title: Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients.
  
  
  METHODS
  A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT.
  
  
  RESULTS
  The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields.
  
  
  CONCLUSIONS
  With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.
authors.affiliation: Department of Haematology, The Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Lillian M
authors.initials: LM
authors.lastname: Fuller
authors.forename: John T
authors.initials: JT
authors.lastname: Manning
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Chul S
authors.initials: CS
authors.lastname: Ha
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Ana
authors.initials: A
authors.lastname: Ayala
authors.forename: Mark
authors.initials: M
authors.lastname: Hess
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabanillas
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011878:Radiotherapy / Q000379:methods; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone