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.     

Definitive‐intent intensity‐modulated radiation therapy provides similar outcomes to those previously published for definitive‐intent three‐dimensional conformal radiation therapy in dogs with primary brain tumors: A multi‐institutional retrospective study

Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three‐dimensional conformal radiotherapy, reports of definitive‐intent, IMRT for canine intracranial tumors are lacking. Intensity‐modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi‐institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty‐two dogs treated with fractionated, definitive‐intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45‐50 Gy (2.25‐2.5 Gy per fraction in 18‐20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3‐26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity‐modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.     

PROOF OF PRINCIPLE OF OCULAR SPARING IN DOGS WITH SINONASAL TUMORS TREATED WITH INTENSITY‐MODULATED RADIATION THERAPY

Intensity‐modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop‐off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty‐one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two‐dimensional radiotherapy (2D‐RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose–volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D‐RT. Overall median survival for IMRT‐treated and 2D‐treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof‐of‐principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D‐RT.     

RESULTS OF RADIATION THERAPY IN 19 DOGS WITH CUTANEOUS MAST CELL TUMOR AND REGIONAL LYMPH NODE METASTASIS

The records of 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis (WHO Stage 2) were reviewed to determine the efficacy of radiation therapy in this population. Dogs with grade I (n = 1), grade II (n = 16), and grade III (n = 2) cutaneous mast cell tumor were included in this study. All dogs were treated with a combination of pre-irradiation surgical cytoreduction of the primary tumor, irradiation of the primary tumor and regional lymph node, and oral prednisone. Total radiation dose to the primary tumor and regional lymph node ranged from 48 to 57 Gray (Gy). The medial iliac and hypogastric lymph nodes were irradiated prophylactically in 11 dogs with primary tumor of the pelvic limb and positive ipsilateral popliteal lymph node. Total radiation dose to these lymph nodes ranged from 48 to 57 Gy. For all radiation fields, dose per fraction was 3 Gy, and therapy was administered on a Monday through Friday schedule. Acute and late radiation side effects observed in this study were considered acceptable. The median disease-free survival was 1,240 days (95% confidence interval 256 to 2,391 days). The disease-free survival in dogs with stage 2 mast cell tumor suggests that the combination of surgery, irradiation, and prednisone for the primary tumor along with irradiation of the positive lymph node is effective.     

Response rate and duration associated with a 4Gy 5 fraction palliative radiation protocol

The purpose of this retrospective study was to determine if 4Gy fractions over 5 consecutive days is an effective and safe palliative radiation protocol for dogs and cats. Eighty patients (22 cats, 58 dogs) with complete follow-up information were evaluated. Overall response rate (ORR) for all patients was 67%. Median progression free survival (MPFS) was 3.3 months and median survival (MST) was 4.2 months. Primary bone tumors were the most common tumors treated. The ORR for primary bone tumors was 66.6%, the MPFS was 3.5 months, and MST was 3 months. The most common tumor treated in cats was oral squamous cell carcinoma and ORR was 54.5 %, the MPFS was 1.8 months, and MST was 3 months. Soft tissue sarcomas were the second most common tumor treated in dogs (10). ORR was 80% and the two other patients had stable disease. MPFS was 5.7 months and MST was 7.9 months. Overall rate of toxicity was 18.4% in 65 sites that were evaluated for toxicity. Acute toxicities were all grade I or II and occurred in 16.9 % of patients evaluated. All late toxicity was grade I alopecia and leukotrichia. There appears to be a comparable response rate for this palliative protocol as compared to others historically. This response was seen over a wide range of tumors. We also documented a low toxicity profile in a shorter overall treatment time, making this protocol more attractive for some clients.     

A Prospective Study of Radiation Therapy for the Treatment of Grade 2 Mast Cell Tumors in 32 Dogs

Surgery, chemotherapy, and irradiation have been used singly or in combination to treat dogs with cutaneous grade-2 mast cell tumors (MCT). However, optimal treatment has not been established. At The Animal Medical Center, 32 dogs with grade 2, stage 0 MCT received cobalt radiation treatment to a dose of 54 Gy; 94% had a disease-free interval of 1 year. The 2–,3–,4–, and 5–year disease-free intervals were 86%. Survival rates were 100% for 1 year and 96% for 2 to 5 years, with only 1 death caused by MCT. Primary site was not a prognostic factor for survival in this study. Minimal toxicity was observed and was limited to acute cutaneous reactions. Late-term reactions to radiation therapy were mild and considered acceptable in all cases. No deaths occurred due to treatment, and no dog was eliminated from the study because of radiation therapy toxicity. Radiation therapy appears to be an effective treatment for dogs with grade 2, stage 0 MCT.     

Outcome in dogs with surgically resected oral fibrosarcoma (1997-2008)

Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32-57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty-nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty-one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression-free interval was >653 days. The median survival time was 743 days. The 1- and 2-year survival rates were 87.7 and 57.8%, respectively. Seven (24.1%) dogs developed local recurrence. Seven dogs (24.1%) developed metastasis.     

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.     

Safety and feasibility of short course pre-operative radiation therapy followed by surgical excision for canine solid tumours

Surgical resection of solid tumours, especially in early stages of disease, remains a cornerstone of cancer treatment in dogs and cats. There are numerous publications that show a strong association between local tumour control and outcome. To achieve local control in some cases radiation therapy and surgery are combined, with radiation therapy being delivered in the neoadjuvant or adjuvant setting. The objective of the study was to report acute toxicity and surgical site complication data in dogs that received a short-course pre-operative (SCPO) radiation therapy protocol, followed by surgical excision for various solid tumours. Medical records were reviewed, and data was analysed retrospectively. Dogs were included if a dermal or subcutaneous solid tumour was treated with SCPO radiation therapy and then was resected on the last day of radiation or 2–3 weeks later. A total of 34 dogs with 35 primary tumours were included. Acute radiation toxicity was diagnosed in 14 sites (40%). VRTOG scores were grade 1 in 50%, grade 2 in 43%, and grade 3 in 7%. Surgical site complications were identified in 17% of dogs with an overall surgical site infection rate of 11%. According to the Clavien-Dindo classification, two dogs required medical intervention (grade 2), 1 dog required surgical intervention under general anaesthesia (grade 3b), and 1 dog died as a result of complications (grade 5). Logistic regression analysis found that anatomic site was significantly associated with complications, where tumours located on the extremity was protective (P = .02; OR 0.06).     

0–7–21 Radiation Therapy for the Treatment of Canine Oral Melanoma

Eighteen dogs with malignant melanoma of the oral cavity were treated with high-dose per fraction (0–7–21) radiation therapy. Eight hundred cGy was administered on days 0, 7, and 21 for a total dose of 2,400 cGy in 3 weeks. Of 17 dogs evaluated, 9 (53%) had a complete remission and 5 (30%) achieved a partial remission with an overall response rate of 83%. Local failure occurred in 2 of the 9 dogs where a complete response was initially observed. One dog died of intercurrent disease, and one died of metastatic disease without evidence of local recurrence. Five dogs are alive and free of disease 9 to nineteen months from the initiation of therapy. The 0–7–21 protocol was well-tolerated, and acute radiation reactions were low-grade and limited to the skin. The results of this study demonstrate that oral melanomas in dogs are responsive to radiation. 0–7–21 radiation therapy offers a viable alternative to radical excision, especially when tumor volume or location would require cosmetically or functionally debilitating surgery.     

Prognostic factors for survival of dogs with inguinal and perineal mast cell tumors treated surgically with or without adjunctive treatment: 68 cases (1994-2002)

OBJECTIVE: To determine the prognostic factors for survival and tumor recurrence in dogs with cutaneous mast cell tumors (MCTs) in the perineal and inguinal regions treated surgically with or without adjunctive radiation therapy, chemotherapy, or both. DESIGN: Retrospective study. ANIMALS: 68 dogs. PROCEDURE: Medical records of dogs with histologically confirmed MCTs in the perineal region, inguinal region, or both treated surgically with or without adjunctive radiation therapy, chemotherapy, or both were reviewed. RESULTS: Mean tumor-free interval was 1,635 days (median not reached), and 1- and 2-year tumor-free rates were 79% and 71%, respectively. Median survival time was 1,111 days (mean, 1,223 days), and 1- and 2-year survival rates were 79% and 61%, respectively. Factors that negatively influenced survival time were age at diagnosis, tumor recurrence, and treatment with lomustine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with MCTs in the inguinal and perineal regions, if appropriately treated, may have survival times and tumor-free intervals similar to dogs with MCTs in other locations.     

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.     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.     

Retrospective study of canine nasal tumor treated with hypofractionated radiotherapy

The object of this study was to evaluate hypofractionated multiportal field and two-portion (rostral and caudal portions divided by the eyelid) radiation therapy for canine nasal tumors. Sixty-three dogs underwent multiportal hypofractionated radiation therapy. The radiation field was divided into rostral and caudal portions by the eyelid. Treatments were performed four times for 57 dogs. The median irradiation dose/fraction was 8 Gy (range, 5-10 Gy); the median total dose was 32 Gy (10-40 Gy). Improvement of clinical symptoms was achieved in 53 (84.1%) of 63 cases. Median survival time was 197 days (range, 2-1,080 days). Median survival times with and without destruction of the cribriform plate before radiotherapy were 163 and 219 days, respectively. There was no significant difference between them. No other factors were related to survival according to a univariate analysis. All radiation side effects, except one, were grade I according to the VRTOG classification. It was not necessary to treat any dogs for skin side effects. One dog (1.6%) developed an oronasal fistula 1 year after completion of radiation therapy. This radiation protocol may be useful in reducing radiation side effects in dogs with cribriform plate destruction.     

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.     

Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases

Oral mucocutaneous lymphoma is rare in dogs. Surgery and chemotherapy do not usually provide effective long-term control. The objective of this study was to retrospectively evaluate survival of dogs with localized oral lymphoma treated with radiation therapy. The medical database of three institutions was searched for dogs with diagnosis of oral lymphoma treated with radiotherapy. Dogs with evidence of systemic disease were excluded. Survival was calculated with the Kaplan-Meier method and prognostic variables analysed with log-rank test. Fourteen dogs were included in the study. Mean survival was 1129 days [95% confidence interval (CI) 711-1546] with median survival of 770 days. The overall response of radiotherapy was 67% (five complete and three partial responses). A survival advantage was seen in dogs with no evidence of lymph node metastasis (P = 0.002) and that achieved a complete response to radiation therapy (P = 0.013). Radiation therapy was a well-tolerated and effective treatment for localized oral lymphoma.     

TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW‐DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA

Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross‐sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once‐daily fractions (Monday–Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first‐line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction.     

Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997)

This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage 1. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10-30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24-2, 163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy.     

Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats

This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.