Diagnosis-to-treatment interval is an important clinical factor in newly diagnosed diffuse large B-cell lymphoma and has implication for bias in clinical trials

Matthew J. Maurer, Hervé Ghesquières, Brian K. Link, Jean Philippe Jais, Thomas M. Habermann, Carrie A. Thompson, Corinne Haioun, Cristine Allmer, Patrick B. Johnston, Richard Delarue, Ivana N. Micallef, Frederic Peyrade, David J. Inwards, Nicolas Ketterer, Umar Farooq, Olivier Fitoussi, William R Macon, Thierry J. Molina, Sergei Syrbu, Andrew L. FeldmanSusan L. Slager, George J. Weiner, Stephen M. Ansell, James R. Cerhan, Gilles A. Salles, Thomas E. Witzig, Hervé Tilly, Grzegorz S. Nowakowski

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosisto-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1, 444). All patients received anthracyclinebased immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P <.001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.

Original languageEnglish (US)
Pages (from-to)1603-1610
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number16
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Maurer, M. J., Ghesquières, H., Link, B. K., Jais, J. P., Habermann, T. M., Thompson, C. A., Haioun, C., Allmer, C., Johnston, P. B., Delarue, R., Micallef, I. N., Peyrade, F., Inwards, D. J., Ketterer, N., Farooq, U., Fitoussi, O., Macon, W. R., Molina, T. J., Syrbu, S., ... Nowakowski, G. S. (2018). Diagnosis-to-treatment interval is an important clinical factor in newly diagnosed diffuse large B-cell lymphoma and has implication for bias in clinical trials. Journal of Clinical Oncology, 36(16), 1603-1610. https://doi.org/10.1200/JCO.2017.76.5198