Dutch Study Shows Increased Risk of Second Cancer for Survivors of Hodgkin Lymphoma During Long-Term Follow-up


Key Points

  • Breast, lung, and gastrointestinal cancers and non-Hodgkin lymphoma accounted for the highest proportions of excess cancers, in a Dutch study of survivors of Hodgkin lymphoma.
  • No difference in the risk for second solid cancers was observed for the most recent vs older study periods.

In a Dutch study reported in The New England Journal of Medicine, Schaapveld et al found that survivors of Hodgkin lymphoma treated between 1965 and 2000 were at a 4.6-fold greater risk of second cancer vs the general population during long-term follow-up. There was no significant difference in the risk of second solid cancers for patients treated between 1989 and 2000 vs those treated in earlier periods.

The study included data from 3,905 patients in the Netherlands who had received treatment for Hodgkin lymphoma between 1965 and 2000, at 15 to 50 years of age, and had survived for at least 5 years after initiation of treatment.

Risk of Second Cancers

After a median follow-up of 19.1 years, 1,055 second cancers were diagnosed in 908 patients, yielding a standardized incidence ratio (SIR) of 4.6 (95% confidence interval [CI] = 4.3–4.9) vs the general population. At ≥ 35 years after treatment, risk vs the general population was still elevated by 3.9-fold (SIR = 3.9, 95% CI = 2.8–5.4). At 40 years, the cumulative incidence of a second cancer was 48.5%.

Breast cancer contributed most to the overall absolute excess risk (excess of 24.9 cases/10,000 person-years among men and women; 20.4% of the excess risk), with the absolute excess risk among women being 54.3 cases per 10,000 person-years (40.5% of the excess risk of any second cancer). Breast cancer was followed by lung cancer (excess of 24.6 cases/10,000 person-years; 20.2% of excess risk), gastrointestinal cancer (19.7% of excess risk), and non-Hodgkin lymphoma (13.1% of excess risk).

There was a lower risk for any second cancer among patients treated in 1989–2000 vs 1965–1976 (hazard ratio = 0.79, P = .02 for trend) but no differences in the cumulative incidence of second solid cancers among the 1965–1976, 1977–1988, and 1989–2000 study periods (P = 0.71 for heterogeneity).

Risk Factors

Risk of breast cancer was lower among patients treated with supradiaphragmatic-field radiotherapy not including the axilla vs those receiving mantle-field irradiation (HR = 0.37, 95% CI = 0.19–0.72), but risk of breast cancer was not reduced for 1989–2000 vs the two earlier periods. A cumulative procarbazine dose of ≥ 4.3 g/m2, which has been associated with premature menopause, was associated with a reduced risk of breast cancer (HR = 0.57, 95% CI = 0.39–0.84, vs no chemotherapy) but an increased risk of gastrointestinal cancer (HR = 2.70, 95% CI = 1.69–4.30).

The investigators concluded: “The risk of second solid cancers did not appear to be lower among patients treated in the most recent calendar period studied (1989–2000) than among those treated in earlier periods. The awareness of an increased risk of second cancer remains crucial for survivors of Hodgkin’s lymphoma.”

The study was funded by the Dutch Cancer Society.

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