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Evidence summaries

Chemotherapy Versus Combined Modality Treatment in Hodgkin's Disease

Chemotherapy plus radiotherapy for treatment of patients with Hodgkin's disease improves overall survival in early stage (I-II) disease compared with adequate chemotherapy alone. For advanced stages (III-IV), combined therapy improves progression free survival but may increase the risk of second malignancies. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 37 studies with a total of 9 312 subjects. Combined chemo-radiotherapy (CRT) was superior to chemotherapy (CT) in terms of progression-free survival (OR=0.77, CI 0.68 to 0.87). Overall survival was better with CRT for early stages only (OR=0.62, CI 0.44 to 0.88). Risk of second malignancies was higher with CRT (OR=1.38, CI 1.00 to 1.89), although not significant for early stages alone. CRT was superior to radiotherapy (RT) in terms of overall survival (OR=0.76, CI=0.66 to 0.89), progression-free survival (OR=0.49, CI=0.43 to 0.56) and risk of second malignancies (OR=0.78. CI=0.62 to 0.98). The superiority of CRT also applied to early and advanced stages (mainly IIIA) separately. Extended-field (EF-) radiotherapy was superior to involved-field (IF-) radiotherapy (each additional to CT in most trials) in terms of progression free survival (OR=81, CI 0.68 to 0.95) but not overall survival.

A meta-analysis 2 including 23 studies with a total of 3 888 subjects was abstracted in DARE. More extensive radiotherapy reduced the risk of failure at 10 years by more than one third (31.3 vs 43.4% failures) but had no apparent effect on survival (77.1 vs 77% alive). The addition of chemotherapy halved the 10-year risk of failure (15.8% vs 32.7%) with a small non-significant improvement in survival (79.4% bs 76.5% alive).

Another meta-analysis 3 included 14 studies with a total of 1 755 subjects. Patients who received additional radiotherapy showed an 11% overall improvement in tumour control rate after 10 years (p<0.0001, 95% CI 4% to 18%). There was no difference in overall survival. In the parallel-design trials there was no difference in tumour control rates, but overall survival at 10 years was significantly better in the group that did not receive radiotherapy (p=0.045, 8%, 95% CI 1% to 15%).

    References

    • Franklin JG, Paus MD, Pluetschow A, Specht L. Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk. Cochrane Database Syst Rev 2005 Oct 19;(4):CD003187. [PubMed]
    • Specht L, Gray RG, Clarke MJ, Peto R. Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group. J Clin Oncol 1998 Mar;16(3):830-43. [PubMed] [DARE]
    • Loeffler M, Brosteanu O, Hasenclever D, Sextro M, Assouline D, Bartolucci AA, Cassileth PA, Crowther D, Diehl V, Fisher RI, Hoppe RT, Jacobs P, Pater JL, Pavlovsky S, Thompson E, Wiernik P. Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol 1998 Mar;16(3):818-29. [PubMed]

Primary/Secondary Keywords