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C Lasset

Publications and source records attributed to C Lasset.

At least 19 recordsLinked to original sources
PubMed2006

[Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas].

BACKGROUND: The HNPCC syndrome (hereditary nonpolyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure. METHODS: Twelve experts have been mandated by the French Health Ministry to analyze and synthesize their consensus position, and the resulting document has been reviewed by an additional group of 4 independent experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a 2-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks, but other organs being at low lifetime risk, no specific surveillance will be proposed.

Adenocarcinoma↗
PubMed2005

[HNPCC syndrome (hereditary non polyposis colon cancer): identification and management].

BACKGROUND: The hereditary non-polyposis colon cancer (HNPCC) syndrome is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for other organs tumors. HNPCC syndrome is responsible for 5% of colorectal cancers. MAJOR ASPECTS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a two-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. FURTHER DEVELOPMENTS: The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks; other organs being at low lifetime risk, no specific surveillance will be proposed.

Adolescent↗
PubMed2002

Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d'Immunothérapie.

Interleukin-2 (IL-2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results have been disappointing, with a majority of treatment failure. Over 6 years, the Groupe Français d'Immunothérapie enrolled 782 patients in successive multicenter trials using cytokine regimens. Univariate and multivariate analyses were performed on this large prospective database to identify prognostic factors for survival. The presence of biological signs of inflammation, short time interval from renal tumor to metastases (<1 year), elevated neutrophil counts, liver metastases, bone metastases, patient performance status (PS), the number of metastatic sites, alkaline phosphatases and hemoglobin levels were predictive of survival outcome. When compared with previous results, our study showed that PS, number of metastatic sites, disease-free interval, biological signs of inflammation and hemoglobin levels can be considered as validated prognostic factors. We also identified four independent factors predictive of rapid progression under cytokine treatment: presence of hepatic metastases, short interval from renal tumor to metastases (<1 year), more than one metastatic site and elevated neutrophil counts. Patients who combined at least three of these factors have >80% probability of rapid progression despite treatment. We think that these results must be taken into account when making the decision to treat with cytokine.

Adult↗
PubMed2001

Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.

Carcinoma, Papillary↗
PubMed2001

Comparison of physicians' and cancer prone women's attitudes about breast/ovarian prophylactic surgery. Results from two national surveys.

Prophylactic surgery is a major issue for breast/ovarian cancer prone women. Bio-clinical data to help in the decision-making are not sufficient. In this context of uncertainty, physicians' and women's attitudes to prophylactic surgery is information of great value. The physicians' attitudes were assessed by a randomised national sample of practitioners involved in breast and ovarian cancer management. The patients' attitudes were appraised with a pre-consultation self- administered questionnaire presented during a one-year period to all women in five cancer genetic clinics chosen, for their representative geographical locations and their activity level. Consent to prophylactic surgery is higher among physicians than among patients (p < 0.0001). Acceptability of mastectomy is lower than that of oophorectomy in both patients and physicians (p < 0.0001 in both groups). In addition, age at which the intervention is proposed to be performed is a key determinant for both mastectomy and oophorectomy acceptability, in both physicians and patients (p < 0.001 for each comparison). Particularly, the age of 40 years seems to be a critical threshold for the acceptability of prophylactic oophorectomy. In contrast, respondents' age at the time of the survey has no significant effect on the acceptability rate. The higher acceptability rate of prophylactic oophorectomy compared to that of mastectomy observed in the physicians' survey is paradoxical because a more substantial medical impact on life expectancy was expected from the latter. Our results indicate that assumed reduced mortality is not the main criterion steering acceptability. It was anticipated that prophylactic mastectomy should be rarely performed in France.

Adult↗
PubMed2001

[Li-Fraumeni syndrome: update, new data and guidelines for clinical management].

The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children and young adults, and characterized by a wide spectrum of tumors, including soft-tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal breast cancers. In most of the families, LFS results from germline mutations of the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were identified in affected families. The LFS working group recommendations are the following: (i) positive testing (screening for a germline TP53 mutation in a patient with a tumor) can be offered both to children and adults in the context of genetic counseling associated to psychological support, to confirm the diagnosis of LFS on a molecular basis. This will allow to offer to the patient a regular clinical review in order to avoid a delay to the diagnosis of another tumor; (ii) the 3 indications for positive testing are: a proband with a tumor belonging to the narrow LFS spectrum and developed before age 36 and, at least, first- or second-degree relative with a LFS spectrum tumor, before age 46, or a patient with multiple primary tumors, 2 of which belonging to the narrow LFS spectrum, the first being developed before 36 or a child with an adenocortical tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young age of onset of the LFS tumors the prognosis of some tumors, the impossibility to ensure an efficient early detection and the risk for mutation carriers to develop multiple primary tumors justify that prenatal diagnosis might be considered in affected families.

Adult↗
PubMed2000

Disclosure to the family of breast/ovarian cancer genetic test results: patient's willingness and associated factors.

Informed probands are key actors for disclosing genetic information to their relatives when a mutation has been identified in the family. The objectives were to study women's attitudes towards the family disclosure of positive breast cancer genetic testing results and to determine the predictive factors of the diffusion patterns observed. A national multi-center cross-sectional survey was carried out at five French cancer genetic clinics during a 1-year period. Self-administered questionnaires were completed after the consultation by 84.5% (398/471) of women attending breast cancer genetic clinics for the first time. Among the 383 respondents who had at least one living first-degree relative to inform, 8.6% would inform none, 33.2% would inform at least one of them, and 58.2% would inform all of them. The sibship would be the most frequently informed blood relatives, sisters in 86.9% and brothers in 79% compared with mother in 71.4%, children in 70.4%, and father in 64.9%. Women of the family would be more frequently informed than men (P < 0.05). After multivariate adjustment, age, the fact to be affected by cancer, the number of daughters, and the emotional disturbance due to cancer in a close relationship were the main determinants (P < 0.05) of the diffusion patterns observed. The first step of the relatives' attendance to genetic counseling and the proband's willingness to disclose breast cancer genetic tests results was high in this study and was clearly dependent on the women's personal and emotional characteristics.

Adult↗
PubMed2000

Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary.

The aim of this study was to determine the efficacy and toxicity of combination cisplatin and etoposide chemotherapy in patients with metastatic carcinoma of unknown primary. Patients were treated with cisplatin (100 mg/m2 iv day 1) followed by etoposide (100 mg/m2 iv days 1-3) every 3 weeks for a maximum of 6 cycles. Patients with progressive disease after two or four courses could receive FAC (fluorouracil, doxorubicin, and cyclophosphamide) until progression. Twenty-five patients were entered and were assessable for response and toxicity. Fifteen (60%) patients had adenocarcinomas. Patients received a median of four courses. Toxicity was mainly hematologic including grade III/IV neutropenia. The overall response rate was 32%. There was no complete response, 32% partial responses, 32% stable disease, and 36% disease progression. Median response duration was 4 months (range: 2-5 months). The median overall survival of the 25 patients was 8 months. No objective response could be obtained with FAC, but 33% of patients achieved stabilization of the disease for at least 3 months. This cisplatin-etoposide combination demonstrated some activity against an usually resistant disease.

Adenocarcinoma↗
PubMed2000

LMCE3 treatment strategy: results in 99 consecutively diagnosed stage 4 neuroblastomas in children older than 1 year at diagnosis.

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P =.004). In the multivariate analysis, only age younger than 3 years at diagnosis (P =.0085) and achievement of complete or very good partial remission after NB87 and surgery (P =.00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P =.005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[The "Action Woman Health" program in three Lyons suburbs].

The cervical cancer screening campaign has been led in three cities in Lyons suburbs from October 1st, 1999 to October 31st, 1999. The objectives of this programme whose title was "Action Femme Santé" (Action Woman Health) were to screen cervical cancer systematically for women who accede with difficulties to smear technique, and to settle in an information, screenings and follow-up system. During the three years, 3,127 smears have been declared and have reached about 2,881 women. The rate of detected disorders is about 2.1%. This campaign has succeeded in its goal about the target public but the participation of health professionals was unsatisfactory because of many obstacles. This implementation of the programme and its results, the weak points and strong points to be kept from such experience, are developed.

Adult↗
PubMed2000

[Reliability of the response rate in oncology: analysis of the causes for variation].

We evaluated the impact of an evaluation committee (EC) on patients' overall response status in a large multicenter trial in oncology. We identified reasons for disagreements between investigators and the EC. The Cancer Renal Cytokine (CRECY) study was a French multicenter trial that tested cytokine therapy in 489 patients with metastatic renal cell carcinoma. Objective response (OR) evaluation included medical imaging and was studied according to international guidelines. A blinded peer review of all responders and litigious cases was performed by an EC. Major disagreements occurred in 43% and minor disagreements in 10.5% of the reviewed files. The number of significant tumor responses was reduced by 23.2% after review by the EC. Reasons for disagreements included errors in tumor measurements, errors in selection of measurable targets, intercurrent diseases, and radiologic technical problems. These reasons for disagreements are analyzed and discussed. We conclude that all therapeutic trial results should be reviewed by peer analysis of all presumed responders by an EC. International guidelines for response evaluation should be updated by including more reliable methods of measurements and definition of minimal imaging procedures.

Antineoplastic Agents↗
PubMed1999

Neurofibromatosis and early onset of cancers in hMLH1-deficient children.

Hereditary nonpolyposis colon cancer is a common hereditary disorder caused by the germ-line mutations of DNA mismatch repair (MMR) genes, especially hMLH1 and hMSH2. We report here the first identification of human compounds with a homozygous inactivation of a MMR gene. In a typical hereditary nonpolyposis colon cancer family, MMR-deficient children conceived from matings between heterozygotes for a hMLH1 deleterious mutation exhibited clinical features of de novo neurofibromatosis type I and early onset of extracolonic cancers. This observation demonstrates that MMR deficiency is compatible with human development but may lead to mutations during embryogenesis. On the basis of clinical symptoms observed in MMR-deficient children, we speculate that the neurofibromatosis type 1 gene is a preferential target for such alterations.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Small-cell lung cancer: patients included in clinical trials are not representative of the patient population as a whole.

PURPOSE: To determine the clinical characteristics of the subpopulation of patients not included in clinical trials, their outcome, and the reasons for their ineligibility and non-participation. PATIENTS AND METHODS: We studied 57 patients (out of 178 consecutive patients with SCLC), who were not included in any of the three successive clinical trials completed at our center during the study period. We also compared 37 patients excluded from the largest clinical trial to their 73 included counterparts. RESULTS: Reasons for ineligibility (n = 53) included low Karnofsky index (n = 17), advanced age (n = 12), non-feasible long-term follow-up (n = 12), previous history of cancer (n = 8), contraindication for anthracyclines (n = 5), and other medical reasons (n = 11). Only four eligible patients were not included in the trials. As compared to patients included in the studies, non-included patients had a significantly lower Karnofsky index, were older, presented more frequently with metastatic disease, and had a lower response rate to treatment and a shorter survival. However, exclusion from the trial was not an independent prognostic factor by multivariate analysis. CONCLUSIONS: Selection biases were unlikely in the three trials, based on the high ratio of included/eligible patients. However, the subgroup of patients included in the trials was not representative of the patient population as a whole because of restrictive eligibility criteria. Results from published clinical trials to the overall population should be extrapolated only with caution. We suggest that the proportion and major characteristics of ineligible and non-participating patients be mentioned in any publication of a clinical trial.

Adult↗
PubMed1999

Four years analysis of cancer genetic clinics activity in France from 1994 to 1997: a survey on 801 patients. French Cooperative Network/Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer.

AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors. METHOD: A questionnaire was sent to all the 29 French non-specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning the cancer genetic clinics, the consultees and the types of consultation were explored. RESULTS: A total number of 801 consultees were seen during the period of analysis. Some prominent characteristics of patients attending cancer genetic clinics were found. The majority of these are women (88%), and the mean age of consultees is 48 years. Fifty five percent of consultees are affected with cancer, and breast (personal and/or family history) is the most frequent site involved (63%). A genetic predisposition is certain or likely in about 53% of cases and unlikely in only 13% of consultations. The majority of consultations are devoted to new families (71%). The mean duration of consultations is 50 minutes, but 40% have a duration of at least 1 hour. Variations of several parameters during the 4 years period were observed and analyzed. Finally, since duration of consultations (more or equal to 1 hour) and personal or family history of breast/ovarian cancer appeared as pivotal elements in our study and consequently may affect the organization of clinics and the structuring as well as the evolution of cancer genetic activity in France, we analyzed more precisely the factors significantly associated with these 2 elements. CONCLUSION: Study compliance was fair (60% of centers) and these results give a good measure of cancer genetic activity in France. The variation of parameters from one year to another may reflect modifications in medical practice (medical orientation rather than research focus and content of cancer genetic clinics) and/or scientific breakthroughs in cancer genetics such as identification of genes predisposing to cancer.

Adult↗
PubMed1999

Cytokines in metastatic renal cell carcinoma: is it useful to switch to interleukin-2 or interferon after failure of a first treatment? Groupe Français d'Immunothérape.

PURPOSE: Interleukin-2 (IL-2) and interferon alfa-2a (IFNalpha2a) have some antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be efficient after failure of the other, we analyzed a series of patients treated with either IL-2 or IFNalpha2a as second-line treatment after failure of the other cytokine. PATIENTS AND METHODS: We recently performed a large multicenter study to determine the respective efficacy of IL-2, IFNalpha2a, or combined treatment in renal cell carcinoma. In this study, patients who progressed on the single-arm treatment could receive the other cytokine in a cross-over trial. IL-2 was administered as a continuous intravenous infusion for 5 days (18 x 10(6) IU/m(2)/d), and IFNalpha2a was administered three times weekly at 18 x 10(6) IU. RESULTS: A total of 113 patients with progressive disease after first-line treatment received either IFNalpha2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment. Only four partial responses were observed (one with IFNalpha2a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable disease or had responded to first-line therapy. Only one patient with confirmed disease progression after receiving IL-2 subsequently responded to IFNalpha2a. CONCLUSION: Cross-over after failure of IL-2 or IFNalpha2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.

Adult↗
PubMed1999

[Cervical cancer screening for high risk women: is it possible? Results of a cervical cancer screening program in three suburban districts of Lyon].

Between november 1993 and october 1996, a cervical screening program was proposed for women 25-65-year-old who tend to have little or no medical supervision, in three suburban districts of Lyon. The data and results of the two last Pap-smears have been collected together with details of gynecological follow-up. Both general practitioners and gynaecologists were actively involved. A total of 3,792 women (12.3% of the target) were registered, with a larger proportion of women over 60 (17.7%). According to the "Consensus of Lille", only 403 women (34.4%) had adequate screening (over 50 y: 25.8%, 35-49 y: 39.4%, 25-35 y: 36.5%) and 2,489 women had inappropriate gynaecological follow-up: no smear for 185 women (4.9%) and inadequate schedule of follow-up visits for 476 others (12.5%). Missing data (date or results of Pap smear) were noted for 1,828 patients (48.2%). The screening procedure for women over 50 years was carried out mainly by general practitioner. Of 3,127 registered smears, 62 positive results were found (2.1%). Of these women, 9 were lost to follow-up and 4 did not have appropriate tests. Others results were: 27 negative further investigations, 9 CIN1, 7 CIN2, 3 CIN3, 1 in situ carcinoma and 2 invasive carcinoma. Despite low participation, this pilot study indicates that a procedure can be established to integrate high risk women in cervical cancer screening programme. Active participation of general practitioners is essential.

Adult↗