Comparative study of the collapsed cone convolution and Monte Carlo algorithms for radiation therapy planning of canine sinonasal tumors reveals significant dosimetric differences.

Computer-based radiation therapy requires high targeting and dosimetric precision. Analytical dosimetric algorithms typically are fast and clinically viable but can have increasing errors near air-bone interfaces. These are commonly found within dogs undergoing radiation planning for sinonasal cancer. This retrospective methods comparison study is designed to compare the dosimetry of both tumor volumes and organs at risk and quantify the differences between collapsed cone convolution (CCC) and Monte Carlo (MC) algorithms. Canine sinonasal tumor plans were optimized with CCC and then recalculated by MC with identical control points and monitor units. Planning target volume (PTV)air , PTVsoft tissue , and PTVbone were created to analyze the dose discrepancy within the PTV. Thirty imaging sets of dogs were included. Monte Carlo served as the gold standard calculation for the dosimetric comparison. Collapsed cone convolution overestimated the mean dose (Dmean ) to PTV and PTVsoft tissue by 0.9% and 0.5%, respectively (both P < 0.001). Collapsed cone convolution overestimated Dmean to PTVbone by 3% (P < 0.001). Collapsed cone convolution underestimated the near-maximum dose (D2 ) to PTVair by 1.1% (P < 0.001), and underestimated conformity index and homogeneity index in PTV (both P < 0.001). Mean doses of contralateral and ipsilateral eyes were overestimated by CCC by 1.6% and 1.7%, respectively (both P < 0.001). Near-maximum doses of skin and brain were overestimated by CCC by 2.2% and 0.7%, respectively (both P < 0.001). As clinical accessibility of Monte Carlo becomes more widespread, dose constraints may need to be re-evaluated with appropriate plan evaluation and follow-up.

Outcomes of 35 dogs with craniomaxillofacial osteosarcoma treated with stereotactic body radiation therapy.

Canine craniomaxillofacial osteosarcoma (OSA) is most commonly treated surgically; however, in cases where surgery is not feasible or non-invasive treatment is desired, stereotactic body radiation therapy (SBRT) may be elected for local tumour control. In this study, we evaluated 35 dogs treated with SBRT. Nine dogs (26%) had calvarial, seven (20%) had mandibular and 19 (54%) had maxillary OSA. Median time to first event (TFE) was 171 days, and overall median survival time (MST) was 232 days. Site-specific MSTs were 144 days for mandible, 236 days for calvarium and 232 days for maxilla (p = .49). Pulmonary metastatic disease was observed in 12/35 (34%) patients and was detected pre-SBRT in six dogs (17%) and post-SBRT in the remaining six dogs (17%). Eighteen adverse events post-SBRT were documented. Per veterinary radiation therapy oncology group criteria, five were acute (14%) and three were late (9%) grade 3 events. Neurological signs in two dogs were suspected to be early-delayed effects. Cause of death was local progression for 22/35 (63%) patients, metastasis for 9/35 (26%) patients and unknown for four. On univariate analysis, administration of chemotherapy was associated with a longer TFE (p = .0163), whereas volume of gross tumour volume was associated with a shorter TFE (p = .023). Administration of chemotherapy and five fractions versus single fraction of SBRT was associated with increased survival time (p = .0021 and .049). Based on these findings, a treatment protocol incorporating chemotherapy and five fractions of SBRT could be considered for dogs with craniomaxillofacial OSA electing SBRT with careful consideration of normal tissues in the field.

The prognostic significance of metabolic tumour volume and total lesion glycolysis for dogs staged for appendicular osteosarcoma with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.

Metabolic tumour volumes (MTV) and total lesion glycolysis (TLG) are metabolic parameters that are becoming more commonly reported in human medicine to quantify tumours detected on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT). In this retrospective study dogs afflicted with appendicular osteosarcoma that were staged with 18 F-FDG PET/CT had MTV and TLG at a variety of set and fixed thresholds calculated by two observers. These values, along with SUVmax , were evaluated for prognostic significance in this population of dogs. There was excellent correlation between two observers for all values. Multiple volumetric parameters were significantly associated with survival. SUVmax had the highest sensitivity for survival and TLG at 2.5 SUV*cm3 had the highest specificity for prediction of survival based on ROC calculations. The SUVmax , MTV at 2.5 SUV and TLG at 2.5 SUV*cm3 were significantly different between dogs that survived more than or less than 1 year. This study is the first of its kind in veterinary medicine that retrospectively evaluated volumetric tumour values for prognostic significance and may provide a basis for standardized method of reporting 18 F-FDG PET/CT results.

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats.

BACKGROUND: The safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described. HYPOTHESIS: Stereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well-tolerated treatment for localized nasal lymphoma in cats. ANIMALS: Thirty-two client owned cats referred to Colorado State University for the treatment of nasal lymphoma. METHODS: Retrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded. RESULTS: Progression free survival was 225 days (95% CI 98-514) and median survival time (MST) was 365 days (95% CI 123-531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty-four cats (75%) had signs consistent with chronic rhinitis. CONCLUSIONS: SBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam's stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy.

Therapeutic Intervention Using a Smad7-Based Tat Protein to Treat Radiation-Induced Oral Mucositis.

PURPOSE: Recent studies reported therapeutic effects of Smad7 on oral mucositis in mice without compromising radiation therapy-induced cancer cell killing in neighboring oral cancer. This study aims to assess whether a Smad7-based biologic can treat oral mucositis in a clinically relevant setting by establishing an oral mucositis model in dogs and analyzing molecular targets. METHODS AND MATERIALS: We created a truncated human Smad7 protein fused with the cell-penetrating Tat tag (Tat-PYC-Smad7). We used intensity modulated radiation therapy to induce oral mucositis in dogs and applied Tat-PYC-Smad7 to the oral mucosa in dose-finding studies after intensity modulated radiation therapy. Clinical outcomes were evaluated. Molecular targets were analyzed in biopsies and serum samples. RESULTS: Tat-PYC-Smad7 treatment significantly shortened the duration of grade 3 oral mucositis based on double-blinded Veterinary Radiation Therapy Oncology Group scores and histopathology evaluations. Topically applied Tat-PYC-Smad7 primarily penetrated epithelial cells and was undetectable in serum. NanoString nCounter Canine IO Panel identified that, compared to the vehicle samples, top molecular changes in Tat-PYC-Smad7 treated samples include reductions in inflammation and cell death and increases in cell growth and DNA repair. Consistently, immunostaining shows that Tat-PYC-Smad7 reduced DNA damage and neutrophil infiltration with attenuated TGF-ß and NFκB signaling. Furthermore, IL-1ß and TNF-α were lower in Tat-PYC-Smad7 treated mucosa and serum samples compared to those in vehicle controls. CONCLUSIONS: Topical Tat-PYC-Smad7 application demonstrated therapeutic effects on oral mucositis induced by intensity modulated radiation therapy in dogs. The local effects of Tat-PYC-Smad7 targeted molecules involved in oral mucositis pathogenesis as well as reduced systemic inflammatory cytokines.

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma.

Thyroid carcinoma develops spontaneously in dogs, with only 25% to 50% of cases amenable to surgery at diagnosis. Local control for unresectable tumours can be provided with external beam radiotherapy. The aim of this retrospective study is to describe the safety and efficacy of stereotactic body radiation therapy (SBRT) for treatment of canine thyroid carcinoma. Twenty-three dogs met inclusion criteria; median tumour volume before SBRT was 129.9 cm3 (range, 2.7-452.8 cm3 ). Sixteen patients (70%) had unresectable tumours. Pulmonary metastasis was present or suspected in 10 patients (44%) before SBRT. Patients were prescribed 15 to 40 Gy to targeted tumour volume in one to five fractions. Twenty patients evaluated had overall response rate of 70% (complete response, n = 4; partial response, n = 10). Thirteen out of sixteen (81%) symptomatic patients had clinical improvement within a median time of 16 days (range, 2-79 days). Median progression free survival (MPFS) was 315 days. Median survival time (MST) was 362 days. Nine patients (39%) had grade 1 acute radiation toxicity. Three patients had grade 1 late radiation toxicity (two leukotrichia and one [4%] with intermittent cough). Responders had significantly longer MPFS (362 vs 90 days; HR 4.3; 95% CI 1.4-13.5; P = .013) and MST (455 vs 90 days; HR 2.9; 95% CI 1-8.4; P = .053). Presenting with metastasis was not a significant negative prognostic factor (MST 347 vs 348 days without metastasis; P = .352). SBRT is a safe and effective treatment modality for non-resectable canine thyroid carcinoma.