Chlorambucil and prednisolone chemotherapy for dogs with inoperable mast cell tumours: 21 cases

O bjectives : To evaluate the response of measurable canine mast cell tumours unsuitable for other treatment modalities to a chemotherapy protocol comprising chlorambucil and prednisolone.
M ethods : Dogs bearing measurable mast cell tumours, unsuitable for treatment by surgery or radiotherapy, were treated with orally administered prednisolone and chlorambucil, and their responses assessed.
R esults : Twenty-one dogs were enrolled in the study; 13 had intermediate-grade mast cell tumour, six were high grade and two were diagnosed by cytology alone. Eight dogs had multiple tumours and 13 dogs had single tumours, and six dogs had lymph node metastases and no dogs had visceral metastases detected. Three dogs achieved complete remission, five achieved partial remission (overall response rate 38 per cent), nine had static disease and four dogs had progressive disease. Median progression-free interval for the eight responders was 533 days, and median survival time for all dogs in the study was 140 days. Progression-free interval and median survival time were not influenced by the age, sex, weight or neutering status of the patient, by the grade or stage of the tumour or whether the patient had single or multiple tumours. No toxicity was detected.
C linical S ignificance : Response and survival rates of inoperable canine MCT to chlorambucil and prednisolone are comparable to previously described protocols, with no apparent toxicity.     

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia

O bjectives : Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging.
M ethods : Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia.
R esults : Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities.
C linical S ignificance : We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity.     

Computer tomographic imaging in 4 dogs with primary nasal canine transmissible venereal tumor and differing cellular phenotype

Primary nasal canine transmissible venereal tumor (CTVT) without genital affection is uncommon. The aim of this report was to describe the primary nasal CTVT findings and CT staging in 4 dogs with different cytological phenotypes. Three male dogs and 1 bitch were evaluated for their chronic histories of sneezing, snoring, mucopurulent nasal discharge and nasal deformation. Cytological examination of nasal secretions suggested CTVT, confirmed by histopathological examination and LINE‐1/c‐myc. Males had the plasmacytoid phenotype of CTVT, and the bitch had the lymphocytoid phenotype. CTVT were staged based on the CT findings using modified Adams staging system. The bitch was classified as stage 1, 2 males were classified as stage 3 and 1 male as stage 4. All dogs had a complete tumoral remission after chemotherapy. Plasmacytoid phenotype was identified in cases with most important damage of the nasal cavity. However, the cytological type did not affect the response to chemotherapy.     

Outcome of definitive fractionated radiation followed by exenteration of the nasal cavity in dogs with sinonasal neoplasia: 16 cases

Local control is a major challenge in treating canine nasal tumours. Surgical cytoreduction prior to radiation therapy has not been shown to offer a survival advantage. Only one study has previously evaluated the outcome when surgery is performed after radiation, which demonstrated an improved survival time compared with radiation alone. The purpose of this study was to investigate the outcome of surgery after definitive radiation on survival times in dogs with sinonasal tumours. Medical records were retrospectively reviewed for dogs with nasal tumours that received definitive radiation followed by surgery. Information obtained from medical record review included signalment, diagnosis, treatment and outcome. The median survival time was 457 days. No long‐term side effects were observed. These findings suggest that exenteration of the nasal cavity following definitive radiation for treatment of dogs with nasal tumours is well‐tolerated and provides a similar survival duration to previous reports of radiation alone.     

Recurrence analysis of intraoperative acridine orange-photodynamic therapy for dogs with intranasal tumors

Intraoperative acridine orange-photodynamic therapy (AO-PDT) and cribriform plate irradiation are used to treat canine intranasal tumors. The purpose of this study was to evaluate the effects of AO-PDT on intranasal tumors and the recurrence rate of tumors after this treatment. Treatments with AO-PDT were performed on 38 dogs through a narrow window of the dorsal nasal cavity. The median progression-free interval was 12 mo and recurrence was detected in 21 dogs. Based on computed tomography, recurrence in 16 dogs was biased to the following areas: lateral (n = 10), medial (n = 2), ventral (n = 0), rostral (n = 0), and caudal (n = 8). Side effects were mild and included subcutaneous emphysema and rhinitis. The median survival time was 24 mo. Although AO-PDT with cribriform irradiation is an effective treatment for intranasal tumors, AO-PDT techniques should be improved to treat the nasal cavity more uniformly and thoroughly.     

Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib

In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse.     

Use of milbemycin oxime in the treatment of dogs with nasal mite (Pneumonyssoides caninum) infection

Clinical diagnosis of canine nasal mite ( Pneumonyssoides caninum ) infection is difficult due to the mite's location in the caudal nasal cavity and frontal sinuses. The current study was performed to evaluate the efficacy of milbemycin oxime in treating dogs with nasal mite infection. A prospective open uncontrolled study included 20 dogs with case histories indicating possible nasal mite infection. Inclusion criteria consisted of either nasal mites being demonstrated (group 1, four dogs), or suspicious clinical signs with no other apparent causes, combined with eosinophilia (group 2, 16 dogs). Milbemycin oxime 1 mg/kg was given orally three times at 10-day intervals. In 17 (85 per cent) dogs, clinical signs resolved completely following milbemycin therapy; within 10 days of the first treatment in 13 cases (group 1, four dogs; group 2, nine dogs) and within 14 days in four cases. In the remaining three dogs clinical signs persisted but were diminished.     

Clinical resolution of nasal aspergillosis following therapy with a homeopathic remedy in a dog

A 6 yr old, male, neutered Weimaraner was treated homeopathically for nasal aspergillosis after failing to respond to two treatments of topical (intranasal) clotrimazole and oral amoxicillin trihydrate/clavulanate potassium. Computed tomography, rhinoscopy, fungal culture, and cytology previously confirmed the diagnosis. At presentation for homeopathic treatment, the dog had aggressive left-sided sinusitis and rhinitis with destruction of nasal turbinates and severe bouts of epistaxis. Erosion and depigmentation of the nasal planum were evident. After two treatments with homeopathic aurum metallicum, resolution of clinical signs occurred and clearance of the aspergillosis organisms was documented by computed tomographic scan, rhinoscopy, and histopathology. Homeopathic aurum metallicum may be beneficial in treating cases of canine nasal aspergillosis.     

Canine nasal aspergillosis

Chronic nasal discharge is a common clinical sign of disease in dogs. Canine sinonasal aspergillosis is a relatively common disease in dogs. The three hallmarks of canine nasal aspergillosis are a profuse mucoid to hemorrhagic chronic nasal discharge that may alternate with periods of epistaxis, ulceration of the external nares with crusting, and pain or discomfort in the facial region. Diagnostic imaging (preferably computed tomography, CT) of the nasal cavity and paranasal sinuses is an important component of the evaluation of dogs with signs of nasal disease. Rhinoscopy is an important part of both the diagnosis and the therapy for nasal aspergillosis. Therapeutic recommendations for sinonasal aspergillosis have included surgery and the use of several systemic and topical antifungal drugs.     

Clotrimazole and enilconazole distribution within the frontal sinuses and nasal cavity of nine dogs with sinonasal aspergillosis

Objectives: Multiple topical treatments are often required for clinical cure of mycotic rhinosinusitis in dogs. The objective of this study was to describe the distribution and retention of enilconazole and clotrimazole solutions using a temporary trephination protocol. Methods: Nine client-owned dogs diagnosed with mycotic rhinosinusitis between March 2008 and December 2009 were prospectively enrolled and were sequentially allocated to receive treatment with either clotrimazole (1% in polyethylene glycol) or enilconazole (10% solution), after imaging and rhinoscopic assessment. Both frontal sinuses were trephined, debrided and flushed with saline. Infusion was administered via frontal sinuses with dogs in sternal recumbency and computed tomography (CT) performed 5 minutes after completion. Distribution was scored 1 to 4 at the canine tooth, premolar 4, cribriform plate and frontal sinus on both sides, for a maximum score of 32. Results: Distribution of antifungal agents to all regions of the nasal cavity and frontal sinuses was achievable, but varied considerably. Retention was poor in 10 of 18 regions assessed. Clinical Significance: Distribution of antifungal agents within the frontal sinuses is achievable using temporary trephination; however, distribution is variable and retention is often poor.     

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.     

Results of rhinoscopy alone or in conjunction with sinuscopy in dogs with aspergillosis: 46 cases (2001-2004)

OBJECTIVE: To determine results of diagnostic testing, including detection of nasal or frontal sinus fungal plaques, in dogs with nasal aspergillosis. DESIGN: Retrospective case series. ANIMALS: 46 dogs with nasal aspergillosis. PROCEDURES: Medical records were reviewed for information on computed tomographic findings; rhinoscopic findings, including whether fungal plaques were seen in the nasal cavity; results of frontal sinus trephination and sinuscopy, including whether fungal plaques were seen in the frontal sinus; and results of histologic examination of biopsy specimens. RESULTS: In 38 (83%) dogs, fungal plaques were seen in the nasal cavity during rhinoscopy, whereas in the remaining 8 (17%), fungal plaques were not seen in the nasal cavity but were seen in the frontal sinus. Duration of clinical signs, proportions of dogs in which the referring veterinarian had performed a nasal examination prior to referral, proportions of dogs with computed tomographic evidence of nasal cavity cavitation or sinus involvement, and proportions of dogs with rhinoscopic evidence of destructive rhinitis were not significantly different between dogs with nasal fungal plaques and dogs with fungal plaques only in the frontal sinus. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm that frontal sinus involvement is common in dogs with nasal aspergillosis and suggest that frontal sinus trephination and sinuscopy may aid in the diagnosis of aspergillosis in dogs, particularly dogs with rhinoscopic evidence of destructive rhinitis and computed tomographic evidence of sinus involvement that lack detectable fungal plaques in the nasal cavity.     

Intramedullary cisplatin chemotherapy: Experience in four dogs with osteosarcoma

Single-agent intramedullary cisplatin chemotherapy provided effective localised control in two of four dogs with advanced stage osteosarcoma unable to withstand an amputation or limb-sparing surgery. Complete remission of the local neoplasm was observed in one of the four dogs, partial remission of the local neoplasm in one dog and progressive disease in the other two. Limb function was preserved in one dog for seven months and that dog was found to be tumour-free when euthanased due to unrelated causes. These preliminary results warrant further investigation into the use of intramedullary cisplatin chemotherapy in the localised management of canine appendicular osteosarcoma. It is possible that this mode of treatment may be combined with other treatments to maximise the survival (ie, systemic control) in other dogs affected with appendicular osteosarcoma.     

FAILURE PATTERNS FOLLOWING COBALT IRRADIATION IN DOGS WITH NASAL CARCINOMA

The pattern of tumor recurrence was assessed in 24 dogs receiving cobalt radiation therapy for nasal carcinoma. Dogs were evaluated using nasal cavity computed tomography prior to treatment, and at 1, 3, 6 and 12 months after treatment, and at 6-month intervals thereafter if still alive. Dogs were treated with various combinations of total dose, and fraction size. Total doses were normalized to equivalent doses given in 3.0 Gy fractions. The extent of tumor regression or duration of tumor control were not dependent on absolute total dose, normalized total dose, or tumor type. The median duration of local control in all dogs was 312 days. Marked tumor regression was observed in 11 of the 24 dogs. Median duration of local control was significantly longer in dogs with marked tumor regression in comparison to dogs without tumor regression; 389 vs. 161 days respectively. When tumor recurrence was documented in dogs having tumor regression, the location of the recurrence was in the nasal cavity. No tumor recurred in a sinus or periorbital region, and only one geographic miss was detected. Tumor recurrence in the irradiated volume, including dogs with and without marked regression, was documented in 13 of the 24 dogs. The high local failure rate, coupled with the recurrence pattern in these dogs, suggests there may be an opportunity for improvement in local control through use of shrinking field techniques.     

USE OF 3'-DEOXY-3'-[18F]FLUOROTHYMIDINE PET/CT FOR EVALUATING RESPONSE TO CYTOTOXIC CHEMOTHERAPY IN DOGS WITH NON-HODGKIN'S LYMPHOMA

Imaging and measurement of proliferation with computed tomography (CT) and positron emission tomography (PET) provide a noninvasive method for improved staging and monitoring of response to cancer treatment. We evaluated prospectively the proliferation marker 3'-deoxy-3'[¹⁸F] fluorothymidine (FLT) in the context of FLT-PET/CT for detection of early response, confirmation of posttreatment response, and prediction of relapse in dogs with non-Hodgkin's lymphoma. Nine dogs with non-Hodgkin's lymphoma who were scheduled to receive five cycles of an investigational cytotoxic chemotherapy agent were included. All dogs received baseline FLT-PET/CT imaging immediately before chemotherapy. Intent was to repeat imaging with FLT-PET/CT at various time points: group 1 ( n =4), 5 days after initiation of chemotherapy and 3 weeks following the last chemotherapy administration; group 2 ( n =5), before the fourth cycle of chemotherapy and 3 weeks following the last administration. Two dogs in group 2 did not undergo repeat PET/CT. Body mass standardized uptake values (SUV) for FLT were calculated for each dog. Eight dogs had initially increased FLT uptake (mean SUV_max=9.8 [2.6–22.3]). Mean SUV decreased significantly for the seven dogs that underwent follow-up PET/CT following chemotherapy (mean SUV_max=3.5 [1.1–7.9], P <0.016). Increased uptake preceded clinical and cytological evidence of relapse in two dogs. Ki-67 immunohistochemistry confirmed decreased proliferation corresponding to decreased SUV in three canine lymph node samples. FLT-PET/CT functional and anatomical imaging shows promise for the evaluation of response to cytotoxic chemotherapy in dogs with non-Hodgkin's lymphoma and for predicting relapse before standard clinical and clinicopathologic confirmation.     

A preliminary assessment of whole-body radiotherapy interposed within a chemotherapy protocol for canine lymphoma

Six dogs with spontaneously occurring, previously untreated lymphoma were treated with half‐body radiation therapy (RT) doses interposed in a CHOP‐based 25‐week chemotherapy regimen. Chemotherapy‐related toxicities were as expected and were mildly increased in severity post‐RT compared with pre‐RT. Treatment was delayed by 1–2 weeks per delay in four dogs due to chemotherapy‐related neutropenia. Radiation therapy was administered in two consecutive day fractions of 4 Gray to the cranial and caudal halves of the body 4 weeks apart. Radiation‐related toxicities consisted of lethargy, alopecia, diarrhoea of less than 2‐day duration and average decreases in neutrophil counts of 50%. Late effects from RT were not evident. Median remission and survival times for the six dogs were 455 and 560 days, respectively. The protocol was well tolerated and should be studied further to evaluate the potential therapeutic gain of the addition of RT to chemotherapy for the treatment of canine lymphoma.     

Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The one- and two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.     

Radiotherapy of brain tumors in dogs

Brain tumors in 4 dogs were treated with external beam, megavoltage radiation. X-ray computed tomography was used to localize and characterize brain tumors and to assess treatment response. Total radiation doses were 3,000 or 3,600 rad, given in 5 or 6 fractions over 14 to 19 days. Complete tumor regression, as determined from computed tomography scans, improvement in clinical signs, and reduction in medication, were documented in all irradiated dogs. The median survival time for irradiated dogs was 322 days, which was significantly (P less than 0.05) longer than the median survival time of 56 days in 8 dogs with brain tumors treated symptomatically. The one-year survival rate for the irradiated dogs, after correcting for deaths from intercurrent disease, was 100%. It was concluded that canine brain tumors may be treated effectively by use of megavoltage radiation.     

Endoscopic photodynamic therapy using talaporfin sodium for recurrent intranasal carcinomas after radiotherapy in three dogs

Radiation is the treatment of choice for canine nasal tumours but, in almost all cases, there is local recurrence associated with poor prognosis. This report describes the effect of endoscopic photodynamic therapy using talaporfin sodium for canine intranasal carcinoma recurring after radiation therapy. Rhinoscopic photodynamic therapy was administered after radiation therapy in three dogs with recurrent intranasal carcinoma. Two to 24 illuminations of a 665‐nm diode laser were performed two hours after intravenous bolus injection of 5·0 mg/kg of talaporfin sodium. Photodynamic therapy induced almost complete remission and prolonged survival time in all cases suggesting that it might be a useful treatment for intranasal carcinomas that recur after radiation.     

Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003)

OBJECTIVE: To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. DESIGN: Retrospective case series. ANIMALS: 139 dogs with histologically confirmed nasal carcinomas. PROCEDURES: Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. RESULTS: Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.