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Second primary cancers in patients continuously disease-free from Hodgkin's
disease: a protective role for the spleen?
PY Dietrich, M Henry-Amar, JM Cosset, S Bodis, J Bosq and M Hayat
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Second primary cancers are a serious late occurrence for patients surviving
Hodgkin's disease (HD). In addition to previously described risk factors
such as age, gender, clinical stage, and treatment modalities, splenectomy
was found to correlate with an increase in risk for secondary acute
leukemia. We assumed that splenic irradiation inducing functional
hyposplenia and splenectomy could have similar consequences on second
cancer risk. We studied a series of 892 continuously disease-free HD adult
patients treated at a single institution between 1960 and 1984. The risk of
second cancer was analyzed (1) relative to the general population and (2)
between risk subgroups using the Cox proportional hazards model. Fifty-six
patients developed a second cancer (8 acute leukemias, 3 myelodysplastic
syndromes, 8 non-Hodgkin's lymphomas, and 37 solid tumors; basal cell and
in situ cervix carcinomas were excluded). The 15-year cumulative incidence
rate (with 95% confidence limits) was 13.2% (9.3% to 17.2%). Relative to
the general population incidence data, the risk of second cancer was
multiplied by 4.68 (3.51 to 6.12; P < .001); it was multiplied by 2.80
(1.63 to 4.48; P < .001) in patients whose spleen was not treated and
multiplied by 6.87 (4.81 to 9.51; P < .001) in splenectomized patients
or patients whose spleen was irradiated. Multivariate regression analysis
that controlled for confounding variables (age, gender, clinical stage,
extent of radiation therapy, and chemotherapy regimen) showed that, in
addition to age above 40 years (relative risk [RR] = 3.72; P < .001),
combination of MOPP chemotherapy and regional irradiation (RR = 4.99; P =
.015) and combination of MOPP chemotherapy and extended irradiation (RR =
10.86; P < .001), splenic irradiation (RR = 3.67; P = .003), and
splenectomy (RR = 2.54; P = .018) also significantly correlated with an
increased risk. The results of this hospital-based registry study strongly
suggest that splenic irradiation and splenectomy might increase the risk
for treatment-related second cancer. These findings, if confirmed, have to
be considered in future HD treatment policies.
Volume 84,
Issue 4,
pp. 1209-1215,
08/15/1994
Copyright © 1994 by The American Society of Hematology
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