and mucosal tissues in ring-necked parakeets (Psittacula krameri) for external beam megavoltage radiation.

Currently used dosages for external-beam megavoltage radiation therapy in birds have been extrapolated from mammalian patients and often appear to provide inadequate doses of radiation for effective tumor control. To determine the tolerance doses of cutaneous and mucosal tissues of normal birds in order to provide more effective radiation treatment for tumors that have been shown to be radiation responsive in other species, ingluvial mucosa and the skin over the ingluvies of 9 ring-necked parakeets (Psittacula krameri) were irradiated in 4-Gy fractions to a total dose of either 48, 60, or 72 Gy using an isocentric cobalt-60 teletherapy unit. Minimal radiation-induced epidermal changes were present in the high-dose group histologically. Neither dose-related acute nor chronic radiation effects could be detected in any group grossly in cutaneous or mucosal tissue over a 9-month period. Radiation doses of 72 Gy in 4-Gy fractions were well tolerated in the small number of ring-necked parakeets in this initial tolerance dose study.

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 clinicaltarget 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.

Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs.

BACKGROUND: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy. HYPOTHESIS: Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs. ANIMALS: Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses. METHODS: Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome. RESULTS: Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.

Ki67 reactivity in nasal and periocular squamous cell carcinomas in cats treated with electron beam radiation therapy.

Squamous cell carcinomas of sparsely haired skin are relatively common tumors in cats, and these tumors likely exhibit a rapid growth rate. Thus, we evaluated response and duration of response in relation to the Ki67 proliferative reactivity in such tumors. Seventeen cats with confirmed squamous cell carcinomas and treated with an accelerated, hypofractionated electron beam radiation protocol were included in the study. For all of them histologic grading, Ki67 reactivity, response, and disease-free interval (DFI) were evaluated. Response to therapy was excellent (94% complete response rate) with a median DFI of 414 days. Only moderate acute and few long-term adverse effects were seen. Cats with tumors with a low Ki67 reactivity had markedly shorter DFIs than cats with tumors with high Ki67 reactivity. We concluded that an accelerated, hypofractionated electron beam radiation therapy protocol is well suited for feline squamous cell carcinomas. The protocol appears especially efficacious in tumors with a high Ki67 reactivity.

Prognostic factors and patterns of treatment failure in dogs with unresectable differentiated thyroid carcinomas treated with megavoltage irradiation.

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with unresectable thyroid carcinomas treated with definitive megavoltage irradiation and analyze prognostic factors of PFS and patterns of failure (local recurrence vs metastasis). DESIGN: Prospective clinical trial. ANIMALS: 25 dogs with locally advanced thyroid carcinomas and no evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy during 4 weeks on an alternate-day schedule of 4 Gy/fraction. RESULTS: Irradiation was safe and effective for treatment of large unresectable thyroid carcinomas. Progression-free survival rates were 80% at 1 year and 72% at 3 years. Time to maximum tumor size reduction ranged from 8 to 22 months. Factors affecting PFS were not found. Twenty-eight percent (7/25) of dogs developed metastasis. Dogs with bilateral tumors had 16 times the risk of developing metastases, compared with dogs with a single tumor. Dogs with no evidence of tumor progression had 15 times less risk of developing metastases. Radiation-induced hypothyroidism was suspected in 2 dogs 13 and 29 months after irradiation. CONCLUSIONS AND CLINICAL RELEVANCE: Irradiation is effective for local control of thyroid tumors, despite their slow regression rate. Results provided evidence that local tumor control affects metastatic outcome in dogs with thyroid carcinomas and is a strong basis for the development of new approaches that include irradiation in the management of dogs with advanced thyroid carcinomas. Improvements in local tumor control alone may be insufficient to improve survival times because of the high risk of metastatic spread before an initial diagnosis is made, which warrants initiation of early systemic treatment.

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs.

OBJECTIVE: To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. DESIGN: Prospective clinical trial. ANIMALS: 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. PROCEDURE: Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. RESULTS: A significant correlation was found between relative tumor size (i.e., size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary-dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. CLINICAL IMPLICATIONS: Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used.

Radiation therapy for incompletely resected canine mast cell tumors.

The records of 56 dogs treated with megavoltage radiation for mast cell neoplasia were reviewed to determine the efficacy of this treatment modality. Total radiation dose ranged from 45 to 57 Gray (Gy), dose per fraction ranged from 3.0 to 4.0 Gy, and radiation treatment time ranged from 14-28 days. Median disease free interval (95% CI) was 32.7 (19-70) months. Median disease free interval for dogs older than 7.5 years was 15 (lower limit 7) months as compared to 62 (lower limit 20) for dogs younger than 7.5 years of age (p = 0.006). Median disease free interval for dogs with measurable disease was 12 (lower limit 5) months as compared to 54 (32-70) months for dogs with microscopic disease (p = 0.006). Radiation treatment time was also significantly related to disease free interval. Median disease free interval for dogs treated longer than 22 days was 12 (7-19) months as compared to greater than 50 (lower limit 20) months for dogs treated in 22 or fewer days (p < 0.001). This appeared to be due to more recurrences in dogs treated with 3-per-week fractionation and suggests that tumor proliferation in the interfraction interval may be important. Sex, tumor location, histologic grade, WHO clinical stage, number of radiation fractions, total radiation dose, and dose-per-fraction, as well as the following "yes/no" variables: steroids given, surgery prior to radiation, lymph nodes irradiated, and development of another mast cell tumor did not appear to influence median disease free interval or survival. Data presented herein support megavoltage radiation as an effective treatment for canine mast cell neoplasia, and suggest that disease free interval in dogs treated with daily fractions may be longer than that achieved with alternating day fractions.

Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation.

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival. DESIGN: Prospective clinical trial. ANIMALS: 105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed. RESULTS: Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy.

Analysis of prognostic factors and patterns of failure in dogs with periodontal tumors treated with megavoltage irradiation.

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with periodontal tumors after definitive megavoltage irradiation and to analyze prognostic factors for PFS time and patterns of treatment failure. DESIGN: Prospective clinical trial. ANIMALS: 47 dogs with acanthomatous, fibromatous, or ossifying epulis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's proportional hazards regression model to determine prognostic factors for PFS time. RESULTS: The only independent prognostic factor for PFS time was tumor T stage. Pattern of local tumor recurrence (marginal vs infield regrowth) was independent of clinical stage, tumor location, and site. In 4% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 6.4% of the dogs, chronic radiation reactions included bone necrosis. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of small (T1 and T2 stage) periodontal tumors. The usefulness of the radiation protocol in this study is limited in dogs with large (T3) tumors, particularly those located in the caudal half of the oral cavity, because of poor results and high risk of acute radiation toxicoses.

Response of 145 spontaneous canine head and neck tumours to radiation versus radiation plus microwave hyperthermia: results of a randomized phase III clinical study.

The results of a phase III, clinical trial of local microwave hyperthermia (target = 2 x 44 degrees C for 30 min) and megavoltage radiation (4 x 9 Gy fractions) in the treatment of 145 naturally occurring canine head and neck cancers are reported. Patients were re-examined at regular intervals following treatment until death. The median follow up time was 90 weeks. Tumour response, patient survival and normal tissue toxicity were analysed by treatment allocation. There was no significant difference in best tumour response nor patient survival between the two treatment groups. There was no difference in acute normal tissue toxicity but there was a suggestion that patients receiving RT and HT may suffer a higher incidence of late skin reactions. Histological type and tumour volume were of prognostic significance with smaller tumours and carcinomas showing higher response rates. There were also positive associations between minimum tumour dose and best tumour response and percentage of tumour heated and best tumour response. The results of this study must be interpreted in the knowledge of limitations on the dose and fractionation schedule for radiation therapy, the small number of hyperthermia treatments applied and the variation in tumour type and size that is inevitable in a clinical study. It is concluded that the quality of hyperthermia in terms of intra-tumour temperatures and the uniformity of heating is of paramount importance in governing response to adjuvant hyperthermia.