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F Bonichon

Publications and source records attributed to F Bonichon.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evolution of BCL-2/IgH hybrid gene RNA expression during treatment of T(14;18)-bearing follicular lymphomas.

Bcl-2, the gene over-expressed in follicular lymphomas (FL), is able to block chemotherapy-induced apoptosis. Consequently, we wondered whether bcl-2/IgH expression variations during treatment of FL could predict the outcome of patients with t(14;18)-bearing FL. For this purpose, we used a reverse transcription polymerase chain reaction (RT-PCR) assay to analyse 180 serial peripheral blood samples (PBS) during 34 treatment phases in 25 patients with t(14;18)-bearing FL. In all patients but two, bcl-2/IgH gene expression was demonstrated in pre-treatment samples. During 16 out of the 34 treatment phases (47%), bcl-2/IgH expression became negative: all but one were responders to chemotherapy. This conversion was transient in six cases. In 18 treatment phases, bcl2/IgH expression remained detectable: eight were clinically considered as treatment failures, while eight others achieved PR and two achieved CR. We observed a significant correlation between treatment response and RNA PCR results (P = 0.002). Three-year overall survival of patients with stable bcl2/IgH-negative conversion was 100% compared to 54% for the remaining patients (P = 0.069); 3-year freedom from progression was respectively 87.5% and 13% (P = 0.005). These results indicate a correlation between bcl-2/IgH expression variations and both clinical response and outcome. Whether this might predict disease outcome early remains to be confirmed.

Adult↗
PubMed1999

Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families.

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.

Adult↗
PubMed1998

Genetic alterations in colorectal cancer, comparative analysis of deletion events, and point mutations.

Although data on genetic alterations leading to the development of colorectal cancer are abundant, no specific genetic alteration, as has been demonstrated for certain rare tumors such as lymphoma, leukemia, or sarcoma, has been shown to be responsible for the development of colorectal carcinomas. The colorectal cancer phenotype undoubtedly originates from an accumulation of different genetic alterations. The nature of these alterations, their order of appearance, and their associations vary greatly from one tumor to another, suggesting that the concept of a unique model of carcinogenesis is not applicable to these tumors. We studied a panel of 40 colorectal tumors in an attempt to identify different carcinoma subsets distinguishable by the pattern of genetic alterations. We examined a series of genetic anomalies frequently implicated in the development of colorectal cancer, including genetic material loss, demonstrated by loss of heterozygosity on chromosome arms 1p, 17p, and 18q; mutations of proto-oncogene K-RAS codons 12, 13, and 61; and gene TP53 mutations, identified by studying the accumulation of the corresponding immunohistochemically detectable protein. Our findings showed an important correlation between the genetic material loss events and an independent distribution of point mutations, which favors the hypothesis of a specific type of genetic instability characterized by the recurrent loss of chromatin fragments implicated in a subset of colorectal cancers.

Adenocarcinoma↗
PubMed1998

[Results of 10 years of a randomized trial of neoadjuvant chemotherapy in breast cancers larger than 3 cm].

AIM OF THE STUDY: The aim of this randomised trial was to determine advantages and drawbacks of neo-adjuvant chemotherapy in patients with operable breast cancers > 3 cm. MATERIAL AND METHODS: Two hundred and seventy-two women (age 70) with operable breast cancers larger than 3 cm (T2-3/N0-1/M0) were included in a randomised trial from January 1, 1985 to April 30, 1989. Patients in group A (n = 138) were treated by mastectomy and axillary node dissection. Adjuvant chemotherapy was indicated for 104 patients with axillary node involvement (n = 82) or negative oestrogen and progesterone receptors (EPR-) (n = 22). Patients in group B (n = 134) were treated by initial chemotherapy (identical as in group A) followed by locoregional treatment according to the response. Before treatment, the average of clinical tumoural diameter was 43 mm. RESULTS: The median follow-up was 124 months. In group B, 49 patients (36.5%) were resistant to chemotherapy; a conservative breast surgical treatment was performed in the other 84 patients sensitive to chemotherapy (62.6%). In this last subgroup, 19 (22.6%) needed a secondary mastectomy because of locoregional recurrence. Survival rates were not different in groups A and B, but loco-regional recurrences were frequent in group B. At 10 years, the overall survival rate was 60% and half of living patients in group B were free of cancer and with their breast. CONCLUSION: Neoadjuvant chemotherapy permitted in two-thirds of cases breast conservation treatment, initially considered to be impossible. Locoregional recurrences are more frequent than after mastectomy and adjuvant chemotherapy.

Aged↗
PubMed1998

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers.

This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5 microns thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P = 6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour size and grade, and was second after tumour grade for OS (P = 0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

Adult↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.

PURPOSE: A randomized unblinded phase III trial was designed to determine the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate recovery from febrile neutropenia induced by chemotherapy. PATIENTS AND METHODS: A total of 68 patients with febrile neutropenia following chemotherapy defined as axillary temperature greater than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk chemotherapy to induce febrile neutropenia, treatment was randomized between GM-CSF at 5 microg/kg/d or control, both being associated with antibiotics. RESULTS: GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L(P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L (P=.024), days of hospitalization required for febrile neutropenia, and duration of antibiotics during hospitalization. The greatest benefit with GM-CSF appeared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L was reduced from 7 to 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10(9)/L (P=.0011), the duration of hospitalization during the study from 7 to 4 days (P=.003), and the duration on antibiotics during hospitalization from 7 to 3.5 days (P < .001). A multivariate analysis, using Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P=.0010) and time interval between the first day of chemotherapy and randomization (P=.030). There was no benefit for GM-CSF when high-risk chemotherapy was considered. CONCLUSION: GM-CSF significantly shortened duration of neutropenia, duration of neutropenic fever-related hospitalization, and duration on antibiotics during hospitalization when febrile neutropenia occurred after low-risk chemotherapy, but not high-risk chemotherapy.

Adolescent↗
PubMed1998

Comparative analysis of prognostic indicators for sarcomas of the soft parts and the viscerae.

Purpose of this study was to determine which parameters may be best applied to determine the prognosis of soft tissue and visceral sarcomas, the two groups being regarded as biologically different. In a cohort of 184 soft tissue tumors (STT) and 53 gastrointestinal stromal tumors (GIST), the following factors were examined for their diagnostic and prognostic relevance: patient age, sex, tumor location, histological type, tumor size, tumor grade, DNA ploidy status, mitotic count, and immunohistochemical proliferation index. Tumors were graded according to the FNCLCC system, and antibody Ki-S11 (Ki-67) served as a proliferation marker. Median clinical follow-up time was 48 months. In STT, morphological criteria allowed a ready discrimination between benign and malignant lesions, which was only warranted by histopathological grading in GIST. 178 of all 236 tumors were thus classified as malignant. Whilst most parameters yielded significant results in the univariate analysis, age, sex, and histological type were irrelevant. A proliferation index > 20% predicted a poor outcome in soft tissue sarcomas, in contrast to a threshold of 10% for GIST. In both groups, the Cox multivariate analysis selected the proliferation index as the sole independent predictor of overall survival, whereas it was superseded by the tumor grade with respect to metastatic spread. In conclusion, soft tissue and visceral sarcomas appear to behave basically in a similar manner. Both tumor grade and immunohistochemical proliferation index are of major prognostic value. Concerning the growth fraction, however, different cut-off points should be selected for sarcomas of the soft tissues and those of the digestive tract.

DNA, Neoplasm↗
PubMed1998

[Internet: importance in cancerology and practical connection sites].

There has been a considerable increase in World Wide Websites on the Internet on medicine and oncology. The clinician has access to an abundance of useful documentary and graphic information. The challenge is firstly to find a relevant site and then to evaluate the quality of the material available on that site. In future, there may well be a service on the network which reviews sites. The aim of this paper is to give practical guidance to connecting on the Internet as well as a list of the best sites for clinicians, researchers, students and oncologists.

Computer Communication Networks↗
PubMed1998

[Interferon alpha in the treatment of non-Hodgkin's lymphomas of low malignancy].

Incidence of non Hodgkin's lymphomas (NHL) has been increased regularly during the last two decades. Overall survival did not progress at all during this period. According to the results of preliminary studies, alpha interferon is an attractive approach for NHL treatment. The review analyze published randomized controlled trials which tested interferon alpha either in addition with polychemotherapy or as maintenance of chemotherapy-induced response in disseminated low grade NHL. After literature search, nine studies have been included. Interpretation of results was complicated by various patient's selection criteria (age, tumoral burden, histology) and heterogeneous treatment schemes (interferon schedule and dose, chemotherapy combination). Significant overall improvement was observed in two studies while only relapse free survival and time to treatment failure were improved in seven trials, always in interferon group. Significant observed toxicities were hematologic ones and asthenia since they led either to dose adjustment or to interferon interruption. Finally, we cannot recommend interferon use out of prospective trials. Further studies are warranted to confirm overall survival benefit and to define optimal strategy to use this molecule.

Antineoplastic Agents↗
PubMed1998

[Review of the literature, search of reports and critical reading of articles in cancerology].

The aim of this paper is to describe: (1) different times where we need to search and to analyse informations and documents in cancer field; (2) the literature process conducting to literature review. It includes, from the formulated question to its answer, the searching of relevant papers, the critical reading of selected papers, the inclusion of clinical research data, or even the elaboration of next research programs which will lead to new papers; (3) different actual means, specially electronic means, to search and select papers: different databases on line or on CD-ROM (Medline, Embase, Cancerlit, Pascal, Toxline, Bioethics, etc.), searching techniques adapted to cancer field, technical equipment required; (4) critical reading of selected papers. It is very easy to obtain lists of hundreds or even thousands of references, and simple rules for selection are needed for entirely reading only a limited number of relevant papers. A compromise is often difficult to find between exhaustivity and limited time we have to search and analyse literature. Synthesis of informations collected in evidence-based comprehensive reviews are useful for helping doctors to implement research results in their treatment practice.

Databases, Bibliographic↗
PubMed1997

Influence of pregnancy on the outcome of breast cancer: a case-control study. Societe Francaise de Senologie et de Pathologie Mammaire Study Group.

The relationship between pregnancy and the outcome of breast cancer remains controversial. The purpose of this study was to determine the prognostic value of pregnancy at the time of diagnosis of primary infiltrating breast cancer. In a retrospective multi-center study we compared a group of 154 patients presenting pregnancy-associated (PA) breast cancer with a control group of 308 patients presenting non-pregnancy-associated (non-PA) breast cancer. Classic prognostic factors, treatment modalities, disease-free survival and overall survival were compared in the 2 groups. The relative importance of pregnancy was assessed by Cox multivariate analysis. There was a significantly higher proportion of inflammatory breast cancer, large tumors and negative receptor status in the PA group. Five-year recurrence-free survival, metastasis-free survival and overall survival were lower both in the whole PA group and in the PA sub-group excluding patients with inflammatory breast cancer than in the corresponding non-PA groups. According to clinical stage, histoprognostic grade and microscopic lymph-node involvement, probability of 5-year metastasis-free survival and overall survival was lower in the PA group. Outcome was significantly poorer after chemotherapy for patients in the PA sub-group than in the non-PA sub-group. Multivariate analysis demonstrated that pregnancy was an independent and significant prognostic factor. Pregnancy has an adverse effect on the outcome of breast cancer. Concurrent or recent pregnancy should be taken into account in the development of new systemic therapies. Our findings have important implications for further research into the basic mechanisms of cancer.

Adult↗
PubMed1997

Flow cytometric DNA content analysis of 185 soft tissue neoplasms indicates that S-phase fraction is a prognostic factor for sarcomas. French Federation of Cancer Centers (FNCLCC) Sarcoma Group.

BACKGROUND: The authors determined the flow cytometric (FCM) DNA characteristics of 53 benign tumors and 132 malignant (71 primary, 61 recurrent) soft tissue sarcomas to investigate their heterogeneity and to evaluate the prognostic values of DNA ploidy status and S-phase fraction (SPF). METHODS: One to 11 frozen samples were collected from 185 tumors at 10 participating centers of the French Federation of Cancer Centers (FNCLCC). All FCM analyses were performed in the same laboratory. Histologic diagnoses were collegially reviewed, and grade was assessed by the pathologists of the FNCLCC Sarcoma Group. Relationships between FCM, clinical, and pathologic data were investigated using univariate and multivariate analyses for risks of mortality and metastasis. RESULTS: All except 2 of the 53 benign lesions were DNA diploid. One schwannoma and one desmoid tumor exhibited small abnormal DNA peaks. SPF was low in all benign lesions. One-third of the sarcomas were DNA diploid, whereas two-thirds were DNA aneuploid. Relationships were found between aneuploidy and mitotic count, grade, and histologic subtype of malignant fibrous histiocytoma. DNA ploidy status did not influence the clinical outcome. Multiple sampling performed in 32 sarcomas showed both diploid and aneuploid samples in 6 tumors. Heterogeneity was related to tumor size. SPF evaluated in 85 sarcomas was related to DNA ploidy status, mitotic count, and grade. SPF > or = 4% was significantly associated with a low overall survival rate. In a multivariate analysis performed for the whole group of 132 patients, the single factors with independent prognostic value for patient mortality were disease free status after the treatment course (P < 0.0001) and SPF (P = 0.03). In the subgroup of patients who were initially free of metastases and free of tumor after the treatment course, SPF remained the only factor that significantly influenced the overall survival rate (P = 0.021). CONCLUSIONS: Despite its high failure rate, SPF is an independent factor in the prognosis of soft tissue sarcoma and should be considered when patients with a high mortality risk need to be selected for adjuvant chemotherapy.

Adolescent↗
PubMed1997

Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

Adolescent↗
PubMed1997

[How to read a scientific article].

Medical literature is too prolific and user's guides are necessary to extract useful information for optimal treatment of our patients. The goal of this paper is to help doctors find relevant articles and to read them efficiently for applying the results to their patients. An excerpt has been written concerning the subject by the Mac Master team and the members of the Cochrane Collaboration in the JAMA, the BMJ and on the Internet: a web site is now devoted to user's guides to medical literature. Simple rules facilitating access to relevant papers and interpretation of the results have been given. They have been applied to oncology, especially to papers concerning effectiveness of therapeutic interventions. It is essential that doctors use simple rules and learn how to select relevant articles and understand and use them to treat their patients according to Evidence-Based Medicine Group.

Cost-Benefit Analysis↗
PubMed1997

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Adolescent↗
PubMed1997

Prognostic relevance of a novel proliferation marker, Ki-S11, for soft-tissue sarcoma. A multivariate study.

In 132 soft-tissue sarcomas and 52 benign soft-tissue tumors, cellular proliferation was examined by immunohistochemistry using monoclonal antibodies Ki-S11 (Ki-67 antigen) and Ki-S1 (topoisomerase II alpha) and by flow cytometric analysis of the S-phase fraction (SPF). Malignant tumors were graded histologically according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. Patient age, sex, tumor location, histological type, and DNA ploidy were considered as additional prognostic variables. Consistent immunoreactivity was seen in approximately 95% of the cases, and determination of SPF was possible in approximately 60% Ki-S11 and Ki-S1 immunolabeling indices correlated in a linear manner. All proliferation parameters yielded significant differences between benign and malignant tumors. Ki-S11 and Ki-S1 immunoreactive scores also co-varied significantly with SPF, mitotic count, and histopathological grade. In univariate analysis, immunohistochemical proliferation indices, histopathological grade, mitotic count, and SPF were predictive of overall survival and the development of metastases. In multivariate analysis, immunolabeling scores of proliferation markers, grade, and SPF emerged as independent predictors of global survival and systemic progression. We conclude that the immunohistochemical assessment of proliferation, being more readily performable and more easily assessable than the equally relevant S phase fraction, may add appreciable information to the current prognostic models for soft-tissue sarcoma.

Adolescent↗
PubMed1997

Comparison of quantitative and semiquantitative methods of assessing MIB-1 with the S-phase fraction in breast carcinoma.

Different methods of assessing cell proliferation in breast cancer are currently being evaluated. Inherent qualities are required for such methods to be used on a routine basis in a pathology laboratory. Such qualities include high sensitivity and specificity in recognizing proliferating cells, simplicity in execution, and reproducibility. The MIB-1 antibody permits the immunohistochemical detection of the Ki67 antigen in fixed and paraffin-embedded tissue sections. The aim of our study was to compare a semiquantitative and quantitative method of assessing MIB-1 immunostaining with the S-phase fraction (SPF) determined by flow cytometry in a series of 112 breast carcinomas. The median semiquantitative MIB-1 score (SQ-MIB-1) in our series was 27.5%. The median quantitative MIB-1 score (B.MIB-1) was 563 positive neoplastic cells per square millimeter of tumor, and, when corrected by the volume percentage nuclei (C.MIB-1), 2844 positive nuclei per square millimeter of total nuclear area. These three indices were strongly correlated to the SPF (r = 0.73, 0.72, 0.72, n = 78), respectively for SQ.MIB-1, B.MIB-1, and C.MIB-1, MIB-1, assessed quantitatively or semiquantitatively, correlated with the Scarff, Bloom, and Richardson grade, including the mitotic index and nuclear grade, as well as with the progesterone receptor status. SQ.MIB-1 determination was easier and faster than B.MIB-1 and C.MIB-1 determination. A high correlation was found for SQ.MIB-1 results between two observers in this series (r = 0.92, n = 112), but the SQ.MIB-1 repeatability coefficient was 17.6%. Semiquantitation of MIB-1 is strongly correlated to the SPF and is an easy and rapid method of assessing cell proliferation. More studies are necessary for additional assessment of its reproducibility and its prognostic value in breast cancer.

Adult↗