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Abstract

BACKGROUND:

Survivors of Hodgkin's lymphoma are at increased risk for treatment-related subsequent malignant neoplasms. The effect of less toxic treatments, introduced in the late 1980s, on the long-term risk of a second cancer remains unknown.

METHODS:

We enrolled 3905 persons in the Netherlands who had survived for at least 5 years after the initiation of treatment for Hodgkin's lymphoma. Patients had received treatment between 1965 and 2000, when they were 15 to 50 years of age. We compared the risk of a second cancer among these patients with the risk that was expected on the basis of cancer incidence in the general population. Treatment-specific risks were compared within the cohort.

RESULTS:

With a median follow-up of 19.1 years, 1055 second cancers were diagnosed in 908 patients, resulting in a standardized incidence ratio (SIR) of 4.6 (95% confidence interval [CI], 4.3 to 4.9) in the study cohort as compared with the general population. The risk was still elevated 35 years or more after treatment (SIR, 3.9; 95% CI, 2.8 to 5.4), and the cumulative incidence of a second cancer in the study cohort at 40 years was 48.5% (95% CI, 45.4 to 51.5). The cumulative incidence of second solid cancers did not differ according to study period (1965-1976, 1977-1988, or 1989-2000) (P=0.71 for heterogeneity). Although the risk of breast cancer was lower among patients who were treated with supradiaphragmatic-field radiotherapy not including the axilla than among those who were exposed to mantle-field irradiation (hazard ratio, 0.37; 95% CI, 0.19 to 0.72), the risk of breast cancer was not lower among patients treated in the 1989-2000 study period than among those treated in the two earlier periods. A cumulative procarbazine dose of 4.3 g or more per square meter of body-surface area (which has been associated with premature menopause) was associated with a significantly lower risk of breast cancer (hazard ratio for the comparison with no chemotherapy, 0.57; 95% CI, 0.39 to 0.84) but a higher risk of gastrointestinal cancer (hazard ratio, 2.70; 95% CI, 1.69 to 4.30).

CONCLUSIONS:

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. (Funded by the Dutch Cancer Society.).

Comment in

Second Cancers after Treatment for Hodgkin's Lymphoma--Continuing Cause for Concern. [N Engl J Med. 2015] 

Author information

Schaapveld M1, Aleman BM, van Eggermond AM, Janus CP, Krol AD, van der Maazen RW, Roesink J, Raemaekers JM, de Boer JP, Zijlstra JM, van Imhoff GW, Petersen EJ, Poortmans PM, Beijert M, Lybeert ML, Mulder I, Visser O, Louwman MW, Krul IM, Lugtenburg PJ, van Leeuwen FE.​

1 From the Departments of Epidemiology (M.S., A.M.E., I.M., I.M.K., F.E.L.), Radiation Oncology (B.M.P.A.), and Hematology (J.P.B.), Netherlands Cancer Institute, and the Department of Hematology, VU University Medical Center Amsterdam (J.M.Z.), Amsterdam, the Netherlands Comprehensive Cancer Organization (M.S., I.M., O.V., M.W.J.L.) and the Departments of Radiation Oncology (J.R.) and Hematology (E.J.P.), University Medical Center Utrecht, Utrecht, the Departments of Radiation Oncology (C.P.M.J.) and Hematology (P.J.L.), Erasmus Medical Center Cancer Institute, Rotterdam, the Department of Radiation Oncology, Leiden University Medical Center, Leiden (A.D.G.K.), the Department of Radiation Oncology, Radboud University Medical Center (R.W.M.M., P.M.P.P.), and the Department of Education and Science, Canisius-Wilhelmina Hospital (I.M.), Nijmegen, the Department of Hematology, Radboud University Medical Center, Nijmegen-Rijnstate, Arnhem (J.M.M.R.), the Departments of Hematology (G.W.I.) and Radiation Oncology (M.B.), University Medical Center Groningen, Groningen, the Department of Radiation Oncology, Dr. Bernard Verbeeten Institute, Tilburg (P.M.P.P.), and the Department of Radiotherapy, Catharina Hospital, Eindhoven (M.L.L.) - all in the Netherlands.