Adjuvant chemotherapy should be initiated in a timely manner following surgery to maximally impact residual neoplasia. However, optimal timing remains unknown. The aim of this retrospective study was to examine whether there was a measurable prognostic impact of the time interval to adjuvant systemic chemotherapy (TI) in dogs with appendicular osteosarcoma following limb amputation. The objectives of the study were to evaluate whether any relationship existed between TI and prognosis and, if so, whether there was an optimal TI or a TI after which the benefit of treatment decreases.

Dogs were included if they underwent limb amputation for a histologically confirmed appendicular osteosarcoma; had no evidence of distant metastases; had a body weight >15 kg; received at least four cycles of adjuvant dose-intense chemotherapy, and had complete clinico-pathologic and follow-up data. The following clinico-pathological factors were analyzed: breed, age, sex, weight, symptom duration, site of osteosarcoma, lymph node metastasis, distant metastasis, alkaline phosphatase, monocytes, lymphocytes, type of imaging, chemotherapy protocol, number of cycles, chemotherapy-related toxicity, and cause of death.

Dogs were classified into eight groups based on whether they received chemotherapy 3, 5, 7, 10, 15, 20, 30 days or >30 days after surgery. Survival analyses were performed to identify potential prognostic factors.

One hundred and thirty dogs were included. The median TI was 14 days (range, 1–70). TI of 7 days was associated with the greatest survival benefit; dogs receiving chemotherapy 8 or more days after surgery had a risk 1.8 times higher for death from osteosarcoma-related causes (p=0.008).

Median time to progression (TTP) for dogs receiving chemotherapy within 7 days [440 (95% CI, 334–546)] was significantly higher than that for dogs being treated after 7 days [243 (95% CI, 200–286)]; p=0.026]. Median overall survival (OS) for dogs receiving chemotherapy within 7 days [533 (95% CI, 397–668)] was significantly higher than that for dogs being treated after 7 days [281 (95% CI, 248–314)]; p=0.007].

No other potential prognostic factors were associated with TTP or OS.

Findings from our study indicate that the timing of chemotherapy initiation is an important prognostic variable. Based on these data, we recommend that great efforts should be made to minimize post-surgical recovery time to enable starting adjuvant chemotherapy within 7 days post-surgery. TI of 7 days was associated with a significant survival benefit in our population of dogs with non-metastatic appendicular osteosarcoma.

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