Post‐radiotherapy hypothyroidism in dogs treated for thyroid carcinomas

Hypothyroidism is a common adverse event after head and neck radiotherapy in human medicine, but uncommonly reported in canine patients. Records of 21 dogs with histologically or cytologically confirmed thyroid carcinoma receiving definitive or hypofractionated radiotherapy were reviewed. Nine cases received 48 Gy in 12 fractions, 10 received 36 Gy in 4 fractions and 2 received 32 Gy in 4 fractions. Seventeen cases had radiotherapy in a post‐operative setting. Ten cases developed hypothyroidism (47.6%) after radiotherapy. The development of hypothyroidism was not associated with the radiotherapy protocol used. Median time to diagnosis of hypothyroidism was 6 months (range, 1–13 months). Hypothyroidism is a common side effect following radiotherapy for thyroid carcinomas. Monitoring of thyroid function following radiotherapy is recommended. No specific risk factors have been identified.     

Evaluation of an enzymatic immunoassay for free thyroxine determination in canine serum

Free thyroxine (FT4) and cholesterol were measured in 400 dogs with either suspected hypothyroidism or dermatological signs such that hypothyroidism needed to be ruled out. Hypothyroidism was diagnosed in 68 dogs from the history, physical examination and stated lower reference limit (<7 pmol/L) for FT4 in euthryoid dogs. Dogs with FT4 concentrations in the range 6–9 pmol/L were finally categorized as hypo- or euthyroid either on the basis of retesting after 2 months or on their clinical response to thyroid replacement therapy over at least 2 months.The enzyme immunoassay evaluated in this paper is considered to be of clinical value and offers many advantages compared with radioimmunoassays.Abbreviations FT4 free thyroxine fraction - MEIA microparticle enzyme immunoassay - RIA radioimmunoassays - T4 thyroxine - TBG thyroxine-binding globulin     

DEFINITIVE RADIATION THERAPY FOR INFILTRATIVE THYROID CARCINOMA IN DOGS

The medical records of eight dogs with histopathologically confirmed infiltrative thyroid carcinoma treated with external beam radiation were reviewed and a retrospective analysis of survival and local tumor control were performed. The dogs received a definitive radiotherapy protocol of 46.8-48 Gray. All dogs had a reduction in tumor size to a clinically undetectable level on follow up examinations. Kaplan-Meier analysis indicated a median survival time of 24.5 months. Pulmonary metastasis was detected in three dogs and one of these dogs had concurrent bone metastasis. One dog had bone metastasis alone. Two dogs were alive at the censor. This study suggests that fractionated, definitive radiation therapy using multiple, moderate doses of radiation is an effective treatment for local control of invasive thyroid carcinoma in dogs.     

Investigation of thyroid function in dogs treated with the tyrosine kinase inhibitor toceranib

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty‐four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow‐up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop‐out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.     

RESULTS OF IRRADIATION OF INFILTRATIVE LIPOMA IN 13 DOGS

Thirteen dogs with infiltrative lipomas were treated with cobalt 60 radiation. Four of the thirteen dogs also received either whole body (n = 2) or combination local/whole body (n = 2) hyperthermia in conjunction with radiation therapy. Cytoreductive surgery was performed prior to radiation in 10 dogs, although only 3 dogs had microscopic disease at the time of radiation therapy. Dogs received a total dose of 45.6 Gy-63 Gy in 2.5-4 Gy/fraction on either a Monday/Wednesday/Friday schedule or on a daily Monday through Friday schedule. Twelve of the 13 dogs had computed tomography (CT) images acquired prior to irradiation. Survival time was determined from the time of completion of radiation therapy. Survival ranged from 6 months to 94 months, with a median (95% confidence interval) of 40 (18.5-77) months and a mean of 46.4 months. Only one dog was euthanized due to persistent signs related to the infiltrative lipoma at 6 months after the end of radiation therapy. There was no apparent difference in response based on whether or not the dogs received hyperthermia in conjunction with irradiation, although the numbers were too small to make any significant conclusions. It appears that dogs with infiltrative lipomas can benefit from external beam irradiation alone or in combination with surgery to effect long-term local tumor control.     

LATE COMPLICATIONS OF PELVIC IRRADIATION IN 16 DOGS

When external beam radiation therapy is administered to the pelvis, normal tissues irradiated may include the colon, small intestine, urethra, bladder, bone, and spinal cord. The objectives of this retrospective study were to determine the incidence and severity of late radiation effects following pelvic irradiation in dogs and to identify factors that increase the risk of these effects. Medical records of all dogs treated with curative intent external beam radiation therapy to the pelvic region between 1993 and 1999 were reviewed. Patients with follow-up longer than 9 months or any patient that developed late complications earlier than 9 months were evaluated. Sixteen dogs met criteria for inclusion in this study. All dogs were treated with a 6-MV linear accelerator with bilaterally opposed beams. Diseases treated included transitional cell carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used: 49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was the major late effect following pelvic irradiation, occurring in nine dogs (56%). Colitis was characterized as mild in three dogs, moderate in one dog, and severe in five dogs. Three of the dogs with severe effects suffered gastrointestinal perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction, and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be administered to the pelvic region with a minimal risk of late effects to the colon by giving smaller doses per fraction and avoiding systemic radiation potentiators.     

Radiation therapy for long-term control of odontogenic tumours and epulis in three cats.

Orthovoltage radiation was used to treat odontogenic tumours in three cats following incomplete surgical resection. Cats received a total radiation dose of 48-52 Gy over a period of 26-29 days. Acute toxicities were mild, consisting of hair loss within the radiation field in all cats, and mild mucositis in one cat. All cats had long-term (>35 months) control of their tumour, and two cats are still alive without recurrence of tumour 60 and 39 months, respectively, after completing treatment. Radiation therapy should be considered to be an adjuvant to incomplete surgery in cats with odontogenic neoplasms or epulides.     

Half-Body Radiotherapy

Eight healthy mongrel dogs were treated with half-body irradiation (HBI) in a pilot study to evaluate the technique and radiotolerance of different organs. Cranial and caudal half-body fields were established using the 13th thoracic vertebra as the dividing point. Under general anesthesia, either 7 or 8 Gray (Gy) were delivered to one half of the body using opposing radiation portals. The other half of the body was similarly treated 28 days later. The dogs were monitored for 12 months. Significant radiation effects included transient bone marrow suppression and radiation sickness. There were no serious or life-threatening problems, but the 8 Gy group consistently showed more severe clinical signs and histologic changes than the 7 Gy group. Total body irradiation in two fractions of 7 or 8 Gy given 1 month apart appears to be a safe treatment that can be developed for therapy in veterinary oncology.     

Computed tomographic features of the normal canine thyroid gland.

The computed tomographic (CT) features of the normal thyroid gland were compiled from images acquired in 25 client-owned dogs without thyroid gland disease. The mean pre- and postcontrast attenuation values were 107.5 and 169.0 Hounsfield Units, respectively. After injection of intravenous contrast medium (600 mg iodine/kg), the apparent thyroid gland volume (both lobes combined) increased from a mean value of 1148.0 nm3 to a mean value of 1188.9 mm3. All thyroid lobes were homogeneous on pre- and postcontrast images. In a craniocaudal direction, the gland spanned a region from the 1st to the 8th tracheal ring and the right lobe was often more cranial than the left. On transverse images the lobe shape was ovoid in 72%, and its location was dorsolateral to the trachea in 90% of dogs. Parathyroid glands could not be identified and an isthmus connecting both thyroid lobes was only seen in one dog. Considering the excellent visibility of the normal canine thyroid gland, CT can be beneficial in the differentiation of thyroidal versus nonthyroidal neck masses. CT also yields potential in the staging of thyroid carcinomas.     

RESPONSE OF NINETEEN CATS WITH NASAL LYMPHOMA TO RADIATION THERAPY AND CHEMOTHERAPY

The records of 19 cats treated for stage I nasal lymphoma with radiation therapy and chemotherapy were reviewed to determine response to therapy, treatment outcome and possible prognostic indicators. All cats were treated with megavoltage radiation therapy to a total dose ranging from 22 to 48 Gy (median dose = 42 Gy). All cats were prescribed at least 6 months of multiagent chemotherapy. The median progression-free interval for all cats was 945 days (31 months). Two cats did not achieve clinical remission. Of 17 cats evaluable for relapse, 10 (58.8%) were progression free during the entire follow-up period. Four cats (23.5%) suffered local recurrence, while three (17.6%) experienced distant relapse. The median survival time was 955 days (31.4 months). The only variable found to have a significant negative impact on survival was destruction of the cribriform plate before therapy (P= 0.002). The long progression free and survival times reported here indicate that cats with stage I nasal lymphoma treated with aggressive local and systemic therapy can have a favorable outcome when compared with other anatomic forms of lymphoma. Despite strong clinical responses to the multimodality therapy used, the fact that three (17.6%) cats relapsed distantly supports the recommendation that treatment with radiation therapy alone is insufficient until further prospective studies can be performed.     

A BOOST TECHNIQUE FOR IRRADIATION OF MALIGNANT CANINE NASAL TUMORS

Eighteen dogs with malignant nasal cavity tumors were treated with radiation therapy, including a boost technique. Three 3:0 Gy boost doses were added to a treatment protocol consisting of sixteen 3.0 Gy daily fractions, bringing the total dose to 57 Gy. This boost technique was implemented without an associated increase in overall treatment time by giving the boost doses on a twice-a-day basis. Boost doses were given during the first half of the radiation therapy period. The treatment was completed as planned in 16 of the 18 dogs; two dogs received lower doses (51 and 54 Gy). Median survival was 177 days, poorer than in some other reported studies of nasal tumor irradiation. Acute effects were unacceptable, with 11 of the 18 dogs developing severe mucositis, desquamation, edema, swelling, and pruritus. The extensive nature of the acute reactions compromised assessment of the effect of the increased radiation dose on the tumor. Although there is justification for assessing more aggressive radiation protocols in canine nasal tumor patients, total doses approximating 60 Gy can not be given as described because of the inability of acutely responding normal tissues to compensate.     

A RETROSPECTIVE ANALYSIS OF 140 DOGS WITH ORAL MELANOMA TREATED WITH EXTERNAL BEAM RADIATION

Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy x 4 fractions; 30 Gy, 10 Gy x 3 fractions; or >45 Gy, 2-4 Gy x 12-19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4-6 months) and the median survival was 7.0 months (95% C.I., 6-9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p < .001, p < .001, and p = .04, respectively) and survival (p < .001, p < .001, and p = .05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.     

Efficacy of stereotactic radiation therapy for the treatment of confirmed or presumed canine glioma

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non-modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy-confirmed glioma or a presumptive diagnosis of intra-cranial glioma based on MRI characteristics that were treated with SRT. Twenty-three client-owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty-one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162–584). Median disease specific survival time was 413 days (95% CI, 217–717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.     

PRE‐ AND POSTTREATMENT ULTRASONOGRAPHY OF THE THYROID GLAND IN HYPERTHYROID CATS

Ultrasonography is useful for assessing the morphology of the thyroid gland in hyperthyroid cats. Our aim was to describe the ultrasonographic changes of the thyroid gland in hyperthyroid cats after ¹³¹I therapy. Ultrasonography was performed in 15 hyperthyroid cats at initial presentation and 6 months after ¹³¹I using a multifrequency linear transducer set at 12 MHz. The following criteria were evaluated: length, width, height, volume, shape, homogeneity, and vascularity, using Power Doppler. Pretreatment, 10 cats had bilaterally abnormal thyroid lobes, four cats one abnormal lobe with the contralateral lobe being normal or reduced in size, and one cat with one normal lobe and one lobe not visible. Six months after ¹³¹I therapy, there was a reduction in median volume from 819 to 210 mm³, reduced rounding, reduced heterogeneity, and decreased vascularity. In conclusion, ultrasonography may be used to monitor thyroid changes in order to assess ¹³¹I treatment response. Further studies are necessary to determine whether ultrasonography could contribute to the detection of a relapsing course of hyperthyroidism.     

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.     

CRETINISM IN A NORTH AMERICAN BLACK BEAR(URSUS AMERICANUS)

Congenital hyperplastic goiter and cretinism were documented in a 16 month-old male North American black bear (Ursus americanus). The cub was captured at approximately 8 months of age and maintained for an additional 8 months in captivity. Clinical signs included growth retardation, clumsiness, and facial dysmorphism. Hypothyroidism was documented by determining serum triiodothyronine (T3) and thyroxine (T4) levels. Lysosomal storage disease was ruled out by measuring various lysosomal enzyme activities. Serologic, radiographic, computed tomographic, necropsy, and histopathologic findings were consistent with congenital hypothyroidism and cretinism.     

Retrospective study of orthovoltage radiation therapy for nasal tumors in 42 dogs

Megavoltage radiation therapy currently is the standard of care for dogs with nasal tumors. Some studies report that surgery and adjunctive orthovoltage radiation therapy result in longer control of these tumors than does megavoltage radiation therapy alone. This study reports less effective control of nasal tumors in dogs treated with surgery and orthovoltage radiation than previously observed, supporting the superiority of megavoltage radiation therapy for these tumors. In addition, this study suggests 2 new prognostic indicators for dogs with nasal tumors and describes toxicity associated with surgery and orthovoltage therapy. Forty-two dogs with nasal tumors were treated with surgical cytoreduction and 48 Gy orthovoltage radiation therapy administered in twelve 4-Gy fractions. Median survival was 7.4 months. One- and 2-year survival rates were 37% and 17%, respectively. Dogs with facial deformity had shorter survival than those without deformity (P = .005). Dogs with resolution of clinical signs after treatment had longer survival than those with chronic nasal signs (P = .0001). Acute radiation toxicity was moderate to severe for skin and eye and negligible for oral mucosa. Toxicity healed within 1 month after radiation therapy. Late toxicity was mild, but 70% of evaluable dogs experienced persistent ocular signs. Only 39% of dogs achieved a disease-free period.     

High dose rate interstitial 192-Ir brachytherapy for the treatment of a recurrent dermal vascular hamartoma in a horse

The successful application of an interstitial brachytherapy course is reported in a 14-month-old male Anglo European Studbook (AES) foal for the treatment of a recurrent dermal vascular hamartoma at the dorsal aspect of the pastern on the right hindlimb. The lesion was irradiated four times over 4 days to a total dose of 28 Gy. Progressive tumour shrinkage and necrosis were observed over 2 months. No significant acute side effect was reported at the end of the treatment, with excellent and long-lasting cosmetic results observed. The only reported late effect was permanent leukotrichia within the treated area, which remained otherwise tumour-free 1224 days after treatment. Results of this report suggest the potential use of radiation therapy (and specifically brachytherapy techniques), as an effective and safe treatment modality for vascular malformations in horses.