title: The clinical features, management and prognostic effects of pathological fractures in a multicenter series of 373 patients with diffuse large B-cell lymphoma of the bone.
abstract: BACKGROUND
  Pathological fractures (PFs) occur in 10%-20% of patients with diffuse large B-cell lymphoma (DLBCL) of the bone. The clinical features and the effects of this severe complication on management and prognosis have not been previously analyzed in a large series.
  
  
  METHODS
  The effects of PF on management and prognosis were reviewed in an international retrospective series of 373 patients with newly diagnosed bone DLBCL, comparing 78 patients with PF at presentation (group 'PF-BL') and 295 patients without PF ('controls').
  
  
  RESULTS
  At a median follow-up of 53 months (range 3-246), PF-BL patients exhibited lower rates of overall response (ORR, 78% versus 85%; P = 0.17), 5-year progression-free survival (PFS, 53 ± 6% versus 61 ± 3%; P = 0.02) and 5-year overall survival (OS, 54 ± 6% versus 68 ± 3%, P = 0.008) than controls. Initial surgical stabilization of the PF did not change therapeutic outcome (5-year OS: 45 ± 9% versus 54 ± 10%; P = 0.20). PF-BL patients referred to irradiation of the fractured bone before chemotherapy exhibited a significantly poorer outcome than patients managed with the inverse sequence (ORR: 52% versus 92%, P = 0.0005; 5-year OS: 22 ± 14% versus 64 ± 9%, P = 0.007). Multivariate analysis confirmed the independent association between PF and worse survival and the negative effect of radiotherapy as initial therapy.
  
  
  CONCLUSIONS
  Fracture is an independent, adverse prognostic event in patients with bone DLBCL. Anthracycline-based chemotherapy followed by radiotherapy seems to be the better treatment sequence. Initial fracture stabilization does not seem to improve outcome; it should be used to improve patient's quality of life only if chemotherapy delays can be avoided.
authors.affiliation: Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Govi
authors.forename: D
authors.initials: D
authors.lastname: Christie
authors.forename: C
authors.initials: C
authors.lastname: Messina
authors.forename: M
authors.initials: M
authors.lastname: Bruno Ventre
authors.forename: E A
authors.initials: EA
authors.lastname: Gracia Medina
authors.forename: D
authors.initials: D
authors.lastname: Porter
authors.forename: J
authors.initials: J
authors.lastname: Radford
authors.forename: D
authors.initials: D
authors.lastname: Seog Heo
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: E
authors.initials: E
authors.lastname: Taylor
authors.forename: H
authors.initials: H
authors.lastname: Lucraft
authors.forename: V
authors.initials: V
authors.lastname: Ballova
authors.forename: E
authors.initials: E
authors.lastname: Zucca
authors.forename: M
authors.initials: M
authors.lastname: Gospodarowicz
authors.forename: A J M
authors.initials: AJ
authors.lastname: Ferreri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D050723:Fractures, Bone / Q000209:etiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
keywords: bone fixation; bone lymphoma; diffuse large B-cell lymphoma; osteolymphoma; pathological fractures; radiotherapy