Abstract
Background:
Despite an initial favorable response to hypofractionated radiotherapy (RT), intranasal neoplasia has a poor long-term prognosis. Re-irradiation (re-RT) has been shown to result in clinical remission in dogs with recurrent intranasal tumors. Hypofractionated re-RT is indicated in cases of recurrence.

Aim:
This study aimed to investigate the response of patients with recurrent intranasal tumors who were initially treated with repeated hypofractionated RT.

Methods:
Medical records of dogs with intranasal tumors that relapsed after undergoing hypofractionated RT at Azabu University Veterinary Teaching Hospital and who underwent re-RT between 2008 and 2022 were retrospectively analyzed.

Results:
Among the 30 dogs included, 20 had adenocarcinomas. Eleven patients underwent second re-irradiation, and five patients underwent third re-irradiation. The median total isocenter dose and total number of fractions were 56 Gy (range, 37.5–102) and 8 fractions (range, 5–14), respectively. The first, second, and third progression-free intervals (PFI) were 315 (n = 30), 185 (n = 11), and 218 days (n = 4), respectively. Overall survival (OS) was 504 days (n = 30). Adverse events such as alopecia (n = 7), white hair (n = 8), cataracts (n = 9), pigmentation (n = 5), keratitis (n = 3), and corneal ulceration (n = 1) were limited to grades 1 and 2. The medians of the first PFI for one course and two or more courses of re-RT were 298 and 331 days, respectively, indicating no significant differences between the groups. The OS after two or more courses of re-RT (758 days) was significantly longer than after one course of re-RT alone (414 days) (P = 0.048). However, the cases were not randomized and most of the tumor types were adenocarcinomas.

Conclusion:
Since it is expected to prolong survival time with few life-threatening adverse events, the findings of the present study suggest that hypofractionated re-RT can be used in dogs with recurrent intranasal tumors initially treated with hypofractionated RT. Therefore, repeated hypofractionated re-RT may be a reasonable option for young dogs with a good initial response and recurrent intranasal tumors.

Key words: Dog, Hypofractionated radiotherapy, Intranasal tumor, Recurrence, Re-irradiation