Second Cancers Following Radiation Treatment for Cervical Cancer. An International Collaboration Among Cancer Registries

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Abstract
The numbers of second cancers among 182,040 women treated for cervical cancer that were reported to 15 cancer registries in 8 countries were compared to the numbers expected had the same risk prevailed as in the general population. A small 9% excess of second cancers (5,146 observed vs. 4,736 expected) occurred 1 or more years after treatment. Large radiation doses experienced by 82,616 women did not dramatically alter their risk of developing a second cancer; at most, about 162 of 3,324 second cancers (≈5%) could be attributed to radiation. The relative risk (RR = 1.1) for developing cancer in organs close to the cervix that had received high radiation exposures—most notably, the bladder, rectum, uterine corpus, ovary, small intestine, bone, and connective tissue—and for developing multiple myeloma increased with time since treatment. No similar increase was seen for 99,424 women not treated with radiation. Only a slight excess of acute and non-lymphocytic leukemia was found among irradiated women (RR = 1.3), and substantially fewer cases were observed than expected on the basis of current radiation risk estimates. The small risk of leukemia may be associated with low doses of radiation absorbed by the bone marrow outside the pelvis, inasmuch as the marrow in the pelvis may have been destroyed or rendered inactive by very large radiotherapy exposures. There was little evidence of a radiation effect for cancers of the stomach, colon, liver, and gallbladder, for melanoma and other skin cancers, or for chronic lymphocytic leukemia despite substantial exposures. An excess of thyroid cancer possibly was related to the low dose received by this organ. Ovarian damage caused by radiation may have been responsible for a low breast cancer risk (RR=0.7), which was evident even among postmenopausal women. A substantial excess of lung cancer (RR=3.7) largely may be due to misclassification of metastases and the confounding influence of cigarette smoking. Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer. The RR, however, was higher among those under age 30 years at exposure (RR=3.9) than among older women. The expression period for radiation-induced solid tumors appeared to continue to the end of life.