title: Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP.
abstract: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies. However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP-treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS; P = .002) and progression-free survival (PFS; P = .038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (P = .002 and .010, respectively) and was independent of the IPI for prediction of OS (P = .008). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Malumbres
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Rob
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Yaso
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Byrne
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008957:Models, Genetic; D015999:Multivariate Analysis; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone