Timing of adjuvant chemotherapy following limb amputation and effect on outcome in dogs with appendicular osteosarcoma without distant metastases

OBJECTIVETo determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosar-coma without distant metastases and whether TIamp-chemo was associated with outcome.ANIMALS168 client-owned dogs treated at 9 veterinary oncology centers.PROCEDURESData were collected from the dogs’ medical records concerning potential prog-nostic variables and outcomes. Dogs were grouped as to whether they re-ceived chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TIamp-chemo.R E S U LT SMedian TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (239 days; 95% CI, 186 to 291 days).CONCLUSIONS AND CLINICAL RELEVANCEFindings indicated that early (within 5 days) initiation of adjuvant chemo-therapy after limb amputation was associated with a significant and clini-cally relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of che-motherapy may be an important prognostic variable. (J Am Vet Med Assoc2021;259:749–756)with or without alternating doxorubicin, has become the standard of care for dogs undergoing limb ampu-tation, yielding a survival benefit for many dogs.3The concept that perioperative administration of chemotherapy may improve outcome is not new. A study4 in mice showed that the temporal relationship between tumor excision and chemotherapy is an im-portant variable in determining outcome for osteosar-coma, with mice receiving chemotherapy at the time of surgery experiencing an enhancement of drug effect. This finding is most likely attributable to the recruitment of resting metastatic cells into the cell cycle once the primary tumor has been removed.5,6 In people with osteosarcoma, early initiation of chemo-therapy after tumor excision is reported to provide a survival benefit, with data suggesting a worse out-come when chemotherapy is delayed.7, 8In dogs, no clear evidence exists that the TIamp-chemo is associated with better survival times. Adju-vant chemotherapy is commonly started 2 weeks af-ter amputation to maximize patient recovery.1,9,10 A ABBREVIATIONSALPAlkaline phosphataseHR Hazard ratioOSTOverall survival timeTBCT Total body computed tomographyTIamp-chemoTime interval between amputation and adjuvant chemotherapyTTPTime to tumor progression