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

Clin Cancer Res. 2006 Nov 1;12(21):6487-93. doi: 10.1158/1078-0432.CCR-06-1420.

Abstract

Purpose: 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.

Experimental design: 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.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Dacarbazine / adverse effects
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Fertility / drug effects
  • Fertility / radiation effects
  • Follow-Up Studies
  • Hodgkin Disease / mortality
  • Hodgkin Disease / therapy*
  • Humans
  • Lung Diseases / epidemiology
  • Lung Diseases / etiology*
  • Male
  • Middle Aged
  • Neoplasms, Radiation-Induced / epidemiology
  • Neoplasms, Radiation-Induced / etiology*
  • Neoplasms, Second Primary / epidemiology
  • Neoplasms, Second Primary / etiology*
  • Pregnancy
  • Radiotherapy, Adjuvant
  • Survival Analysis
  • Vinblastine / adverse effects
  • Vinblastine / therapeutic use

Substances

  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin