title: Comparative effectiveness of anthracycline-containing chemotherapy in United States veterans age 80 and older with diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  While anthracycline-based treatment can cure diffuse large B-cell lymphoma, most patients over age 80 do not receive doxorubicin due to toxicity concerns. This study evaluated this practice, as patients age 80 and older are largely excluded from clinical trials. The primary outcome of interest was overall survival. Secondary outcomes included treatment-related mortality and anthracycline dose intensity.
  
  
  METHODS
  We assembled a cohort of 530 newly diagnosed diffuse large B-cell lymphoma patients age 80 or older diagnosed within United States Veterans Health Administration. Treatment and survival information were obtained to determine associations between anthracycline use, dose intensity, treatment-related mortality and overall survival.
  
  
  RESULTS
  Of the 530 patients, 285 received systemic treatment and 193 received an anthracycline. After controlling for potential confounders, rituximab decreased mortality (hazard ratio, 0.62; 95% confidence interval [CI]: 0.44-0.88), while doxorubicin was not significantly associated with mortality (hazard ratio, 0.87; 95% CI: 0.64-1.17). Completion of treatment with anthracycline dose intensity ≥85% of expected was only 14%. Patients treated with anthracycline dose intensity <85% had better one year survival compared to those treated at ≥85% (70% vs. 59%, p=0.029).
  
  
  CONCLUSIONS
  These results suggest that full dose anthracycline therapy may be less important in the treatment of diffuse large B-cell lymphoma patients over age 80. The low frequency of completion of full dose intensity treatment suggests that standard doses are an unrealistic standard of care for patients this age. Alternate treatment strategies and risk stratification should be considered for these patients.
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA; Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA; Division of Public Health Sciences, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA. Electronic address: kcarson@dom.wustl.edu.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Carson
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Riedell
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Lynch
authors.affiliation: Division of Hematology/Oncology, Advocate Lutheran General Hospital, 1775 Dempster St, Park Ridge, IL 60068, USA.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA; Division of Public Health Sciences, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Wildes
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA; Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Weijian
authors.initials: W
authors.lastname: Liu
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Ganti
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA; Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Roop
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA; Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Sanfilippo
authors.affiliation: Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO 63103, USA; Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Katiuscia
authors.initials: K
authors.lastname: O'Brian
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cashen
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Wagner-Johnston
authors.affiliation: Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fehniger
authors.affiliation: Division of Public Health Sciences, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Colditz
mesh_terms: D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D000069283:Rituximab / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014728:Veterans
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000069283:Rituximab; D004317:Doxorubicin
keywords: Doxorubicin; Elderly; Lymphoma; Veterans