Surgery and postoperative definitive radiotherapy for management of canine soft tissue sarcoma: a multi-institutional retrospective study of 272 dogs (2010-2020).

OBJECTIVE: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival. METHODS: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted. Selected variables were assessed for association with local progression and overall survival. RESULTS: 272 dogs were included. Histologic grade was reported in 249 dogs: 102 were grade 1 (40.9%), 120 were grade 2 (48.2%), and 27 were grade 3 (10.8%). Local progression was suspected or confirmed in 56 dogs. Local progression rates were similar for grade 1 (24 of 89 [26.7%]), grade 2 (23 of 111 [20.7%]), and grade 3 tumors (6 of 22 [27.3%]). Previous recurrence (P = .010) and subsequent distant metastasis (P = .014) were associated with more frequent local progression; intensity-modulated radiotherapy was associated with decreased local progression (P = .025) compared to other forms of delivery. Age (P = .049), grade (P = .009), previous recurrence (P = .009), and institution type for surgery (P = .043) were associated with overall survival. CONCLUSIONS: Outcomes for most dogs were good; however, the frequency of local progression indicates an ongoing need to critically appraise local management strategies, particularly for low-grade STS. Intensity-modulated radiotherapy was associated with lower rates of local progression and may be preferred to less precise forms of delivery. CLINICAL RELEVANCE: These data may guide clinicians when making decisions regarding dRT for management of STS.

Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma.

Introduction: Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL's radiosensitization has not been fully elucidated. Methods: We investigated ZOL's ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks). Results: We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT (p = 0.027). Discussion: ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.