Abir Al Ghuzlan

Institut de Cancérologie Gustave Roussy, Île-de-France, France

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Publications (40)164.69 Total impact

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    ABSTRACT: Mitotane (o,p'DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that o,p'DDA may represent the active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of o,p'DDA. Functional consequences of o,p'DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with o,p'DDD or o,p'DDA and in human adrenal tissues. Dose-response curves up to 300 μM showed that, as opposed to o,p'DDD, o,p'DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis, o,p'DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While o,p'DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation, o,p'DDA levels remained unchanged suggesting that o,p'DDA was not efficiently transported into the cells. o,p'DDA was not detected in cell homogenates or supernatants after 48 h exposure to o,p'DDD, consistent with the absence of o,p'DDA production in these models. Finally, unlike o'p'DDD, we found that o,p'DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that o,p'DDD, but not o,p'DDA, induces functional alterations in adrenal cells.
    Hormones & cancer. 07/2014;
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    ABSTRACT: Mestastatic pheochromocytoma and paraganglioma (MPP) present clinicians with three major challenges: scarcity, complexity of characterization, and heterogeneous behavior and prognosis. As with the treatment of all neuroendocrine tumors, the control of hormonal symptoms and tumor growth are the main therapeutic objectives in MPP patients. A significant number of MPP patients still die from uncontrolled hormone secretion. In addition, the management of MPP remains palliative. Steps forward include proper characterization of MPP patients at large cancer referral centers with multidisciplinary teams; improved strategies to stratify patients prognostically; and implementation of trials within national and international networks. Progress in the molecular characterization and staging of MPP constitutes the basis for significant treatment breakthroughs.
    European journal of endocrinology / European Federation of Endocrine Societies. 06/2014;
  • Annales d Endocrinologie 05/2014; 38(3):136. · 1.02 Impact Factor
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    ABSTRACT: Cyclophosphamide-dacarbazine-vincristine (CVD) regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP.This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation-wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression-free survival (PFS) according to RECIST and PERCIST criteria was the primary endpoint.Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m²/d for five days every 28 days. Median PFS was 13.3 months after a median follow-up of 35 months. There were five partial responses (33%), seven stable (47%), and three progressive diseases (20%). Grade 3 toxicities lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation-wide independent cohort.This study demonstrates that TMZ is an effective anti-tumour agent in patients with SDHB-related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumours may explain this finding. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: Objective To evaluate the performance of 18FDG-PET/CT for detecting infra-clinic paraganglioma (PGL) in SDHx mutation carriers (relatives). Patients and methods Sixty-six patients, from 13 distinct families underwent a genetic testing on the SHD genes between 2003 and 2012. Among the 45 patients with a mutation, 30 with a 18FDG-PET performed at initial work-up were included in this retrospective study. A gadolinium-enhanced magnetic resonance angiography of the neck (angio-MR) was performed in all cases, a thoracoabdominal-pelvic contrast-enhanced computed tomography (TAP-CT) in 25 cases, a TAP-MR in 20 cases, a 123I-metaiodo-benzylguanidine scintigraphy (123I-MIBG) in 20 cases and a somatostatin receptor scintigraphy (SRS) in 20 cases. Gold standard was histologic or composite (confirmation by another imaging method and follow-up). Results A tumor was found in five subjects: 2 abdominal PGL, 1 pheochromocytoma and 2 PGL of the neck. The sensitivity of 18FDG-PET was 100 %, of SRS was 80 %, of 123I-MIBG was 60 % and of anatomical imaging (association between angio-MR of the neck and TAP-CT and/or TAP-MR) was 100 %. Three false positive lesions were described: 2 with the 18FDG-PET imaging and 1 with the TAP-MR technique. Conclusion 18FDG-PET/CT is an excellent tool for screening SDHx relatives and should be completed by an angio-MR of the neck if suspicion of abnormality. Association of angio-MR of the neck and TAP-MR has the advantage of being a non-irradiating imaging method but with limited access in some countries.
    Medecine Nucleaire 02/2014; · 0.25 Impact Factor
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    ABSTRACT: Insulin-like growth factor 2 (IGF2) overexpression is an important molecular marker of adrenocortical carcinoma (ACC), which is a rare but devastating endocrine cancer. It is not clear whether IGF2 overexpression modifies the biology and growth of this cancer, thus more studies are required before IGF2 can be considered as a major therapeutic target. We compared the phenotypical, clinical, biological, and molecular characteristics of ACC with or without the overexpression of IGF2, to address these issues. We also carried out a similar analysis in an ACC cell line (H295R) in which IGF2 expression was knocked down with si- or shRNA. We found no significant differences in the clinical, biological and molecular (transcriptomic) traits between IGF2-high and IGF2-low ACC. The absence of IGF2 overexpression had little influence on the activation of tyrosine kinase pathways both in tumors and in H295 cells that express low levels of IGF2. In IGF2-low tumors, other growth factors (FGF9, PDGFA) are more expressed than in IGF2-high tumors, suggesting that they play a compensatory role in tumor progression. In addition, IGF2 knock-down in H295R cells substantially impaired growth (>50% inhibition), blocked cells in G1 phase, and promoted apoptosis (>2-fold). Finally, analysis of the 11p15 locus showed a paternal uniparental disomy in both IGF2-high and IGF2-low tumors, but low IGF2 expression could be explained in most IGF2-low ACC by an additional epigenetic modification at the 11p15 locus. Altogether, these observations confirm the active role of IGF2 in adrenocortical tumor growth, but also suggest that other growth promoting pathways may be involved in a subset of ACC with low IGF2 expression, which creates opportunities for the use of other targeted therapies.
    PLoS ONE 01/2014; 9(8):e103744. · 3.53 Impact Factor
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    ABSTRACT: Prophylactic lateral neck dissection (PLND) is generally not performed for papillary thyroid carcinoma (PTC). When performed, occult metastases are found in up to 50 % of patients, although the incidence of occult level II nodes seems low. Our aim was to evaluate frozen section analysis-oriented elective level II PLND in patients with clinically node-negative (cN0) PTC. This retrospective study included patients with cN0 PTC treated with total thyroidectomy and prophylactic bilateral central and lateral neck dissection of ipsilateral levels III and IV. Frozen section analysis of PLND III and IV was performed. If positive, the PLND was extended to level II. We measured the accuracy of frozen section analysis, the incidence of occult level II metastasis, and oncologic outcomes. A total of 295 patients were included. For frozen section analysis, the sensitivity was 71.0 %, specificity 99.6 %, positive predictive value 97.8 %, negative predictive value 92.4 %, overall accuracy 93.2 %. Definitive analysis found lateral node metastases in 63 of the 295 (21 %) patients. Extension to level II was performed in 27 of 46 cases (59 %). Level II contained metastatic nodes in 12 of 27 (44 %) patients. There was no difference in total doses of (131)I administered to patients with or without level II disease. Even when extension of PLND to level II was not performed, no cases of recurrent or persistent disease in level II occurred. Frozen section analysis was highly accurate. The rate of occult metastases in level II was low. Detection of additional metastases in level II did not modify subsequent treatment or the rate of recurrence and is not useful for routine application.
    World Journal of Surgery 11/2013; · 2.23 Impact Factor
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    ABSTRACT: Context:Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. In ACC, no personalized approach has emerged but no extensive molecular screening has been performed to date.Objective:The objective of the study was to evaluate the presence of a large number of potentially targetable molecular events in a large cohort of advanced ACC.Design, Setting, and Participants:We used hot spot gene sequencing (Ion Torrent, 40 patients) and comparative genomic hybridization (CGH; 28 patients; a subset of the entire cohort) in adult stage III-IV ACC samples to screen for mutations and copy number abnormalities of potential interest for therapeutic use in 46 and 130 genes, respectively.Results:At least one copy number alteration or mutation was found in 19 patients (47.5%). The most frequent mutations were detected on TP53, ATM, and CTNNB1 [6 of 40 (15%), 5 of 40 (12.5%), and 4 of 40 (10%), respectively]. The most frequent copy number alterations identified were: amplification of the CDK4 oncogene (5 of 28; 17.9%) and deletion of the CDKN2A (4 of 28; 14.3%) and CDKN2B (3 of 28; 10.7%) tumor suppressor genes. Amplifications of FGFR1, FGF9, or FRS2 were discovered in three subjects (10.7%). Associated alterations were: deletions of CDKN2A, CDKN2B with ATM mutations, and TP53 mutations with CTNNB1 mutations.Conclusions:No simple targetable molecular event emerged. Drugs targeting the cell cycle could be the most relevant new therapeutic approach for patients with advanced ACC. Inhibitors of the fibroblast growth factor receptor pathway could also be a therapeutic option in a subset of patients, whereas other targeted therapies should be considered on a case-by-case basis.
    The Journal of Clinical Endocrinology and Metabolism 08/2013; · 6.31 Impact Factor
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    ABSTRACT: Thyroglobulin (Tg) measurement is a major tool for the follow-up of differentiated thyroid cancer (DTC) patients, however, in patients who do not undergo radioactive iodine (RAI) ablation, normal ultrasensitive Tg levels measured under levothyroxine treatment (usTg/LT4) are not well defined. This single centre retrospective study assessed usTg/LT4 level in 86 consecutive patients treated with total thyroidectomy without RAI ablation for low risk DTC (n=77) or for tumors of uncertain malignant potential (TUMP) (n=9). Results: DTC were classified as pT1, pT2 and pT3 in 75, 1 and 1 case, respectively and pN0, pN1 and pNx in 40, 6 and 31, respectively. Following surgery, 10 patients had Tg antibodies (TgAb). Among those without TgAb, the first usTg/LT4 determination obtained at a mean time of 9 months after surgery was ≤ 0.1 ng/mL in 62% of cases, ≤ 0.3 ng/mL in 82%, ≤ 1 ng/mL in 91% and ≤ 2 ng/mL in 96% of cases. After a median follow up of 2.5 years (range: 0.6-7.2 yr), one patient had persistent disease with an usTg/LT4 at 11 ng/mL and an abnormal neck ultrasonography and two patients had usTg/LT4 level greater than 2 ng/mL (3.9 and 4.9 ng/mL) with a normal neck ultrasonography. Within the first two years following total thyroidectomy without RAI ablation, usTg/LT4 level is ≤ 2 ng/mL in 96% of the cases. After total thyroidectomy, sensitive serum Tg/LT4 level is ≤ 2 ng/mL in most patients and can be used for patient follow-up.
    European Journal of Endocrinology 08/2013; · 3.14 Impact Factor
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    ABSTRACT: Medullary thyroid carcinoma (MTC) is rare in children. MTC is almost always inherited and occurs as part of a multiple endocrine neoplasia type 2A and B, due to germline mutation in the RET proto-oncogene. MTC in the pediatric population is most often diagnosed in the course of a familial genetic investigation. But when the child is the proband, a de novo mutation is most often founded. The main aim is to treat MTC before extrathyroidal extension occurs because when distant metastases are present, it is rarely curable. Treatment is based on total thyroidectomy with cervical lymph node dissection.
    Bulletin du cancer 07/2013; · 0.61 Impact Factor
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    ABSTRACT: Context. Mitotane plasma concentrations ≥ 14 mg/l have been shown to predict tumor response and better survival in patients with advanced adrenocortical cancer (ACC). A correlation between mitotane concentrations and patient outcome has not been demonstrated in an adjuvant setting.Objective. To compare recurrence-free survival (RFS) in patients who reached and maintained mitotane concentrations ≥ 14 mg/l versus patients who did not. Design and setting. Retrospective analysis at 6 referral European centers. Patients. Patients with ACC who were radically resected between 1999 and 2009 and were treated adjuvantly with mitotane targeting concentrations of 14-20 mg/l. Main outcome measures. RFS (primary) and overall survival (secondary). Results. Of the 122 patients included, 63 patients (52%) reached and maintained during a median follow-up of 36 months the target mitotane concentrations [group 1] and 59 patients (48%) did not [group 2]. ACC recurrence was observed in 22 patients of group 1 (35%) and 36 patients in group 2 (61%). In multivariate analysis, the maintenance of target mitotane concentrations was associated with a significantly prolonged RFS (HR of recurrence, 0.418, 0.22-0.79; P=0.007) while the risk of death was not significantly altered (HR, 0.59, 0.26-1.34; P=0.20). Grade 3-4 toxicity was observed in 11 patients (9%) and was managed with temporary mitotane discontinuation. None of the patients discontinued mitotane definitively for toxicity.Conclusions. Mitotane concentrations ≥14 mg/l predict response to adjuvant treatment being associated with a prolonged RFS. A monitored adjuvant mitotane treatment may benefit patients after radical removal of ACC.
    European Journal of Endocrinology 05/2013; · 3.14 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; · 3.14 Impact Factor
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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; · 6.31 Impact Factor
  • Annales d'Endocrinologie. 09/2012; 73(4):253–254.
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    ABSTRACT: Context: Medullary thyroid carcinoma (MTC) is characterized by proto-oncogene RET mutations in almost all hereditary cases as well as in more than 40% of sporadic cases. Recently, a high prevalence of RAS mutations was reported in sporadic MTC, suggesting an alternative genetic event in sporadic MTC tumorigenesis. Objective: This study aimed to extend this observation by screening somatic mutational status of RET, BRAF, and the three RAS proto-oncogenes in a large series of patients with MTC. Materials and Methods: Direct sequencing of RET (exons 8, 10, 11, 13, 14, 15, 16), BRAF (exons 11 and 15), and KRAS, HRAS, and NRAS genes (exons 2, 3, and 4) was performed on DNA prepared from 50 MTC samples, including 30 sporadic cases. Results: Activating RET mutations were detected in the 20 hereditary cases (germline mutations) and in 14 sporadic cases (somatic mutations). Among the 16 sporadic MTC without any RET mutation, eight H-RAS mutations and five K-RAS mutations were found. Interestingly, nine RAS mutations correspond to mutation hot spots in exons 2 and 3, but the other four mutations were detected in exon 4. The RET and RAS mutations were mutually exclusive. No RAS gene mutation was found in hereditary MTC, and no BRAF or NRAS mutation was observed in any of the 50 samples. Conclusions: Our study confirms that RAS mutations are frequent events in sporadic MTC. Moreover, we showed that RAS mutation analysis should not be limited to the classical mutational hot spots of RAS genes and should include analysis of exon 4.
    The Journal of Clinical Endocrinology and Metabolism 08/2012; 97(10):E2031-5. · 6.31 Impact Factor
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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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    ABSTRACT: The Weiss score is the reference method to distinguish between a benign and a malignant adrenocortical tumor (ACT). A program was initiated to improve the reproducibility of the pathologic diagnosis of ACTs in France through the National INCa-COMETE Network. Twelve pathologists from all Reference Centers of the Network analyzed 50 selected ACTs using a web-based virtual microscopy approach in a blind design, allowing to determine the intraobserver and interobserver reproducibilities of the Weiss system. All ACTs were read twice in random order before and after a coaching meeting organized to harmonize and improve analyses and create an online tutorial. The validity of the virtual approach was first established by comparing the 2 consensuses (virtual and microscopic) obtained for each tumor by 3 pathologists who performed the 2 approaches in a blinded manner. For the "dichotomized Weiss score" (separating malignant ≥3 from benign ≤2 tumors) interobserver reproducibility was "substantial" at the first "virtual" reading (κ = 0.70) and increased at the second "virtual" reading (κ = 0.75). In parallel, 7 of the 9 items of the Weiss system showed improvement. The diagnostic accuracy of the observers as a group, using the modal group score approach, showed an improved sensitivity from 86% to 95% for the diagnosis of malignant ACTs. We show the validity of the virtual microscopy approach and that the program improved the practice of the Weiss system reading and therefore the diagnosis of ACT. This tool can now be extended for other research and/or routine purposes in this rare cancer.
    The American journal of surgical pathology 08/2012; 36(8):1194-201. · 4.06 Impact Factor
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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: 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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    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