title: Outcome prediction by extranodal involvement, IPI, R-IPI, and NCCN-IPI in the PET/CT and rituximab era: A Danish-Canadian study of 443 patients with diffuse-large B-cell lymphoma.
abstract: 18F-fluorodeoxyglucose PET/CT (PET/CT) is the current state-of-the-art in the staging of diffuse large B-cell lymphoma (DLBCL) and has a high sensitivity for extranodal involvement. Therefore, reassessment of extranodal involvement and the current prognostic indices in the PET/CT era is warranted. We screened patients with newly diagnosed DLBCL seen at the academic centers of Aalborg, Copenhagen, and British Columbia for eligibility. Patients that had been staged with PET/CT and treated with R-CHOP(-like) 1(st) line treatment were retrospectively included. In total 443 patients met the inclusion criteria. With a median follow-up of 2.4 years, the 3-year overall (OS) and progression-free survival (PFS) were 73% and 69%, respectively. The Ann Arbor classification had no prognostic impact in itself with the exception of stage IV disease (HR 2.14 for PFS, P<0.01). Extranodal involvement was associated with a worse outcome in general, and in particular for patients with involvement of >2 extranodal sites, including HR 7.81 (P < 0.001) for PFS for >3 sites. Bone/bone marrow involvement was the most commonly involved extranodal site identified by PET/CT (29%) and was associated with an inferior PFS and OS. The IPI, R-IPI, and NCCN-IPI were predictive of PFS and OS, and the two latter could identify a very good prognostic subgroup with 3-year PFS and OS of 100%. PET/CT-ascertained extranodal involvement in DLBCL is common and involvement of >2 extranodal sites is associated with a dismal outcome. The IPI, R-IPI, and NCCN-IPI predict outcome with high accuracy.
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.|Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Tarec Christoffer
authors.initials: TC
authors.lastname: El-Galaly
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Diego
authors.initials: D
authors.lastname: Villa
authors.affiliation: Department of Hematology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|King Saud University, Riyadh, Saudi Arabia.
authors.forename: Musa
authors.initials: M
authors.lastname: Alzahrani
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jakob Werner
authors.initials: JW
authors.lastname: Hansen
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.affiliation: Department of Functional Imaging, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Don
authors.initials: D
authors.lastname: Wilson
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: de Nully Brown
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Loft
authors.affiliation: Department of Nuclear Medicine, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Victor
authors.initials: V
authors.lastname: Iyer
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.|Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, BC, Canada.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Hutchings
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D001853:Bone Marrow / Q000473:pathology; D002170:Canada; D003520:Cyclophosphamide; D003718:Denmark; D004317:Doxorubicin; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010053:Ovary / Q000473:pathology; D010994:Pleura / Q000473:pathology; D049268:Positron-Emission Tomography; D011241:Prednisone; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D014750:Vincristine
chemical_list: D019788:Fluorodeoxyglucose F18; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone