Abstract

BackgroundAssessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms.ResultsAn increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival.ConclusionsPredicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.

Highlights

  • Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter

  • Analysis of the rRNA fragmentation patterns using the RNA electropherograms led to the creation of an RNA Disruption Index (RDI), which quantifies the degree of rRNA fragmentation in a given sample

  • RNA disruption occurred in samples from breast cancer patients treated with zoledronic acid [20] and in human prostate tumour xenografts treated with docetaxel or a docetaxel/relaxin hormone receptor agonist (AT-001) combination [21]

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Summary

Introduction

Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. The use of RNA integrity was first identified as a prognostic marker in a human breast cancer clinical trial in which patients undergoing treatment with neoadjuvant chemotherapy had core needle-biopsy samples taken pre-, mid- and post-therapy. An additional study found a strong correlation between RNA disruption after one cycle of docetaxel, carboplatin, trastuzumab ± lapatinib and pCR in a small group of Her2+ breast cancer patients [22]

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