Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20-100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7-10 months, resulting in a median survival of 10-14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature.

https://www.tandfonline.com/doi/pdf/10.1080/01652176.2016.1152633

Canine lymphoma: a review.

Background
Limited information is available regarding the treatment and outcome of dogs with epitheliotropic lymphoma. The disease typically has a poor prognosis.

Objectives
To characterize the clinical signs, identify prognostic factors and evaluate the treatment outcome of dogs with epitheliotropic lymphoma.

Methods
A retrospective review of medical records from 2003 to 2015. Treatment details, tumour response and survival time were recorded for 148 dogs. Potential prognostic factors were evaluated for their statistical effect on median survival time.

Results
The overall median survival time for dogs was 264 days (cutaneous: 130 days; mucocutaneous/mucosal: 491 days). On multivariate analysis, a shorter median survival time was associated with the cutaneous form (P < 0.001) and the presence of multiple lesions (P < 0.001). Among 80 dogs with cutaneous lesions, chemotherapy treatment (P < 0.001) and having a solitary lesion (P < 0.001) were associated with longer median survival. In 72 dogs with multiple cutaneous lesions, chemotherapy intervention (P < 0.001), retinoid treatment (P = 0.001) and complete remission (P = 0.001) were associated with longer median survival. In 68 dogs with mucocutaneous/mucosal lesions, decreasing age (P = 0.020) and a solitary lesion (P = 0.015) were associated with longer median survival.

Conclusion
Canine epitheliotropic lymphoma may be divided into cutaneous and mucocutaneous/mucosal forms. Solitary lesions have a better prognosis. Dogs with multiple lesions appear to benefit from chemotherapy and retinoid treatment, with those attaining complete remission having longer survival times. Multi-agent chemotherapy could be considered in dogs with cutaneous lesions that fail to respond to single-agent chemotherapy.

Clinical outcome and prognosis of dogs with histopathological features consistent with epitheliotropic lymphoma: a retrospective study of 148 cases (2003–2015)

CCNU and other treatment protocols are commonly offered to owners for the treatment of dogs diagnosed with cutaneous (epitheliotropic) T-cell lymphoma (CTCL). Chemotherapy protocols provide variable benefits; they have different side-effects, and they typically require monitoring to detect drug toxicity at a non-negligible cost to the owner. At this time, even though CCNU is most often recommended to treat dogs with CTCL, there is no clear consensus on the benefit of this drug. Knowing which chemotherapy protocol yields the highest rate of complete remission and longest survival times would help veterinarians and pet owners select treatment options based on the best evidence available. Our objective was to review the literature to compare the complete remission rates and survival times of CCNU-based protocols to those of other interventions. We critically assessed the data included in articles reporting treatment outcome in at least five dogs with CTCL. Single case reports and case series with less than five patients were not reviewed to avoid anecdotal evidence of lower quality. The search for, and review and analysis of, the best evidence available as of February 8, 2017, suggests that CCNU and pegylated liposomal doxorubicin appear to yield the highest rate of complete remission in approximately one-third of dogs with CTCL. Other treatment protocols did not report usable information on remission rates. Without any treatment, the mean/median survival time in dogs with CTCL varied between 3 and 5 months. With CCNU protocols, the median survival time was 6 months and the one with retinoids (isotretinoin and/or etretinate), PEG L-asparaginase or prednisolone monotherapy was 11, 9 and 4 months, respectively; all these durations were obtained from small numbers of dogs, however. CCNU leads to a complete remission of signs in approximately one-third of dogs with CTCL, but such remissions are of short duration. The median survival time after CCNU appears longer than that without treatment, but other drugs appear to provide a better long-term prognosis. Further studies are required to investigate the effect of CCNU, alone or in combination, on remission rates, survival times and impact on quality of life.

/pdf/is-ccnu-lomustine-valuable-for-treatment-of-cutaneous-3d23gi1a61.pdf

Is CCNU (lomustine) valuable for treatment of cutaneous epitheliotropic lymphoma in dogs? A critically appraised topic

https://www.vetexotic.theclinics.com/article/S1094-9194(18)30012-4/pdf

Update on Cancer Treatment in Exotics

Simple Summary Canine lymphoma is a common cancer of one of the white blood cells that is commonly treated with chemotherapy. Many papers have been published about this disease and treatment, but few comprehensive reviews of the outcomes reported after chemotherapy, and the prognostic factors that influence the outcomes, have been published. Knowledge of the potential outcomes for this disease is important for veterinarians as they guide dog owners in the decision making about treatment options. This review evaluated the papers published on this topic and found that there is a wide variation in outcomes reported, as well as the factors that influence the outlook. Additionally, while individual papers have shown a much better survival, over the last 40 years, the overall improvement in outcome has been modest at best. The use of uniform reporting in the studies is needed, and novel approaches are likely needed to significantly improve the outlook for dogs with this disease. Abstract While canine lymphoma is a relatively common and important disease seen by veterinarians, there are limited comprehensive reviews of the literature regarding the remission and survival times following chemotherapy, and the associated prognostic factors. This comprehensive thematic review covers the available veterinary literature covering treatment outcomes and identified prognostic factors. A lack of standardised approaches to evaluate and report the outcomes was identified, including factors that would alter the duration of responses by weeks, or occasionally months. After publication of the suggested reporting criteria, this has improved but is still not uniformly applied. The prognostic factors included for evaluation varied from as few as three to seventeen, with over 50 studies using only univariate analysis. Individual papers reported much longer outcomes than others, but assessing the outcomes overall, there has been minimal change over the last 40 years. This supports the belief that novel approaches for lymphoma therapy will be required to substantively improve outcomes.

/pdf/review-of-canine-lymphoma-treated-with-chemotherapy-outcomes-2lhxg7x5.pdf

Review of Canine Lymphoma Treated with Chemotherapy—Outcomes and Prognostic Factors

This study evaluated efficacy and side effects of masitinib in canine epitheliotropic lymphoma. Complete remission occurred in 2 of 10 dogs and lasted for median 85 days. Five dogs went into partial remission for median 60.5 days. Three pretreated dogs did not respond to therapy. Side effects occurred in six dogs and were mostly mild to moderate. Immunohistochemistry was available for eight dogs. KIT receptor was negative in all of them, six of eight lymphomas stained strongly positive for stem cell factor (SCF). platelet-derived growth factor (PDGF)-AA was weakly positive in two and negative in six. PDGF-BB was negative in four tumours, weakly positive in one and strongly positive in three. One was strongly positive for PDGF receptor (PDGFR)-β, seven were negative for that receptor. Five showed strong expression of PDGFR-α, two showed weak expression, one was negative. In conclusion, masitinib is effective in treating canine epitheliotropic lymphoma. But its effects are most likely not generated through the KIT receptor.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/vco.12157

Masitinib monotherapy in canine epitheliotropic lymphoma

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Masitinib monotherapy in canine epitheliotropic lymphoma