Sumanry Of a cohort of 634 children treated from 1942 to 1969 at the Gustave Roussy Institute for a first cancer and alive 5 years after treatment, 32 later developed second malignant neoplasms (SMN). A casecontrol study was performed to determine the relationship between the dose of radiotherapy received on a given anatomical site for the treatment of a first cancer, and the risk of SMN development at the same anatomical site. Another aim of the study was to analyse the effects of the association of radiotherapy with chemotherapy on the risk of SMN. The 32 cases of second malignant neoplasms were individually matched with one to nine patients of the cohort (a total of 162) who did not develop a SMN after a first cancer, matching on age, sex, type of first cancer and follow-up duration. The doses of radiotherapy delivered for the treatment of the first cancer were retrospectively estimated at the 26 anatomical sites of SMN. When the SMN was a leukaemia, the mean active bone-marrow dose was estimated as a weighted mean of the doses received by 20 bone sites. As compared to anatomical sites in children who had not received radiotherapy, the sites which had received 5OGy or more had a relative risk of SMN of 5.8 (P<0.05). When taking into account the dose received at the site of the SMN, neither the number of fractions nor the type of radiations were related to the nrsk of SMN. Children who had received chemotherapy had a relative risk of SMN of 2.7 (95% CI: 1.2-6.4), adjusted for the dose of radiotherapy, as compared to those who had not. The relative risk of SMN did not vary with the dose nor the duration of the chemotherapy. Dactinomycin was found to increase the relative risk of second soft tissue and bone sarcomas. Cyclophosphamide was found to be less carcinogenic than the other alkylants. The relative risk of SMN was equal to 2.0 (n.s.) after radiotherapy of more than 25Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P<0.01) after the combination of these two treatments modalities, as compared to patients treated by surgery alone. This study suggests that the oncogenic effect of radiations might be increased by chemotherapy, and that the combination of the two treatment modalities might be one of the major factors responsible for overall risk of SMN.The study of the carcinogenic effects of radiotherapy and chemotherapy is of major clinical interest, because these treatments may be responsible for a great part of the second malignant neoplasms (SMN) which occur after a first cancer (Tucker et al., 1984). It is also useful in theoretical studies about carcinogenicity because therapeutic exposure to radiations and to cytostatic agents is much more precisely documented than environmental and professional exposures. The study of SMN occurring after a first cancer in childhood is particularly interesting because children may survive for a long period of time after the treatment of a first cancer, at ages where the natural incidence of cancer is very low, and where most environmental factors are less likely to p...

Summary The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs=32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% Cl: 2.8-6.6%), 7.8% (95% Cl: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp=2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.

(Uriel eta/., 1967(Uriel eta/., , 1968. Abelev also found fetuin in sera of adult patients with testicular teratoblastomas (Abelev et al., 1967).The present work resulted from screening for the presence of fetuin in sera of children with malignant tumours, with special reference to embryonal carcinomas, either ovarian or testicular. STUDY GROUP AND METHODSControl data were obtained from sera of 21 children with no evidence of malignancy (Dr. Jean Weill, Paediatric Department, HBpital Bretonneau, Paris) and 62 children with congenital heart diseases (Dr. Nouailles, Paediatric and Cardiologic Department, HBpital Parrot, Hic@tre).Sera from 93 children with malignant diseases were collected in the Childrens' Department of the lnstitut Gustave Roussy (Villejuif). These included 12 embryonal carcinomas, 34 nephroblastomas, 29 neuroblastomas and 18 cancers of various organs, mainly malignant lymphomas. Tuniour extractsSoluble tumour extracts were prepared from the tumours obtained at surgery. The supernatant fluid was then lyophilized. A solution containing 15 mg/ml total proteins was tested. AntiseraRabbit antisera were prepared against either human cord serum, foetal serum or fetuin-rich serum from a primary carcinoma of the liver. A detailed outline of the immunization schedule is described in the paper of Uriel et af. (1967).

The clinicopathologic features of radiation enteritis are reviewed in 44 children receiving whole abdominal radiation therapy between 1961–1972 at the Institut Gustave‐Roussy. Five of 14 long‐term survivors (36%) developed severe delayed radiation injury with small bowel obstruction, occurring within 2 months after completion of irradiation. All had previously had acute radiation reaction during therapy. Histologic appearance in the small bowel at the time of delayed radiation injury revealed severe villus blunting, lymphatic dilatation, and moderately dense inflammatory infiltrate. All patients with delayed radiation injury showed marked clinical improvement coincident with a fractionated low‐residue, low‐fat diet, free of gluten and free of milk and milk products. The abnormal small bowel roentgenographs and small bowel biopsies reverted to a normal appearance in association with the diet. No exacerbation of radiation enteritis has been seen following dietary therapy.