Response of Spontaneous Oral Tumors in Canine Cancer Patients Treated with Stereotactic Body Radiation Therapy (SBRT)

Abstract

The objective of this study is describe outcome and toxicity for dogs with oral tumors, specifically oral malignant melanoma (OMM), squamous cell carcinoma (SCC), and soft tissue sarcoma (STS) after stereotactic body radiation therapy (SBRT). A single institution retrospective study was conducted. Outcomes were analyzed using Kaplan-Meier analysis and Cox proportional hazard analysis. Treatment responses at different time points were evaluated with Pearson's Chi-squared test to identify prognostic factors. Acute and late toxicities were recorded according to VRTOG criteria and were analyzed to identify risk factors. Adverse events other than acute and late toxicities were recorded. A total of 98 patients met the inclusion criteria (OMM n = 37; SCC n = 18; STS n = 43). The SBRT prescription was 1-6 fractions, with a total dose range of 12-40 Gy. Local progression-free survival (PFS) for OMM, SCC, and STS was 187, 253, and 161 days, respectively. Overall PFS was 152 days and median survival time (MST) was 270 days, with no statistical difference between tumor types. The presence of lymph node metastasis and the use of elective nodal irradiation (ENI) were associated with shorted PFS and MST. Severe acute toxicities to organs at risk affected 10/85 (11.8%) of patients. Osteoradionecrosis and oronasal fistula formation occurred in 23/81 (28.4%) of patients and was significantly associated with tumor type (SCC, P = 0.006). SBRT can be offered as a treatment option for oral tumors in dogs. Toxicities were common and warrant risk factor considerations and adjustments to current SBRT protocols.

FIG. 1.

Specific tumor location amongst the total population (%) and between tumor types (n) and specific anatomical extension amongst the total population. Created with Biorender.com. Abbreviations: OMM, oral malignant melanoma; SCC, squamous cell carcinoma; STS, soft tissue sarcoma; PM4, fourth premolar; M2/3, 2nd and 3rd molar; R-C, rostral-caudal; C-O, caudal-oropharyngeal; R-C-O, rostral-caudal-oropharyngeal.

FIG. 2.

Timeline summarizing local response of oral tumors to SBRT. Chi-square and Fisher’s exact test were used to analyze the association between response and tumor type, primary tumor size (T stage, pre-RT LTD), tumor extension (rostral, caudal, oropharyngeal, rostral-caudal, caudal-oropharyngeal, rostral-caudal-oropharyngeal), radiation treatment (total dose, dose/fraction). Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CB, clinical benefit: RECIST criteria cannot be applied; N/A, not applicable: patient diseased or tumor underwent local treatment post-RT; N/D, patient alive, response not documented; LTD, longest tumor diameter; fx, fraction; CBR, Clinical benefit rate (CR + PR + SD + CB).

FIG. 3.

Survival analysis using Kaplan-Meier curves by tumor types. Panel a: Local progression-free survival (L-PFS). Panel b: Overall progression-free survival (PFS). Panel c: Overall survival time (OST). Panel d: Disease-specific survival time (DSS).

FIG. 4.

Impact of nodal irradiation on PFS and OST. A total of 5 dogs had confirmed lymph node metastasis irradiation without elective nodal irradiation (ENI) and were grouped with the mLN + ENI. Panels a and b: Dogs were divided into three groups. If lymph nodes were included, but not confirmed to be metastatic with sampling, they were categorized as ENI. Panels c and d: Dogs in the above ENI only group were further divided into ENI when lymph nodes were sampled and had low clinical concern for undetected metastasis, and smLN PNRT when lymph nodes were not sampled and there was concern for metastasis on advanced imaging and medical record review. Abbreviations: ENI, elective nodal irradiation; mLN RT, metastatic lymph node radiation therapy; smLN, suspected metastatic lymph node.

FIG. 5.

Summary of the use of ENI in the canine population with oral tumors treated with SBRT and outcomes associated with regional lymph node disease progression. The incidence of new nodal progressive disease post-SBRT was compared using Fisher’s exact test (P = 0.53). The time to nodal progression between no ENI and ENI use was compared using Kaplan-Meier curve analysis and Log-Rank test (P = 0.82). Created with Biorender.com. Abbreviations: ENI, elective nodal irradiation; mLN RT, metastatic lymph node radiation therapy; smLN, suspected metastatic lymph node; LN PD, regional lymph node progressive disease.