Ultrasonography of Osteosarcoma in Dogs
Sonography Atlas of Dogs

Survival Time

No dogs were confirmed alive at the time of analysis. Nine dogs (16.7%) were lost to follow‐up and were censored by the last known date that they were alive. Of the dogs confirmed to be deceased, 2 died, 40 were euthanized, and the cause of death was unknown in 3. Median ST for dogs with OSA was 192.5 days (20–1,271 days) and there was no association with BCS category (P = .474). On univariate survival analysis, anemia (P = .005), hypoalbuminemia (P = .002), and change in body weight after diagnosis (P = .003) were associated with ST. Only weight change remained significant on multivariate analysis with dogs gaining more than 10% of body weight living longer than those gaining <10% or losing <10% (both P < .001).

Discussion

Contrary to one of our hypotheses, obesity was not associated with shorter ST or PFI among dogs with LSA and OSA. For dogs with LSA, there was also no difference among the groups for MTR or whether the dogs achieved clinical remission within 6 weeks of starting treatment among BCS categories. This is in contrast to studies that have shown increased tumor aggressiveness2 along with a higher risk of death caused by cancer1, 7, 20 and shorter survival times21 in overweight humans.

There are several possible reasons why a detrimental association between overweight or obese body condition and outcomes was not observed in this study. The first is that the majority of dogs in the overweight group for both cancers had BCS between 6 and 7 (“overweight”) rather than 8 or 9 (“obese”). It might be that being overweight is not as harmful as being obese. If that is true, then the relative lack of dogs of BCS 8–9 versus 6–7 could have obscured a survival difference between the normal weight and obese dogs. Another possibility is that the effects of obesity might differ with different types of cancer. Indeed, while it is well accepted that obesity increases the risk of development of many types of cancers in people,5 thus far it has only been clearly reported to increase cancer‐related mortality in colorectal cancer and postmenopausal breast cancer.3, 6 Canine LSA is most similar to non‐Hodgkin's lymphoma in humans and the literature is rather inconsistent on the association between obesity and this type of cancer: studies indicating longer, shorter, or no change in ST among overweight or obese people have each been reported.15, 20, 22, 23, 24 Another possibility to explain the lack of association noted in this study is that the effect might be relatively modest and might require a much larger study population to see a difference among BCS categories. Most of the human studies that have demonstrated inverse relationships between body mass index and ST have included considerably higher numbers of cases than did this study.

A similar effect was not seen in dogs with OSA likely because of small numbers of dogs with OSA and the different disease course seen with this cancer compared with LSA. One study reported shorter ST in overweight children with OSA,25 but this study has been contested.26, 27 Overall, there is not nearly as much literature investigating obesity and OSA in people as there is for many other types of cancer, so there is not much consensus. In addition, as OSA typically affects human children, whereas it is most common in older dogs, the mechanisms and associations might differ, and it might be harder to translate findings in humans to those in dogs.

As we hypothesized, median ST was significantly shorter for dogs with LSA categorized as underweight compared to ST for the ideal and overweight groups in the univariate analysis, as occurs in humans with LSA,16, 23 urothelial carcinoma,28 esophageal cancer,29 and gastric cancer,30 and cats with various types of cancers.17 Similar results were not seen for OSA, but there were very few underweight dogs with OSA included in this study. It has been reported that people with OSA who lost more than 4.5 kg (10 pounds) of body weight had a poorer prognosis, but it remains unclear what percentage of body weight loss this represented, whether the patients were at a normal weight at the time of diagnosis or whether the weight of an amputated limb was taken into account;31 therefore, it is hard to draw conclusions on the associations between being underweight and survival in people with OSA.

For dogs with either LSA or OSA, gaining 10% or more body weight during the course of treatment was associated with longer ST than those that gained less than 10%, maintained, or lost weight. A similar situation has been reported in dogs with heart disease, where dogs that gained weight had longer survival compared to those that lost or maintained weight.32 This might be a secondary, rather than a primary effect (ie, dogs that live longer have a longer duration of time to gain weight), but weight loss (and particularly muscle loss) can have a primary role in survival as well. Shorter ST in underweight dogs might be a reflection of more severe disease, loss of lean body mass, or chronic malnutrition, all of which can compromise host defenses and alter treatment protocols. Dog owners might also be more likely to opt for euthanasia for dogs that lose weight compared to dogs that maintain or gain weight during treatment, which can confound survival time. While it is likely that weight loss during treatment reflects a poorer response to treatment, more aggressive disease, or the contribution of comorbid conditions, suboptimal calorie and nutrient intake also can play a role, making careful attention to nutrition important. This strategy can be achieved by a nutritional assessment at every visit, which includes assessment of body weight, BCS, muscle condition score, and diet history.33, 34 In addition, making specific nutritional recommendations and adjusting these recommendations based on patient response can play a role in maintaining optimal nutritional status in dogs with cancer.

Other factors associated with shorter survival for dogs with LSA included anemia and T‐cell LSA. These data agree with previous studies and suggest that hematocrit at time of diagnosis might be a useful prognostic indicator.35, 36, 37, 38

There are some limitations to this study. Body condition score, our main variable of interest, is subjective39 and we had to rely on BCS performed by numerous clinicians across and within cases. It has been the authors’ experience that clinicians tend to underestimate BCS, so it is possible that some overweight animals were included in the ideal weight group, but less likely that the reverse occurred. Coat length and thickness can also complicate estimation of BCS as the authors appreciate that thick‐coated dogs might feel like they have more “fat padding” over their ribs than thin‐coated dogs. Another potential limitation is that the BCS within a month of the time of diagnosis was used to categorize cases into underweight, ideal weight, and overweight; however, this value might not be the most accurate marker of a dog's nutritional status at the time that the cancer first developed. For example, a history of anorexia or weight loss prior to diagnosis could result in a BCS at the time of diagnosis that was not reflective of the typical BCS of the animal prior to the development of cancer. In addition, BCS measurements were not always available on the exact day of diagnosis—some of the BCS measurements were recorded after the diagnosis, others before, and some on the day of diagnosis (although all within 1 month of diagnosis). It has been suggested that the timing of body mass index measurement (ie, prediagnosis versus at the time of diagnosis) in humans might alter interpretation of associations among various body mass index categories and cancer prognosis.40 Moreover, body condition scoring is an estimate of body fat, but changes in BCS do not correlate with loss of muscle until the very lowest scores (1 and 2/9).39 In humans, cachexia, or muscle loss because of systemic illness, regardless of overall body weight and BMI, has been associated with poorer survival.41 Although several different subjective muscle condition scoring systems for dogs have been proposed, these systems have not been well validated and adoption by individual clinicians is quite variable.12, 34 We were thus unable to assess muscle condition reliably from the medical records of dogs in this study. Unlike in studies of rodents and humans, dogs with cancer can be euthanized as a result of owner's financial constraints, progressive disease, treatment failure, or treatment adverse effects, and including euthanasia as a cause of death could confound true assessment of ST. Nearly all of the dogs in this study were euthanized versus dying from their cancer directly. Finally, animals presented to our teaching hospital might not reflect the general population of dogs with LSA and OSA.

The number of LSA dogs with clinical substage b was higher in this study than has been reported in previous studies.35, 38 The retrospective nature of this study made it difficult to assess severity of the systemic signs, so clinical substage was frequently assigned based on systemic signs reported in the record (such as decreased appetite, lethargy, weight loss, vomiting, or diarrhea). It is possible that some of these animals might have been categorized as substage a if evaluated prospectively. The PFI and ST for both LSA and OSA reported here are shorter than those documented in other clinical studies. This is likely as a result of the inclusion of dogs that received palliative care rather than just regular standard‐of‐care treatment in this investigation.

In conclusion, our data do not indicate that overweightedness/obesity as defined as a BCS ≥6/9 at diagnosis adversely affects progression or survival in dogs with LSA or OSA. However, weight gain during treatment was associated with increased survival for both OSA and LSA, whereas anemia, T‐cell phenotype, and higher stage in dogs with LSA were associated with shorter ST. A large, prospective case–control study would enable more definitive conclusions to be drawn about these relationships. We are aware of one such study in golden Retrievers that is ongoing³ which will provide additional data that could help elucidate these complex issues in dogs.

Acknowledgments