Abstract
Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during 1963-91. A total of 77 second malignancies occurred. There were significantly raised risks of stomach [standardized incidence ratio (SIR)=4.0], lung (SIR=3.8), bone (SIR=26.5), soft tissue (SIR=16.9) and non-melanoma skin (SIR=3.9) cancers, non-Hodgkin's lymphoma (SIR=4.6), and acute and non-lymphocytic leukaemia (SIR=31.3), with a relative risk of 3.3 for all second cancers other than non-melanoma skin cancer. Solid cancer risk was raised to a similar extent in patients treated only with radiotherapy (SIR=2.6, P<0.001), only with chemotherapy (SIR=2.1, P=0.08) and with both (SIR=3.1, P<0.001). Leukaemia risk was raised only in those receiving chemotherapy, whether alone or with radiotherapy. The relative risk for solid cancers was much greater in patients who were younger at first treatment (trend P<0.001), whereas leukaemia risk was greatest for those first treated at ages 25-44. For solid cancers (P<0.001) but not leukaemia (P=0.05) there was a strong gradient of greater relative risks at younger attained ages. The relative risk of second cancers overall was 27.5 at ages under 25 and 2.0 at ages 55 and above. Leukaemia and solid cancer risks in patients treated with chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) were not significantly greater than those in patients treated with mustine, vincristine, procarbazine and prednisone (MOPP). Number of cycles of chemotherapy was significantly related to risk of leukaemia (P<0.001), and there was a trend in the same direction for solid cancers (P=0.07). The study adds to evidence that alkylating chemotherapy may increase the risk of solid cancers, and that ChlVPP does not provide a less carcinogenic alternative to MOPP chemotherapy. The very large relative risks found for solid cancers at young attained ages and in patients treated when young may have important implications as, in the long term, the majority of second malignancies after Hodgkin's disease are solid cancers. The risks of solid malignancies need clarification by larger collaborative epidemiological studies.
Highlights
The transformation in prognosis of Hodgkin's disease following the introduction of intensive radiotherapy and chemotherapy is one of the great successes of modem medicine, but it has brought with it a raised risk of second malignancy
The present analyses extend the numbers and length of follow-up for Hodgkin's disease patients at the Royal Marsden Hospital (RMH), and extend the range of analyses of risks in these patients, especially with regard to solid cancer
The regional cancer registry receives from the National Health Service Central Registers notification of second malignancies occurring anywhere in the country in patients resident in the registry region at the time of the initial Hodgkin's disease
Summary
The transformation in prognosis of Hodgkin's disease following the introduction of intensive radiotherapy and chemotherapy is one of the great successes of modem medicine, but it has brought with it a raised risk of second malignancy. Acute or nonlymphocytic leukaemia (ANLL) occurs in the first few years after treatment, mainly as a consequence of chemotherapy (Tucker et al, 1988; Kaldor et al, 1990; Swerdlow et al, 1992; van Leeuwen et al, 1994a; Boivin et al, 1995). Four recent papers have suggested that chemotherapy without radiotherapy can lead to an increase in solid cancer risk (Kaldor et al, 1992; Swerdlow, 1992; Biti et al, 1994; Boivin et al, 1995), but other studies did not support this (Abrahamsen et al, 1993; van Leeuwen et al, 1994a). The issue is important because in the long term solid malignancies form the great majority of second cancers after Hodgkin's disease.
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