title: Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736.
abstract: Utility of combined-modality therapy for patients with limited-stage diffuse large B-cell lymphoma (DLBCL) was shown in the Southwest Oncology Group (SWOG) S8736 study, where three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus radiotherapy (CHOP3RT) improved 5-year progression-free (PFS) and overall survival (OS) compared with eight cycles of CHOP (CHOP8). Subsequent analysis showed an unexpected overlap of the PFS curves. We aimed to confirm and investigate this observation by performing long-term analysis of SWOG S8736 and evaluating these data alongside data from similar patients receiving rituximab and CHOP3RT (SWOG S0014 study).
  
  
  
  A subset of patients with limited-stage DLBCL randomly assigned to CHOP8 (n = 150) or CHOP3RT (n = 158) in S8736 was analyzed along with a 56-patient subset treated in S0014 for long-term PFS and OS.
  
  
  
  Median follow-up in S8736 was 17.7 years. In patients receiving CHOP8 and CHOP3RT, median PFS was 12.0 (95% CI, 8.8 to 14.3) and 11.1 years (95% CI, 8.9 to 14.4), respectively. There were no statistically significant differences in PFS between the groups (P = .73). Median OS was 13.0 (95% CI, 10.4 to 15.2) and 13.7 years (95% CI, 11.1 to 19.4) for patients treated with CHOP8 and CHOP3RT, respectively. Similarly, there were no statistically significant differences in OS between the groups (P = .38). With a median follow-up time 12 years in S0014, 5- and 10-year OS were 82% and 67%, respectively, with a persistent pattern of relapse despite the addition of rituximab.
  
  
  
  Although 5-year PFS and OS were improved after early analysis in patients with limited-stage DLBCL receiving CHOP3RT versus CHOP8, extended survival data showed similar PFS and OS, with continuous treatment failure. The addition of rituximab (S0014) to combined-modality therapy did not mitigate the continued relapse risk, underscoring the value of prolonged clinical trial patient observation and possible unique biology of limited-stage DLBCL.
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Stephens
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Michael L
authors.initials: ML
authors.lastname: LeBlanc
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Soham D
authors.initials: SD
authors.lastname: Puvvada
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Daniel
authors.initials: D
authors.lastname: Persky
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: Deborah M. Stephens, University of Utah, Salt Lake City, UT; Hongli Li and Michael L. LeBlanc, Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Soham D. Puvvada and Daniel Persky, University of Arizona, Tucson, AZ; Jonathan W. Friedberg, Wilmot Cancer Institute, University of Rochester, Rochester, NY; and Sonali M. Smith, University of Chicago, Chicago, IL. smsmith@medicine.bsd.uchicago.edu.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012306:Risk; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D011241:Prednisone