Bone Sarcomas Linked to Radiotherapy and Chemotherapy in Children

We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (±SE) 20-year cumulative risk of 2.8±0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose–response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose–response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer. (N Engl J Med 1987; 317:588–93.), IONIZING radiation has long been known to induce bone cancers. In 1929 Martland observed bone sarcomas among workers painting radium on watch dials,¹ and the relation of bone cancers to the use of various bone-seeking radioisotopes is now well documented.² Therapeutic external beam radiation was convincingly linked to bone sarcomas in 1948,^{3 , 4} but even today few quantitative data exist. In recent surveys, radiation risks have seemed especially high among patients treated at a young age, notably for retinoblastoma, Ewing's sarcoma, or Hodgkin's disease.^{4 5 6 7 8 9 10 11 12} Bone cancers have also occurred after lower doses of radiation were given in childhood for nonmalignant diseases…