Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987-1998)

OBJECTIVE: To determine the efficacy (durations of remission and survival) of an alternating-day radiation protocol for incompletely excised histologic grade-III solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS: 31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol) was delivered to an area bordered by margins > or = 3 cm around the surgical scar and to the associated local-regional lymph nodes. Dogs were not given chemotherapeutic agents concurrently or after radiation. Information on signalment, duration of remission, and survival time was obtained from medical records. RESULTS: Median and mean durations of remission were 27.7 and 17.0 months, respectively (range, 1 to 47 months). Median and mean durations of survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with tumors located on the skin of the pinna, perineum, and prepuce had a median duration of remission greater than dogs with tumors located at other sites (27.7 and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months, respectively). The remission rate was 65% and survival rate was 71% at 1 year after treatment. Sixteen dogs that were euthanatized had complications associated with local-regional tumor progression. Systemic metastases to liver, spleen, intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Without further treatment, incompletely excised grade-III mast cell tumors have high local-regional recurrence; local-regional treatment with radiation may effectively be used to manage many such tumors.     

Recurrence rates and sites for grade II canine cutaneous mast cell tumors following complete surgical excision.

A retrospective study was performed on 31 dogs with completely excised, grade II, cutaneous mast cell tumors in order to determine recurrence rates and sites. Distant tumor recurrence developed in 22% of dogs, and local tumor recurrence developed in 11% of dogs; however, the vast majority of these animals were incompletely staged initially. Complete surgical excision of grade II mast cell tumors was associated with effective local control in 89% of these dogs. Therefore, adjuvant radiation therapy might not be indicated in the majority of dogs with complete surgical excision.     

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.     

Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs

The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft-tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four-year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods.     

Evaluation of radiotherapy alone or in combination with doxorubicin chemotherapy for the treatment of cats with incompletely excised soft tissue sarcomas: 71 cases (1989-1999)

OBJECTIVE: To determine whether the addition of doxorubicin chemotherapy affected the outcome of cats with incompletely excised, nonvisceral soft tissue sarcomas undergoing postoperative radiotherapy. DESIGN: Retrospective case series. ANIMALS: 71 cats. PROCEDURES: Medical records were reviewed for clinically relevant data on cats that underwent postoperative radiotherapy for treatment of incompletely excised soft tissue sarcomas with or without concurrent doxorubicin chemotherapy. Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8 to 63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3 to 5 cycles. Follow-up information was obtained by means of physical examination or through telephone conversations with refer-ring veterinarians or owners. RESULTS: Median disease-free interval with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months; range, 2.4 to 44.9 months) was significantly longer than median disease-free interval with radiotherapy alone (5.7 months; range, 1.0 to 50.8 months). However, survival time was not significantly different between groups. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that doxorubicin chemotherapy may play a role in extending the disease-free interval in cats undergoing radiotherapy for treatment of incompletely excised soft tissue sarcomas.     

External-beam Co-60 radiotherapy for canine nasal tumors: a comparison of survival by treatment protocol

A retrospective analysis of survival times in dogs with intranasal tumors was performed comparing those treated using hypofractionated or full course Co-60 radiotherapy protocols alone or with surgical adjuvant therapy and those receiving no radiation treatment. One hundred thirty-nine dogs presented to the University of Minnesota Veterinary Medical Center for treatment of histologically-confirmed nasal neoplasia between July 1983 and October 2001 met the criteria for review. Statistically analyzed parameters included age at diagnosis, tumor histologic classification, fractionation schedule (number of treatments, and number of treatment days/week) (classified as hypofractionated if 2 or less treatments/week); calculated minimum tumor dose/fraction; calculated total minimum tumor dose (classified as hypofractionated if less than 37 Gy in six or fewer fractions); number of radiotherapy portals, a treatment gap of more than 7 days in a full course (3-5 treatments/week, 3-3.5 week treatment time) radiotherapy protocol, the influence of eye shields on survival following single portal DV fields, the survey radiographic extent of the disease, and the presence or absence of cytoreductive surgery. There was a significant relationship only between protocols using 3 or more treatments/week and at least 37 Gy cumulative minimum tumor dose and survival. However, there was no significant relationship between either total minimum tumor dose or dose/fraction and survival and there were no significant relationships between survival and any of the other variables analyzed including tumor histologic type.     

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.     

Radiotherapy of a recurrent ossifying fibroma in the paranasal sinuses of a horse

A 7-year-old female Thoroughbred was admitted with a history of labored breathing, stridor, and exercise intolerance. Examination revealed a mass in the left paranasal sinuses that was determined to be an ossifying fibroma. Initial treatment consisted of surgical removal of the mass alone; however, the mass recurred 9 months after surgery. The mass was again removed, and adjunctive radiotherapy consisting of 3,000 cGy of cobalt radiation was administered. This time, the tumor did not recur for > 6 years. A third surgery was performed to remove the mass, and adjunctive radiotherapy consisting of 4,000 cGy of photon beam radiation from a linear accelerator was administered. The mass did not recur during the subsequent 3 years. Ossifying fibromas are uncommon tumors that frequently recur if incompletely excised. Results in this horse suggest that adjunctive radiotherapy may delay or prevent tumor recurrence in affected horses.     

Radiation therapy for incompletely excised grade II canine mast cell tumors

Forty-five dogs with incompletely excised grade II mast cell tumors were treated with radiation using a cobalt 60 teletherapy unit (15 fractions of 3.2 Gy for a total of 48 Gy). Twenty-four of the dogs underwent prophylactic regional lymph node irradiation. Three (6.7%) dogs had tumor recurrence, two (4.4%) dogs developed metastasis, and 14 (31%) dogs developed a second cutaneous mast cell tumor. No difference in overall survival rate was observed between the dogs receiving and not receiving prophylactic irradiation of the regional lymph node.     

Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994-2002)

The objectives of this study were to determine local recurrence rate, clinical outcome, and prognostic value of the number of argyrophylic nucleolar organizer regions (AgNORs), presence of proliferating cell nuclear antigen (PCNA), and number of Ki-67-positive nuclei after incomplete surgical excision of canine cutaneous grade II mast cell tumors (MCTs). This retrospective study included 30 MCTs in 28 dogs. Medical records were examined and follow-up information was obtained from owners and referring veterinarians. Only cases in which excision was incomplete and no anvcillary therapy (other than prednisone) for MCT was given were included. Paraffin-embedded tumor tissues were retrieved for AgNORs, PCNA, and Ki-67 staining. Median follow-up time was 811.5 days. Seven (23.3%) tumors recurred locally. Median time to local recurrence was not reached with a mean of 1,713 days. The estimated proportions of tumors that recurred locally at 1, 2, and 5 years were 17.3, 22.1, and 33.3%, respectively. Eleven (39.3%) dogs developed MCTs at other cutaneous locations. Median progression-free survival was 1,044 days. Median overall survival was 1,426 days. The combination of Ki-67 and PCNA scores was prognostic for local recurrence (P = .03) and development of local recurrence was prognostic for decreased overall survival (P = .04). Results suggest that a minority of incompletely excised MCTs recur. Therefore, ancillary local therapies may not always be necessary. However, local recurrence can negatively affect survival of the affected dogs. Cellular proliferation indices may indicate the likelihood of MCT recurrence after incomplete excision.     

Radiation treatment for incompletely resected soft-tissue sarcomas in dogs

OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely resected soft-tissue sarcomas in dogs. DESIGN: Prospective serial study. ANIMALS: 48 dogs with soft-tissue sarcomas. PROCEDURE: Tumors were resected to < 3 cm3 prior to radiation. Tumors were treated on alternate days (three 3-Gy fractions/wk) until 21 fractions had been administered. Cobalt 60 radiation was used for all treatments. RESULTS: Five-year survival rate was 76%, and survival rate was not different among tumor types or locations. Four (8%) dogs developed metastases. Eight (17%) dogs had tumor recurrence after radiation. Development of metastases and local recurrence were significantly associated with reduced survival rate. Median survival time in dogs that developed metastases was 250 days. Median disease-free interval for all dogs was 1,082 days. Median time to recurrence was 700 days. Dogs that developed recurrence after a prolonged period responded well to a second surgery. Acute radiation toxicosis was minimal; osteosarcoma developed at the radiation site in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: An excellent long-term survival rate may be achieved by treating soft-tissue sarcomas in dogs with resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in limbs. Development of metastases and recurrence of local tumors after radiation treatment are associated with decreased survival rate. Acute and delayed radiation toxicosis was minimal with the protocol used in this study.     

Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996)

OBJECTIVE: To evaluate time to first recurrence (TFR) and overall survival in cats with presumed vaccine-associated sarcomas (VAS) treated with excision. DESIGN: Retrospective study. ANIMALS: 61 cats with presumed VAS. PROCEDURE: Medical records of cats that received excision as the only initial treatment for presumed VAS were reviewed to evaluate prognosis. Overall survival curves and TFR were determined. RESULTS: Median TFR was 94 days. Median TFR for tumors treated with excision performed at a referral institution (274 days) was significantly longer than that for tumors excised by a referring veterinarian (66 days). Radical first excision yielded significantly longer median TFR (325 days) than did marginal first excision (79 days). Cats with tumors located on the limbs had longer median TFR (325 days) than cats with tumors located in other sites (66 days). Median overall survival time was 576 days. Significant differences in survival times between groups were not detected. Few cats (13.8%) receiving only surgical treatment had long-term (> 2 years) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Radical first excision of presumed VAS is essential for extended TFR. Current recommendations for vaccination of the distal portions of the extremities are appropriate, because this practice permits radical excision of tumors (amputation) that develop at vaccination sites; however, surgery alone is seldom curative.     

Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001-2006)

OBJECTIVE: To evaluate outcome associated with subcutaneous and intramuscular hemangiosarcomas treated with adjuvant doxorubicin in dogs. DESIGN: Retrospective case series. ANIMALS: 21 dogs. PROCEDURES: Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death. RESULTS: 17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.     

SURVIVAL TIMES FOR CANINE INTRANASAL SARCOMAS TREATED WITH RADIATION THERAPY: 86 CASES (1996–2011)

Sarcomas comprise approximately one‐third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily‐fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily‐fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily‐fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits.     

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.     

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.     

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004)

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.     

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.     

Hypofractionated Radiation Therapy of Brain Masses in Dogs: A Retrospective Analysis of Survival of 83 Cases (1991–1996)

There are few reports of radiation treatment for brain tumors in dogs, and the optimal treatment protocol has yet to be established. We completed a retrospective analysis of the survival times of a series of 83 dogs with intracranial masses that were treated by hypofractionated megavoltage radiation therapy. A total tumor dose of 38 Gray was given over 5 weeks as once weekly fractions via 3 perpendicular portals. The median survival time from the start of radiotherapy for the whole cohort was 43.7 weeks (range, 0.1-172 weeks). Extra-axial masses had a better survival time (49.7 weeks) than did other intracranial masses (intra-axial, 40.4 weeks; pituitary, 21.0 weeks). Delayed radiation toxicity was suspected as the cause of death or reason for euthanasia in 12 dogs. The hypofractionated radiation protocol resulted in survival times similar to those obtained using more conventional multifractionated regimens, and this protocol may be a useful, less intensive alternative treatment for brain tumors in dogs.