Aggressive Non-Hodgkin Lymphoma: Predictive Value Of Sarcopenia and Skeletal Muscle Density On Prognosis With Rituximab Containing Therapy
Authors: Chu Michael P , Lieffers Jessica , Belch Andrew R , Chua Neil , Fontaine Amelie , Sangha Randeep , Turner A. Robert , Ghosh Sunita , Sawyer Michael 
Published: October 2019

Abstract

Introduction
Sarcopenia is an established adverse risk factor for solid organ malignancies. Recent evidence suggests sarcopenia predicts a poor prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL) independent of Revised International Prognostic Index (R-IPI) scores. Because of the focus on an elderly population, it is difficult to generalize to the DLBCL population as a whole. Newer evidence suggests low skeletal muscle density (SMD) is a more significant indicator of poor prognosis in renal cell carcinoma and melanoma than sarcopenia. SMD can be approximated using computed tomography (CT) images and measuring muscle radiation attenuation in Hounsfield Units (HU). An average muscle SMD of <30 HU is considered to be poorly functioning muscle and has the appearance of ectopic fat production. This study examines sarcopenia and SMD in DLBCL.

Methods
DLBCL patients from 2004-2009 who received rituximab-based chemotherapy through our institution were retrospectively reviewed. Aside from baseline information (stage, age, gender, height, weight, performance status, R-IPI score, chemotherapy regimen and cycles received), progression free survival (PFS) and overall survival (OS) were collected as primary endpoints. Sarcopenia and SMD were calculated using Slice-o-Matic (Tomovision, Montreal Canada) with patients’ pre-treatment CT images. Skeletal muscle was defined as between -29 to 150 HU, intramuscular adipose tissue -190 to -30 HU; and visceral adipose tissue -150 to -50 HU. Skeletal muscle surface area and average radiation attenuation at the L3 vertebral body level were measured. Sarcopenia was pre-defined using skeletal muscle surface area cut-offs outlined in prior solid organ malignancy studies and from the elderly DLBCL study.

Results
We identified 224 DLBCL patients. Median age at diagnosis was 62 years (range 21-88 years), with 124 male, and 100 female. Median stage at diagnosis was III with a median IPI score of 3. The majority received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with a median of 6 cycles (range 1-8). Median PFS and OS were 55.2 and 56.3 months, respectively. Patients with sarcopenia did not have a significant difference in either PFS or OS. In fact, the PFS hazard ratio (HR) of 0.70 would suggest sarcopenia as being protective but it was not statistically significant (p=0.19). Subgroup analysis of elderly DLBCL patients (defined as >70 years), found sarcopenia was protective for both PFS and OS yielding HRs of 0.24 and 0.45, respectively (p=0.002 and 0.05). A statistically insignificant PFS improvement by SMD was seen above and below the median SMD with 61.0 and 52.8 months, HR 1.28 (p=0.32), respectively. However, OS was significantly better in those above the median SMD at 65.5 vs 51.4 months, HR 2.02 (p=0.006). A cut-off point in SMD was noticeable at 26.63 HU where PFS was significantly worse in those that had lower SMD with 53.3 vs 56.3 months, HR 1.74 (p=0.03). OS was also significantly poorer with SMD lower than this cut-off, 51.9 vs 59.2 months, HR 1.92 (p=0.01), respectively. This difference though failed to maintain significance in multivariate analysis taking into consideration R-IPI and gender.

Conclusions
Contrary to recent evidence suggesting sarcopenia as a poor prognostic factor in elderly patients with DLBCL, our study demonstrates that sarcopenia may in fact be protective. Perhaps patients with lower lean body mass may be exposing their disease to relatively higher concentrations of chemoimmunotherapy. SMD is more prognostic than sarcopenia in DLBCL patients. While these findings suggest muscle mass and muscle quality play a strong role in the disease process, factors captured in the R-IPI score predict clinical course more strongly.

Disclosures:
No relevant conflicts of interest to declare.