Introduction

Canine lymphoma is one of the most investigated cancers in veterinary oncology. Multiple studies evaluating prognostic factors, biomarkers, a multitude of single and multi-agent chemotherapy protocols, multimodality treatment approaches, evaluation of minimal residual disease, novel therapeutic approaches as well as novel information on advanced imaging procedures in the diagnosis of canine lymphoma patients have been reported. In addition, studies comparing maintenance free chemotherapy (discontinuous) to continuous protocols including maintenance chemotherapy have been published.

Standard of Care?

Despite these efforts, standard of care (SOC) for diagnosis, staging, treatment and follow-up management has not been defined for canine lymphoma. This is most likely because many patients are not consistently diagnosed, staged or classified according to currently possible classification schemes. Furthermore, the majority of studies are retrospective in nature encompassing a multitude of lymphoma types, anatomic locations and inconsistent diagnostic and staging criteria prior to therapy. Many patients only have a cytological diagnosis and some are not staged prior to therapy as cost issues may favor spending the client’s resources on treatment rather than diagnostics. In addition, the current treatment approach is a “one-size fits all” approach which is hugely discordant with the diagnostic and treatment approaches in human oncology.

European Canine Lymphoma Network

In 2016, The European Canine Lymphoma Network (ECLN) (Marconata et al. VCO, 2016), reported a systematic review of the past 15 years of canine lymphoma study publications representing the latest collected information on canine lymphoma. This commendable effort was undertaken to learn from previous studies and to potentially supply future recommendations for the diagnosis, management and follow-up of canine lymphoma. The authors evaluated 63 treatment studies of which only 8 were randomized controlled trials and of these only 2 concerned a single lymphoma diagnosis. One of the expected conclusions of the systematic review was that the majority of studies do not have the consistency required to make valid conclusions and recommendations. Therefore, the overall conclusion was a set of recommendations to be followed in future prospective studies as a minimum, but preferentially also to be followed in all canine lymphoma patients to improve the possibility to compare results across studies and patients. A short version of the recommendations is provided below but no recommendation was made regarding treatment regimen. Please refer to Marconato et al. VCO 2016 for the full review and more detailed information.

ECLN recommendation regarding:

• Diagnosis: As a minimum WHO classification of lymphoma type as to B or T immune-phenotype should be performed (flow cytometry, immunohistochemistry [IHC]). For histopathology excisional lymph node biopsies should be preferred.
• Clinical staging prior to initiation of therapy: A minimum database (MDB) consisting of a complete hemogram including blood smear evaluation, biochemistry, and urinalysis, thoracic and abdominal imaging by either ray, ultrasound, CT or MRI as appropriate. Hepatic and splenic fine-needle aspirates (FNAsp) for cytology as well as bone marrow aspirates and core biopsies.
• Response evaluation criteria: Restaging including if possible evaluation for minimal residual disease (MRD): For discontinuous protocols: 2–4 weeks following administration of final chemotherapy treatment; for continuous protocols: 4–6 months after initiation of therapy.
• MDB with a complete hemogram incl. blood smear evaluation, biochemistry, and urinalysis, thoracic and abdominal imaging by either X-ray, ultrasound, CT or MRI as appropriate. Hepatic and splenic FNAsp for cytology as well as bone marrow aspirates and core biopsies and MRD determination.
• Follow-up: Monthly for one year and bimonthly thereafter: physical examination, lymph node FNAsp. If suspicion of relapse confirmation by cytology or histopathology.

On the Horizon

The future diagnosis, management and prognostication of canine lymphoma likely will include biomarkers, scoring systems such as the modified Glasgow prognostication score (mGPS), molecular diagnostic techniques, molecular imaging (PET-CT, PET-MRI and potentially also HyperPET) as well as species-specific immune therapeutic approaches.

References

1.  Comazzi S, Marconato L, et al.; European Canine Lymphoma Network. The European canine lymphoma network: a joining initiative to generate consensus guidelines for the diagnosis and therapy in canine lymphoma and research partnership. Vet Comp Oncol. 2015;3(4):494–497.

2.  Marconato L, Polton GA, et al.; European Canine Lymphoma Network. Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature. Vet Comp Oncol. 2016;Jul 14. doi: 10.1111/vco.12244

3.  Vail OM, Michels GM, Khanna C, Selting KA, London CA; Veterinary Cooperative Oncology Group. Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0) - a Veterinary Cooperative Oncology Group (VCOG) consensus document. Vet Comp Oncol. 2010 Mar;8(1):28–37.

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5.  Panjwani MK, Smith JB, Schutsky K, Gnanandarajah J, O’Connor CM, Powell DJ Jr, Mason NJ. Feasibility and safety of RNA-transfected CD20-specific chimeric antigen receptor T cells in dogs with spontaneous B cell lymphoma. Mol Ther. 2016;24(9):1602–1614.