title: Long-term events in adult patients with clinical stage IA-IIA nonbulky Hodgkin's lymphoma treated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine and adjuvant radiotherapy: a single-institution 15-year follow-up.
abstract: OBJECTIVE
  To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma.
  
  
  METHODS
  We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia.
  
  
  RESULTS
  Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P=0.029) and females (9.4; P=0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved.
  
  
  CONCLUSIONS
  Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated.
authors.affiliation: Clinica Ematologica and Servizio di Radioterapia Oncologica, Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, University of Pavia, Pavia, Italy. ebrusa@smatteo.pv.it
authors.forename: Ercole
authors.initials: E
authors.lastname: Brusamolino
authors.forename: Ambrogia
authors.initials: A
authors.lastname: Baio
authors.forename: Ester
authors.initials: E
authors.lastname: Orlandi
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Griva
authors.forename: William
authors.initials: W
authors.lastname: Casagrande
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Pietro
authors.initials: P
authors.lastname: Franchini
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000528:radiation effects; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008171:Lung Diseases / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin