Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

J Cachexia Sarcopenia Muscle. 2016 Dec;7(5):567-576. doi: 10.1002/jcsm.12115. Epub 2016 Apr 12.

Abstract

Background: Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL).

Methods: In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS).

Results: Treatment-related mortality (21.7 vs. 5.0%, P = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group (P < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group (P < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P = 0.009; revised-IPI, 0.74, P < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P = 0.062).

Conclusions: Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

Keywords: Diffuse large B‐cell lymphoma; Nomogram; Prognosis; Sarcopenia; Toxicity.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / complications*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Neoplasm Staging
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Rituximab
  • Sarcopenia / diagnosis
  • Sarcopenia / etiology*
  • Sarcopenia / mortality*
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone