A toxicity study of low‐dose rate half‐body irradiation and chemotherapy in dogs with lymphoma

Abstract

Thirteen dogs with previously untreated multicentric lymphoma were enrolled in a prospective study investigating the effects of low-dose rate total body irradiation (TBI) and chemotherapy. Dogs received either 6 or 8 Gy TBI in half-body fractions, 2 weeks apart. Toxicity consisted of mild to moderate haematological and gastrointestinal (GI) signs. One dog died from treatment complications. Anorexia was noted independent of dose. Haematological toxicity was more common and more severe after 8 Gy treatment. GI toxicity was more likely postcaudal half-body irradiation with 8 Gy. Other than leukotrichia, late effects from radiation were not observed. Results indicated that haematological and nonhaematological toxicity was dose dependent. However, the protocol was well tolerated and treatment intensification using a 2-week inter-radiation interval was possible in all dogs treated with 6 Gy. Preliminary survival data for these dogs were very encouraging, providing a strong rationale to analyse the efficacy of low-dose rate irradiation (LDRI) in canine lymphoma.

Sequential Low‐Dose Rate Half‐Body Irradiation and Chemotherapy for the Treatment of Canine Multicentric Lymphoma

“…Dogs included in the analysis had stage 3, 4, or 5 multicentric lymphoma, substage a or b. Immunophenotype was not a criterion for inclusion nor was remission status at the time of the 1st scheduled HBI treatment. Dogs were excluded if induction chemotherapy treatments deviated in any way from the previously outlined protocol 13 or if they were treated with radiation doses other than 6 Gy. Thirty‐eight dogs with multicentric lymphoma were included for analysis.…”

“…All dogs were treated with 6 Gy LDR (8–14 cGy/min) sequential HBI incorporated into a standard chemotherapy protocol as described previously (Table 1). 13 Five dogs were treated with an abbreviated chemotherapy protocol in which an actinomycin D‐based maintenance regimen was not used (Table 1). All dogs received prednisone treatment on a tapering dose schedule (starting at 2 mg/kg) for the 1st 4 weeks of induction chemotherapy.…”

“…Criteria for patients to receive caudal half‐body irradiation (CdRT) have been outlined 13 . Patients were divided into 2 groups based on the duration of their maintenance chemotherapy protocol.…”

“…All dogs were evaluated weekly during induction and toxicity was graded according to Veterinary Co‐operative Oncology Group (VCOG) guidelines 17 ; grades 1–5 being mild, moderate, severe, life‐threatening, and death, respectively. Complete toxicity data for 6/38 dogs in this study has been presented in a previous study evaluating the toxicity profile of this combination LDRI/chemotherapy protocol 13 . Given that the protocol was generally well tolerated in the 6 Gy HBI group in that study, BM aspirates after CdRT, serum biochemistry, and bile acid analysis pre‐ and post‐HBI were not routinely conducted in the remaining 32 dogs in this study.…”

“…This approach may inadvertently affect efficacy by allowing repopulation of the irradiated half by neoplastic cells from the nonirradiated half. We have recently reported on the toxicity profile of an alternative low‐dose rate irradiation (LDRI) protocol, which allowed treatment intensification by shortening the interradiation interval to 2 weeks in the majority of dogs 13 . This protocol proved to be well tolerated at the 6 Gy dose level and preliminary efficacy data were very promising.…”