[Sem: a suitable statistical software adaptated for research in oncology]. / Sem: un outil de gestion informatique et statistique adapté à la recherche en cancérologie.

Many softwares have been adapted for medical use; they rarely enable conveniently both data management and statistics. A recent cooperative work ended up in a new software, Sem (Statistics Epidemiology Medicine), which allows data management of trials and, as well, statistical treatments on them. Very convenient, it can be used by non professional in statistics (biologists, doctors, researchers, data managers), since usually (excepted with multivariate models), the software performs by itself the most adequate test, after what complementary tests can be requested if needed. Sem data base manager (DBM) is not compatible with usual DBM: this constitutes a first protection against loss of privacy. Other shields (passwords, cryptage...) strengthen data security, all the more necessary today since Sem can be run on computers nets. Data organization enables multiplicity: forms can be duplicated by patient. Dates are treated in a special but transparent manner (sorting, date and delay calculations...). Sem communicates with common desktop softwares, often with a simple copy/paste. So, statistics can be easily performed on data stored in external calculation sheets, and slides by pasting graphs with a single mouse click (survival curves...). Already used over fifty places in different hospitals for daily work, this product, combining data management and statistics, appears to be a convenient and innovative solution.

[Survivorship of breast implants used in breast reconstruction. 949 implants]. / Durée de vie des implants mammaires en reconstruction mammaire. A propos de 949 implants.

The authors present from a series of 949 implants their method to calculate the life span of a mammary implant in the framework of breast reconstruction after cancer. In this statistical study, they have calculated the median life span of breast implants (loss of half of staff) by distinguishing it according to each type of implant (content, brand, indication...). The global median life span of a breast implant is 127 months. The median life span of a silicone gel-filled implant is superior than a saline implant because the frequency of deflation of saline implants is more important than the first one, despite that the real rupture percentage of silicone gel-filled implants is under-evaluated by the number of asymptomatic rupture. For saline implants, the median life span is clearly decreased by the initial under-inflation (108 months against 127 months) doubling the secondary deflation risk. In this series, the authors have been able to compare the evolution of implants according to their initial indication (reconstruction or aesthetic) and sometimes at a same patient, they have not observed significant difference of the median life span over a period of five years for an implant used in breast reconstruction after cancer or for an implant used in symmetricalization. In this series, the life span of saline implants is significant different in function of the brand of the implant demonstrating the comparative study usefulness by brands.

Polyadenylic-polyuridylic acid plus locoregional radiotherapy versus chemotherapy with CMF in operable breast cancer: a 14 year follow-up analysis of a randomized trial of the Fédération Nationale des Centres de Lutte contre le Cancer (FNCLCC).

With a median follow-up of 14 years, the combination of polyadenylic-polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.

Navigation through vector addition.

During short foraging excursions away from their home, central place foragers update their position relative to their point of departure by processing signals generated by locomotion. They therefore can home along a self-generated vector without using learned references. In rodents and other mammals, this path integration process (dead reckoning) can occur on the basis of purely internal signals, such as vestibular or proprioceptive (re)afferences. We report here that hamsters are also capable of proceeding to a previously learned feeding site through vector information from locomotion only. The subjects compute the direction and distance to the goal by subtracting their current-position vector from the stored nest-to-goal vector. This computation pertains to locations per se and therefore occurs in absolute space, independently of landmark objects. If available, prominent visual cues merely serve to confirm the path planned through the addition of self-generated vectors, whereas visual as well as nonvisual references confirm that the subject has arrived at the goal site.

[Treatment of breast cancer after 70 years of age. Report of 1143 cases]. / Le traitement du cancer du sein après 70 ans. A propos de 1143 cas.

STUDY AIM: Breast cancer is the most frequent type of cancer in women, increasing in frequency with the elderly. In Europe, a third of new breast cancers occur in women over 70 years of age. The aim of this retrospective study was to analyse the tumoural lesions and therapeutic results in a female population over 70, treated in the same medical centre over a 15-year period. PATIENTS AND METHODS: From 1978 to 1992, 1,143 female patients aged 70 or over were treated for a unilateral breast cancer without metastases and followed-up during a mean 6-year period. The initial treatment was surgical in 1,012 patients: radical mastectomy in 95% of the cases with axillary node dissection in 97.6%. Adjuvant radiotherapy was performed in 289 patients and adjuvant treatment with Tamoxifen in 411 patients. The results were compared with those obtained in 2,947 patients aged 50 to 69, treated during the same period in the same medical centre. RESULTS: The 5-year survival rate in women 70 and over was 80% vs 85.5% in women aged 50 to 69 (P < 0.000001). The same rate of loco-regional recurrences and metastases occurred in both populations. In the patients who initially underwent surgery, after multivariate analysis according to the Cox model, the prognosis factors (similar to those observed in the group of younger women) were: the number of involved nodes (P = 0.000001), the clinical size of the tumour (P = 0.00001), the histological grade (P = 0.01), and the estrogen receptors (P = 0.02). CONCLUSIONS: In this series, the treatment was focused on surgery complemented with adjuvant radiotherapy according to node invasion and adjuvant hormonotherapy according mostly to hormonal receptors. However, the complete treatment could not be applied to all cases: only 50% of patients with node involvement were irradiated. The 5-year survival rate lower than that of younger patients may be attributed to incomplete adjuvant treatment. Specific controlled trials taking into account quality of life had to be undertaken in elderly patients in order to adjust the treatment in relation with the patients' age and physiological condition.

Mitomycin-vinorelbine as second line chemotherapy in metastatic breast cancer

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive.eventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracyclin (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclins and 5 resistant. No toxic death nor hemolytic uremic syndrom were observed.even (3,7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37,5% with 2 complete responses (CR) and 13 partial responses (PR).even patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11,5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclins.

[Mitomycin-vinorelbine combination as second-line chemotherapy in metastatic cancer of the breast]. / Association mitomycine-vinorelbine en deuxième ligne chimiothérapique dans le cancer du sein métastatique.

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive. Seventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracycline (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclines and 5 resistant. No toxic death nor hemolytic uremic syndrome were observed. Seven (3.7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37.5% with 2 complete responses (CR) and 13 partial responses (PR). Seven patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11.5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclines.

Ductal carcinoma in situ of the male breast. Analysis of 31 cases.

From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

Alpha-2 adrenergic receptors in the bovine retina. Presence of only the alpha-2D subtype.

PURPOSE: To identify and characterize the alpha-2 adrenergic receptor subtypes present in the bovine neurosensory retina. METHODS: Radioligand saturation and inhibition binding assays were performed with the antagonist radioligands [3H]RX821002 and [3H]rauwolscine. RESULTS: [3H]RX821002 bound to a single class of receptors with the characteristics of an alpha-2 adrenergic receptor with an affinity (KD) of 0.16 nM and a receptor density (Bmax) of 1500 fmol/mg protein. Correlation of the affinities (pKi values) for nine antagonists in the bovine neurosensory retina with the alpha-2D receptor of the bovine pineal gave a correlation coefficient of 0.99. The correlation coefficients for the alpha-2A (0.84), alpha-2B (0.36), and alpha-2C (0.39) subtypes were much lower. The presence of a minor population of alpha-2B or alpha-2C receptors was excluded. CONCLUSIONS: A high density of alpha-2D adrenergic receptors is present in the bovine neurosensory retina. Neither the alpha-2B nor the alpha-2C subtype is detectable.

[Retrospective study of 139 cases of epidermoid carcinoma of the upper respiratory and digestive tracts treated by induction chemotherapy with cisplatin-5FU. Influence of the result on the therapeutic protocol]. / Etude rétrospective de 139 carcinomes épidermoïdes des voies aéro-digestives supérieures (VADS) traités par chimothérapie d'induction cisplatyl-5FU. Influence du résultat sur le protocole thérapeutique.

A retrospective study of 139 untreated staged III and IV epidermoid carcinomas of the upper aero digestive tract is reported concerning oropharynx, oral cavity, hypopharynx and larynx, all of them received as a first treatment, chemotherapy using a five days course of Cisplatinium (20 mg/m2/D) and 5FU (1,000 mg/m2/D). The aim of the trial was to determine: a) a free of disease survival and a global survival rate's increase, b) a more conservative treatment. The results of chemotherapy were clinically evaluated in two groups: Responders (a total or a more than 50% response), and no responders. The results were: on the tumor site: 64% responders (25% total response)--more in smaller lesion; on the lymphatic nodes: 54% responders (more in N1-N2). The results vary in inverse ratio to the stage of the lesion; usually, 2 cycles of chemotherapy are used but in case of efficiency: 2 to 6 cycles are provided increasing to 20% the rate of the total responders; toxicity of the drugs was neligible: 6 cases, 3 of them were renal insufficiency. The global survival rate at 3 months reaches 56.7%. The median line of survival reaches 32 months in responders reverse 15 months (NR); but there are no significant difference between the two groups concerning the recurrences, or the metastasis. The local treatment (after chemotherapy) decided in the 137 patients was surgery, in 40 cases and radiotherapy, in 97 cases (conservative treatment; 80%).(ABSTRACT TRUNCATED AT 250 WORDS)

Polyadenylic-polyuridylic acid plus locoregional and pelvic radiotherapy versus chemotherapy with CMF as adjuvants in operable breast cancer. A 6 1/2 year follow-up analysis of a randomized trial of the French Federation of Cancer Centers (F.F.C.C.).

In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1-14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D. = 13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p = 0.05) in the RXAU group compared to the MCF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments.

[Epidemiologic and prognostic factors of cancer of the breast]. / Facteurs épidémiologiques et pronostiques du cancer du sein.

Breast cancer is the most common of all cancers affecting women in France; its frequency increases in countries with a high standard of living. A family history and certain types of mastosis are unquestionable risk factors, although their weight has not yet been well established, but there is no absolute proof that feeding habits (notably fats and alcohol), which have been blamed by some authors, play a role in the genesis of breast cancer. Among the classical prognostic factors, which are necessary for surgical decisions, the size of the tumour, its histological grade and above all the number of axillary lymph nodes involved are the most important. However, a better knowledge of breast cancer biology has yielded factors that seem to be more promising than hormonal receptors, notably the DNA content of tumoral cells and the presence or absence of a protease, procathepsin 52 K, which reflects tumoral aggressiveness. As for the study of oncogens described elsewhere in this monograph, it will provide a better definition of high risk subjects and more precise information on the progress of the cancer.

[Randomized trial of initial chemotherapy in 151 locally advanced carcinoma of the cervix (T2b-N1, T3b, MO)]. / Essai randomisé de chimiothérapie initiale dans 151 carcinomes du col utérin localement étendus (T2b-N1, T3b, M0).

From 1982 to 1987, a randomized phase III trial was performed in order to determine the long-term effect of induction chemotherapy before standard pelvic irradiation in stage IIb-N1, III squamous cell carcinomas of the cervix. Patients were randomized to either chemotherapy and radiotherapy (C + R group) vs radiotherapy alone (R group). Radiotherapy for all patients consisted of 50 Gy in the pelvis with a boost by external irradiation or by brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen was an association of methotrexate (10 mg/m2, D2-4), chlorambucil (4 mg/m2, D1-5), vincristine (0,7 mg/m2, D1), cisplatin (80 mg/m2, D5), given every 3 wks; at least 2 courses were to be given before assessing efficacy and 2 more courses were given to patients who responded. One hundred and fifty-one patients were fully evaluable, after a mean follow-up of 38 mths (range 2-7 years), 76 in the R arm and 75 in the C + R arm. The response rate (greater than 50%) to chemotherapy was 42.5%. After completion of treatment, the complete response rate was 86.8% in the R arm and 86.3% in the C + R arm. The 3 year disease-free survival was 58.7% in the C + R group and 54.5% in the R group, and the median survival was 39.5% and 47 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group (when chemotherapy had been active) than in the R group (p = 0.04). Although radiotherapy was not modified whether patients had initial chemotherapy or not, tolerance was not significantly different between the 2 groups. The data collected in this study indicate that: 1) efficacy of induction chemotherapy is the only available predictive test for long-term results, 2) tolerance to treatment is crucial for optimal chemotherapy delivery, 3) higher dose intensity of chemotherapy in cervical carcinoma is associated with a better tumor reduction, and probably a better survival.

[Cancer of the prostate. Epidemiologic evaluation, incidence, and trends, especially in France]. / Cancer de la prostate. Bilan épidémiologique, fréquence, tendance, en particulier en France.

With 7,172 deaths in 1982, prostatic cancer is a frequent cancer in France observed among old men, coming just after the lungs cancers and representing 9.6% of male mortality from malignant disease. Its incidence in the French regional population based on departmental registries is about 25/100.000 (age adjusted to the world standard population). The geographical distribution throughout the world shows a high incidence rate among the black american, the Scandinavian countries and low rates in the south-east of Asia. As well as incidence as for mortality low trends of increase all over the world are observed. In the clinical data from the "Enquete Permanente Cancer" (E.P.C.) the high proportion of metastatic dissemination (48%) at initial time of diagnosis, and also the high proportion of epithelial cancer (92%) emerge from a series of 1,223 prostatic cancer registered between 1975 and 1982. The 9 year-survival relative rate (32%) for the whole group lets appear a level of cure observed after the 8 years of follow-up. Few risk factors have been yet recognized so that it is not easy to identify risk population and propose them any preventions.

[Cardiac risks of adriamycin. Early detection of high-risk patients by isotopic cardiac function study]. / Risque cardiaque de l'adriamycine. Repérage précoce des sujets á haut risque par l'étude fonctionnelle cardiaque isotopique.

Adriamycin is known to be effective in the treatment of breast cancer. Serial radionuclide determinations of the left ejection fraction can provide advanced warning of adriamycin cardiotoxicity, prior to clinical signs of the left ventricular dysfunction. Patients at high risk of congestive heart failure can be detected. Depending on the results of the second course of chemotherapy, guidelines and criteria can be laid down to predict the appropriate time for drug discontinuation.

[Proposal for a surgical evaluation index card for ovarian cancers]. / Proposition d'une "fiche de bilan chirurgical" des cancers de l'ovaire.

The authors propose a computer card for registering the main information required in the management of ovarian cancers. The data include a detailed description of the lesions noted at operation, the surgical procedure, and postoperative lesions. They concern both the initial laparotomy and any second-look operations.

[Ovarian cancer in France. Epidemiological, clinical and histological status]. / Le cancer de l'ovaire en France. Bilan épidémiologique, clinique et histologique.

With 2 436 deaths in 1979, ovarian cancer is relatively infrequent in France comprising but 5 per cent of female mortality from malignant disease. However, the rate of increase in mortality is considerable, 70 per cent between 1955 and 1979 or 2,9 per cent per year, greater than that for female bladder and breast cancer. The estimated morbidity and mortality rates (age-adjusted to the world standard population) were 7,5 and 5,4 per 100,000 per annum respectively for 1979, figures in the mid range of international data. This is situated below the rates observed in Scandinavia and North America which occupied the first ranks. The high proportion of metastatic dissemination (55%) at the time of diagnosis and the variety of morphological types (80% being epithelial cancers) emerges from clinical data relating to a series of 2,937 ovarian cancers diagnosed by the "Enquête Permanente Cancer". The 5-year survival rate was 13 per cent with only 50 per cent being alive at the end of the first year. To improve these poor results it is necessary to identify new risk factors in a future French epidemiological study using case control and prospective approaches.