Risk of Second Cancers after Treatment for Hodgkin's Disease

Summary 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=1 6.9) 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 (ChIVPP) 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 ChIVPP 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.

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 67%

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Second malignancy in patients with Hodgkin's disease treated at the Royal Marsden Hospital

Swerdlow

Barber²,

Horwich³

et al. 1997

“…However, long-term follow-up of survivors has demonstrated that a price of this success has been an increased risk of second cancers. Acute leukaemia frequently occurs in the first decade after treatment, mainly as a consequence of chemotherapy regimens that included an alkylating agent (Tucker et al, 1988;Kaldor et al, 1990;Swerdlow et al, 2000). In the long term, however, the absolute excess risks of a second solid cancer are higher (Swerdlow et al, 2000;Ng et al, 2002b; and are linked mainly with radiotherapy, although for some sites, such as lung cancer, there may be a substantial risk also from chemotherapy (Swerdlow et al, 2000;Travis et al, 2002).…”

mentioning

confidence: 99%

Second primary breast cancer after Hodgkin's disease

Horwich

Swerdlow

2004

Although the potential carcinogenic risk of radiotherapy is well known, it has become clear that there is a particularly high risk of radiation-induced breast cancer in women treated for Hodgkin's disease at young ages. Thankfully, death from breast cancer in this population is uncommon, but it is important to understand factors contributing to the risk, including treatment parameters, and to develop a logical and efficient method for medical management of those at risk. In this minireview, we examine the evidence which should inform such a management policy. The prognosis of patients with Hodgkin's disease has been improved dramatically over the last 40 years by the development of extended field radiotherapy techniques and then by combination chemotherapy (DeVita et al, 1980;Rosenberg and Kaplan, 1985). However, long-term follow-up of survivors has demonstrated that a price of this success has been an increased risk of second cancers. Acute leukaemia frequently occurs in the first decade after treatment, mainly as a consequence of chemotherapy regimens that included an alkylating agent (Tucker et al, 1988;Kaldor et al, 1990;Swerdlow et al, 2000). In the long term, however, the absolute excess risks of a second solid cancer are higher (Swerdlow et al, 2000;Ng et al, 2002b; and are linked mainly with radiotherapy, although for some sites, such as lung cancer, there may be a substantial risk also from chemotherapy (Swerdlow et al, 2000;Travis et al, 2002). Recent reports from The Netherlands and from an international consortium of cancer registries have refined our understanding of how therapy may affect breast cancer risk.The relative risks of many cancers are higher if patients have been treated for Hodgkin's disease at a younger age (Swerdlow et al, 2000;van Leeuwen et al, 2000;Dores et al, 2002). Thus, although the risk of breast cancer is only about 50% increased in most all-age studies of women with Hodgkin's disease (van Leeuwen et al, 1999), relative risks are far larger than this in patients treated at young ages, especially those treated in childhood and adolescence (Hancock et al, 1993;Bhatia et al, 1996b); for them this is one of the main long-term sequelae of radiotherapy. This effect of age is unsurprising, as similar gradients are seen in other cohorts of radiation-exposed women (United Nations Scientific Committee on the Effects of Atomic Radiation, 1994).The size of risk of breast cancer found in Hodgkin's disease patients has varied between studies. For patients treated under age 21 years relative risks have generally been around 15 -25 (Hancock et al, 1993;Sankila et al, 1996;Wolden et al, 1998;Metayer et al, 2000;van Leeuwen et al, 2000;Dores et al, 2002), although they have been less raised (Neglia et al, 2001) or more raised (Mauch et al, 1996;Bhatia et al, 1996b;Aisenberg et al, 1997;Ng et al, 2002b) than this in a few studies; absolute excess risks have generally been of the order of 20 -40 per 10 000 per annum. Relative risks have been greater for patients treated at ages 10 -16 than at...

“…In this context, conventional cytopathology can define tumour histotype only in a small fraction of cases. In this study, we have evaluated whether selected combinations of monoclonal antibodies (MAbs) to tumour-associated antigens (TAAs) al, 1986;Tucker et al, 1988) and solid tumours (Lee, 1986;Kaldor et al, 1987). As early diagnosis of SPTs has major therapeutic and epidemiological relevance (Kaldor et al, 1987;Giardini et al, 1993), the development of new methods for the accurate detection of second malignancies should be attempted.…”

mentioning

confidence: 99%

Identification of second malignancies on effusions and fine-needle aspirates using a panel of monoclonal antibodies

Mottolese¹,

Venturo

Rinaldi

et al. 1997

Summary The longer survival of neoplastic patients achieved through improvements of therapeutic regimens has increased the relative risk of developing a second primary tumour (SPT). In this context, conventional cytopathology can define tumour histotype only in a small fraction of cases. In this study, we have evaluated whether selected combinations of monoclonal antibodies (MAbs) to tumour-associated antigens (TAAs) al, 1986;Tucker et al, 1988) and solid tumours (Lee, 1986;Kaldor et al, 1987). As early diagnosis of SPTs has major therapeutic and epidemiological relevance (Kaldor et al, 1987;Giardini et al, 1993), the development of new methods for the accurate detection of second malignancies should be attempted. In this context, exfoliative and FNA cytology may be considered a valuable and accurate diagnostic technique, easy to perform on a large scale during the follow-up of patients previously treated for malignant tumours. These methods also have the advantage of minimal morbidity and low cost (Koss, 1988). While this approach has been reported to be highly accurate in identifying metastatic cells, the possibility of defining the tumour histotype has been far less successful (Friedman et al, 1983;Hajdu et al, 1984). We have previously reported that the use of selected combinations of MAbs to TAAs can be applied to a number of areas of cytodiagnosis of solid tumours, thus increasing the accuracy of conventional morphology in identifying metastases from unknown primary tumour and in differentiating primary from metastatic lesions (Mottolese et al, 1993). In the present study, we have analysed, in a large group of patients with a past history of malignancy, whether the use of a similar panel of reagents may also be useful in detecting SPTs in two areas of cytopathology, which are particularly difficult on the basis of morphological criteria, namely that of effusions and of pulmonary FNA. MATERIALS AND METHODS PatientsFrom January 1990 to June 1995, 334 cytological specimens, of which 91 were pulmonary FNA and 243 pleural and peritoneal effusions sampled from patients previously treated with chemo and/or radiotherapy for different malignant tumours, were analysed both cytologically and immunocytochemically (ICC). The series consisted of 93 patients with effusions and 52 with solitary or multiple pulmonary masses, which appeared within 5 years of a previous tumour, while 189 patients developed effusions (150 cases) or radiologically assessed lung lesions (39 cases) at least 5 years after the first tumour. Only those cases in which morphological examination assessed the presence of malignant cells on cytological specimens have been included in this study. Unsatisfactory or insufficient specimens were excluded. Preparation of cell substratesPleural and peritoneal effusions were collected in sterile conditions using heparin (Liquemin Roche) as anticoagulant. Samples were centrifuged at 160 g for 10 min and the recovered cells were resuspended, after three washings with Hanks' balanced salt solution (Gibco Labor...