Second primary malignancies in thyroid cancer patients.

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.

Quality of life in long-term survivors of testicular cancer: a population-based case-control study.

PURPOSE: To evaluate quality of life and social problems in long-term survivors of testicular cancer. PATIENTS AND METHODS: In 1998, 71 testicular cancer survivors (cases) identified from the Calvados General Tumor Registry were enrolled onto a case-control study. One hundred nineteen healthy control subjects (controls), matched by age and location of residence, were selected at random from electoral rolls. Three self-administered questionnaires were used: two health-related quality-of-life questionnaires (Short Form-36 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 core questionnaires) and one life situation questionnaire. Specific questions concerning sexuality were also added. RESULTS: With a mean follow-up of 11 years, health-related quality-of-life scores did not differ significantly between cases and controls, nor did general symptom scores. Psychosocial problems were reported equally by cases and controls. Cases reported more modification of sexual life (P =.04) with decreased sexual enjoyment (P <.01), decreased desire (P =.02), and infertility (P <.01). Cases did not report more divorce than controls; they reported fewer changes in relationships with friends (P =.03). Although a similar proportion of cases and controls were at work, cases expressed less ambitious professional plans (P =.002). Cases had greater difficulty in borrowing from banks (P <.001). CONCLUSION: French long-term survivors of testicular cancer do not express more impairment of health-related quality of life or familial or professional life in comparison with healthy men. They did have more sexual life problems and found difficulty in borrowing from banks. This information should be used by practitioners to help their patients cope with their disease and return to normal life.

Clinical relevance of gallium-67 scintigraphy in lymphoma before and after therapy.

The clinical impact of gallium-67 scintigraphy before and after therapy for lymphoma remains controversial. The aims of this study were: (1) to compare the staging of lymphoma by 67Ga scintigraphy only with staging by clinical examination and conventional imaging (CI), and (2) to analyse the clinical relevance of both 67Ga imaging and CI after treatment. From March 1995 to November 1998, 86 67Ga scintigraphy studies were performed in 62 patients with Hodgkin's disease (n=52) or non-Hodgkin's lymphoma (n=10). 67Ga scintigraphy was performed at diagnosis (n=44) or after therapy (n=42) using 185-220 MBq 67Ga citrate and planar and single-photon emission tomography (SPET) studies. Treatment comprised radiotherapy, chemotherapy or combined modalities. CI included plain chest radiography, computed tomography (CT) of the chest and abdomen/pelvis, ultrasound of the abdomen, lymphography, bone marrow biopsy and, when necessary, magnetic resonance imaging (MRI) and bone scintigraphy. For individual suspected sites of disease before treatment, complete agreement between clinical examination and CI on the one hand and 67Ga scintigraphy on the other hand was observed in 25/44 patients (57%; 95% confidence interval 41%-72%). Clinical examination and CI showed more sites than did 67Ga scintigraphy in 12/44 patients (27%) and 67Ga imaging demonstrated more sites than CI in 6/44 patients (11%). The clinical stage of the disease as assessed using 67Ga scintigraphy only was in agreement with that using all diagnostic procedures in 34/44 patients (77%; 95% confidence interval 62%-89%). Compared with CI staging, 67Ga scintigraphy downstaged seven patients (16%) and upstaged three (7%). 67Ga scintigraphy downstaged mainly because of the limited value of the technique below the diaphragm and upstaged owing to the good sensitivity in the lung. After therapy, both CI and 67Ga scintigraphy were normal in 11 patients. All but one of these patients were in complete remission after a median follow-up of 31 months. In contrast, radiological residual mass was observed in 31/42 patients. 67Ga imaging was normal in 22/31 (71%); 17 of these 22 patients, including nine with a large residual mass (> or =2 cm), were in complete remission after a median follow-up of 32 months, while four suffered relapses 8-45 months later. The cause of death remained unknown in one patient. 67Ga scintigraphy showed abnormal uptake in 9 of the 31 patients with a large residual mass. Active disease was demonstrated in eight patients and one patient was in complete remission 30 months thereafter. Our data show that 67Ga imaging cannot replace CI in initial staging but can demonstrate additional individual sites of disease in more than 10% of patients and can lead to clinical upstaging with potential prognostic and therapeutic consequences. After therapy, 67Ga scintigraphy has a clinical impact when radiological abnormalities persist because it can either avoid unnecessary complementary treatment or confirm the need to change treatment modalities.

A multicenter phase II study with triptorelin (sustained-release LHRH agonist) in advanced or recurrent endometrial carcinoma: a French anticancer federation study.

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.

Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer.

PURPOSE: To evaluate late physical and psychosocial sequelae in patients treated with an association of external beam irradiation (EBI) and brachytherapy (BT) for localized prostate cancer. PATIENTS AND METHODS: Seventy-one patients free of disease, treated at the Centre François Baclesse from 1988 to 1992, were enrolled in a case-control study. Seventy-one healthy controls, matched on age and residence, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in January 1996. The French translation of the Nottingham Health Profile questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire were used to evaluate physical, role, emotional, cognitive and social functioning, global health status as well as energy and sleep disturbance. Specific problems related to prostate cancer were explored using the prostate specific module developed by the EORTC Genito-Urinary Tract Cancer Cooperative Group. Concordance between clinical complications reported by patients and those reported by physicians was also analyzed. RESULTS: General health quality of life scale scores did not significantly differ between patients and controls, nor did general symptom scale scores. Furthermore, no more late psychosocial sequelae were reported by patients than by controls. No major digestive complications were observed among patients. However, statistical differences were observed concerning interest in sex (P = 0.016) and sexual activity (P < 0.001), urinary incontinence (P < 0.001) and cystitis (P = 0.01). Late subjective morbidity (dysuria, nocturia, urinary incontinence, pelvic pain) appraisal differed slightly between patients and physicians who generally underestimate its severity. While nocturia was reported more often by physicians than by patients (P = 0.0016), patients reported urinary incontinence and pelvic pain more often than physicians (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The study demonstrates that survivors from localized prostate cancer treated with an association of BT and EBI have good global health status. Major problems that persist are sexual disorders, urinary incontinence and cystitis while digestive disorders were rare. This association could be an alternative to standard EBI in patients with localized prostate cancer. Whatever the treatment choice, patients should be involved in the therapeutic decision which should consider not only expected survival rate but also quality of life.

Exposure to radioactive iodine-131 for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients.

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.

Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d'Etude des Tumeurs a Calcitonine (GETC).

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.

Combination therapy for anaplastic giant cell thyroid carcinoma.

Since 1981, 20 patients with anaplastic giant cell carcinoma of the thyroid have been prospectively treated according to a combination regimen of chemotherapy and external beam radiation therapy. Two types of chemotherapy were used every 4 weeks, depending on the patient's age. For those younger than 65 years, a combination of doxorubicin (60 mg/m2) and cisplatin (90 mg/m2) was given, and for older patients mitoxantrone (14 mg/m2) was used. Radiotherapy was carried out between Day 10 and Day 20 of the first four cycles of chemotherapy. It delivered 17.5 Gy in 7 fractions to the neck and the superior mediastinum. Survival exceeding 20 months was observed in three patients. Complete neck tumor response was observed in five patients, among whom four had undergone previous operations. No response was seen in distant metastases, which were the cause of death in 14 patients. These treatment modalities are effective in some patients, both in terms of survival and of local control, avoiding death from local invasion. Gross tumor resection should be performed whenever possible but should not delay the commencement of this protocol. Toxicity was high and remains the main limiting factor.

A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer.

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.

Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial.

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.

[Rational choice of a diagnostic test for the detection of bone metastases in breast cancer as a function of prevalence (based on the Bayes theorem)]. / Choix rationnel d'un test diagnostique pour la recherche des métastases osseuses dans le cancer du sein en fonction de la prévalence (d'après le théorème de Bayes).

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.

Adjuvant tamoxifen in postmenopausal breast cancer: preliminary results of a randomized trial.

Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls). The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.

[Para-aortic lymphadenectomy in the surgical evaluation of ovarian cancer]. / La lymphadénectomie para-aortique dans le bilan chirurgical des cancers de l'ovaire.

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.

[Reliability of cytologic puncture. Who should perform the puncture of breast tumors?]. / Fiabilité de la ponction cytologique. Qui doit ponctionner les tumeurs du sein?

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.

Hydroxy-9-methyl-2-ellipticinium for osseous metastases from breast cancer: a 5-year experience.

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.

[Hydroxy-9-methyl-2-ellipticinium (NSC 264-137) for osseous metastases from breast cancer. A 4 year experience (author's transl)]. / L'hydroxy-9-methyl-2-ellipticinium (NSC 264-137) dans le traitement des métastases osseuses du cancer du sein. Bilan d'une expérimentation de 4 années.

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.