[show abstract][hide abstract] ABSTRACT: Because genetic predisposition probably plays an important role in the aetiology of most of childhood cancers, studies of second primaries occurring after these cancers may be particularly informative about possible common genetic mechanisms in both of these cancers. We have studied the incidence of thyroid tumours occurring after cancer in childhood in a cohort of 592 children treated before 1970. Among these children, six later developed a thyroid carcinoma, and 18 developed a thyroid adenoma. Radiation doses received to the thyroid by each of the irradiated children have been estimated using individual radiotherapeutic technical records. Thyroid carcinomas and thyroid adenomas were five times more frequent after irradiation for neuroblastoma than after irradiation for any other first cancer. This ratio did not depend on sex, nor on time elapsed since irradiation, nor on dose of radiation received for the thyroid gland. This result suggests that there is a common mechanism for the occurrence of neuroblastoma and of differentiated thyroid tumour.
British Journal of Cancer 04/1992; 65(3):425-8. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 case-control 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 50 Gy or more had a relative risk of SMN of 5.8 (P less than 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 risk 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 25 Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P less than 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.
British Journal of Cancer 06/1989; 59(5):792-6. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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% CI: 2.8-6.6%), 7.8% (95% CI: 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.
British Journal of Cancer 04/1989; 59(3):448-52. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Between 1982 and 1985, a case-control study of nulliparous women, aged 25-45, was conducted to analyse the relationships between the risk of breast cancer and causes of nulliparity, including contraceptive methods. Fifty-one cases of breast cancer diagnosed less than 3 months before interview were matched with 95 controls on age at diagnosis, year of interview, and medical center. The causes of nulliparity related to female sterility or subfertility (mechanical or hormonal disorders) were not found to be associated with a significantly higher risk of breast cancer. The causes related to fertilization failure, i.e. no sexual partner, rare sexual intercourse (less than once per month), or partner with abnormal semen, were found to lead to an increased risk. Detailed analysis of contraceptive methods showed that the risk of breast cancer increased (p = 0.02) with a longer duration of use of barrier methods (withdrawal or condom). Conversely, the risk significantly decreased (p = 0.004) with a longer duration of use of non-barrier methods (oral contraceptives, IUD, cap, local spermicides, vaginal douche, safe period, or no method), i.e. methods allowing a direct exposure to human semen.
Journal of Clinical Epidemiology 02/1989; 42(12):1227-33. · 5.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).
European Journal of Surgical Oncology 09/1987; 13(4):309-14. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.
[show abstract][hide abstract] ABSTRACT: In a French case-control study of 1,010 breast cancer cases and 1,950 controls with nonmalignant diseases, the risk of breast cancer was found to be positively associated with frequency of cheese consumption and the level of fat in the milk consumed. A negative association was found between frequency of yogurt consumption and the risk of breast cancer. No association was found between the consumption of butter and the risk of breast cancer. The positive association between a daily consumption of alcohol and the risk of breast cancer previously reported was not altered when dairy produce consumption was taken into account.
JNCI Journal of the National Cancer Institute 10/1986; 77(3):633-6. · 14.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: HLA complex is made up of numerous loci whose alleles are codominant. Several associations between HLA antigens and diseases have been identified. Analysis of these associations require statistical methods taking into account the number of tests and the existence of alleles which have not yet been identified. Statistical methods for the estimation and the comparison of alleles frequencies are presented for genotypic, phenotypic and marginal data. An example concerning patients with medullary thyroid carcinoma illustrates these methods.
Revue d Épidémiologie et de Santé Publique 02/1986; 34(1):1-9. · 0.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at operation, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, esophagus, blood vessels or mediastinum. Of 539 patients with differentiated thyroid cancer treated at Villejuif, France, until 1976, 97 were treated by external radiotherapy after an incomplete surgical excision. Fifteen years after irradiation, the survival rate is 57% and is approximately 40% at 25 years. The relapse-free survival is lower (39% at 15 years). In patients irradiated with an adequate dose (greater than or equal to 50 Gy) to residual neoplastic tissue after incomplete surgery, the incidence of local recurrence is low (actuarial probability of local recurrence 11% at 15 years versus 23% for patients treated by surgery alone, although the irradiated patients had larger and more extensive tumors). This demonstrates the efficacy of external-beam radiotherapy. The effects of radiotherapy on a residual tumor can be monitored by a serum thyroglobulin assay. With regard to local control of tumors, the effectiveness of radioiodine administration is clearly lower. However, since radioiodine facilitates early detection of distant metastases, a combination of external RT and radioiodine is indicated and is well-tolerated. For inoperable patients, the results of RT are limited: although complete remissions are sometimes obtained, the incidence of local recurrence is high. External RT is effective in medullary carcinoma despite the slow shrinkage of the tumor after irradiation. Assay of the calcitonin level helps to monitor the effects of the treatment during follow-up and has demonstrated in some patients the efficacy of cervical RT. In undifferentiated cancers, the results of RT are poor. Combination of RT and chemotherapy are being explored despite the disappointing preliminary results of this combination.
Cancer 06/1985; 55(9 Suppl):2062-71. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: There are conflicting reports on trends in tobacco consumption for France. We present here a synthesis of the available evidence from total sales and from population surveys. The consequences on future lung cancer death rates are briefly discussed and some possible actions are suggested.
Revue d Épidémiologie et de Santé Publique 02/1985; 33(6):387-95. · 0.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thyroid iodine content (TIC) was measured in nine patients with hyperthyroid Graves' disease for 5-26 months after treatment with 131I (100-125 muCi/g tissue). In all patients, TIC decreased; in eight patients it became undetectable within 5 +/- 3 (SD) months. This fall was parallel to those of serum T3 and T4 levels and was not prevented by the administration of large doses of stable iodine. In four patients, this decrease was irreversible and they became clinically hypothyroid. In the five other patients, it was partly reversible: the secondary increase of TIC was parallel to those of serum T3 and T4 and to a decrease in TSH levels. These data suggest that during the months after 131I treatment, determination of TIC may help to distinguish transient from irreversible hypothyroidism. The late effects of 131I were studied in 38 patients who had been treated for hyperthyroid Graves' disease from 1.5-22 yr previously. The 16 patients who, at the time of examination, were euthyroid with normal serum TSH levels (less than 8 microU/ml) had a TIC [3.2 +/- 3 (SD) mg] significantly lower than that of 10 euthyroid patients previously treated only with antithyroid drug therapy (16.7 +/- 8.2 mg). A significant negative correlation was found between log basal TSH and log TIC (r = 0.61, P less than 0.001) and a positive correlation between log T4 and log TIC (r = 0.56, P less than 0.002). The T3/T4 ratio in patients with undetectable TIC (19.9 +/- 7.9) was higher than that of the other patients (14.6 +/- 3.2) (P = 0.02, Wilcoxon test). This hormonal profile was not modified by iodide supplementation, which increased TIC only transiently. The turnover of thyroid iodine was accelerated, which appeared to be the consequence of a small thyroid functional mass and of hyperstimulation by TSH.
[show abstract][hide abstract] ABSTRACT: An association between regular consumption of alcohol with meals and breast cancer was found in a French case-control study of 1,010 women with breast cancer and 1,950 women with nonmalignant diseases; the relative risk of breast cancer for women drinking alcoholic beverages with meals compared with nondrinkers was 1.47 (p = 10(-4) allowing for classical risk factors. Detailed information on alcohol consumption was obtained from 500 cases and 945 controls; the risks of breast cancer were greater for women drinking beer and for women drinking wine than for nondrinkers, and the risk increased with the amount of beer, of wine and of total alcohol consumption in grams of pure alcohol.
American Journal of Epidemiology 10/1984; 120(3):350-7. · 4.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: A clinical trial was conducted at the Institut Gustave Roussy between October 1972 and December 1980 to compare mastectomy with local excision plus Cobalt-irradiation, in patients with breast cancer tumors of 20 mm in diameter or less at macroscopic examination. Low-axillary dissection and extemporaneous histologic examination were carried out for all patients. If one or more positive nodes were found, complete axillary dissection was performed. The study included 179 patients. No significant difference was detected in either overall or relapse-free survival between the two groups, although the conservatively treated group showed slightly better results. The results of conservative treatment were esthetically satisfactory in 92% of the cases. The trial included a second randomization for the patients with positive axillary nodes to assess the value of nodal area irradiation; 72 patients were studied in this part of the trial. No significant differences were found between the two groups after adjustment for the number of positive axillary nodes, although the no-nodal irradiation group showed better results and less complications than the nodal irradiation group.
Cancer 04/1984; 53(5):1209-13. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: A multicentric randomized trial evaluated the interest of internal mammary dissection on operable breast cancer patients. One thousand four hundred and fifty-three patients were included in the study and were followed for ten years. There is no difference in survival or in relapse-free survival between the two groups. There were significantly more local recurrences in the group without internal mammary dissection, but these recurrences occurred mainly on patients who developed metastases. A great difference between centers was observed in the number of nodes examined and there is therefore a difference in the prognostic value of the number of nodes invaded.
Cancer 06/1983; 51(10):1941-3. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of five days of antibiotic prophylaxis with cefazolin injections (beginning just before surgery) on postoperative infections (beginning just before surgery) on postoperative infectious complications was evaluated in a double-blind, randomised, placebo-controlled trial in nine centres on 2137 patients undergoing hip replacement. Antibiotic prophylaxis reduced the number of hip infections significantly from 3.3% (placebo) to 0.9% (cefazolin). Positive peroperative blood samples and positive bacteriological examination of the drain were risk factors for hip infection but the prognostic value of obesity, diabetes, or previous hip surgery was not confirmed. Development of a urinary infection was not related to hip infection. Hip infections were less common in the four centres with hypersterile operating theatres, and the benefits of prophylactic antibiotics were restricted to patients having hip replacement operations in conventional theatres.
The Lancet 05/1981; 1(8224):795-6. · 39.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: The retrospective analysis of 288 cases of neonatal cholestasis showed that 4 clinical data allowed to separate extra- and intra-hepatic cholestasis in 82% of cases. These results should facilitate the diagnosis and lead to early surgery, when required.
Archives françaises de pédiatrie 01/1977; 34(7 Suppl):CCXIII-CCXX.