- Email: [email protected]
Prognostic significance of weight changes during treatment of feline lymphoma
Journal of Feline Medicine and Surgery (2011) 13, 976e983 doi:10.1016/j.jfms.2011.08.002
Prognostic significance of weight changes during treatment of feline lymphoma* Erika L Krick VMD, DACVIM (Oncology)1*, Renee´ H Moore Karin U Sorenmo DVM, DACVIM, DECVIM-CA (Oncology)1 1
Department of Clinical Studies, Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, 3900 Delancey St, PA 19104, USA 2 Department of Biostatistics and Epidemiology, University of Pennsylvania, PA, USA
Date accepted: 7 August 2011
L
The work for this study was performed at the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA. This study was performed without grant or other financial support. This study was presented in part at the 30th Annual Conference of the Veterinary Cancer Society, Fort Lauderdale, FL, November 2007. *Corresponding author. E-mail: [email protected]
1098-612X/11/120976+08 $36.00/0
Rachel B Cohen
1 CVT ,
The study purpose was to determine the prognostic significance of weight changes during feline lymphoma treatment. A secondary purpose was to compare weight changes according to baseline body weight, cell type and location. Records of 209 cats treated for lymphoma with chemotherapy from 1995 to 2007 were evaluated. Signalment, cell type, lymphoma location, baseline body weight, weight during treatment, and outcome information were collected. Lymphoma specific survival (LSS) was compared according to baseline weight and weight changes during treatment. Weight change over time was compared according to cell type (small versus large), location (gastrointestinal versus non-gastrointestinal) and baseline weight. Cats with large cell lymphoma that lost 5% body weight at 1 month had significantly shorter LSS than those that gained or had stable weight (P ¼ 0.004). Percentage weight change over time differed significantly according to baseline weight group. These findings demonstrate the prognostic importance of weight loss in feline large cell lymphoma. Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
ymphoma is the most common hematopoietic cancer diagnosed in the feline population, and several prognostic factors have been documented, including anatomic location and stage, grade/cell type, feline leukemia virus status, response to therapy, and substage.1e11 Another prognostic factor recently evaluated in the literature is body weight.12 The authors of this study found that underweight cats with cancer had a significantly shorter survival time than larger cats. When only cats with lymphoma were evaluated, the survival differences according to body condition score, not body weight, were statistically significant. In addition, cats in remission had a higher body condition score than cats that were not in remission. A second study found that cats with lymphoma that lost weight prior to starting chemotherapy had shorter survival times.13 These findings show that a very simple objective measure such as body weight and/or body condition score at
*
2 PhD ,
diagnosis can provide valuable and practical clinical and prognostic information. No evaluation of the prognostic impact of change in body weight over time during treatment has been performed, however. A recent study reporting the results of a questionnaire administered to owners of cats that had undergone chemotherapy for lymphoma found that the majority of owners noted appetite as a marker of quality of life of their cat.14 Because the majority of cats with lymphoma have internally located disease, as the gastrointestinal (GI) tract is the most common location, it can be challenging to assess response to therapy based on history and physical exam findings alone.15 The expense and stress of repeated abdominal ultrasounds coupled with the subjective results of abdominal palpation illustrate the need for finding an objective, easily measured marker or combination of markers for response to therapy. Although baseline body condition score has been associated with survival in cats with lymphoma, body weight may be a more practical marker of patient status over time. Accurate assessment of feline body condition requires training in the technique and is more subjective than body weight measurement. In addition, body condition score is unlikely to change on a weekly basis, and it cannot be assessed retrospectively. Body weight is routinely measured as part of the physical exam
Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
Body weight and feline lymphoma prognosis
and is an objective, repeatable, and simple measurement. Although body weight alone is not a specific marker for response to chemotherapy in cats with lymphoma (it is also affected by chemotherapy side effects and co-morbidities), repeated measurements in the same patient could be used to assess the need for more invasive diagnostic procedures to clarify a patient’s remission status. It is common in the authors’ clinical practice to use body weight as an assessment of both response to and tolerance of therapy, particularly in feline lymphoma patients; however, the potential effect on outcome of changes in weight during the course of treatment has not been formally evaluated in the literature. The purpose of this study was to determine the prognostic significance of weight changes in cats undergoing chemotherapy for lymphoma. Evaluation of changes in body weight over time may also identify patients who are at increased risk for weight loss during treatment, and thus may benefit the most from interventions to increase body weight; therefore, a second study purpose was to evaluate the association between weight changes during treatment and lymphoma cell type, location, and baseline body weight. We hypothesized that cats that gained weight during treatment would live longer than those that lost weight and that tumor cell type and location would be correlated with weight changes during treatment. Specifically, it was expected that cats with large cell lymphoma would have weight changes over a larger range than cats with small cell lymphoma, and cats with GI lymphoma would lose more weight than cats with non-GI lymphoma. An additional purpose was to evaluate the prognostic significance of baseline body weight, and we hypothesized that an indirect association between body weight and survival time exists.
Materials and methods The medical records database of the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania (MJR-VHUP) was searched for cats with a diagnosis of lymphoma from January 1995 to December 2007. Cats were included if they had a confirmed diagnosis of lymphoma based on cytology or histopathology, received chemotherapy at MJR-VHUP (excluding prednisone alone) as their only treatment modality, and the medical record contained a baseline treatment weight and at least one follow-up body weight measurement taken at least 20 days (1 month time point with a 10-day range as described below) after initiation of therapy. Cats that had surgical biopsies for diagnostic purposes only and had gross disease at the time chemotherapy was initiated were included. The following data were recorded from the medical records by two of the authors (EK, RC) using standardized data collection forms: signalment, method of diagnosis (cytology or histopathology), lymphoma
977
cell type and location, baseline weight, weight at 1, 2, 3, and 6 months into treatment, weight at last visit, chemotherapy protocol, whether or not an enteral feeding tube was placed, and, if so, the type of tube and duration of placement. Any weight recorded within a 10-day range around each time point was considered a weight for that time point. Follow-up information was obtained from telephone conversations with referring veterinarians, and this information was recorded on standardized data collection forms. Weight change over time was determined by comparing the time point (1, 2, 3, 6 months) weight to the diagnosis weight. This weight change was used to categorize cats as having gained, lost, or stable weight between the two compared time points. A 5% change in body weight was the cut-off for categorizing into those three groups. Cats that gained 5% or lost 5% of their body weight were categorized as increased or decreased weight, respectively, while cats whose body weight changed less than 5% in either direction were placed in the stable weight category.
Statistical analysis Lymphoma specific survival (LSS) time was defined as the interval from treatment initiation to death from lymphoma or an unknown cause. Cats that were lost to follow-up, died due to unrelated disease, or alive at the time of data analysis (April 2010) were censored at their date of last contact or date of analysis. Cats were categorized according to baseline weight into three groups: <3 kg, 3e5 kg, and >5 kg. Cats were categorized according to how their weight changed at month 1 and 2 compared to baseline as described above. KaplaneMeier survival analysis was used to determine LSS according to baseline body weight and weight change at 1 and 2 months into treatment. The log rank test was used to compare survival among the three baseline weight groups and the three weight change groups at months 1 and 2. Cats were then stratified according to cell type (large versus small), and KaplaneMeier and log rank tests were used to compare LSS among the baseline weight and month 1 and 2 weight change groups. Repeated measures, mixed model analyses were used to compare changes in weight according to tumor grade, location, and initial body weight over time. Specifically for these analyses, cats were categorized according to tumor cell type (large versus small cell), location (GI versus non-GI), and baseline body weight (<3 kg, 3e5 kg, or >5 kg). Only cats with cytological or histopathological confirmation of GI lymphoma were included in that category. Cats in which lymphoma was diagnosed based on abdominal lymph node aspirates may have had GI lymphoma, but if no aspirates of the GI tract were performed, they were categorized as having non-GI lymphoma for the purposes of this study. The frequency of enteral feeding tube placement was compared
978
EL Krick et al
according to the tumor cell type, location, and baseline body weight categories described above using c2 tests. Cats were stratified according to cell type (large versus small), and repeated measures mixed model analyses were used to compare changes in weight over time according to whether or not an enteral feeding tube was placed. Statistical significance was set at P < 0.05. Statistical analyses were performed using SAS software, version 9.2, Cary, NC, USA.
Results Over the 13-year period, 426 cats were treated with chemotherapy for lymphoma at MJR-VHUP. Of those, 192 were excluded for the following reasons: record incomplete (n ¼ 3) or unavailable (n ¼ 10), no baseline weight recorded (n ¼ 22), treated with prednisone only (n ¼ 26), no follow-up weight recorded (n ¼ 131), or follow-up weight data recorded prior to 20 days into treatment (n ¼ 25). Records of 209 cats were included (Table 1).
Survival analysis by baseline weight Among all cats included, LSS did not significantly differ according to baseline body weight categories of <3 kg, 3e5 kg, and >5 kg [median (95% confidence interval (CI)) 7.8 (2.8, 18.6) versus 8.2 (5.8, 13.0) versus 16.0 (6.8, 19.6) months; P ¼ 0.64]. LSS did not significantly differ according to baseline weight when cats were stratified by tumor cell type (large versus small).
Survival analysis by weight at months 1 and 2 Cats that gained or had stable weight at months 1 and 2 had a significantly longer LSS than those that lost weight [median (95% CI) 36.9 (6.5, e (insufficient numbers to determine upper limit of 95% CI)) and 13.9 (7.4, 18.7) versus 4.5 (3.0, 7.8) months; P ¼ 0.0002] and [18.6 (7.8, 45.1) and 14.8 (8.8, 21.1) versus 7.8 (4.5, 14.0) months; P ¼ 0.02] (Table 2), respectively. When cats were stratified according to cell type (large versus small cell), cats with large cell lymphoma that gained or had stable weight at month 1 had a significantly longer LSS compared to cats that lost weight [7.0 (3.4, 63.1) and 7.0 (4.8, 14.8) versus 3.1(2.3, 5.1) months; P ¼ 0.004] (Fig 1, Table 1), but the difference in survival was not significant according to weight change at month 2. No significant associations were noted between survival and weight change at month 1 or 2 among cats with small cell lymphoma. Cell type was prognostic, with cats with small cell lymphoma having a significantly longer LSS compared to cats with large cell lymphoma [21.1 (15.1, 36.4) versus 5.7 (4.4, 7.6) months; P ¼ 0.0002].
Weight changes The number of cats for which weight was recorded at each study time point is given in Table 1. Overall,
body weight changed significantly over time (P ¼ 0.009); specifically, most cats lost weight compared to baseline weight. When cats were stratified according to cell type (large versus small), the mean change in weight in cats with large cell lymphoma significantly differed from zero, meaning the cats lost weight during the first 2 months of treatment [month 1 (4.1 1.0% change compared to baseline, P < 0.0001); month 2 (3.4 1.1% change compared to baseline, P ¼ 0.0025)]. This difference was not found in cats with small cell lymphoma. Furthermore, when mean percentage weight change over time was compared between lymphoma cell type (large versus small) and anatomic location groups (GI versus nonGI), no difference was noted. Percent weight change collapsed over time was significantly different according to baseline weight group (P ¼ 0.0004). Fig 2 shows weight change at the 1, 2, 3, and 6 month time points for cats in each of the three baseline weight groups. In summary, collapsed across all time points, cats that weighed <3 kg at baseline gained weight compared to cats that weighed 3e5 kg (mean percentage weight change 8.3 2.2% versus 2.2 0.9%, P < 0.0001) or >5 kg (mean percentage weight change 8.3 2.2% versus 5.9 1.3%, P < 0.0001) at baseline. Cats that weighed >5 kg at baseline lost more weight over time than cats that weighed 3e5 kg at baseline (5.9 1.3% versus 2.2 0.9%, P ¼ 0.0209).
Enteral feeding Enteral feeding tubes were placed in 22 cats. Duration and type of tube placement was varied, and statistical analyses were not performed on those data due to the small sample size. A significantly higher percentage of cats with small cell lymphoma had feeding tubes placed compared to cats with large cell lymphoma (20% versus 6%, P ¼ 0.003). The mean weights of cats with and without feeding tubes were similar (4.3 versus 4.4 kg). Cats with GI lymphoma were not significantly more likely to have feeding tubes placed compared to cats with non-GI lymphoma (13% versus 6%, P ¼ 0.06). Feeding tube placement was not associated with weight change for all cats, and when cats were stratified according to cell type (large versus small), there was no association between weight change over time and feeding tube placement.
Discussion This study is the first to evaluate the prognostic significance of weight changes over time in feline lymphoma and veterinary oncology. The results indicate that weight loss during the first 2 months of treatment has the most negative prognostic significance in cats with large cell lymphoma; therefore, the first 2 months of treatment may be the optimal time to initiate therapeutic interventions and nutritional support in addition to chemotherapy in order to decrease weight loss.
Body weight and feline lymphoma prognosis
979
Table 1. Study population demographics. Although 200 cats had weights recorded at 1 month, 209 cats were included in the study because nine cats had weights recorded at time points after 1 month even though they did not have recorded weights at 1 month. Signalment Sex Male castrated Male intact Female spayed Female intact Age (years; mean SD) Breed Domestic shorthair Domestic longhair Japanese Bobtail, Siamese, unknown Maine Coon, Persian Baseline weight (kg; mean SD) Lymphoma grade/cell type High/large Small/low Hodgkin’s-like Unknown Anatomic location GI Abdominal non-GI (liver, spleen, kidney, etc) Thoracic (mediastinal mass, pleural effusion) Peripheral lymph nodes (LNs) (systemic disease) Extranodal (nasal, extraocular, etc) Bone marrow/peripheral lymphoblasts Other (mixed locations/body cavities) Baseline weight group <3 kg 3e5 kg >5 kg Weight recorded after baseline Month 1 Months 1 and 2 Months 1, 2 and 3 Months 1, 2, 3 and 6
It is important to keep in mind that nutritional support alone will not reverse tumor-related weight loss, particularly in patients that are not responding to chemotherapy. Such nutritional support (in addition to chemotherapy) would likely be of most benefit in cats that are responding to chemotherapy but whose caloric intake and GI function are not yet sufficient enough to result in weight gain. These results stated above regarding month 1 are specific to large cell lymphoma and do not apply to small cell lymphoma. This difference between small and large cell lymphoma may be due to the difference in biological behavior. Large cell lymphomas are clinically aggressive tumors and may, therefore, respond quickly to chemotherapy, thus resulting in improved body weight; or, alternatively, they may progress quickly and result in rapid clinical decline and weight loss. In contrast, small cell lymphomas are more
n
Percent (%)
124 1 83 1
59.3 0.5 39.7 0.5
188 13 2 1
10.5 4.2
4.4 1.4
90.0 6.2 1.0 0.5
145 47 2 15
69.4 22.5 1.0 7.2
119 30 13 9 23 4 11
56.9 14.4 6.2 4.3 11.0 1.9 5.3
24 129 56
11.5 61.7 26.8
200 151 115 72
95.7 72.2 55.0 34.4
indolent, such that a response to therapy may occur slowly over time and, similarly, lack of response may also result in less severe and more protracted weight loss over time. The difference in survival according to weight change at month 2 for small cell lymphoma cats appears to be clinically (though not statistically) significant, and it is possible that with a larger number of cats, the difference would be statistically significant. It makes sense with the biological behavior of feline small cell lymphoma that weight changes further along the treatment timeline would be better predictors of response and survival. The lack of a statistically significant different survival for large cell lymphoma cats according to weight change at month 2 could be due to type II statistical error; however, it could also show that month 1 is where the primary effect of weight change on survival occurs. Cats that survive to the month 2 time point
980
EL Krick et al
Table 2. Survival according to weight change at months 1 and 2 for all cats and cats stratified by cell type. LSS is given in months, and ‘e’ instead of a number for the upper limit of the 95% CI means that there were not enough cats to calculate the upper limit. Population
Month 1 n
All Gained weight Stable weight Lost weight P-value Large cell Gained weight Stable weight Lost weight P-value Small cell Gained weight Stable weight Lost weight P-value
200 30 83 87 143 19 64 60 40 8 19 13
Month 2
LSS (95% CI) 36.9 (6.5, e) 13.9 (7.4, 18.7) 4.5 (3.0, 7.8) 0.0002 7.0 (4.0, 63.0) 7.0 (4.8, 14.8) 3.1 (2.3, 5.1) 0.004 36.9 (4.1, e) 19.0 (14.8, 36.4) 16.0 (2.2, 36.0) 0.25
are more likely to be responding to chemotherapy, and thus, the impact of weight change may not be as significant for that group. The cut-offs for categorization into weight change groups of 5% change in body weight was chosen because that is considered to be clinically significant in the authors’ practice. It is possible, however, that using a different weight
n 158 47 45 66 104 33 28 43 40 11 13 16
LSS (95% CI) 18.6 (7.8, 45.1) 14.8 (8.8, 21.1) 7.8 (4.5, 14.0) 0.02 10.1 (6.4, 20.6) 8.8 (4.7, 16.6) 6.8 (3.1, 10.6) 0.33 45.1 (6.8, e) 25.9 (13.3, 36.4) 16.0 (3.9, 36.0) 0.07
change cut-off would result in a more significant impact on survival. Previous literature has demonstrated the clinical implications of body weight and body condition score in canine oncology and cardiology patients and in feline oncology patients. The majority of canine patients presenting to the oncology department of
Fig 1. KaplaneMeier survival curve of cats with large cell lymphoma comparing survival according to weight change (gained, lost or stable) at month 1 into treatment. Cats that gained (n ¼ 19) or had stable weight (n ¼ 64) had a significantly longer median LSS compared to cats that lost weight (n ¼ 60) [7.0 (4.0, 63.0) and 7.0 (4.8, 14.8) versus 3.1 (2.3, 5.1) months; P ¼ 0.004]. Of 45 cats censored, three were alive and 42 were lost to follow-up.
Body weight and feline lymphoma prognosis
981
Fig 2. Mean percent weight change at individual time points according to baseline weight. For each time point (months 1, 2, 3, and 6), mean percent weight change is the change from baseline to that time point. The P values for the mixed model fixed effects are as follows: for all cats together, weight changed significantly over time (P ¼ 0.009); when data from each baseline weight group was collapsed over time, weight changed significantly (P < 0.0001); weight changes over time were different according to baseline weight group (P ¼ 0.0004).
a referral veterinary hospital were overweight, while only 4% of canine patients exhibited a body condition score of 3 out of 9, which is consistent with being underweight or cachectic.16 A comparison of body weight and body condition with survival in canine patients with heart failure found that dogs with heart failure that gained weight lived longer than those who lost weight or whose weight was unchanged. In addition, cachectic dogs in heart failure had a shorter survival time than those that were obese.17 A previous study found that baseline body weight was prognostic for cats with a variety of cancers but not for lymphoma; specifically cats of lower body weight had shorter survival times.12 These studies indicate that weight loss before or during treatment can negatively impact survival, and weight loss appears to be more common in feline versus canine cancer patients. Baseline weight was not prognostic for survival for all cats or for cats with large or small cell lymphoma in the current study. The exclusion of cats that did not have a follow-up weight at least 1 month after
starting treatment could have biased our population by excluding cats that died or were lost to follow-up within the first month after starting treatment. If most of those cats had a low baseline weight, then their exclusion would have biased our survival analysis toward the null hypothesis. In the current study only baseline body weight was predictive of weight changes over time, with smaller cats gaining weight and larger cats losing weight. There is potential bias in this data, however, as only cats that lived to the 1 month time point were included in this analysis; therefore, the weight gain seen in cats weighing <3 kg at baseline may have been based on a select population of those cats that responded to therapy and gained weight. Neither anatomic location of lymphoma (GI versus non-GI) nor cell type (large versus small cell) affected how weight changed over time. It is possible that the prevalence of GI lymphoma was under-reported, however, as only cats with confirmed GI lymphoma were included in that group.
982
EL Krick et al
Placement of an enteral feeding tube occurred more frequently in cats with small cell lymphoma. Small cell lymphoma is most commonly diagnosed on histopathology. Because patients are anesthetized for either endoscopy or abdominal exploratory surgery, clinicians may be more likely to place an enteral feeding tube in these patients during the diagnostic procedure. In contrast, cats with large cell lymphoma generally are not anesthetized for diagnostic procedures, so placing an enteral feeding tube would require separate anesthesia and thus additional stress on the cat and cost for the owners. Additional limitations of this study are primarily related to its retrospective nature. Hydration status may have affected body weight, particularly in patients that lost weight. If they were clinically unwell and dehydrated, that could have contributed to weight loss. The portion of weight change that was due to hydration status could not be determined due to the retrospective nature of the study. Although treatment could not be standardized, the chemotherapy protocol most commonly used for large cell lymphoma in cats remained the same during the time period of this study. The protocol for small cell lymphoma did change over time: before this type of lymphoma was recognized separately from large cell lymphoma, these cats received the same protocol used for cats with large cell lymphoma. The protocol for small cell lymphoma used at the author’s institution has been different from that for large cell lymphoma and unchanged since the year 2000. Having body condition score data on all cats in the study would strengthen the data and allow for more comparison to other published reports; however, the retrospective nature of this study prevented that. In addition, as cat breeds have less size variation than dog breeds, body condition score in addition to body weight may not be as essential in cats compared to dogs for the purpose of this study. In addition, repeat body weight measurements have been shown to detect smaller changes in body mass compared to repeat body condition scoring.18 The results of this study have indicated that cats with lymphoma are at risk for weight loss during chemotherapy and provide evidence that this weight loss has a significant negative effect on survival for cats with large cell lymphoma. Weight loss experienced by cats during lymphoma treatment may be a result of the disease itself as well as chemotherapy side effects, and it can be challenging to differentiate between these causes of nausea, decreased appetite, and weight loss. Both owners and veterinarians associate poor appetite and weight loss with a reduced quality of life.15 Because weight loss in cats with lymphoma is a multi-faceted clinical challenge, it is important to consider the patient’s lymphoma status, chemotherapy tolerance, and existing co-morbidities when considering supportive care mediations and nutritional intervention. The impact of weight loss on quality and length of life in cats with lymphoma
warrants further investigation into therapies that combine chemotherapy with supportive care and nutritional interventions.
Acknowledgments The authors thank Nicholas B Lehmann for assistance with figure preparation.
References 1. Vail DM. Feline lymphoma and leukemia. In: Withrow SJ, Vail DM, eds. Withrow & MacEwan’s small animal clinical oncology. 4th edn. St Louis, MO: Saunders Elsevier, 2007: 733e56. 2. Mooney SC, Hayes AA, MacEwen GE, Matus RE, Geary A, Shurgot BA. Treatment and prognostic factors in lymphoma in cats: 103 cases (1977e1981). J Vet Intern Med 1989; 194: 696e9. 3. Simon D, Eberle N, Laacke-Singer L, Nolte I. Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats. J Vet Intern Med 2008; 22: 394e400. 4. Fondacaro JV, Richter KP, Carpenter JL, Hart JR, Hill SL, Fettman MJ. Feline gastrointestinal lymphoma: 67 cases (1988e1996). Eur J Comp Gastroenterol 1999; 4: 5e11. 5. Kiselow MA, Rassnick KM, McDonough SP, et al. Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995e2005). J Am Vet Med Assoc 2008; 232: 405e10. 6. Vail DM, Moore AS, Ogilvie GK, Volk LM. Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3 immunoreactivity, and their association with prognosis in 90 cats. J Vet Intern Med 1998; 12: 349e54. 7. Kristal O, Lana SE, Ogilvie GK, Rand WM, Cotter SM, Moore AS. Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases (1994e1997). J Vet Intern Med 2001; 15: 125e30. 8. Zwalen CH, Lucroy MD, Kraegel SA, Madwell BR. Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993e1997). J Am Vet Med Assoc 1998; 213: 1144e9. 9. Malik R, Gabor LJ, Foster SF, McCorkell BE, Canfield PJ. Therapy for Australian cats with lymphosarcoma. Aust Vet J 2001; 79: 808e17. 10. Teske E, van Straten G, van Noort R, Rutteman G. Chemotherapy with cyclophosphamide, vincristine, and prednisolone (COP) in cats with malignant lymphoma: new results with an old protocol. J Vet Intern Med 2002; 16: 179e86. 11. Milner RJ, Peyton J, Cooke K, et al. Response rates and survival times for cats with lymphoma treated with the University of WisconsineMadison chemotherapy protocol: 38 cases (1996e2003). J Am Vet Med Assoc 2005; 227: 1118e22. 12. Baez JL, Michel KE, Sorenmo K, Shofer FS. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Feline Med Surg 2007; 9: 411e7. 13. Hadden AG, Cotter SM, Rand W, Moore AS, Davis RM, Morrissey P. Efficacy and toxicosis of VELCAP-C treatment of lymphoma in cats. J Vet Intern Med 2008; 22: 153e7.
Body weight and feline lymphoma prognosis
14. Tzannes S, Hammond MF, Murphy S, Sparkes A, Blackwood L. Owners ‘perception of their cats’ quality of life during COP chemotherapy for lymphoma. J Feline Med Surg 2008; 10: 73e81. 15. Louwerens M, London CA, Pederson NC, Lyons LA. Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med 2005; 19: 329e35. 16. Michel KE, Sorenmo K, Shofer FS. Evaluation of body condition and weight loss in dogs presented to
983
a veterinary oncology service. J Vet Intern Med 2004; 18: 692e5. 17. Slupe JL, Freeman LM, Rush JE. Association of body weight and body condition with survival in dogs with heart failure. J Vet Intern Med 2008; 22: 561e5. 18. Burkholder WJ. Precision and practicality of methods assessing body composition of dogs and cats. Compend Contin Educ for Pract Vet 2001; 23: 1e10.
Available online at www.sciencedirect.com
Prognostic significance of weight changes during treatment of feline lymphoma* Erika L Krick VMD, DACVIM (Oncology)1*, Renee´ H Moore Karin U Sorenmo DVM, DACVIM, DECVIM-CA (Oncology)1 1
Department of Clinical Studies, Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, 3900 Delancey St, PA 19104, USA 2 Department of Biostatistics and Epidemiology, University of Pennsylvania, PA, USA
Date accepted: 7 August 2011
L
The work for this study was performed at the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA. This study was performed without grant or other financial support. This study was presented in part at the 30th Annual Conference of the Veterinary Cancer Society, Fort Lauderdale, FL, November 2007. *Corresponding author. E-mail: [email protected]
1098-612X/11/120976+08 $36.00/0
Rachel B Cohen
1 CVT ,
The study purpose was to determine the prognostic significance of weight changes during feline lymphoma treatment. A secondary purpose was to compare weight changes according to baseline body weight, cell type and location. Records of 209 cats treated for lymphoma with chemotherapy from 1995 to 2007 were evaluated. Signalment, cell type, lymphoma location, baseline body weight, weight during treatment, and outcome information were collected. Lymphoma specific survival (LSS) was compared according to baseline weight and weight changes during treatment. Weight change over time was compared according to cell type (small versus large), location (gastrointestinal versus non-gastrointestinal) and baseline weight. Cats with large cell lymphoma that lost 5% body weight at 1 month had significantly shorter LSS than those that gained or had stable weight (P ¼ 0.004). Percentage weight change over time differed significantly according to baseline weight group. These findings demonstrate the prognostic importance of weight loss in feline large cell lymphoma. Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
ymphoma is the most common hematopoietic cancer diagnosed in the feline population, and several prognostic factors have been documented, including anatomic location and stage, grade/cell type, feline leukemia virus status, response to therapy, and substage.1e11 Another prognostic factor recently evaluated in the literature is body weight.12 The authors of this study found that underweight cats with cancer had a significantly shorter survival time than larger cats. When only cats with lymphoma were evaluated, the survival differences according to body condition score, not body weight, were statistically significant. In addition, cats in remission had a higher body condition score than cats that were not in remission. A second study found that cats with lymphoma that lost weight prior to starting chemotherapy had shorter survival times.13 These findings show that a very simple objective measure such as body weight and/or body condition score at
*
2 PhD ,
diagnosis can provide valuable and practical clinical and prognostic information. No evaluation of the prognostic impact of change in body weight over time during treatment has been performed, however. A recent study reporting the results of a questionnaire administered to owners of cats that had undergone chemotherapy for lymphoma found that the majority of owners noted appetite as a marker of quality of life of their cat.14 Because the majority of cats with lymphoma have internally located disease, as the gastrointestinal (GI) tract is the most common location, it can be challenging to assess response to therapy based on history and physical exam findings alone.15 The expense and stress of repeated abdominal ultrasounds coupled with the subjective results of abdominal palpation illustrate the need for finding an objective, easily measured marker or combination of markers for response to therapy. Although baseline body condition score has been associated with survival in cats with lymphoma, body weight may be a more practical marker of patient status over time. Accurate assessment of feline body condition requires training in the technique and is more subjective than body weight measurement. In addition, body condition score is unlikely to change on a weekly basis, and it cannot be assessed retrospectively. Body weight is routinely measured as part of the physical exam
Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
Body weight and feline lymphoma prognosis
and is an objective, repeatable, and simple measurement. Although body weight alone is not a specific marker for response to chemotherapy in cats with lymphoma (it is also affected by chemotherapy side effects and co-morbidities), repeated measurements in the same patient could be used to assess the need for more invasive diagnostic procedures to clarify a patient’s remission status. It is common in the authors’ clinical practice to use body weight as an assessment of both response to and tolerance of therapy, particularly in feline lymphoma patients; however, the potential effect on outcome of changes in weight during the course of treatment has not been formally evaluated in the literature. The purpose of this study was to determine the prognostic significance of weight changes in cats undergoing chemotherapy for lymphoma. Evaluation of changes in body weight over time may also identify patients who are at increased risk for weight loss during treatment, and thus may benefit the most from interventions to increase body weight; therefore, a second study purpose was to evaluate the association between weight changes during treatment and lymphoma cell type, location, and baseline body weight. We hypothesized that cats that gained weight during treatment would live longer than those that lost weight and that tumor cell type and location would be correlated with weight changes during treatment. Specifically, it was expected that cats with large cell lymphoma would have weight changes over a larger range than cats with small cell lymphoma, and cats with GI lymphoma would lose more weight than cats with non-GI lymphoma. An additional purpose was to evaluate the prognostic significance of baseline body weight, and we hypothesized that an indirect association between body weight and survival time exists.
Materials and methods The medical records database of the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania (MJR-VHUP) was searched for cats with a diagnosis of lymphoma from January 1995 to December 2007. Cats were included if they had a confirmed diagnosis of lymphoma based on cytology or histopathology, received chemotherapy at MJR-VHUP (excluding prednisone alone) as their only treatment modality, and the medical record contained a baseline treatment weight and at least one follow-up body weight measurement taken at least 20 days (1 month time point with a 10-day range as described below) after initiation of therapy. Cats that had surgical biopsies for diagnostic purposes only and had gross disease at the time chemotherapy was initiated were included. The following data were recorded from the medical records by two of the authors (EK, RC) using standardized data collection forms: signalment, method of diagnosis (cytology or histopathology), lymphoma
977
cell type and location, baseline weight, weight at 1, 2, 3, and 6 months into treatment, weight at last visit, chemotherapy protocol, whether or not an enteral feeding tube was placed, and, if so, the type of tube and duration of placement. Any weight recorded within a 10-day range around each time point was considered a weight for that time point. Follow-up information was obtained from telephone conversations with referring veterinarians, and this information was recorded on standardized data collection forms. Weight change over time was determined by comparing the time point (1, 2, 3, 6 months) weight to the diagnosis weight. This weight change was used to categorize cats as having gained, lost, or stable weight between the two compared time points. A 5% change in body weight was the cut-off for categorizing into those three groups. Cats that gained 5% or lost 5% of their body weight were categorized as increased or decreased weight, respectively, while cats whose body weight changed less than 5% in either direction were placed in the stable weight category.
Statistical analysis Lymphoma specific survival (LSS) time was defined as the interval from treatment initiation to death from lymphoma or an unknown cause. Cats that were lost to follow-up, died due to unrelated disease, or alive at the time of data analysis (April 2010) were censored at their date of last contact or date of analysis. Cats were categorized according to baseline weight into three groups: <3 kg, 3e5 kg, and >5 kg. Cats were categorized according to how their weight changed at month 1 and 2 compared to baseline as described above. KaplaneMeier survival analysis was used to determine LSS according to baseline body weight and weight change at 1 and 2 months into treatment. The log rank test was used to compare survival among the three baseline weight groups and the three weight change groups at months 1 and 2. Cats were then stratified according to cell type (large versus small), and KaplaneMeier and log rank tests were used to compare LSS among the baseline weight and month 1 and 2 weight change groups. Repeated measures, mixed model analyses were used to compare changes in weight according to tumor grade, location, and initial body weight over time. Specifically for these analyses, cats were categorized according to tumor cell type (large versus small cell), location (GI versus non-GI), and baseline body weight (<3 kg, 3e5 kg, or >5 kg). Only cats with cytological or histopathological confirmation of GI lymphoma were included in that category. Cats in which lymphoma was diagnosed based on abdominal lymph node aspirates may have had GI lymphoma, but if no aspirates of the GI tract were performed, they were categorized as having non-GI lymphoma for the purposes of this study. The frequency of enteral feeding tube placement was compared
978
EL Krick et al
according to the tumor cell type, location, and baseline body weight categories described above using c2 tests. Cats were stratified according to cell type (large versus small), and repeated measures mixed model analyses were used to compare changes in weight over time according to whether or not an enteral feeding tube was placed. Statistical significance was set at P < 0.05. Statistical analyses were performed using SAS software, version 9.2, Cary, NC, USA.
Results Over the 13-year period, 426 cats were treated with chemotherapy for lymphoma at MJR-VHUP. Of those, 192 were excluded for the following reasons: record incomplete (n ¼ 3) or unavailable (n ¼ 10), no baseline weight recorded (n ¼ 22), treated with prednisone only (n ¼ 26), no follow-up weight recorded (n ¼ 131), or follow-up weight data recorded prior to 20 days into treatment (n ¼ 25). Records of 209 cats were included (Table 1).
Survival analysis by baseline weight Among all cats included, LSS did not significantly differ according to baseline body weight categories of <3 kg, 3e5 kg, and >5 kg [median (95% confidence interval (CI)) 7.8 (2.8, 18.6) versus 8.2 (5.8, 13.0) versus 16.0 (6.8, 19.6) months; P ¼ 0.64]. LSS did not significantly differ according to baseline weight when cats were stratified by tumor cell type (large versus small).
Survival analysis by weight at months 1 and 2 Cats that gained or had stable weight at months 1 and 2 had a significantly longer LSS than those that lost weight [median (95% CI) 36.9 (6.5, e (insufficient numbers to determine upper limit of 95% CI)) and 13.9 (7.4, 18.7) versus 4.5 (3.0, 7.8) months; P ¼ 0.0002] and [18.6 (7.8, 45.1) and 14.8 (8.8, 21.1) versus 7.8 (4.5, 14.0) months; P ¼ 0.02] (Table 2), respectively. When cats were stratified according to cell type (large versus small cell), cats with large cell lymphoma that gained or had stable weight at month 1 had a significantly longer LSS compared to cats that lost weight [7.0 (3.4, 63.1) and 7.0 (4.8, 14.8) versus 3.1(2.3, 5.1) months; P ¼ 0.004] (Fig 1, Table 1), but the difference in survival was not significant according to weight change at month 2. No significant associations were noted between survival and weight change at month 1 or 2 among cats with small cell lymphoma. Cell type was prognostic, with cats with small cell lymphoma having a significantly longer LSS compared to cats with large cell lymphoma [21.1 (15.1, 36.4) versus 5.7 (4.4, 7.6) months; P ¼ 0.0002].
Weight changes The number of cats for which weight was recorded at each study time point is given in Table 1. Overall,
body weight changed significantly over time (P ¼ 0.009); specifically, most cats lost weight compared to baseline weight. When cats were stratified according to cell type (large versus small), the mean change in weight in cats with large cell lymphoma significantly differed from zero, meaning the cats lost weight during the first 2 months of treatment [month 1 (4.1 1.0% change compared to baseline, P < 0.0001); month 2 (3.4 1.1% change compared to baseline, P ¼ 0.0025)]. This difference was not found in cats with small cell lymphoma. Furthermore, when mean percentage weight change over time was compared between lymphoma cell type (large versus small) and anatomic location groups (GI versus nonGI), no difference was noted. Percent weight change collapsed over time was significantly different according to baseline weight group (P ¼ 0.0004). Fig 2 shows weight change at the 1, 2, 3, and 6 month time points for cats in each of the three baseline weight groups. In summary, collapsed across all time points, cats that weighed <3 kg at baseline gained weight compared to cats that weighed 3e5 kg (mean percentage weight change 8.3 2.2% versus 2.2 0.9%, P < 0.0001) or >5 kg (mean percentage weight change 8.3 2.2% versus 5.9 1.3%, P < 0.0001) at baseline. Cats that weighed >5 kg at baseline lost more weight over time than cats that weighed 3e5 kg at baseline (5.9 1.3% versus 2.2 0.9%, P ¼ 0.0209).
Enteral feeding Enteral feeding tubes were placed in 22 cats. Duration and type of tube placement was varied, and statistical analyses were not performed on those data due to the small sample size. A significantly higher percentage of cats with small cell lymphoma had feeding tubes placed compared to cats with large cell lymphoma (20% versus 6%, P ¼ 0.003). The mean weights of cats with and without feeding tubes were similar (4.3 versus 4.4 kg). Cats with GI lymphoma were not significantly more likely to have feeding tubes placed compared to cats with non-GI lymphoma (13% versus 6%, P ¼ 0.06). Feeding tube placement was not associated with weight change for all cats, and when cats were stratified according to cell type (large versus small), there was no association between weight change over time and feeding tube placement.
Discussion This study is the first to evaluate the prognostic significance of weight changes over time in feline lymphoma and veterinary oncology. The results indicate that weight loss during the first 2 months of treatment has the most negative prognostic significance in cats with large cell lymphoma; therefore, the first 2 months of treatment may be the optimal time to initiate therapeutic interventions and nutritional support in addition to chemotherapy in order to decrease weight loss.
Body weight and feline lymphoma prognosis
979
Table 1. Study population demographics. Although 200 cats had weights recorded at 1 month, 209 cats were included in the study because nine cats had weights recorded at time points after 1 month even though they did not have recorded weights at 1 month. Signalment Sex Male castrated Male intact Female spayed Female intact Age (years; mean SD) Breed Domestic shorthair Domestic longhair Japanese Bobtail, Siamese, unknown Maine Coon, Persian Baseline weight (kg; mean SD) Lymphoma grade/cell type High/large Small/low Hodgkin’s-like Unknown Anatomic location GI Abdominal non-GI (liver, spleen, kidney, etc) Thoracic (mediastinal mass, pleural effusion) Peripheral lymph nodes (LNs) (systemic disease) Extranodal (nasal, extraocular, etc) Bone marrow/peripheral lymphoblasts Other (mixed locations/body cavities) Baseline weight group <3 kg 3e5 kg >5 kg Weight recorded after baseline Month 1 Months 1 and 2 Months 1, 2 and 3 Months 1, 2, 3 and 6
It is important to keep in mind that nutritional support alone will not reverse tumor-related weight loss, particularly in patients that are not responding to chemotherapy. Such nutritional support (in addition to chemotherapy) would likely be of most benefit in cats that are responding to chemotherapy but whose caloric intake and GI function are not yet sufficient enough to result in weight gain. These results stated above regarding month 1 are specific to large cell lymphoma and do not apply to small cell lymphoma. This difference between small and large cell lymphoma may be due to the difference in biological behavior. Large cell lymphomas are clinically aggressive tumors and may, therefore, respond quickly to chemotherapy, thus resulting in improved body weight; or, alternatively, they may progress quickly and result in rapid clinical decline and weight loss. In contrast, small cell lymphomas are more
n
Percent (%)
124 1 83 1
59.3 0.5 39.7 0.5
188 13 2 1
10.5 4.2
4.4 1.4
90.0 6.2 1.0 0.5
145 47 2 15
69.4 22.5 1.0 7.2
119 30 13 9 23 4 11
56.9 14.4 6.2 4.3 11.0 1.9 5.3
24 129 56
11.5 61.7 26.8
200 151 115 72
95.7 72.2 55.0 34.4
indolent, such that a response to therapy may occur slowly over time and, similarly, lack of response may also result in less severe and more protracted weight loss over time. The difference in survival according to weight change at month 2 for small cell lymphoma cats appears to be clinically (though not statistically) significant, and it is possible that with a larger number of cats, the difference would be statistically significant. It makes sense with the biological behavior of feline small cell lymphoma that weight changes further along the treatment timeline would be better predictors of response and survival. The lack of a statistically significant different survival for large cell lymphoma cats according to weight change at month 2 could be due to type II statistical error; however, it could also show that month 1 is where the primary effect of weight change on survival occurs. Cats that survive to the month 2 time point
980
EL Krick et al
Table 2. Survival according to weight change at months 1 and 2 for all cats and cats stratified by cell type. LSS is given in months, and ‘e’ instead of a number for the upper limit of the 95% CI means that there were not enough cats to calculate the upper limit. Population
Month 1 n
All Gained weight Stable weight Lost weight P-value Large cell Gained weight Stable weight Lost weight P-value Small cell Gained weight Stable weight Lost weight P-value
200 30 83 87 143 19 64 60 40 8 19 13
Month 2
LSS (95% CI) 36.9 (6.5, e) 13.9 (7.4, 18.7) 4.5 (3.0, 7.8) 0.0002 7.0 (4.0, 63.0) 7.0 (4.8, 14.8) 3.1 (2.3, 5.1) 0.004 36.9 (4.1, e) 19.0 (14.8, 36.4) 16.0 (2.2, 36.0) 0.25
are more likely to be responding to chemotherapy, and thus, the impact of weight change may not be as significant for that group. The cut-offs for categorization into weight change groups of 5% change in body weight was chosen because that is considered to be clinically significant in the authors’ practice. It is possible, however, that using a different weight
n 158 47 45 66 104 33 28 43 40 11 13 16
LSS (95% CI) 18.6 (7.8, 45.1) 14.8 (8.8, 21.1) 7.8 (4.5, 14.0) 0.02 10.1 (6.4, 20.6) 8.8 (4.7, 16.6) 6.8 (3.1, 10.6) 0.33 45.1 (6.8, e) 25.9 (13.3, 36.4) 16.0 (3.9, 36.0) 0.07
change cut-off would result in a more significant impact on survival. Previous literature has demonstrated the clinical implications of body weight and body condition score in canine oncology and cardiology patients and in feline oncology patients. The majority of canine patients presenting to the oncology department of
Fig 1. KaplaneMeier survival curve of cats with large cell lymphoma comparing survival according to weight change (gained, lost or stable) at month 1 into treatment. Cats that gained (n ¼ 19) or had stable weight (n ¼ 64) had a significantly longer median LSS compared to cats that lost weight (n ¼ 60) [7.0 (4.0, 63.0) and 7.0 (4.8, 14.8) versus 3.1 (2.3, 5.1) months; P ¼ 0.004]. Of 45 cats censored, three were alive and 42 were lost to follow-up.
Body weight and feline lymphoma prognosis
981
Fig 2. Mean percent weight change at individual time points according to baseline weight. For each time point (months 1, 2, 3, and 6), mean percent weight change is the change from baseline to that time point. The P values for the mixed model fixed effects are as follows: for all cats together, weight changed significantly over time (P ¼ 0.009); when data from each baseline weight group was collapsed over time, weight changed significantly (P < 0.0001); weight changes over time were different according to baseline weight group (P ¼ 0.0004).
a referral veterinary hospital were overweight, while only 4% of canine patients exhibited a body condition score of 3 out of 9, which is consistent with being underweight or cachectic.16 A comparison of body weight and body condition with survival in canine patients with heart failure found that dogs with heart failure that gained weight lived longer than those who lost weight or whose weight was unchanged. In addition, cachectic dogs in heart failure had a shorter survival time than those that were obese.17 A previous study found that baseline body weight was prognostic for cats with a variety of cancers but not for lymphoma; specifically cats of lower body weight had shorter survival times.12 These studies indicate that weight loss before or during treatment can negatively impact survival, and weight loss appears to be more common in feline versus canine cancer patients. Baseline weight was not prognostic for survival for all cats or for cats with large or small cell lymphoma in the current study. The exclusion of cats that did not have a follow-up weight at least 1 month after
starting treatment could have biased our population by excluding cats that died or were lost to follow-up within the first month after starting treatment. If most of those cats had a low baseline weight, then their exclusion would have biased our survival analysis toward the null hypothesis. In the current study only baseline body weight was predictive of weight changes over time, with smaller cats gaining weight and larger cats losing weight. There is potential bias in this data, however, as only cats that lived to the 1 month time point were included in this analysis; therefore, the weight gain seen in cats weighing <3 kg at baseline may have been based on a select population of those cats that responded to therapy and gained weight. Neither anatomic location of lymphoma (GI versus non-GI) nor cell type (large versus small cell) affected how weight changed over time. It is possible that the prevalence of GI lymphoma was under-reported, however, as only cats with confirmed GI lymphoma were included in that group.
982
EL Krick et al
Placement of an enteral feeding tube occurred more frequently in cats with small cell lymphoma. Small cell lymphoma is most commonly diagnosed on histopathology. Because patients are anesthetized for either endoscopy or abdominal exploratory surgery, clinicians may be more likely to place an enteral feeding tube in these patients during the diagnostic procedure. In contrast, cats with large cell lymphoma generally are not anesthetized for diagnostic procedures, so placing an enteral feeding tube would require separate anesthesia and thus additional stress on the cat and cost for the owners. Additional limitations of this study are primarily related to its retrospective nature. Hydration status may have affected body weight, particularly in patients that lost weight. If they were clinically unwell and dehydrated, that could have contributed to weight loss. The portion of weight change that was due to hydration status could not be determined due to the retrospective nature of the study. Although treatment could not be standardized, the chemotherapy protocol most commonly used for large cell lymphoma in cats remained the same during the time period of this study. The protocol for small cell lymphoma did change over time: before this type of lymphoma was recognized separately from large cell lymphoma, these cats received the same protocol used for cats with large cell lymphoma. The protocol for small cell lymphoma used at the author’s institution has been different from that for large cell lymphoma and unchanged since the year 2000. Having body condition score data on all cats in the study would strengthen the data and allow for more comparison to other published reports; however, the retrospective nature of this study prevented that. In addition, as cat breeds have less size variation than dog breeds, body condition score in addition to body weight may not be as essential in cats compared to dogs for the purpose of this study. In addition, repeat body weight measurements have been shown to detect smaller changes in body mass compared to repeat body condition scoring.18 The results of this study have indicated that cats with lymphoma are at risk for weight loss during chemotherapy and provide evidence that this weight loss has a significant negative effect on survival for cats with large cell lymphoma. Weight loss experienced by cats during lymphoma treatment may be a result of the disease itself as well as chemotherapy side effects, and it can be challenging to differentiate between these causes of nausea, decreased appetite, and weight loss. Both owners and veterinarians associate poor appetite and weight loss with a reduced quality of life.15 Because weight loss in cats with lymphoma is a multi-faceted clinical challenge, it is important to consider the patient’s lymphoma status, chemotherapy tolerance, and existing co-morbidities when considering supportive care mediations and nutritional intervention. The impact of weight loss on quality and length of life in cats with lymphoma
warrants further investigation into therapies that combine chemotherapy with supportive care and nutritional interventions.
Acknowledgments The authors thank Nicholas B Lehmann for assistance with figure preparation.
References 1. Vail DM. Feline lymphoma and leukemia. In: Withrow SJ, Vail DM, eds. Withrow & MacEwan’s small animal clinical oncology. 4th edn. St Louis, MO: Saunders Elsevier, 2007: 733e56. 2. Mooney SC, Hayes AA, MacEwen GE, Matus RE, Geary A, Shurgot BA. Treatment and prognostic factors in lymphoma in cats: 103 cases (1977e1981). J Vet Intern Med 1989; 194: 696e9. 3. Simon D, Eberle N, Laacke-Singer L, Nolte I. Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats. J Vet Intern Med 2008; 22: 394e400. 4. Fondacaro JV, Richter KP, Carpenter JL, Hart JR, Hill SL, Fettman MJ. Feline gastrointestinal lymphoma: 67 cases (1988e1996). Eur J Comp Gastroenterol 1999; 4: 5e11. 5. Kiselow MA, Rassnick KM, McDonough SP, et al. Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995e2005). J Am Vet Med Assoc 2008; 232: 405e10. 6. Vail DM, Moore AS, Ogilvie GK, Volk LM. Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3 immunoreactivity, and their association with prognosis in 90 cats. J Vet Intern Med 1998; 12: 349e54. 7. Kristal O, Lana SE, Ogilvie GK, Rand WM, Cotter SM, Moore AS. Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases (1994e1997). J Vet Intern Med 2001; 15: 125e30. 8. Zwalen CH, Lucroy MD, Kraegel SA, Madwell BR. Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993e1997). J Am Vet Med Assoc 1998; 213: 1144e9. 9. Malik R, Gabor LJ, Foster SF, McCorkell BE, Canfield PJ. Therapy for Australian cats with lymphosarcoma. Aust Vet J 2001; 79: 808e17. 10. Teske E, van Straten G, van Noort R, Rutteman G. Chemotherapy with cyclophosphamide, vincristine, and prednisolone (COP) in cats with malignant lymphoma: new results with an old protocol. J Vet Intern Med 2002; 16: 179e86. 11. Milner RJ, Peyton J, Cooke K, et al. Response rates and survival times for cats with lymphoma treated with the University of WisconsineMadison chemotherapy protocol: 38 cases (1996e2003). J Am Vet Med Assoc 2005; 227: 1118e22. 12. Baez JL, Michel KE, Sorenmo K, Shofer FS. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Feline Med Surg 2007; 9: 411e7. 13. Hadden AG, Cotter SM, Rand W, Moore AS, Davis RM, Morrissey P. Efficacy and toxicosis of VELCAP-C treatment of lymphoma in cats. J Vet Intern Med 2008; 22: 153e7.
Body weight and feline lymphoma prognosis
14. Tzannes S, Hammond MF, Murphy S, Sparkes A, Blackwood L. Owners ‘perception of their cats’ quality of life during COP chemotherapy for lymphoma. J Feline Med Surg 2008; 10: 73e81. 15. Louwerens M, London CA, Pederson NC, Lyons LA. Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med 2005; 19: 329e35. 16. Michel KE, Sorenmo K, Shofer FS. Evaluation of body condition and weight loss in dogs presented to
983
a veterinary oncology service. J Vet Intern Med 2004; 18: 692e5. 17. Slupe JL, Freeman LM, Rush JE. Association of body weight and body condition with survival in dogs with heart failure. J Vet Intern Med 2008; 22: 561e5. 18. Burkholder WJ. Precision and practicality of methods assessing body composition of dogs and cats. Compend Contin Educ for Pract Vet 2001; 23: 1e10.
Available online at www.sciencedirect.com