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ABSTRACT: Objectives:Vandetanib was approved by the United States Food and Drug Association for the treatment of advanced medullary thyroid cancer (MTC). As body weight (BW) loss is observed in MTC and as low skeletal muscle mass (SM) is associated with drug toxicity, this study assessed effects of vandetanib on SM and adipose tissue (AT) and explored the association between SM, toxicity and serum concentration (SC) of vandetanib.Methods:33 patients with MTC received vandetanib (n=23) or placebo (n=10) in the ZETA study. Visceral AT (VAT), subcutaneous AT (SAT) and SM were assessed with computed tomography imaging by measuring tissue cross-sectional areas (cm(2)/m(2)). Dose-limiting toxicities (DLT) were prospectively recorded.Results:Early at 3 months, compared to placebo group who lost BW, muscle and SAT, patients treated with vandetanib gained 1.5 kg of BW (p=0.02), 1.3 cm(2)/m(2) (≈0.7 kg) of SM (p=0.009), 4.5 cm(2)/m(2) (≈0.5 kg) of SAT (p=0.004) and gained more VAT 5.1 cm(2)/m(2) (≈0.7 kg) (p=0.02).Patients with DLT had lower SM index (37.2 vs. 44.3 cm(2)/m(2), p=0.003) and a higher vandetanib SC (1091 vs. 739 ng/ml, p=0.03). Patients with SM index <43.1 cm(2)/m(2) had a higher probability of DLT (73% vs. 14%, p=0.004) and a higher vandetanib SC (1037 vs. 745 ng/ml, p=0.04). Patients with the highest compared with the intermediate and lower levels of vandetanib SC experienced more DLT, respectively 78% vs. 40% vs. 20% (p=0.04).Conclusions:Muscle and adipose tissues are restored after only 3 months of vandetanib treatment. Patients with low muscle mass had high vandetanib serum concentration and high incidence of toxicities.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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Cecile N Chougnet, Sophie Leboulleux,
Caroline Caramella,
Isabelle Borget,
Désirée Deandreis,
Jean Lumbroso,
Pierre Duvillard,
Dominique Elias,
Thierry de Baere,
Fritz-Line Velayoudom,
Joel Guigay,
Michel Ducreux,
Martin Schlumberger,
Eric Baudin
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ABSTRACT: Recent studies suggest that the Somatostatin Receptor Scintigraphy (SRS) grade of uptake is a predictor of response to peptide-receptor radionuclide therapy (PRRT). The aim of the study was to identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by 3 independent readers and classified into 4 subgroups based on a modified Krenning's scale (mKS): no uptake (group-0), homogeneous grade 1-2 uptake (group-1), homogeneous grade 3-4 (group-2), heterogeneous grade 1-4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high grade uptake. 106 WD NEN patients were enrolled. Group-0, group-1, group-2 and group-3 were found in 17%, 8%, 33% and 42% of cases, respectively. High grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranine-A level, Grade-1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. In concluion, 33% to 75% of metastatic NEN can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.
Endocrine Related Cancer 02/2013; · 4.36 Impact Factor
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Sophie Leboulleux,
Isabelle Borget,
Stephanie Labro,
Sophie Bidault,
Philippe Vielh,
Dana M Hartl,
Sarah Dauchy,
Cecile N Chougnet,
Elizabeth Girard,
Sandy Azoulay,
Haitham Mirghani,
Amandine Berdelou,
Jean Lumbroso,
Desiree Deandreis,
Eric Baudin,
Martin Schlumberger,
Sophie Laurent
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ABSTRACT: Background: Quality of life is an important issue in endocrine tumors because of the high prevalence of benign tumors and the indolent course of most malignant tumors. Objective: To evaluate the frequency and the intensity of pain and anxiety in patients undergoing thyroid nodule fine needle aspiration cytology (FNAC), and to identify factors associated with pain. Method: Single center prospective study in the setting of a one-stop outpatient diagnostic clinic for thyroid nodules. Pain was evaluated using a 100-mm visual analogue scale (VAS) immediately following (VAS1) and 30 minutes after (VAS2) FNAC and was considered significant if ≥30. Anxiety symptoms were assessed prior to FNAC using a self-report measure questionnaire: the state form of Spielberger State-Trait Anxiety Inventory (STAI, form Y-A). FNAC was performed with a 25-Gauge needle and a moderate aspiration and two passes for each nodule. Results: 218 consecutive patients (163 females, 55 males; mean age 53 years, range 12-84) undergoing FNAC of 1 to 3 nodules were included. VAS1 was ≥30 in 24% of the patients and VAS2 was 30 in 13% of the patients. Independent significant factors correlated to a VAS1 30 were age under 25 and the number of nodules being biopsied. Independent significant factors correlated to a VAS2 30 were VAS1 30 and female gender. No correlation was found between pain and nodule size or nodule depth, nor the duration of application of the Eutectic Mixture of Local Anesthetics (EMLA patch) prior to FNAC. The mean STAI score for anxiety was 37 12. The average STAI score was significantly higher in women (39) than in men (33) (p=0.01). There was no significant correlation between STAI score and age under 25, previous FNAC, number of nodules biopsied or acetaminophen administration, but the STAI score was significantly correlated to VAS1 and VAS2 Conclusions: FNAC-related pain is frequent and correlates with the number of nodules biopsied, age under 25, female gender and anxiety.
Thyroid: official journal of the American Thyroid Association 02/2013; · 2.60 Impact Factor
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Anne-Paule Gimenez-Roqueplo,
Aurore Caumont-Prim,
Claire Houzard,
Chantal Hignette,
Anne Hernigou,
Philippe Halimi,
Patricia Niccoli, Sophie Leboulleux,
Laurence Amar,
Françoise Borson-Chazot, [......],
Brigitte Delemer,
Frédéric Chabolle,
Isabelle Coupier,
Rossella Libé,
Mirko Peitzsch,
Séverine Peyrard,
Florence Tenenbaum,
Pierre-François Plouin,
Gilles Chatellier,
Vincent Rohmer
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ABSTRACT: Context:Recommendations have not been established concerning imaging to screen SDHx mutation carriers for paraganglioma and pheochromocytoma.Objective:Our objective was to compare the performance of gadolinium-enhanced magnetic resonance angiography, contrast-enhanced computed tomography, and [(123)I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx mutation carriers.Design and Setting:We conducted a prospective, multicenter study from June 2005 to December 2009 at 23 French medical centers.Patients:A total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC genes were included.Intervention:Images obtained by each technique were analyzed blind, without knowledge of results from other tests, first in each local center and then centrally.Main Outcome Measures:We evaluated sensitivity, specificity, and likelihood ratios for individual and combinations of tests, the gold standard being the consensus of an expert committee.Results:Two hundred two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of anatomical imaging for detecting all tumors was higher (85.7%) than that of both scintigraphic techniques (42.7% for [(123)I]metaiodo-benzylguanidine and 69.5% for somatostatin receptor scintigraphy), except for thoracic localizations where somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for anatomical imaging and 30.8% for [(123)I]metaiodo-benzylguanidine scintigraphy). The best diagnostic performance during local assessment was obtained by combining anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity 91.7%). Central assessment significantly increased the sensitivity (98.6%) of tests in combination.Conclusions:In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.
The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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ABSTRACT: Thyroid carcinoma is a rare disease in children, and is mostly of the papillary histological type. Lymph node metastases are frequent at diagnosis, being present in 23 to 74% of the cases and can reveal the cancer in about one fourth of cases. Lung metastases are present at initial diagnosis in 6 to 20% of cases. The main known risk factor for thyroid cancer is a previous history of radiation exposure. Treatment includes surgery with total thyroidectomy and lymph node dissection and radioiodine therapy in case of extensive disease and distant metastases. Life-long thyroxine treatment is given to all patients. Long term prognosis is favourable, but thyroid cancer related deaths have been reported some decades after initial treatment.
Bulletin du cancer 11/2012; · 0.67 Impact Factor
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ABSTRACT: INTRODUCTION: The prognostic value of serum calcitonin (CT) and carcino-embryonic antigen (CEA) doubling time has been recently demonstrated in medullary thyroid carcinoma (MTC) patients. No study has yet validated the surrogate role of these markers for survival during treatment. The aim of this study was to evaluate, in patients with advanced MTC treated with cytotoxic chemotherapy, the relationship between early changes of serum CT or CEA levels and progression-free survival (PFS). PATIENTS AND METHODS: The files of 28 consecutive metastatic MTC patients with progressive disease, treated with cytotoxic chemotherapy in a single tertiary referral center between 2000 and 2010, were retrospectively reviewed. Serum CT and CEA measurements and radiological RECIST evaluations were collected every three months. Relationship between changes in serum CT and CEA levels at 3 months, defined by an increase or a decrease of at least 20%, and PFS according to RECIST 1.0, was estimated using Kaplan-Meier curves and log-rank test. RESULTS: The median follow-up for the 28 patients was 68 months. According to RECIST, a partial response, a stabilization or a progression was observed in 14, 43 and 43% of cases, respectively. Median PFS from the initiation of cytotoxic chemotherapy was 4.5 months. Median PFS among patients with and without significant CT increase at 3 months was 4.6 and 3.3 months, respectively (p=0.75). Median PFS among patients with a significant CEA increase at 3 months was 2.7 months, whereas it was 19.1 months in whom CEA did not increase (p=0.02). CONCLUSION: At 3 months, an increase of serum CEA but not of CT levels appears as a valuable surrogate marker of short progression-free survival in MTC patients treated with cytotoxic chemotherapy. A prospective validation is expected.
European Journal of Endocrinology 10/2012; · 3.42 Impact Factor
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Montserrat Ayala-Ramirez,
Cecile N Chougnet,
Mouhammed Amir Habra,
J Lynn Palmer, Sophie Leboulleux,
Maria E Cabanillas,
Caroline Caramella,
Pete Anderson,
Abir Al Ghuzlan,
Steven G Waguespack,
Desirée Deandreis,
Eric Baudin,
Camilo Jimenez
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ABSTRACT: Context:Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited.Objectives:The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [(18)F]fluorodeoxyglucose/computed tomography ([(18)F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety.Design:We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed.Patients and Setting:Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center.Interventions:Patients treated with sunitinib.Results:According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [(18)F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4-11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations.Conclusion:Sunitinib is associated with tumor size reduction, decreased [(18)F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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Sophie Leboulleux,
Intidhar El Bez,
Isabelle Borget,
Manel Elleuch,
Désirée Déandreis,
Abir Al Ghuzlan,
Cécile Chougnet,
François Bidault,
Haitham Mirghani,
Jean Lumbroso,
Dana Hartl,
Eric Baudin,
Martin Schlumberger
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ABSTRACT: Patients with differentiated thyroid cancer (DTC) who have a suspicious recurrent or persistent disease based on an elevated serum thyroglobulin (Tg) or Tg antibodies (TgAb) are usually referred for empiric radioiodine ((131)I) administration to localize and treat the disease. The aim of this retrospective monocentric study was to assess the sensitivity of postempiric (131)I whole-body scan (WBS) compared to 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in such patients who had an initial normal postablation WBS.
Among 47 consecutive patients with DTC who had a normal postablation WBS and were referred for empiric (131)I administration, 34 patients (12M, 22F; mean age 53 years) underwent FDG PET/CT and form the basis of this report: 23 patients had persistently elevated serum Tg levels, 10 had elevated Tg levels observed during follow-up after they initially became under 1 ng/mL, and 1 had appearance of TgAb during follow-up. Postempiric (131)I WBS and FDG PET/CT were analyzed by independent readers.
A total of 75 lesions were found in 23 patients, distributed in 36 organs. Lesions were located in the neck (30), lungs (28), mediastinum (11), and bones (6). The sensitivities for the detection of individual lesions and for the diagnosis of metastatic organs were 88% and 97% for PET/CT and 16% and 22% for WBS, respectively (p<0.01). PET/CT was abnormal in 22 patients, among which 5 also had an abnormal postempiric (131)I WBS. There was only one patient with an abnormal postempiric (131)I WBS and a normal FDG PET/CT. This patient underwent two further (131)I administrations, with the last WBS being normal and the last stimulated Tg level being undetectable. Other patients were either treated with surgery, or classified as radioactive iodine refractory and treated with levothyroxine suppressive therapy or tyrosine kinase inhibitors.
In patients with suspicious recurrence based on the Tg level after a normal postablation WBS, FDG PET/CT is the preferred scintigraphic method to localize disease rather than postempiric (131)I WBS. Empiric (131)I administration may be used only in patients who do not have a significant FDG uptake.
Thyroid: official journal of the American Thyroid Association 08/2012; 22(8):832-8. · 2.60 Impact Factor
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Sophie Leboulleux,
Intidhar El Bez,
Isabelle Borget,
Manel Elleuch,
Desiree Deandreis,
Abir Al Ghuzlan,
Cecile N Chougnet,
François Bidault,
Haitham Mirghani,
Jean Lumbroso,
Dana M Hartl,
Eric Baudin,
Martin Schlumberger
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ABSTRACT: Differentiated thyroid cancer (DTC) patients with a suspicious recurrent or persistent disease based on an elevated serum thyroglobulin (Tg) or Tg antibodies (TgAb) are usually referred for empiric radioiodine (I-131) administration to localize and treat the disease. The aim of this retrospective monocentric study was to assess the sensitivity of post-empiric I-131 whole body scan (WBS) compared to 18-fluorodesoxyglucose positron emission computed tomography (FDG-PET/CT) in such patients who had an initial normal post-ablation whole body scan (WBS). Methods: Among 47 consecutive DTC patients with a normal post-ablation WBS who were referred for empiric I-131 administration, 34 patients (12M, 22F; mean age 53 yrs) underwent FDG PET/CT and form the basis of this report: 23 patients had persistenly elevated serum Tg level, 10 had elevated Tg level observed during follow-up after it became initially under 1 ng/mL and 1 had appearance of Tg Ab during follow-up. Post-empiric I-131 WBS and FDG-PET/CT were analysed by independent readers. Results: A total of 75 lesions were found in 23 patients, distributed in 36 organs. Lesions were located in the neck (30), lungs (28), mediastinum (11) and bones (6). The sensitivities for the detection of individual lesions and for the diagnosis of metastatic organs were 88 and 97% for PET/CT and 16 and 22% for WBS, respectively (P<0.01). PET/CT was abnormal in 22 patients among which 5 also had an abnormal post-empiric I-131 WBS. There was only one patient with an abnormal post-empiric I-131 WBS and a normal FDG PET/CT. This patient underwent two further I-131 administration, with the last WBS being normal and last stimulated Tg level being undetectable Other patients were either treated with surgery, or classified as radioactive iodine refractory and treated with levothyroxine suppressive therapy or tyrosine kinase inhibitors Conclusion: In patients with suspicious recurrence based on the Tg level after a normal post-ablation WBS, FDG PET/CT is the preferred scintigraphic method to localize disease rather than post-empiric I-131 WBS. Empiric I-131 administration may be used only in patients who do not have significant FDG uptake.
Thyroid: official journal of the American Thyroid Association 06/2012; · 2.60 Impact Factor
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ABSTRACT: In patients treated for differentiated thyroid cancer with radioiodine (131I), abnormal uptake on post-therapeutic whole-body scan may lead to repeated administration of 131I. Uptake not linked to thyroid cancer but to other conditions should be recognized so that patients are not overtreated. We describe 3 cases of unilateral thoracic 131I uptake in patients previously treated by pneumonectomy for lung cancer, without evidence of persistent lung cancer.
Clinical nuclear medicine 06/2012; 37(6):587-90. · 3.92 Impact Factor
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Martin Schlumberger,
Bogdan Catargi,
Isabelle Borget,
Désirée Deandreis,
Slimane Zerdoud,
Boumédiène Bridji,
Stéphane Bardet,
Laurence Leenhardt,
Delphine Bastie,
Claire Schvartz,
Pierre Vera,
Olivier Morel,
Danielle Benisvy,
Claire Bournaud,
Françoise Bonichon,
Catherine Dejax,
Marie-Elisabeth Toubert, Sophie Leboulleux,
Marcel Ricard,
Ellen Benhamou
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ABSTRACT: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care.
In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework.
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 use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).
New England Journal of Medicine 05/2012; 366(18):1663-73. · 53.30 Impact Factor
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Martin Fassnacht,
Massimo Terzolo,
Bruno Allolio,
Eric Baudin,
Harm Haak,
Alfredo Berruti,
Staffan Welin,
Carmen Schade-Brittinger,
André Lacroix,
Barbara Jarzab, [......],
Dirk Weismann,
Felix Beuschlein,
Hans Gelderblom,
Hanneke Wilmink,
Monica Sender,
Maureen Edgerly,
Werner Kenn,
Tito Fojo,
Hans-Helge Müller,
Britt Skogseid
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ABSTRACT: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.
We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival.
For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments.
Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.).
New England Journal of Medicine 05/2012; 366(23):2189-97. · 53.30 Impact Factor
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ABSTRACT: To analyze the yield and rate of node metastases (pN1) for prophylactic central (CND) and lateral neck dissection (LND) for papillary thyroid carcinoma, the risk factors for pN1, and outcomes.
Prophylactic CND and LND are not routinely employed. Adjuvant radioiodine treatment may be modulated, however, by surgical staging of the neck.
Retrospective study, consecutive patients ultrasonographically classified cN0 treated with prophylactic CND, and lateral LND (levels III and IV). The number of nodes was resected and the incidence of pN1 was recorded.
For 317 patients (254 women, mean age 44 years, mean tumor size 17 mm), the number of lymph nodes was 5 for unilateral CND, 9 for bilateral CND, and 12 for LND. pN1 stage was 42% overall: 23% for unilateral CND, 39% for bilateral CND, and 23% for LND (median number of metastatic nodes = 2 for each). Fifty-five percent of the patients staged pN1 had metastatic nodes in the lateral neck. Ten percent had more than 10 metastatic nodes and/or more than 3 nodes with extra capsular spread. pN1 was correlated with tumor size (P = 0.0025), extrathyroidal tumor extension (P < 0.0001), male sex (P = 0.0006), and age younger than 45 years (P = 0.0003). Permanent hypoparathyroidism and unintentional recurrent nerve paralysis occurred in 2 cases each. Patients staged pN0 received less radioiodine than patients staged pN1 (median 30 vs 100 mCi, P < 0.0001).
For staging, bilateral prophylactic CND is preferable to unilateral CND. Prophylactic CND with LND optimizes staging providing a basis for a personalized approach for adjuvant radioiodine.
Annals of surgery 04/2012; 255(4):777-83. · 7.90 Impact Factor
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Boris Guiu,
Frédéric Deschamps,
Serge Aho,
Flore Munck,
Clarisse Dromain,
Valérie Boige,
David Malka, Sophie Leboulleux,
Michel Ducreux,
Martin Schlumberger,
Eric Baudin,
Thierry de Baere
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ABSTRACT: Transarterial chemoembolisation (TACE) is usually performed by injecting an emulsion of a drug and iodised oil. Drug-eluting beads (DEBs) have undeniable pharmacological advantages by offering simultaneous embolisation and sustained release of the drug to the tumour. No data are currently available on liver/biliary injury following DEB-TACE. This study describes and compares liver/biliary injuries encountered with TACE in tumours developed in cirrhotic (hepatocellular carcinoma (HCC)) and non-cirrhotic (endocrine tumours (NETs)) livers.
In consecutive patients treated for a well-differentiated metastatic NET (n=120) or a HCC (n=88), 684 CT- and MR-scans were analysed. Liver/biliary injuries were classified as follows: dilated bile duct, portal vein narrowing, portal venous thrombosis and biloma/liver infarct. A generalised estimating equation logistic regression model was used.
A liver/biliary injury followed 17.2% (82/476) of sessions in 30.8% (64/208) of patients. The occurrence of liver/biliary injury was associated with DEB-TACE (OR=6.63; p<0.001) irrespectively of the tumour type. Biloma/parenchymal infarct was strongly associated with both DEB-TACE (OR=9.78; p=0.002) and NETs (OR: 8.13; p=0.04). Biloma/liver infarcts were managed conservatively but were associated with an increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatases, and gamma glutamyl transpeptidase (p=0.005, p=0.005, p=0.012, and p=0.006, respectively).
Liver/biliary injuries are independently associated with DEB-TACE. Biloma/liver infarct, the most serious injury, is independently associated with both DEB-TACE and NETs. The absence of such an association in TACE of HCC may be explained by the hypertrophied peribiliary plexus observed in cirrhosis, which protects against the ischemic/chemical insult of bile ducts. We suggest caution when using DEB-TACE in the non-cirrhotic liver.
Journal of Hepatology 03/2012; 56(3):609-17. · 9.26 Impact Factor
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Desiree Deandreis,
Abir Al Ghuzlan,
Anne Auperin,
Philippe Vielh,
Bernard Caillou,
Linda Chami,
Jean Lumbroso,
Jean Paul Travagli,
Dana Hartl,
Eric Baudin,
Martin Schlumberger, Sophie Leboulleux
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ABSTRACT: Thyroid nodules found incidentally on (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) have been shown to be malignant in 30%-50% of cases. The American Thyroid Association recommends performing fine needle aspiration cytology (FNAC) for thyroid nodules showing FDG uptake. On the other hand, the role of FDG-PET in characterizing thyroid nodules with indeterminate cytology before surgery is not clear. The goal of this study was to evaluate the role of FDG-PET/computed tomography (CT) in predicting malignancy of thyroid nodules with indeterminate FNAC and to correlate FDG uptake with pathological and ultrasonographic (US) features.
Between November 2006 and October 2009, 55 patients (42 women, mean age: 50 years) planned for surgery for 56 thyroid nodules with indeterminate FNAC were prospectively included and considered for analysis. All patients underwent presurgical FDG-PET/CT (Siemens Biograph, mean FDG injected activity: 165 MBq) and neck US. Pathology of the corresponding surgical specimen was the gold standard for statistical analysis.
At pathology 34 nodules were benign, 10 were malignant (7 papillary and 3 follicular carcinomas), and 12 were tumors of uncertain malignant potential (TUMP). The median size of the thyroid nodules was 21 mm (range: 10-57). Sensitivity, specificity, positive (PPV), and negative predictive (NPV) values of FDG-PET in detecting cancer/TUMP were 77%, 62%, 57%, and 81%, respectively. In multivariate analysis, cellular atypia was the only factor predictive of FDG uptake (p<0.001). Hurthle cells and poorly differentiated components were independent predictive factors of high (≥5) SUV Max (p=0.02 and p=0.02). Sensitivity, specificity, PPV, and NPV of US in detecting cancer/TUMP were 82%, 47%, 50%, and 80%, respectively. In multivariate analysis, hypervascularization was correlated with malignancy/TUMP (p=0.007) and cystic features were correlated with benignity (p=0.03).
Adding FDG-PET findings to neck US provided no diagnostic benefit. The sensitivity and specificity of FDG-PET in the presurgical evaluation of indeterminate thyroid nodules are too low to recommend FDG-PET routinely.
Thyroid: official journal of the American Thyroid Association 02/2012; 22(2):165-72. · 2.60 Impact Factor
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ABSTRACT: The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.
Clinics (São Paulo, Brazil) 01/2012; 67 Suppl 1:125-9. · 1.59 Impact Factor
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Alfredo Berruti,
Paola Sperone,
Anna Ferrero,
Antonina Germano,
Arianna Ardito,
Adriano Massimiliano Priola,
Silvia De Francia,
Marco Volante,
Fulvia Daffara,
Daniele Generali, Sophie Leboulleux,
Paola Perotti,
Eric Baudin,
Mauro Papotti,
Massimo Terzolo
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ABSTRACT: There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.
We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.
Multicenter, prospective phase II trial. Setting Referral centers for ACC.
Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m(2) every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.
Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose-response and time-response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.
Despite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.
European Journal of Endocrinology 12/2011; 166(3):451-8. · 3.42 Impact Factor
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ABSTRACT: Adrenocortical carcinoma (ACC) is a rare tumor with aggressive behavior, high recurrence rate, and rapid evolution. Surgery is the only curative modality, while systemic treatments such as mitotane and chemotherapy associated to locoregional therapeutic tools remain as palliative options. Imaging has an important role in the management of patients with ACC both at diagnosis and during follow-up. First, it is necessary to characterize undetermined adrenal masses, selecting patients for surgery. Then, in case of malignancy, it is mandatory to assess disease extension, to detect early relapse during follow-up, and to evaluate treatment response. Computed tomography scan and magnetic resonance imaging are actually the most used techniques for these intents as they are widely available in clinical practice. (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) is routinely used for other malignancies and, on the basis of published data, is also becoming a promising tool in the management of ACC. Not only is it a diagnostic tool complementary to morphological imaging in the characterization of adrenal masses and in tumoral lesions detection, but it can be also useful to evaluate tumor response to treatment. New tracers and indications for the clinical use of FDG PET in this specific disease still have to be evaluated to assess its role in clinical practice.
Hormones and Cancer 11/2011; 2(6):354-62.
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ABSTRACT: Refractory thyroid cancers include medullary and differentiated cancers with locally advanced disease that is not amenable to surgery or with distant metastases, differentiated thyroid carcinomas being refractory to radio-iodine treatment and all anaplastic carcinomas. These carcinomas are rare, with an estimated incidence in France of 350 new cases per year. Their management may benefit from the TUTHYREF network. Kinase inhibitors inhibit kinases of the VEGF receptors, and this inhibits angiogenesis, and some of these agents also inhibit other kinases of the MAPkinase pathway. These inhibitors are effective in differentiated and medullary thyroid cancers, and induce a partial response or a long-term stabilisation in more than half of patients. Their toxicity is significant and these treatments should be given only to selected patients with locally advanced or metastatic disease, with progression or with clinical symptoms.
La Presse Médicale 11/2011; 40(12 Pt 1):1189-98. · 0.67 Impact Factor
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Sophie Mauclère-Denost, Sophie Leboulleux,
Isabelle Borget,
Angelo Paci,
Jacques Young,
Abir Al Ghuzlan,
Desiree Deandreis,
Laurence Drouard,
Antoine Tabarin,
Philippe Chanson,
Martin Schlumberger,
Eric Baudin
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ABSTRACT: The benefit-to-risk ratio of a high-dose strategy at the initiation of mitotane treatment of adrenocortical carcinoma (ACC) remains unknown.
To evaluate the performance of a high-dose strategy, defined as the highest tolerated dose administered within 2 weeks and maintenance therapy over 4 weeks, we conducted a single-center, prospective study with two main objectives: to evaluate the percentage of patients who achieve a plasma mitotane level above 14 mg/l and to evaluate the tolerance of mitotane within the first 3 months of treatment. Plasma mitotane levels were measured monthly using HPLC.
Twenty-two patients with ACC were prospectively enrolled. The high-dose mitotane strategy (4 g/day or more in all patients, with a median of 6 g/day within 2 weeks) enabled to reach the therapeutic threshold of >14 mg/l at 1, 2, or 3 months in 6/22 patients (27%), 7/22 patients (32%), and 7/22 patients (32%) respectively. In total, a therapeutic plasma mitotane level was reached in 14 out of 22 patients (63.6%) during the first 3 months in ten patients, and after 3 months in four patients. Grade 3-4 neurological or hematological toxicities were observed in three patients (13.6%).
Employing a high-dose strategy at the time of mitotane initiation enabled therapeutic plasma levels of mitotane to be reached within 1 month in 27% of the total group of patients. If this strategy is adopted, we suggest that mitotane dose is readjusted according to plasma mitotane levels at 1 or/and 2 months and patient tolerance.
European Journal of Endocrinology 11/2011; 166(2):261-8. · 3.42 Impact Factor
