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    F. Bonichon

    Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over the last fifteen years in the field of oncology. RF directed toward a specific tumor mass is known to be very effective (over 90%) for treating tumors less... more
    Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over the last fifteen years in the field of oncology. RF directed toward a specific tumor mass is known to be very effective (over 90%) for treating tumors less than 2.5 cm. RF is used for patients with early-stage lung or liver cancers who are not surgical candidates, With improvements in systemic therapy, increasing interest in the use of local therapy for metastases has arisen. Eradication of residual metastases via local therapies has a sense in patients with stabilized disease. Nonsurgical alternative like RF has become popular because it is less invasive than surgery and has demonstrated great efficiency. Nevertheless prospective randomized trials to compare RF with surgery are difficult to achieve, prospective studies are needed to better evaluate the technique.
    To compare the diagnosis performances of radiologists on screen film versus digital mammography. and methods: Two sets of 123 mammograms, screen film mammography and storage phosphor digital mammography, are studied comparatively with ROC... more
    To compare the diagnosis performances of radiologists on screen film versus digital mammography. and methods: Two sets of 123 mammograms, screen film mammography and storage phosphor digital mammography, are studied comparatively with ROC analysis. Phantom study show that conventional method give better scores for usual tension but the detectability of smaller microcalcification is equivalent. To obtain with digital technic the same conventional score you have to increase the radiation dose. Roc Curves, simulated "detection" mode showed that radiologists performed with higher accuracy with conventional system but this difference is weekly statistically significant. ROC Curves, simulated "diagnostic" mode showed the same results wit no statistically significant difference but when the decision to go to the biopsy is the gold standard, ROC Curves were essentially equivalent for both film screen and digital mammography system. The readers consistently considered the...
    Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid... more
    Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid cancer patients from five French oncology centers. THERE WERE 62 PATIENTS (37 MEN, MEAN AGE: 61 years) treated with sorafenib (62%), sunitinib (22%), and vandetanib (16%) outside of clinical trials; 22 had papillary, five had follicular, five had Hürthle cell, 13 had poorly differentiated, and 17 had medullary thyroid carcinoma (MTC). Thirty-three, 25, and four patients were treated with one, two, and three lines of TKIs respectively. Primary endpoints were objective tumor response rate and progression-free survival (PFS). Sequential treatments and tumor response according to metastatic sites were secondary endpoints. Among the 39 sorafenib and 12 sunitinib treatments in differentiated thyroid carcinoma (DTC) patients, partial response (PR) rate was 15 and 8% respectively. In the 11 MTC patients treated with vandetanib, 36% had PR. Median PFS was similar in second-line compared with first-line sorafenib or sunitinib therapy (6.7 vs 7.0 months) in DTC patients, but there was no PR with second- and third-line treatments. Bone and pleural lesions were the most refractory sites to treatment. This is the largest retrospective study evaluating TKI therapies outside of clinical trials. DTC patients treated with second-line therapy had stable disease as best response, but had a similar median PFS compared with the first-line treatment.
    The authors present a series of 140 patients who underwent surgical biopsy guided by an isolated anomaly on mammography without any clinical sign. 27 cases presented an opacity with a long axis less than 10 mm, 59 cases presented isolated... more
    The authors present a series of 140 patients who underwent surgical biopsy guided by an isolated anomaly on mammography without any clinical sign. 27 cases presented an opacity with a long axis less than 10 mm, 59 cases presented isolated areas of micro-calcification and 54 cases presented images of focal distorsion of the glandular architecture. By means of pre- and intra-operative radiographic guidance, the histological analysis of serial sections of these abnormalities was possible in every case, resulting in the diagnosis of 54 cases of benign dysplasia, 31 transitional lesion, including 16 in situ carcinomas and 55 carcinomas, including 34 invasive cancers. The advantage and limitations of this diagnostic approach are analysed. The discovery of a large number of sub-clinical carcinomas, the favourable implications for preservation of the breast and the survival justify the indications for surgical biopsy on the discovery of an isolated mammographic abnormality.
    From January 1985 to December 1987, 228 women with breast cancer smaller than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR-).... more
    From January 1985 to December 1987, 228 women with breast cancer smaller than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR-). They were randomized in an adjuvant chemotherapy trial comparing 9 intravenous CMF courses (cyclophosphamide, methotrexate, 5FU)--113 patients--to a polychemotherapy consisting of 3 courses of MTV (mitomycin C, thiotepa, vindesine) plus 3 courses of EVM (epirubicin, vincristine, methotrexate)--115 patients. Prognostic factors were well balanced between the two treatment groups. With a 59-month median follow-up, local breast relapses are more frequent in the CMF group, but regional and metastatic recurrences are the same in the two groups. Overall survival is identical. Toxicity is different: alopecia and neurotoxicity are more frequent in the MTV+EVM group, but general and digestive toxicities are equivalent. Haematologic toxicity is greater in the ...
    To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the... more
    To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adv...
    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... more
    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 res...
    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... more
    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 an...
    The aim of this randomised trial was to determine advantages and drawbacks of neo-adjuvant chemotherapy in patients with operable breast cancers > 3 cm. Two hundred and seventy-two women (age 70) with operable breast cancers larger... more
    The aim of this randomised trial was to determine advantages and drawbacks of neo-adjuvant chemotherapy in patients with operable breast cancers > 3 cm. 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. 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 sensitiv...
    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. A total of 68 patients with... more
    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. 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. 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 chemother...
    Résumé Contexte  La mise à jour des recommandations pour la pratique clinique (RPC) pour la prise en charge des patients atteints d’un sarcome des tissus mous a été élaborée par la Fédération nationale des centres de lutte contre le... more
    Résumé Contexte  La mise à jour des recommandations pour la pratique clinique (RPC) pour la prise en charge des patients atteints d’un sarcome des tissus mous a été élaborée par la Fédération nationale des centres de lutte contre le cancer (FNCLCC), en collaboration avec le Groupe sarcome français et le Groupe d’étude des tumeurs osseuses (GSF-GETO), des partenaires des secteurs publics
    The evolution of techniques has increased the number of diagnosed thyroid papillary microcarcinoma challenging the previous therapeutic guidelines. We have studied all thyroid cancers in our data base (from 1953 to 1994, N = 698).... more
    The evolution of techniques has increased the number of diagnosed thyroid papillary microcarcinoma challenging the previous therapeutic guidelines. We have studied all thyroid cancers in our data base (from 1953 to 1994, N = 698). One-hundred and eleven were papillary microcarcinomas (none before 1967): 83 M0N0, 24 M0N+ et 4 M+. One-hundred and eight pathologic slides could be obtained and were checked by one of us (pathologist). The mean follow-up was 8.6 yr [1-28]. Two clinical and pathological features were different between M0N0 and M0N+ (groups: i) the sex-ratio, 12 vs 50% men (M0N0 vs M0N+, p < or = 0.0001), ii) the invasiveness of the tumor, 54/83 vs 20/24 (M0N0 vs M0N+, p = 0.01). All patients received a suppressing treatment by thyroid hormones (except lobectomy). The other treatments were: for 64/83 M0N0 a total thyroidectomy followed by a I131 treatment, for the remaining no I131 (15 partial thyroidectomies and 4 total thyroidectomies). None of the M0N0 patients displa...
    Seventy-four post menopausal patients with primary non-metastatic invasive ductal carcinomas of the breast were first treated with tamoxifen alone (30 mg p.o. daily) for 5 months. To study changes induced by tamoxifen, core biopsies... more
    Seventy-four post menopausal patients with primary non-metastatic invasive ductal carcinomas of the breast were first treated with tamoxifen alone (30 mg p.o. daily) for 5 months. To study changes induced by tamoxifen, core biopsies before treatment and surgical specimens after hormonal therapy were assayed by immunohistochemistry for oestrogen (ER) and progesterone receptors (PR), pS2, GSTpi and c-erbB2. After tamoxifen, ER and PR significantly decreased in 60 and 44 cases respectively, whereas 11 and 19 cases showed no variation and 2 and 11 cases showed an increase (P<10(-4)). GSTpi and pS2 showed a significant increase in 43 and 41 cases, a decrease in 2 and 21 cases and no variation in 29 and 12 cases (P<10(-4) and P=0.04 respectively). c-erbB-2 showed no significant variation under tamoxifen, increased in only three cases and decreased in 13 cases. No relation was found between these variations and efficiency of hormone therapy. Our results allow a better knowledge of pr...
    This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma... more
    This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy. Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner. Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with t...
    Lymph nodes in breast cancer have been examined by two histological techniques in 324 patients who underwent axillary node dissection. A routine pathologic examination consisted in the examination of only one pathological section while in... more
    Lymph nodes in breast cancer have been examined by two histological techniques in 324 patients who underwent axillary node dissection. A routine pathologic examination consisted in the examination of only one pathological section while in the other, the lymph nodes were macroscopically serially sectioned. With the latter, an increase of 18.8 per cent in the number of detected metastases was noted. However this increase can be considered of prognostic and therapeutic importance only in 8.6 per cent of cases: half corresponding to those cases in which more than the initial threshold number of three lymph nodes were found, the other half corresponding to those cases in which one lymph node was found while the initial examination was negative. In the latter case, the increase of lymph node involvement was mainly due to "clandestine" metastases, i.e. lymphatic embolisation of micrometastases.
    Metastases to axillary lymph nodes is an important factor in predicting prognosis and survival in primary operable carcinoma of the breast. A series of post mastectomy lymph nodes (150 cases) was selected in this retrospective study, in... more
    Metastases to axillary lymph nodes is an important factor in predicting prognosis and survival in primary operable carcinoma of the breast. A series of post mastectomy lymph nodes (150 cases) was selected in this retrospective study, in which the initial diagnosis had been no metastases by light microscopy and in which a long follow-up was available (average 10 years). The original H&E sections from these cases were immunostained to detect metastases which might not have been previously appreciated. The study was performed using a cocktail of 5 monoclonal antibodies directed against epithelial antigens. The object was to explore the possibility of detection of occult micrometastases by immunohistochemistry and to evaluate their prognostic significance. Micrometastases with individual cells and cell clusters were readily detected by this technique in 14% of all cases. It also became apparent towards the end of the study that micrometastases could be detected with equal sensitivity by...
    A series of 377 low-grade non-Hodgkin's lymphomas, observed in the same Institute, was analysed. Pathological types following the Kiel classification were crossed with the usual parameters of patients (sex, age) and disease (tumoural... more
    A series of 377 low-grade non-Hodgkin's lymphomas, observed in the same Institute, was analysed. Pathological types following the Kiel classification were crossed with the usual parameters of patients (sex, age) and disease (tumoural extension, main anatomical involvement, biological data, course of the disease). Small differences appeared for the survivals for the overall series. By contrast many significant differences were observed for sex, age, dissemination of the disease, special tissue involvement, monoclonal gammopathy, complete remission rate and further involvement in case of relapse. These parameters allow one to distinguish different clinicopathological entities after the morphological cellular features. Such correspondences appear meaningful and might be offered by any other classification which should not be based only on the prognosis.
    The purpose of this report is to assess whether phenotyping by three monoclonal antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to be the most useful for diagnosis may be a predictive factor for recurrences.... more
    The purpose of this report is to assess whether phenotyping by three monoclonal antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to be the most useful for diagnosis may be a predictive factor for recurrences. Among 563 patients diagnosed as having Hodgkin's disease (24% of whom had recurrence), we selected 153 patients with and without recurrence, with matching clinical stage. For all of these cases, histologic material was tested by immunostainings with satisfactory control samples. No phenotype was specific for Hodgkin's disease, although the phenotype Ber-H2-Leu-M1-EMA was predominant. No phenotype was found to be a predictive factor for recurrences, and none was unchanged during the clinical course, except when recurrence occurred as non-Hodgkin's lymphoma.
    The prognosis for adenocarcinoma of the endometrium is dependent on the findings of the histopathological assessment of the tumor. In a retrospective study of patients treated in initially by surgery, the estrogen and progesterone... more
    The prognosis for adenocarcinoma of the endometrium is dependent on the findings of the histopathological assessment of the tumor. In a retrospective study of patients treated in initially by surgery, the estrogen and progesterone receptors were assayed 89 times and the androgen receptors 64 times. No statistically significant correlation was found between any of these receptors and the degree of structural differentiation or degree of infiltration of the myometrium. The absence of any one of these receptors had no negative impact on the overall survival nor on recurrence-free survival. The same was true for the 9 tumors which were devoid of both estrogen and progesterone receptors. In the authors' experience, the results of these hormone assays did not provide any further information on which to base the prognosis of endometrial cancers.
    Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and... more
    Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node-negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH ...
    From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on... more
    From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5-year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS:...
    This study was undertaken to study the behavior of superficial soft tissue sarcomas (STS) and determine the factors related to prognosis. The clinical records of 105 adults (56 men, 49 women, mean age: 56.4 years) were retrospectively... more
    This study was undertaken to study the behavior of superficial soft tissue sarcomas (STS) and determine the factors related to prognosis. The clinical records of 105 adults (56 men, 49 women, mean age: 56.4 years) were retrospectively analyzed. Univariate analysis was performed on the entire group for overall survival (OS), and metastasis-free survival (MFS). Local recurrence-free survival (LRFS) was studied only on patients first treated in our institute. With a median follow-up of 111.9 months, 66 (62.9%) patients were alive; 25 (23.8%) had died of their disease. For the entire series, 10-year OS and MFS were 62.5% and 71.9% respectively. For fifty-two patients treated for their sarcoma at the Institution since the first tumor occurrence event, 10-year LRFS was 80%. Tumor grade was the only factor correlated with OS and MFS, while tumor size was the main factor correlated with LRFS. Tumor size affects local control in STS while tumor grade is correlated with OS and MFS.
    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... more
    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. 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. 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). 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.
    Estrogen and progesterone receptors (ER-PR) are (questionable) prognostic factors for survival and disease-free survival. We have studied their prognostic value in a long term analysis which included 1203 women operated on for a breast... more
    Estrogen and progesterone receptors (ER-PR) are (questionable) prognostic factors for survival and disease-free survival. We have studied their prognostic value in a long term analysis which included 1203 women operated on for a breast cancer from 1980 to 1985 ...

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