|Utility of Serum Biomarkers in the Treatment of Canine Lymphoma|
Lymphoma is the most common immune system cancer affecting dogs with an estimated incidence of 25 per 100,000 dogs. The high grade, lymphoblastic form is most common in dogs and typically presents as a multicentric disease process. Various prognostic factors exist for predicting survival times of canine lymphoma with chemotherapy treatment such as:
However, additional biochemical markers could be useful in predicting response, remission duration, and survival time.
Although canine lymphoma is very difficult to cure, a large majority of patients initially respond favorably to treatment with chemotherapy. According to numerous studies, the expected first remission rate is 70-90%. Due to the inability to use curative intent dosing of chemotherapy agents in veterinary medicine and simultaneously preserve quality of life, the disease invariably relapses with <10% of dogs being cured.
Depending on the timing of relapse, the success of inducing subsequent remissions is around 50-70% and the duration of those remissions is typically half the length of the previous remission. Monitoring patients’ remission status during the treatment protocol and after completion of chemotherapy involves physical examination and palpation of lymph nodes.
This can be very subjective and only detects gross changes in the lymph nodes themselves. The disease can be relapsing at the molecular level for weeks prior to the detection of enlarged peripheral lymph nodes. By the time that lymph nodes are palpably enlarged, the tumor burden is exponentially higher when compared to the tumor burden at the time of onset of relapse. Biochemical methods for evaluating biomarkers present in the blood have the potential to provide a more objective assessment of a patient’s remission status. In addition, a detectable rise in serum biomarkers would likely precede the development of enlarged peripheral lymph nodes, allowing relapse to be detected earlier in the disease progression. Such biomarkers do exist in people with non-Hodgkin’s lymphoma but have not gained utility in veterinary medicine.
A recent study published in 2014 by Alexandrakis (et al1) evaluated two such biomarkers (C-reactive protein, and haptoglobin, which are both acute phase proteins) to determine their usefulness in monitoring remission status and relapse in dogs with lymphoma being treated with chemotherapy.
Over the four year study period, 196 serum samples from 57 dogs undergoing chemotherapy treatment for lymphoma were collected and analyzed. The results of these biochemical tests in conjunction with a computer algorithm were combined to create a canine lymphoma blood test (cLBT) that was compared to the treating clinician’s assessment of remission status and relapse. Reference ranges were established for the test and were evaluated for any impact on prognosis.
Several interesting findings were noted in this preliminary, fact finding study. First, dogs that had cLBT levels below a specific cutoff value at diagnosis had a significantly longer survival time compared to dogs that had higher initial cLBT levels (Figure 1).
This is important as it could represent an additional test that we can offer at the time of initial consultation to help educate clients about their dog’s expected prognosis and potentially help guide their decision regarding treatment. Second, the lowest cLBT score achieved during the treatment was significant. The survival time was longer for dogs whose lowest cLBT fell below cutoff values established in the study compared to dogs whose cLBT never fell below that value. Such information could be important in order to assess a patient’s initial response to therapy and to determine if any changes to the remainder of the protocol are warranted in an effort to move toward individualized treatment.
Finally, they found that for patients who relapsed, the cLBT began to rise in the 8 weeks prior to the clinician’s detection of palpable lymphadenopathy and subjective assessment of relapse (Figure 2). This finding could be an important factor in detecting early relapse and improving survival times for dogs with lymphoma.
Although the results of this study are interesting and encouraging, there is still work to be done and ongoing investigation in a prospective fashion is certainly warranted.
The utility of these biochemical markers in detecting remission and providing prognostic information has been established. The next step is to determine the benefit of detecting early relapse in dogs with lymphoma. A group of dogs with lymphoma in which chemotherapy protocol changes are made based on cLBT scores would need to be evaluated in a prospective fashion. If modifying treatments based on cLBT scores proves a significant patient survival advantage, the use of biomarkers will become important in the treatment of canine lymphoma patients. Until such a time when we can ensure the benefit of these additional diagnostics we should use caution in recommending them for all patients given the added client cost of running repeated biochemical analysis at diagnosis and throughout therapy. Continued investigation is currently underway and promising additional information is expected to be forthcoming.