Abstract
Background:
Sarcopenia, which is defined as the loss of skeletal muscle mass, is considered a poor prognostic factor in chronic disease and solid tumors. Recently, several studies revealed that sarcopenia is an important risk factor in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). Physical status varies depending on the race, and the prognostic value of sarcopenia remains unclear in Japanese patients with DLBCL. Furthermore, the clinical impact of change in the skeletal muscle mass during chemotherapy on the outcomes of DLBCL is unknown.
Materials and methods:
We retrospectively analyzed newly diagnosed>16-years-old patients with DLBCL who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone between 2004 and 2014 at the Yokohama City University Hospital or Yokohama City University Medical Center.
The skeletal muscle mass was assessed using computed tomography (CT)-based methods. Body composition analysis was performed using CT scan before the initial chemotherapy. The cross-sectional area (cm2) of the skeletal muscle at the level of the third lumbar vertebra [rectus abdominis, abdominal (lateral and oblique), psoas, and paraspinal (quadratus lumborum, erector spinae) muscle] was calculated. The surface of the muscle tissue was selected on the basis of the Hounsfield units, ranging from −29 to 150 for skeletal muscles. Measurements were normalized by the patient's height and expressed as the skeletal muscle index (SMI) (cm2/m2). Sarcopenia was defined as SMI <52.4 cm2/m2 in men and <38.5 cm2/m2 in women based on previously published values. To assess the change in the skeletal muscle mass during chemotherapy, we compared pre- and post-treatment SMI. The association between sarcopenia and overall survival (OS) and progression-free survival (PFS) were analyzed in all patients. The association between skeletal muscle mass change and relapse-free survival (RFS) was analyzed in patients who achieved complete remission.
To assess the clinical impact of sarcopenia and change in the skeletal muscle mass, we performed multivariate analysis. Covariates, such as PS, CS, EN, LDH, sIL-2R, found to be significant in univariate analysis (p< 0.1) were included in the model. Sarcopenia or change in the skeletal muscle mass was added to the final model.
Results:
Of the 181 patients, 103 were men and 78 were women. The median age at diagnosis was 63 years (range, 21-80 years). The median SMI was 47.8 cm2/m2 (27.1-103.7 cm2/m2) in men and 37.8 cm2/m2 (19.0-80.6 cm2/m2) in women. One hundred and twenty one patients (66.9%) were defined as having sarcopenia. Sarcopenia was more common in men (P = 0.02) and in patients with a lower body mass index (P = 0.002). One hundred and sixty two patients achieved complete remission after consecutive treatment.There were no significant differences in the 5-years OS (84.4% vs. 88.8%, P = 0.94) and PFS (65.7% vs. 78.3%, P = 0.58) between patients with and without sarcopenia.
Multivariate analysis showed that sarcopenia had no significant impact on PFS (HR, 0.78; 95% CI, 0.43-1.40; P = 0.40). In terms of change in the skeletal muscle mass during chemotherapy, no significant difference in RFS was observed between the gain and loss groups (84.7% vs. 73.9%, P = 0.20). However, multivariate analysis showed that a gain in the skeletal muscle mass was associated with a favorable RFS, with borderline significance (HR, 0.48; 95% CI, 0.22-1.05; P = 0.07).
Conclusions:
The current study showed a higher proportion of patients with sarcopenia compared with previously published reports, and sarcopenia had no significant negative impact on outcomes of DLBCL, which is in contrast to previous studies. These data suggest that an optimal definition of sarcopenia is yet to be established in the Japanese population. However, a change in the skeletal muscle mass during treatment may be a useful prognostic factor for DLBCL.
Fujisawa: Celgene: Honoraria; Chugai Pharmaceutical: Honoraria; Bristol-Myers squibb: Honoraria.
