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The objective of this phase II multicenter study was to assess the efficacy and tolerance of triptorelin (a sustained-release LHRH agonist) in advanced or recurrent endometrial cancer. A total of 101 monthly intramuscular injections were administered to 24 eligible patients (median number/patient = 3; range 1-12). Mainly due to progression, only 16 patients received 3 or more injections. Among the 23 evaluable patients, 1 complete and 1 partial response (response rate of 8.7%) and 5 disease stabilizations were observed, often of long duration, but never in an irradiated area or after progestogens treatment failure. Median survival for eligible patients was 7.2 months (range: 1-36 months). Only grade 1 toxicities possibly related to the treatment were observed in 4 patients. In conclusion, triptorelin was safe, well tolerated, and easily manageable, and the very low toxicity did not impair the quality of life in these patients with a very poor prognosis. Although the response rate was disappointing, several patients showed early evidence of efficacy which may be of long duration. Response rates range between 0 and 45% in different published studies. Additional studies with stricter inclusion criteria and a larger sample size are necessary to better evaluate the role of LHRH agonists in endometrial adenocarcinomas., (Copyright 1999 Academic Press.)

Unlabelled: Radiation is known to be mutagenic. The aim of the present study was to ascertain whether exposure to 131I induces genetic damage, as assessed by pregnancy outcomes and the health status of offspring of women previously exposed to 131I during thyroid carcinoma treatment., Methods: Data on 2113 pregnancies were obtained by interviewing female patients treated for thyroid carcinoma who had not received any significant external radiation to the ovaries., Results: The incidence of miscarriages was 11% before any treatment for thyroid cancer; this number increased slightly after surgery for thyroid cancer, both before (20%) and after (20%) 131I, but did not vary with the cumulative 131I dose. Miscarriages were more frequent (40%) in the ten women who were treated with 131I [mean dose: 3.8 GBq (108 mCi)] during the year preceding conception. Incidences of stillbirth, preterm birth, low birth weight, congenital malformation and death during the first year of life were not significantly different before or after 131I therapy. The incidence of thyroid disease and nonthyroidal malignancy was similar in children born either before or after their mothers were exposed to 131I., Conclusion: With the exception of miscarriages, there is no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring. The question of whether an increased incidence of miscarriages within 1 yr of 131I administration relates to gonadal irradiation or to insufficient control of hormonal thyroid status remains to be established.

Combinations of 5-fluorouracil (5-FU) and streptozocin and 5-FU and dacarbazine were given alternately to 20 patients with metastatic medullary thyroid carcinoma. Three partial responses and 11 long-term stabilizations were observed. No unexpected toxicity occurred.

A randomized double-blind study with a 3-yr follow-up comparing the two arms "orchiectomy + Anandron (300 mg)" vs "orchiectomy + placebo" in 125 patients with stage D prostate cancer has confirmed the beneficial effects of the combined Anandron therapy on subjective parameters and on the best objective response (NPCP criteria), although these effects were not statistically significant, but failed to detect any improvement in time-to-disease progression or survival. Comparison with the results of other trials emphasizes the urgent need to establish suitable prognostic factors by further clinical research before evaluating the benefits of individual drugs.

The purpose of the present work is to "quantify" bone scanning, in order to calculate indices of localized uptake that will make it possible to differentiate between normal and pathological uptake, and approach an etiologicial diagnosis. The authors use an Elscint dual head whole body scanner and an offline video display calculator. The patient is given 8 mc technetium 99m pyrophosphate 4 hours prior to scanning. The whole body count is expressed in thousands of counts multipled by two so that the knee to whole body ratio is close to one, to facilitate comparison of the indices. Results show that the presence of metastases is demonstrated more clearly by using a ratio bone segment to whole body. Quantitative scanning with 99mTc-pyrophosphate makes it possible to: 1) detect bone metastases easily, 2) follow the metastases during treatment, 3) avoid the gross errors that can be made in nomquantitative scanning.

I.--The inverse relationship of risk with parity is one of the earliest known features of the epidemiology of human mammary cancer. But recently knowledge of this relationship was refined when Mac Mahon and his colleagues found that the protective effect is actually correlated to the age of the mother at the first birth rather than to the total number of children, so that a woman who has a child before the age of 18 is one third as likely to suffer breast cancer in later life as a woman first delivered at 35. II.--A study was undertaken in the Centre Francois Baclesse on the hypothesis that age at first birth may also be related to the age of the patient at clinical onset of the mammary malignancy. One would expect to find a retardative effect of early delivery since this factor was found to be protective as far as mammary cancer risk is concerned. The conclusions of our investigations are in complete opposition to the original hypothesis: in our series, breast cancer appears to occur significantly earlier in women whose first delivery occurred early. III.--Thus the same process appears to be protective as far as total mammary cancer risk is concerned but accelerating as far as age at tumor onset is concerned. These apparently inconsistent observations led to the hypothesis that both studies might express the same biologic process which, in the case of early delivery, inhibits the mechanism of carcinogenic induction and therefore reduces the total number of cancer but which subsequently quickens the evolution of the inducted disease. Such a conjecture implies that breast cancer should be more severe following early first birth. The analysis of our series, as well as the series of Ontario Cancer Clinics, substantiates this hypothesis. But these conclusions are built on indirect proofs or direct proofs which are still short of statistical significance.

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Lymph node involvement was demonstrated by para-aortic lymphadenectomy in 6 out of 20 women treated for ovarian cancer with macroscopically limited lesions at first and second-look laparotomy. When added to those reported in the literature, these results suggest that 20% of stages I and II ovarian cancers involve the lymph nodes, which considerably influences the prognosis and treatment of cancers otherwise considered as limited. We therefore suggest that biopsy of the lumbar aortic lymph nodes should be systematically performed in the surgical evaluation of ovarian cancers at an early stage.

The authors propose an endo-uterine catheter which will permit a hysterographic examination to be made during utero-vaginal radium therapy, thus making it possible to check: --that the catheter has advancec correctly after insertion; --that the uterine cavity intact: --that the catheter is in the correct place; --its retention during treatment. By using radio-opaque rings and small balloons in the hysterographic examination, it is possible to locate: --the external orifice of the cervix; --the urethral meatus; --the anterior wall of the rectum and the posterior wall of the bladder. In this way, the target volume is loated with precision, and the length, position and activity of the various radio-active sources can be adapted accordingly.

In a period of 18 months, 187 cytology aspiration biopsies of the breast were performed at the Centre François Baclesse by clinicians and radiologists, using the conventional technique. Comparison of the results with clinical, radiological and histological findings by different specialists showed that one out of two aspiration biopsies gave an erroneous diagnosis. The authors believe that this failure was due to the fact that the biopsies were not performed by a cytologist. This prime condition of success should be more clearly expressed in the literature.

A group of 135 patients with osseous metastases from breast cancer were treated with hydroxy-9-methyl-2-ellipticinium (100 mg/m2 weekly). Although it was impossible to grade the response precisely, because only indirect criteria are available for assessing the course of bone metastases (radiographs, quantified 99mTc pyrophosphate scintigrams, CEA), it was considered that an objective response was obtained in 44 cases. These responses lasted from 3 to 17 months. The main characteristic of the compound is its lack of marrow toxicity, a valuable property in osseous lesions, where frequent marrow involvement makes it difficult to use conventional drugs. The major and most unpleasant side effect was an inhibition of salivary secretion, which causes other complications such as tongue mycosis, anorexia, and asthenia. Immunologic disorders were less frequent, and four patients developed severe tubular renal insufficiency.

In 96 patients (95 women--1 man) with osseous metastases from breast cancer suitable for analysis an objective remission was obtained with hydroxy-9-methyl-2-ellipticinium (100 mg/m2 weekly) in 31 cases. These responses lasted from 3 to 17 months. The main characteristic of this compound is its lack of marrow toxicity, a property of value in osseous lesions where marrow is so frequently involved, making difficult the use of conventional chemical drugs. The principal unpleasant drawback is an inhibition of the salivary secretion which causes other side effects such as tongue mycosis, anorexia, and asthenia. Less frequently immunologic disorders and a few cases of renal insufficiency were observed.

The sex of the first child of patients who underwent mastectomy for potentially curable breast cancer appeared to be a valuable prognostic factor: patients whose first child was a boy had a better outcome than those whose first child was a girl. The difference was statistically significant. This may have been because the male/female sex ratio among first children was significantly higher in those patients without node involvement than in those with node involvement. But the favourable effect of a male first birth was still seen when only patients with an equal degree of node involvement (greater than or equal to 4 nodes) were studied. The "protection" resulting from a male first-born could be the result of fetal testicular secretions. This protection did not apply to the risk of breast cancer--the male/female sex ratio of first children in our series was 1.08, a figure not statistically different from that of the overall French population (1.05).

Since 1976 to 1978 inclusive, 465 patients with primary breast cancers underwent whole body analogical scintiscans, 456 numerical scans, and 453 were X-rayed. Ninety per cent received axillary node ablation, 62% presented adenopathies of which a third were capsular ruptures and 54% were T3 and T4. In 53 patients, the presence of metastasis was estimated by clinical evaluation. In 38 patients, metastasis were confirmed. Probability for the patient to present metastasis when the test is positive, is: P (M/T +) = Se.p/(Se.p) + (1-p) + (1-p) (1-Spe) Probability when the test is negative is: P (M/T -) = p(1-Spe)/p(1-Se) + (1-p)Spe p = prevalence Se = sensibility Spe = specificity Performance of the test is the probability of obtaining a correct result is: P = (f1) - (f2) = (f3) The (f3) curves were plotted for each of the three tests. For a prevalence of 11% (clinical estimate) the X-ray or analogical scintiscans tests achieve the same performance, but that for a prevalence of 8% (exact number) the radiological examination yields the best. In two cases, numerical scan is better.

The use of polymorphic DNA segments as markers for the gene for the multiple endocrine neoplasia (MEN) syndrome, type 2a, allows the identification of family members at high risk for developing medullary carcinoma of the thyroid and other tumors, especially pheochromocytoma. Several families have also been identified in which medullary thyroid carcinoma is inherited, but pheochromocytoma is not seen. We have analysed 18 families, 9 with MEN 2A and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and conclude that the mutations for the two presentations are closely situated. Genetic heterogeneity of the susceptibility locus was not seen among this sample of 18 families. The genetic mutation for medullary carcinoma was in disequilibrium with the marker alleles of the two closely linked probes, IRBPH4 and MCK2. These data suggest that different mutant alleles of the same gene or closely linked mutations account for the variation in penetrance of pheochromocytoma in families with hereditary medullary thyroid carcinoma.

This study was aimed at determining the influence of time factor in local radiotherapy in patients with spindle cell neoplasms of the skin or basal cell carcinomas of the face, treatable in a single plane. These neoplasma were treated using identical doses (6,000 rads distributed over the envelope isodose), but divided at random into two groups corresponsing to two different spreads (60 +/- 12 hours and 156 +/- 12 hours). The biological effects observed (rate of disappearance of the lesion, intensity of skin reaction, duration of skin reaction) showed no difference between the two types of treatment. This results is unexpected considering the important influence of time factor in the case of fractionated irradiation. In fact, if it is accepted that between 60 and 156 hours, cellular multiplication phenomena are equivalent to approximately 30 rads per day, the difference in spread the two types of treatment is not sufficient to give a significant result.