Papers by Françoise Bonichon
British journal of cancer, 1996
Seventy-four post menopausal patients with primary non-metastatic invasive ductal carcinomas of t... 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...
To assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemis... more To assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.
Thyroid, 2014
Brain metastases (BM) from differentiated thyroid carcinoma (DTC) are uncommon, and many question... more Brain metastases (BM) from differentiated thyroid carcinoma (DTC) are uncommon, and many questions about their management remain unsolved. The objective of this retrospective study was to analyze the characteristics, treatments, and outcomes of patients with BM from DTC. Among the 1523 patients with a DTC prospectively recorded in institutional databases between 1989 and 2012, 21 patients (1.4%) with BM were retrospectively retrieved. Patient characteristics, histological findings on initial thyroidectomy specimen, treatments, and time to death were reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method. Survival curves for various subgroups of patients according to baseline characteristics and treatment received were compared. The mean age at initial and BM diagnosis was, respectively, 52.7 and 63.2 years. World Health Organization performance status (PS) at BM diagnosis was good (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2) for 12 patients and poor (≥2) for 9. The initial carcinoma was papillary for 12 patients, follicular for 5, and poorly differentiated for 4. Eighteen patients had other previous and/or synchronous distant metastases: lung (11), bone (10), and others (2 peritoneum, 1 liver, 1 adrenal gland, and 1 uterine cervix). The average interval between the first metastasis and the BM was 3 years (range 0-35.6 years). The mean number and the mean size of BM were, respectively, 2.8 (range 1-10) and 22.5 mm (range 3-44 mm). Surgery was performed for 10 patients and radiotherapy (RT) for 18, with 2 stereotactic radiosurgery (SRS), 2 conformal RT limited to the metastasis, and 15 whole-brain RT. The median OS after BM was 7.1 months. OS at 1 and 2 years were 41.6% and 35.6%. PS and realization of surgery or SRS had an impact on survival, with OS of 27 months when PS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 versus 3 months when PS ≥2 (p=0.0009), and OS of 11.9 months after surgery or SRS versus 3.6 months in their absence (p=0.04). BM from thyroid cancer may have an indolent evolution with survival of one to two years or longer for specific groups of patients. Therefore, aggressive treatment options such as neurosurgery and RT should be strongly considered in patients with good PS.
Case Reports in Endocrinology, 2013
Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These ... more Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT) found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg). The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis.
PLoS ONE, 2014
Thyroid carcinoma is the most common endocrine malignant tumor and accounts for 1% of all new mal... more Thyroid carcinoma is the most common endocrine malignant tumor and accounts for 1% of all new malignant diseases. Among all types and subtypes of thyroid cancers that have been described so far, papillary thyroid carcinoma is the most frequent. The standard management treatment of these tumors consists of surgery, followed by radioiodine treatment in case of high risk of relapse. The most aggressive forms are commonly treated by chemotherapy, radiotherapy or experimental drug testing. We recently reported the case of a patient presenting an anaplastic thyroid carcinoma with lung metastases. Fluorescence in situ hybridization analysis allowed us to detect a rearrangement of the anaplastic lymphoma kinase (ALK) gene in both tumors. The patient was treated with crizotinib and presented an excellent drug response. We present here the subsequent investigations carried out to further characterize this genetic alteration and to assess the prevalence of ALK rearrangements in thyroid lesions. High resolution array-comparative genomic hybridization data complemented by RT-PCR and sequencing analyses, allowed us to demonstrate the presence of a STRN/ALK fusion. The STRN/ALK transcript consisted of the fusion between exon 3 of STRN and exon 20 of ALK. Subsequent screening of 75 various thyroid tumors by RT-PCR revealed that 2 out of 29 papillary thyroid carcinomas exhibited the same fusion transcript. None was detected in other types of malignant or benign thyroid lesions analyzed. These findings could pave the way for the development of new targeted therapeutic strategies in the treatment of papillary thyroid carcinomas and point to ALK inhibitors as promising agents that merit rapid evaluation.
New England Journal of Medicine, 2012
There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no u... more There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the 131 I doses and between the thyrotropin-stimulation methods.
The Lancet Oncology, 2012
Background No eff ective standard treatment exists for patients with radioiodine-refractory, adva... more Background No eff ective standard treatment exists for patients with radioiodine-refractory, advanced diff erentiated thyroid carcinoma. We aimed to assess effi cacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting.
Journal of Clinical Oncology, 2014
The Journal of Clinical Endocrinology & Metabolism, 2013
An increased cancer mortality is reported in transplanted patients. This multicentric study aimed... more An increased cancer mortality is reported in transplanted patients. This multicentric study aimed to investigate the rate of thyroid cancer recurrence after transplantation. Sixty-eight patients (35 male/33 female) with a history of both thyroid cancer and organ transplantation were recruited via two nationwide French networks. Histological analysis identified 58 papillary (88%), 5 follicular (7.5%), and 3 poorly differentiated cancer cases (4.5 %). Thirty-one patients (52%) presented high recurrence risk tumors. In the 36 patients with thyroid cancer diagnosed after transplantation, the 5-year disease-free survival (DFS) was 74.7% (SE: 7.3%). One patient died after progression of a poorly differentiated cancer. Persistent disease was observed in six high-risk patients. One of them underwent a second transplantation and disease remained stable after 5 years of follow-up. Thyroid cancer had been diagnosed before transplantation in 32 patients. One patient with cystic fibrosis and thyroid lung metastases at the time of lung transplantation underwent a 4-year remission. For the 31 patients in remission at the time of transplantation, the 5-year DFS was 93.1% (SE: 4.8%). Two patients with local recurrence presented subsequent remission. For the entire study population, the 5-year and 9-year DFS were 81.9% (SE: 5.5%) and 75.6% (SE: 7.9%), respectively. Recurrence or persistent disease occurred in patients with high-risk tumors. The prognosis of thyroid cancer does not seem to be altered by transplantation. This suggests that a history of thyroid cancer should not be considered a contraindication.
The Journal of Clinical Endocrinology & Metabolism, 2007
Background: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial... more Background: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease.
The Journal of Clinical Endocrinology & Metabolism, 2011
Purpose: This prospective study evaluated the recurrence rate in 715 patients with differentiated... more Purpose: This prospective study evaluated the recurrence rate in 715 patients with differentiated thyroid cancer who had no evidence of persistent disease after total thyroidectomy and lymph node dissection in 94% of them followed up by radioiodine ablation (30 -100 mCi) and assessed the predictive value of the initial thyroglobulin (Tg) levels for detecting recurrence, both during levothyroxine (LT4) treatment and after TSH stimulation.
European Journal of Endocrinology, 2014
Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We re... 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.
Critical Reviews in Oncology/Hematology, 2002
In the elderly population, cancer treatment aims to cure and/or maintain Quality of Life (QoL). H... more In the elderly population, cancer treatment aims to cure and/or maintain Quality of Life (QoL). However, there is little QoL data to provide evidence for QoL benefits for some of the cancer treatments. This pilot study developed valid QoL questionnaires in French, for patients over 65 years with a diagnosis of large cell lymphoma, part of the Lymâge phase II study. They were asked to complete two questionnaires, the Medical Outcomes Study Short Form 20 (MOS SF20; generic) and the Rotterdam symptom checklist (RSCL; cancer-specific). Between June 1995 and April 1997, questionnaires were returned by 63 of 89 patients. This article reports the process undertaken to adapt the English version to a French setting, and provides the results of factor analysis, convergent and discriminant validity and reliability. Our data suggest that QoL questionnaires can be used in elderly patients. These two questionnaires are validated in French and would help us to analyse the QoL of elderly patients with the development of new treatments as done in the Lymâge study.
Clinical Nuclear Medicine, 2013
Whole-body (131I) scintigraphy (WBS) is used to detect residual or metastatic tissue during treat... more Whole-body (131I) scintigraphy (WBS) is used to detect residual or metastatic tissue during treatment of differentiated thyroid carcinoma in combination with thyroglobulin (Tg) and ultrasonography of the neck. It is a highly sensitive method, but there is a high rate of false positives. We report the case of a 52-year-old woman with false-positive iodine accumulation in a benign cystic mesothelioma discovered during treatment for a oncocytic follicular thyroid carcinoma (stage pT2 pNx Mx). This lesion was detected by WBS and confirmed by surgery and histopathologic analysis.
Cancer, 1997
The authors determined the flow cytometric (FCM) DNA characteristics of 53 benign tumors and 132 ... more 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). 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. 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 &gt; 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 &lt; 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). 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.
Annals of Oncology, 2012
Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven... more Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.
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Papers by Françoise Bonichon