Muscle Mass in Elderly Patients with DLBCL Treated with RCHOP

Sarcopenia is defined as reduced muscle mass and loss of strength or function and can be part of normal aging as well as a component of cachexia. Multiple studies found correlation between reduced muscle mass and negative outcomes in chronic diseases and solid tumors. Little research exist on similar relationship in hematological malignancies and no studies investigated impact of longitudinal muscle mass changes on clinical outcomes in elderly lymphoma patients undergoing treatment.

To evaluate the muscle mass during the course of chemotherapy in patients 70 years or older with DLBCL and its effect on survival and toxicity, we performed a retrospective cohort study. We included patients diagnosed between the years 2007-2014, and treated with RCHOP at the Rabin Medical Center. We collected data on age, sex, performance status (PS), number of extranodal involvement sites, Ann Arbor stage, international prognostic index (IPI), Charlson comorbidity index (CCI), hemoglobin (Hb), LDH, neutrophil, lymphocyte, monocyte, and platelet count, creatinine, albumin, CRP, treatment date, response and survival. We evaluated muscle mass by adding bilateral psoas muscle cross-sectional areas measured at the level of the third lumbar vertebra in a semi-automated manner on standard PET CT images. The ratio of the total psoas area normalized to height square (expressed in cm²/m²) was defined as muscle index. The change in muscle index after vs. before treatment was estimated. Correlation was estimated in a non-parametric test. The effect of pre-treatment muscle mass index and the above mentioned variables was estimated in a univariate Cox regression analysis. Variables potentially associated with mortality were entered into a Cox regression multivariate analysis.

Results: Ninety three patients treated with RCHOP with baseline PETCT were included in the cohort. Median age was 78 years (range 70-90). Half of patients were female. Sixty percent had an IPI score of 3 or more. Mean muscle index before treatment was 4.66 cm²/m², median 4.4 cm²/m². End of treatment PETCT was available for 76 patients. Mean post treatment index was 4.2 cm²/m², median 3.92 cm²/m². A decrease in muscle index was observed in 76% of patients. The change in index ranged from -7.5 to 0.8, with a mean change of -0.58, SE0.12.

No statistically significant correlation between pre treatment index and dose intensity was shown (p = 0.46). A negative correlation was shown between pre treatment index and days of hospitalization in cycles 1-2 (p=0.007, r=-0.28). Pre-treatment muscle index was not associated with overall survival (p = 0.43). In a sub-group analysis by sex a higher muscle index was associated with a longer overall survival among men (HR 0.59, 95% CI 0.44 to 78, p<0.001), while such an association was not demonstrated among women. Factors associated with overall survival (p<0.05 unless otherwise specified) were dose of adriamycin and cyclophosphamide in the first cycle, low hemoglobin, albumin, lymphocyte count (p=0.08), and platelet count (p=0.052) and LDH level. In a multivariate model that included these variables, albumin and chemotherapy dose remained statistically significant. In a second model with these variables as well as age and gender, the variables that were associated with overall survival were albumin, age, and gender, while chemotherapy dose became of borderline significance (p=0.08).

Conclusion: based on our data including 93 elderly patients with DLBCL a higher muscle mass before RCHOP was associated with longer overall survival among men, but not among women. No association was found between muscle mass measured as total psoas area corrected to height and dose intensity and infection. During the course of chemotherapy we observed a loss of muscle mass in most of the patients.