Long‐term survival with stereotactic radiotherapy for imaging‐diagnosed pituitary tumors in dogs

Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging‐diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009–2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226–410 days [range 1–2134 days]). Thirty‐two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221–427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2–626 days]). Twenty‐nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P = 0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.     

Long‐term outcomes with conventional fractionated and stereotactic radiotherapy for suspected heart‐base tumours in dogs

Published radiotherapy results for suspected heart‐based tumours in dogs are limited. In this retrospective longitudinal study (3/2014‐2019), eight dogs with either clinical signs attributable to a heart‐base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post‐radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post‐treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114‐868 days, [range 114‐1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days‐not reached [range 155‐1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days‐not reached [range 114‐414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow‐up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart‐base masses.     

Surgical treatment of mammary carcinomas in dogs with or without postoperative chemotherapy

This retrospective study identified prognostic factors associated with survival; and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of dogs with poor prognostic factors. On multivariate analysis independent predictors of median survival time (MST) were clinical stage, lymphatic invasion (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443 days) and surgical margins (incomplete 70 days; complete 872 days). Complete surgical margins were associated with MST in dogs with stages 1–3 MCA (incomplete 68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347 days). There was no statistically significant improvement in MST in dogs with advanced disease (stage 4 or LI) treated with adjunctive chemotherapy (chemotherapy 228 days; none 194 days); although five dogs with complete surgical margins that received mitoxantrone and carboplatin had a mean survival of 1139 days.     

COMPARISON OF TWO COARSE FRACTIONATED RADIATION PROTOCOLS FOR THE MANAGEMENT OF CANINE PITUITARY MACROTUMOR: AN OBSERVATIONAL STUDY OF 24 DOGS

Radiotherapy is a commonly used treatment for pituitary macrotumors in dogs, but the optimum protocol has not been established. Twenty four dogs with MRI confirmed pituitary macrotumors were treated with one of two radiotherapy protocols. Twelve dogs were treated with 10 fractions of 3.8 Gy/fraction on a “Monday–Wednesday–Friday” schedule, the remaining 12 with five “once‐a‐week” protocols (1 × 5 Gy, followed by 4 × 8.25 Gy) to a total dose of 38 Gy. The overall median survival time for all dogs was 235 days (range 28–1,328), dogs treated with 10 fractions had a median survival time of 961 days (range 28–1,328) compared to 182 days (range 42–507) in the five‐fraction group (P = 0.006). Clinical improvement was found in both groups, and no significant side effects were noted in either group. These results suggest that a “Monday–Wednesday–Friday” schedule may improve survival times, as compared to a “once‐a‐week” protocol. As this study was of an observational nonrandomized nature, future work is necessary to establish whether more highly fractionated protocols or different total doses will further improve outcome.     

AN ACCELERATED TECHNIQUE FOR IRRADIATION OF MALIGNANT CANINE NASAL AND PARANASAL SINUS TUMORS

Tumor and normal tissue response was assessed in 21 dogs with malignant nasal tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days. Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free interval (RFI) of 270 days. Median survival was 428 days. One year survival for all dogs was 60%. RFI and survival times are better than, or similar to, previous reports of dogs treated with radiotherapy only. Acute radiation effects were severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable tumor control. Late effects included bilateral blindness (3), osteoradionecrosis (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT findings were predictive for survival duration. Tumor histology was not predictive of outcome. Labrador Retrievers were significantly over-represented. Despite comparable or improved tumor control and survival times provided by this accelerated protocol, relative to other radiotherapy reports, local failure remains the major cause of death, and late radiation effects can be severe in dogs with durable tumor control.     

Canine spinal nephroblastoma: long-term outcomes associated with treatment of 10 cases (1996-2009)

Objective: To report clinical outcome associated with treatment of canine spinal cord nephroblastoma (CSN). Study Design: Case series. Animals: Dogs (n=10) with histopathologically confirmed CSN. Methods: Records of dogs with CSN were reviewed and clinicopathologic, diagnostic imaging, treatment, outcome, and survival data were collected. Results: CSN resulted in clinical signs of chronic, progressive T3–L3 myelopathy in young, large breed dogs, with an overrepresentation of German Shepherd Dogs (n=4). All CSN were located between T9 and L2. Dogs treated with cytoreductive surgery (n=6) or radiotherapy (1) survived longer (median, 374 days; range, 226–560 days) than dogs treated palliatively (3; median, 55 days; range, 38–176 days). Tumors confined to an intradural–extramedullary (ID–EM) location were associated with superior survival (n=6; median, 380 days; range, 176–560 days) than tumors with intramedullary (IM) involvement (n=4; median, 140 days; range, 38–269 days). Treatment resulted in temporary improvement in neurologic function in 9 dogs, including all dogs treated surgically, but local disease progression resulted in death of 8 dogs. Conclusions: Results of this observational study suggest that surgical cytoreduction and radiotherapy are effective at improving survival in dogs with CSN, and that ID–EM tumors may be associated with a more favorable prognosis than IM neoplasms.     

Intraoperative radiotherapy of carcinoma of the prostate gland in ten dogs

Ten dogs with carcinoma of the prostate gland were treated with intraoperative orthovoltage radiotherapy (radiation therapy to surgically exposed tumors). Seven dogs had tumor growth confined to the prostate gland and urethra, and 3 dogs had carcinoma of the prostate gland and regional lymph node involvement. Total radiation doses delivered to the prostate gland of 9 dogs and the affected regional lymph nodes of 3 dogs, using orthovoltage x-rays, ranged from 20 to 30 Gy. Carcinoma of the prostate gland of one dog was intraoperatively irradiated to 15 Gy and was then given a boost of 40 Gy, using cobalt-60 teletherapy. Survival time ranged from 41 to 750 days after intraoperative radiotherapy. Median and mean survival times for all dogs were 114 and 196 days, respectively. The median survival time for 7 dogs with localized prostatic carcinoma was 180 days, which was longer, but not significantly longer (P = 0.09), than the median survival time of 80 days in 3 dogs having prostatic carcinoma and metastatic disease. Intraoperative radiotherapy was tolerated well and caused complete response in 5 dogs. However, surgical complications in 2 dogs, which had subtotal lymphadenectomy or prostatic biopsy performed concurrently at the time of irradiation, resulted ultimately in their deaths. The 2 other dogs with metastatic disease and 1 dog without metastatic disease also had poor response to treatment. Our results indicated that intraoperative radiotherapy is an effective treatment for localized prostatic carcinoma in the dog.     

Definitive‐intent intensity‐modulated radiation therapy for treatment of canine prostatic carcinoma: A multi‐institutional retrospective study

No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive‐intent, intensity‐modulated radiation therapy (RT) in dogs with PC. Medical records review was performed, including 18 patients from four institutions undergoing definitive‐intent intensity‐modulated radiotherapy to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco‐regional lymph nodes at diagnosis. Seventeen patients received concurrent non‐steroidal anti‐inflammatory drugs; 15/18 (83%) patients received maximally‐tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48 to 54 Gy (median 50 Gy) delivered as daily doses of 2.5‐2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1‐2 diarrhoea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture and hindlimb oedema) was observed in three patients. Median event‐free survival (EFS) following RT was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 vs 220 days in symptomatic dogs, P = .042). EFS was significantly longer in patients treated with MTD chemotherapy (241 vs 25 days, P < .001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = .008). These findings suggest that definitive‐intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity.     

Description and efficacy of a response-based “QUAD” cyclical hypofractionated palliative-intent radiation protocol in dogs with macroscopic solid tumours: 108 cases

Palliative-intent radiation therapy can alleviate pain and clinical signs in dogs with cancer, but optimal fractionation scheme is unknown. The objective of this retrospective case series is to evaluate clinical benefit, objective response, adverse effects, and outcomes in 108 dogs with macroscopic solid tumours treated with a cyclical “QUAD” hypofractionated palliative-intent radiation therapy protocol. Median QUAD dose was 14 Gy (14–16 Gy). Median total dose was 28 Gy (14–48 Gy). Clinical benefit rate was 93%, with median onset of subjective palliation 21 days after the first QUAD, lasting a median of 134 days. Tumour volumetric objective response was assessed with CT prior to the third QUAD in 36 dogs, with stable disease in 24 dogs (67%) and partial response in 9 dogs (25%). Sinonasal and oral were the most common tumour locations in 32 and 30 dogs, respectively. Median progression-free survival was 153 days (95% CI 114–200). Median overall survival was 212 days (95% CI 152–259). Number of QUAD cycles completed, clinical benefit achieved, anti-inflammatory received, total radiation dose, time to maximum clinical benefit, and response duration were positively associated with progression-free and overall survival. Acute toxicities were observed in 15 dogs (14%) with 3 high-grade (grade 3) toxicities (3%). Low-grade (grade 1 and 2) late skin and ocular toxicities were observed in 31 dogs (29%), predominantly leukotrichia, alopecia, keratoconjunctivitis sicca, and cataracts. This report demonstrates that QUAD radiation is an alternative protocol to be considered for palliation of dogs with inoperable or advanced stage solid tumours.     

Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma

Soft tissue sarcomas (STSs) are locally invasive and surgery with or without radiation therapy is the current standard of care in dogs. Typical protocols for treating incompletely excised STSs involve curative intent radiation with total dose in excess of 50 Gy. Forty‐eight dogs with histologically confirmed incomplete or closely excised STSs were treated with a hypofractionated protocol that is typically reserved for palliative radiation therapy (RT) (6–8 Gy/weekly fractions to a total dose of 24–32 Gy). Ten dogs (21%) developed local recurrence, 11 dogs (23%) developed metastasis, and 3 dogs developed both (included in each group). The median progression free survival was 698 days. The local failure‐free probability at 1 and 3 years was 81 and 73%. The 1 and 3 years tumour‐specific overall survival was 81 and 61%. Long‐term local tumour control was achieved in the majority of dogs. This protocol is reasonable to prescribe in older patients or when financial limitations exist.     

Stereotactic radiotherapy outcomes for intraventricular brain tumours in 11 dogs

Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011–2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)-diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33–1593 days). The survival time for two pathology-diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short-lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation-specific complications are possible due to the small dataset and limited follow-up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long-term survivors are noted.     

Three‐dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three‐dimensional conformal radiation therapy (3D‐CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross‐sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272–829 days; range = 30–1942 days) when all deaths were considered and 906 days (interquartile range = 336–912 days; range = 101–1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D‐CRT may be a viable alternative to surgery.     

Efficacy of cobalt-60 radiation therapy for the treatment of nasal cavity nonkeratinizing squamous cell carcinoma in the dog

The purposes of this study were to evaluate the efficacy of cobalt-60 radiotherapy in the treatment of nonkeratinizing squamous cell carcinoma of the nasal cavity in dogs and to compare this treatment group to historical controls. Six dogs with histopathologically confirmed nasal cavity nonkeratinizing squamous cell carcinoma were treated with cobalt-60 radiotherapy to a total dose of either 63 Gy or 54 Gy. Overall survival times ranged from 30 days to 330 days, with a median survival time of 165 days. Nasal cavity nonkeratinizing squamous cell carcinoma in the dog is an aggressive tumor that responds poorly to radiotherapy.     

Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001)

The medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with concurrent curative‐intent radiotherapy and mitoxantrone (MX) after surgical removal of the primary tumour were reviewed retrospectively. Radiation was prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was given intravenously at a dosage of 5 mg m^?2 every 3 weeks for five treatment sessions. Twelve dogs received pelvic irradiation to include the regional lymph nodes (LNs) and three received radiation only to the perineum. At the time of diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional LN metastasis. All the dogs with regional LN metastasis received pelvic irradiation, and in three cases, metastatic LNs were treated in the macroscopic disease setting. The median event‐free survival was 287 days, and the median overall survival was 956 days. Acute and chronic radiation complications were common and non‐life threatening, although chronic complications contributed to the decision to euthanize two dogs. The results observed in this retrospective analysis compare favourably with cases of ASAC in the literature related to treatment with surgery and/or chemotherapy.     

Treatment of canine oral papillary squamous cell carcinoma using definitive‐intent radiation as a monotherapy—a case series

Canine oral papillary squamous cell carcinoma (COPSCC) is a rare neoplasm and although locally invasive it carries a favourable prognosis following wide surgical excision. Radiotherapy has been reported to be effective as an adjunct treatment to surgery. However, limited information is available on the role of radiotherapy as single treatment. This single‐institution retrospective study describes a series of 10 dogs diagnosed with macroscopic COPSCC that were treated with definitive‐intent radiotherapy (DRT) as a monotherapy. These dogs had a median age of 4 years (range: 0.4‐9.6 years). The tumour was located in the rostral oral cavity in all cases with a median tumour size of 2.5 cm (range: 0.8‐6.8 cm). No local or distant metastases were identified. All dogs were treated with electron beam DRT (>32Gy, 10‐16 daily fractions of 3.2Gy). The median follow‐up time was 961 days (range: 333‐3.498 days) with nine dogs achieving a complete response and one dog a partial response. The dog with the partial response developed disease progression at 228 days after initiation of radiotherapy. Two dogs died from non‐tumour‐related causes. The remaining seven dogs were still alive and in complete remission at the time of last follow‐up. Median progression‐free survival time and median survival time were not reached. DRT was generally well tolerated, but all dogs experienced self‐limiting acute radiation mucositis (grade 2‐3) and/or dermatitis (grade 1). No late radiation toxicity was observed. Macroscopic COPSCC appears to be a radiosensitive tumour that can be successfully treated with DRT eliminating the need for aggressive surgery in advanced cases.     

Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: a retrospective study of 12 cases

The efficacy of low doses of radiotherapy for the treatment of pituitary corticotroph macrotumors in dogs is evaluated retrospectively. Twelve dogs with pituitary-dependent hyperadrenocorticism and a large pituitary tumor treated with 36 Gy of radiation were included. Radiation was delivered in 12 fractions of 3 Gy over a 4- to 6-week period. Effects of radiation therapy on tumor size were assessed by computed tomography scans; a decrease was observed in 11 dogs (decrease > 50% in 6 dogs). Three dogs were reirradiated due to major tumor regrowth or a lack of tumor decrease (mean total dose: 22 Gy given in 3-Gy fractions over 3 or 4 weeks). The mean and median survival times following the initiation of radiotherapy were 22.6 months (688 days) and 17.7 months (539 days), respectively. These data are consistent with previous findings, based on high-dose radiation, showing that radiotherapy is a useful option for treating pituitary corticotroph macrotumors in dogs. Furthermore, computed tomography follow-up of the treated dogs demonstrates objectively the efficacy of radiotherapy against corticotroph tumors in dogs.