title: Patterns of failure in advanced stage diffuse large B-cell lymphoma patients after complete response to R-CHOP immunochemotherapy and the emerging role of consolidative radiation therapy.
abstract: OBJECTIVE
  The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients.
  
  
  METHODS
  We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our institution. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using the log-rank test. Multivariate analyses were also performed using Cox proportional hazards model.
  
  
  RESULTS
  Detailed treatment records were available for 163 patients. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate analysis, consolidative RT and nonbulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Consolidative RT was also associated with marginal improved OS.
  
  
  CONCLUSIONS
  Forty-four percent of patients with advanced stage DLBCL failed at initial presenting sites after achieving CR to R-CHOP. Incorporation of consolidative RT as part of upfront treatment in these patients was associated with improved LC, PFS, and a trend towards improved OS.
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Shi
authors.forename: Satya
authors.initials: S
authors.lastname: Das
authors.forename: Derick
authors.initials: D
authors.lastname: Okwan-Duodu
authors.forename: Natia
authors.initials: N
authors.lastname: Esiashvili
authors.forename: Christopher
authors.initials: C
authors.lastname: Flowers
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Loretta J
authors.initials: LJ
authors.lastname: Nastoupil
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D060828:Induction Chemotherapy / Q000379:methods; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000379:methods; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D017211:Treatment Failure; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone