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1.
Breast Cancer Res Treat ; 207(3): 551-559, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38837087

RESUMO

PURPOSE: While 18F-FDG PET/CT (FDG-PET/CT) is consensual for clinical stage ≥ IIB breast cancers (BC), its benefit for stage I or IIA HER2+ or triple-negative breast cancer (TNBC) patients lacks sufficient evidence. We reported a single-institution, retrospective study evaluating FDG-PET/CT impact on patient management and staging for stage I or IIA HER2+ or Triple-Negative BC. METHODS: Patients who underwent FDG-PET/CT staging before any treatment between January 2015 and December 2020 at Oscar Lambret Center were included. EXCLUSIONS: patients with symptoms or conventional imaging suggestive of metastatic dissemination, or with prior malignancies. Initial stage was determined from mammography, breast ultrasound, breast MRI, and clinical examination. Staging and therapeutic impact based on FDG-PET/CT findings collected, including intra- (modification of dose/site/strategy in a type of management previously indicated) and inter-modality (modification of planned treatment strategy) changes. RESULTS: The cohort included 287 female patients with clinical stage I or IIA, HER2+ , or TNBC. Therapeutic impact observed for 18% of patients (n = 52), with 2% (n = 7) undergoing inter-modality change with omission of planned surgery. The impact on patient management was higher for stage IIA patients (20%, 47/237) than for stage I patients (10%, 5/50). Among stage IIA disease, changes in management were more important for T2N0 patients (22%, 44/205) than for T1N1 patients (9%, 3/32). While not statistically significant, trends suggest usefulness of FDG-PET/CT for T2N0 patients. CONCLUSION: Considering substantial therapeutic implications, our study suggests the usefulness of FDG-PET/CT for patients with stage IIA, HER2-positive, or Triple-Negative BC with tumor size > 2 cm (T2N0).


Assuntos
Fluordesoxiglucose F18 , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Adulto , Idoso , Compostos Radiofarmacêuticos , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo
2.
Pediatr Blood Cancer ; 70(11): e30615, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37574821

RESUMO

PURPOSE: We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131 I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL). METHODS: Patients received 131 I-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of 131 I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31. RESULTS: Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years). CONCLUSION: MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.


Assuntos
Neuroblastoma , Topotecan , Adolescente , Criança , Pré-Escolar , Humanos , Adulto Jovem , 3-Iodobenzilguanidina/efeitos adversos , Bussulfano/uso terapêutico , Doença Crônica , Melfalan , Recidiva Local de Neoplasia/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/radioterapia
3.
Eur J Nucl Med Mol Imaging ; 45(2): 292-305, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28940046

RESUMO

BACKGROUND: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations. RESULTS: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response. CONCLUSIONS: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.


Assuntos
3-Iodobenzilguanidina/metabolismo , Neuroblastoma/diagnóstico , Neuroblastoma/metabolismo , Sociedades Médicas , Adolescente , Transporte Biológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Risco
4.
J Pediatr Hematol Oncol ; 40(6): 426-432, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29642099

RESUMO

High-risk neuroblastoma is characterized by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). The benefits of a tandem high-dose therapy and hematologic stem cell reinfusion (HSCR) have been shown in these patients. Further dose escalation will be limited by toxicity. It is thus important to evaluate the efficacy and tolerability of the addition of new agents such as I-MIBG (131Iode metaiodobenzylguanidine) to be combined with high-dose therapy in the consolidation phase. We report the feasibility of busulfan/melphalan (BuMel) after I-MIBG therapy with HSCR in patients with refractory or relapsed metastatic neuroblastoma. From November 2008 to March 2015, 9 patients received BuMel after I-MIBG therapy and topotecan. The main toxicity was digestive with only 1 patient developing grade 4 sinusoidal obstructive syndrome. Seven patients are alive at a median follow-up of 25 months. Among them, 2 are in ongoing complete remission and 1 in ongoing stable disease. These results suggest that BuMel with HSCR can be administered safely 2 months after I-MIBG therapy associated with topotecan for VHR patients. This strategy will be compared with tandem high-dose chemotherapy (thiotepa and busulfan-melphalan), followed by HSCR in the upcoming SIOPEN VHR Neuroblastoma Protocol.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Neuroblastoma/terapia , 3-Iodobenzilguanidina/administração & dosagem , 3-Iodobenzilguanidina/efeitos adversos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Metástase Neoplásica , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Fatores de Risco , Topotecan/administração & dosagem , Topotecan/efeitos adversos
5.
Support Care Cancer ; 26(3): 751-758, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28920149

RESUMO

PURPOSE: The purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting. METHODS: We have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question "Do you think you obtained a benefit from treatment?" Success of treatment was defined by the combination of these four parameters. RESULTS: Three hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases. CONCLUSION: 153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.


Assuntos
Neoplasias Ósseas/secundário , Dor/tratamento farmacológico , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos/farmacologia , Estudos Retrospectivos , Samário/farmacologia , Resultado do Tratamento
6.
Eur J Nucl Med Mol Imaging ; 37(7): 1270-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20306032

RESUMO

PURPOSE: The aim of this retrospective study was to evaluate the contribution of (18)F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. METHODS: A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. RESULTS: The final diagnosis was established pathologically (n = 25) or by median clinical follow-up for 48 months after the PET (n = 15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (> 3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with < or = 1 focus for which the median survival was not attained (p = 0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (> 3 foci) was the most significant factor (p < 0.03) for death from cervical cancer. CONCLUSION: FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome.


Assuntos
Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/terapia
7.
Presse Med ; 48(10): 1101-1111, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31676215

RESUMO

Breast cancer imaging is always improving for the last 20 years in spite of digitalization and computer development. News tools in mammography (Digital Breast Tomosynthesis, Contrast enhanced mammography), sonography (elastography, Automated echography), MRI (Diffusion, abbreviated MRI) and Nuclear medicine has the great potential to be the future of breats imaging. But true revolution will be to use the huge volume of "hidden" imaging data, by Intelligence Artificial process or Biological progress (in genomics, proteiomics) to purpose to our patient a personalized imaging.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Angiografia/métodos , Inteligência Artificial/tendências , Neoplasias da Mama/irrigação sanguínea , Meios de Contraste , Diagnóstico por Imagem/tendências , Técnicas de Imagem por Elasticidade/métodos , Feminino , Genômica , Humanos , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Mamografia/tendências , Tomografia por Emissão de Pósitrons/métodos , Proteômica , Linfonodo Sentinela/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Ultrassonografia Mamária/métodos
8.
J Nucl Med ; 59(3): 502-508, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28887399

RESUMO

A semiquantitative 123I-metaiodobenzylguanidine (123I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children's Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. Methods: A retrospective analysis of 123I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited 123I-MIBG-avid, International Neuroblastoma Staging System stage 4 neuroblastoma. 123I-MIBG scans were evaluated at 2 time points, diagnosis (n = 345) and postinduction (n = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0-3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. Results: The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% [CS ≤ 12] vs. 21.4% ± 3.6% [CS > 12], P < 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% [CS ≤ 2] vs. 16.4% ± 4.2% [CS > 2], P < 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and MYCN gene copy number. Conclusion: The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.


Assuntos
Neuroblastoma/diagnóstico , Relatório de Pesquisa , Sociedades Médicas , 3-Iodobenzilguanidina , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neuroblastoma/diagnóstico por imagem , Prognóstico , Risco
9.
J Clin Endocrinol Metab ; 92(12): 4590-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17878252

RESUMO

CONTEXT: Patients with progressive medullary thyroid carcinoma (MTC) undergo multiple imaging procedures for diagnosis of relapse and staging. OBJECTIVE: Our objective was to assess the sensitivity and prognostic value of 18F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and the imaging sensitivity of pretargeted iodine-131-radioimmunotherapy (RIT) in patients with progressive MTC. DESIGN/SETTING/PATIENTS: We performed a prospective multicenter study in high-risk patients with rapidly progressing MTC enrolled in a phase-II pretargeted RIT study, as documented by short serum calcitonin (Ct) or carcinoembryonic antigen (CEA) doubling time (DT). INTERVENTIONS/MAIN OUTCOME MEASURES: Patients underwent neck-thoracic-abdominal CT, spine and pelvic magnetic resonance imaging, whole-body post-RIT immunoscintigraphy (IS) with iodine-131, and whole-body 18F-FDG-PET/CT imaging. Imaging sensitivity and the correlation between FDG uptake and biomarkers DT were evaluated. RESULTS: A total of 33 patients with mean CEA and Ct DTs of 1.90 yr (range 0.21-8.50) and 1.52 yr (range 0.09-6.01), respectively, were evaluated. Sensitivity of FDG-PET/CT was 83% for neck, 85% for mediastinal, 75% for lung, 60% for liver, and 67% for bone metastases; overall sensitivity was 76%. Median standardized uptake value (SUVmax) was 5.23 (2.06-13.90). SUVmax correlated significantly with Ct DT (P = 0.011) and minimal DT (minimal value between CEA DT and Ct DT) (P = 0.027). Overall sensitivity of post-RIT IS, CT, and bone magnetic resonance imaging were 94, 74, and 85%, respectively. CONCLUSIONS: These results demonstrate the value of FDG-PET/CT for staging of patients with progressive MTC, especially in the neck and mediastinum, with possible prognostication by SUV quantification. Post-RIT IS was the most sensitive of the imaging modalities studied prospectively.


Assuntos
Antígeno Carcinoembrionário/imunologia , Carcinoma Medular/diagnóstico por imagem , Carcinoma Medular/imunologia , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Radioisótopos do Iodo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Radioimunodetecção , Radioimunoterapia , Tomografia Computadorizada de Emissão
10.
Radiat Prot Dosimetry ; 173(4): 395-404, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26940442

RESUMO

The objective of the present multicentric phase II study (MIITOP) was to determine the response rate, survival and toxicity of tandem infusions of 131I-meta-iodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory neuroblastoma. High-dose 131I-mIBG therapy programme requires a deal of planning, availability of hospital resources and the commitment of individuals with training and expertise in multiple disciplines. Here in the present study, procedures and the results of patient's dosimetry, as well as family and worker's exposures, were reported for the patients treated in Lille. A total of 15 children were treated with 131I-mIBG between 2009 and 2011 according to the MIITOP protocol. High activity of 131I-mIBG (444 MBq kg-1) was administered on Day 0. In vivo dosimetry was used to calculate a second activity, to be given on Day 21, to obtain a total whole body absorbed dose of 4 Gy. Family and worker's exposures were performed too. The injected activity by treatment was from 703 to 11470 MBq. Total whole body absorbed dose by patient ranged from 2.74 to 5.2 Gy. Concerning relatives, whole body exposure ranged from 0.018 to 2.8 mSv. The mean whole body exposure of the radiopharmacist was 4.4 nSv MBq-1, and the mean exposure of fingers ranged from 0.18 to 0.24 µSv MBq-1 according to each finger. The mean whole body exposure was 33.6 and 20.2 µSv d-1 per person, for night nurses and day nurses, respectively. Exposure of doctors was less than 5 µSv d-1. Under strict radiation protection precautions, this study shows the feasibility of high-activity 131I-mIBG therapy in France.


Assuntos
3-Iodobenzilguanidina/uso terapêutico , Cuidadores , Radioisótopos do Iodo/uso terapêutico , Neuroblastoma/radioterapia , Exposição à Radiação , Adulto , Criança , Feminino , França , Humanos , Masculino , Recidiva Local de Neoplasia , Neuroblastoma/tratamento farmacológico , Radiometria , Inibidores da Topoisomerase I/uso terapêutico , Topotecan/uso terapêutico
11.
Gynecol Oncol Rep ; 17: 56-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27355004

RESUMO

Malignant struma ovarii (SO) is a rare tumor, and as a consequence, treatments and follow-up procedures are not clearly established. Presented in this study are two cases of suspicious ovarian masses, resected and corresponding to malignant SO on histopathology. Similar to thyroid cancer, we proposed complementary radioiodine therapy ((131)I) after total thyroidectomy (no malignancy was observed at this level in our two patients). Patients underwent treatment with 3.7 GBq (131)I followed by post-therapy whole-body scintigraphy, which can detect residual disease or occult metastases. Thyroid remnant ablation increases the sensitivity and specificity of follow-up testing using serum thyroglobulin levels as a tumor marker. Our two patients remained disease-free for 3 and 5 years, respectively, after treatment.

12.
Gastroenterol Clin Biol ; 29(8-9): 935-8, 2005.
Artigo em Francês | MEDLINE | ID: mdl-16294166

RESUMO

We report different treatment options (currently used and on trial) for a patient with a gastrointestinal carcinoid tumor and metastases in the liver, and discuss the advantages of using internal radiotherapy with 131I-MIBG rather than other treatments. According to the literature, this pathology has a poor prognosis, and considering the significant efficacy of this radiopharmaceutical treatment on symptoms, tumor reduction, and biochemical parameters, it seems to be under used. There are currently no standard treatment options. We present a management strategy for gastrointestinal carcinoid tumors with 131I-MIBG.


Assuntos
3-Iodobenzilguanidina/uso terapêutico , Tumor Carcinoide/radioterapia , Neoplasias Intestinais/radioterapia , Intestino Delgado/patologia , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Tumor Carcinoide/patologia , Feminino , Humanos , Neoplasias Intestinais/patologia , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade
13.
J Nucl Med ; 53(8): 1185-92, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22743249

RESUMO

UNLABELLED: The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. METHODS: From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m(2)), followed by (131)I-di-DTPA-indium bivalent hapten (1.8 GBq/m(2)) 4-6 d later. RESULTS: The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63-17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P = 0.004). CONCLUSION: pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/imunologia , Progressão da Doença , Radioimunoterapia/métodos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Neuroendócrino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Ácido Pentético/imunologia , Radioimunoterapia/efeitos adversos , Análise de Sobrevida , Neoplasias da Glândula Tireoide/metabolismo , Resultado do Tratamento , Adulto Jovem
14.
Cancer ; 116(4 Suppl): 1118-25, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20127952

RESUMO

Medullary thyroid cancer (MTC) patients with localized residual disease and/or distant metastases may survive for several years or rapidly progress and die of their disease. Thus, highly reliable prognostic factors are needed for an early distinction between high-risk patients who need to be treated and low-risk patients who warrant a watch-and-wait approach. Calcitonin doubling time is an independent predictor of survival, with a high predictive value in a population of patients who have not normalized their calcitonin, even after repeated surgery. Several imaging methods should be proposed for patients with abnormal residual calcitonin levels persisting after complete surgery: ultrasonography and computed tomography (CT) for neck exploration, and CT for chest, abdomen, and pelvis. Magnetic resonance imaging (MRI) appears to have an advantage over CT for the detection of liver metastases from endocrine tumors. Moreover, MRI appears to be a sensitive imaging technique for detecting the spread of MTC to bone/bone marrow. 2-Fluoro-2-deoxy-D-glucose positron emission tomography/CT could be used for staging patients with progressive MTC, with possible prognostication by standard uptake value quantification. For systemic treatment of patients with rapidly progressing metastatic MTC, chemotherapy is not considered a valid therapeutic option. It is too early to evaluate the potential effectiveness of multikinase inhibitors, although interesting results of phase 2 studies have shown a transient stabilization in 30% to 50% of patients. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit when compared with a historical untreated control group.


Assuntos
Carcinoma Medular/radioterapia , Radioimunoterapia/métodos , Neoplasias da Glândula Tireoide/radioterapia , Carcinoma Medular/diagnóstico , Carcinoma Medular/mortalidade , Carcinoma Medular/patologia , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/secundário , Metástase Linfática , Risco , Análise de Sobrevida , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
15.
Cancer ; 116(4 Suppl): 1053-8, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20127950

RESUMO

BACKGROUND: Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells. METHODS: Groups of 4-6 nude mice were treated with 5 microg/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of (131)I-F6. For combined therapy, bevacizumab was given at Day 0 followed by (131)I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months. RESULTS: Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 +/- 1% and 15 +/- 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 +/- 0.24 and 0.15 +/- 0.07%, respectively, and time to progression of 35 +/- 5 and 56 +/- 11 days, respectively. CONCLUSIONS: Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Carcinoma Medular/terapia , Radioimunoterapia , Neoplasias da Glândula Tireoide/terapia , Animais , Anticorpos Monoclonais Humanizados , Bevacizumab , Antígeno Carcinoembrionário/imunologia , Linhagem Celular Tumoral , Terapia Combinada , Humanos , Camundongos , Camundongos Nus , Radioimunoterapia/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Eur J Nucl Med Mol Imaging ; 35(3): 637-43, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17960377

RESUMO

PURPOSE: A pinhole collimator is routinely used to increase the resolution of scintigraphy. This prospective study was conducted to determine the interest of (99m)Tc-MIBI pinhole single-photon emission computed tomography (SPECT) for the preoperative localisation of parathyroid lesions in primary hyperparathyroidism. METHODS: All patients underwent a neck ultrasonography (US), (99m)TcO4- and (99m)Tc-MIBI planar images and two consecutive SPECT with a parallel (C-SPECT) and a pinhole collimator (P-SPECT). P-SPECT was performed with a tilted detector equipped with a pinhole collimator and reconstructed with a dedicated OSEM algorithm. A diagnostic confidence score (CS) was assigned to each procedure considering intensity and extra-thyroidal location of suspected lesions: 0 = negative, 1 = doubtful, 2 = moderately positive, 3 = positive. The results of these preoperative localisation studies were compared with surgical, pathological and 6-month biological findings. RESULTS: Fifty-one patients cured after surgery were included. Surgery revealed 55 lesions (median weight 0.5 g, 11 in ectopy). Sensitivities of US, planar imaging, C-SPECT and P-SPECT were, respectively, 51, 76, 82 and 87%. Nine glands were only detected by tomography and five glands only by P-SPECT. 99mTc-MIBI/99mTcO4- planar scans and P-SPECT were complementary and, when combined together, showed the highest sensitivity (93%). Compared with planar imaging and C-SPECT, P-SPECT increased CS for 42 and 53% of lesions, respectively, and contributed to markedly reduce the number of uncertain results. CONCLUSIONS: A combination of planar 99mTc-MIBI/99mTcO4- scintigraphy and P-SPECT appears to be a highly accurate preoperative imaging procedure in primary hyperparathyroidism.


Assuntos
Hiperparatireoidismo/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
17.
Ann Hematol ; 85(11): 759-67, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16871391

RESUMO

Early therapy response assessment with metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma and, thus, can guide first-line therapy. Forty-eight patients with aggressive lymphoma [24 Hodgkin's disease (HD); 24 non-Hodgkin's lymphoma (NHL)] underwent fluoro-deoxyglucose positron emission tomography (FDG-PET) before chemotherapy (PET1) and at mid-treatment (PET2). Therapeutic response was evaluated using conventional methods at mid-treatment. PET2 results were related to event-free survival (EFS) and overall survival (OS) using Kaplan-Meier analyses. PET1 was positive in all patients. PET2 was negative in 38 patients (18 NHL-20 HD) and positive in 10 (6 NHL-4 HD). Of the PET-negative patients, 61 and 65% achieved complete remission, and only 50 and 25% of PET-positive patients, respectively, for NHL and HD, achieved complete remission. Significant associations were found between PET2 and EFS (p = 0.0006) and OS (p = 0.04) for NHL, and EFS (p < 0.0001) for HD (but not for OS, because no HD patient died). FDG-PET at mid-treatment can predict the outcome of patients with aggressive lymphoma and should be a useful tool to modify an ineffective therapy.


Assuntos
Doença de Hodgkin/diagnóstico , Linfoma não Hodgkin/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes , Tomografia Computadorizada de Emissão/métodos , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida
18.
J Heart Lung Transplant ; 25(9): 1077-83, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16962469

RESUMO

BACKGROUND: The purpose of this study was to assess the rate of gastric emptying (GE) in cystic fibrosis patients scheduled for lung transplantation. METHODS: Thirty patients (20 males, 10 females, 22.6 +/- 6.4 years) were evaluated by GE scintigraphy before (1.58 +/- 1.11 years) and early after (5.8 +/- 2.6 weeks) heart-lung transplantation (n = 13) or lung transplantation (n = 17). Solid retention rates at 2 hours (RR2) and 3 hours (RR3) and half-emptying times (T50) of solids and liquids obtained before transplantation were compared with those after transplantation. Data were also compared with those obtained from a control group of 53 healthy volunteers. RESULTS: Before surgery, 20 patients (67%) showed a delayed GE (T50 of solids: patients 160.86 +/- 59.21 minutes vs controls 75.43 +/- 15.13 minutes, p < 0.0001), and 4 of them also had a delayed T50 of liquids. After surgery, the T50 of solids was considered unreliable (too much stasis) in 24 patients. Thus, analyses were done on the basis of solid retention rates. Twenty-nine patients (97%) showed very delayed GE compared with controls (p < 0.0001), 20 of whom also had a delayed T50 of liquids. RR2 and RR3 were significantly higher after surgery than before (RR2 = 86 +/- 17% and RR3 = 77 +/- 22% vs 50 +/- 24% and 27 +/- 24% after and before surgery, respectively, p < 0.0001). However, there was no correlation between pre- and post-transplantation scintigraphy results. CONCLUSIONS: Delayed GE of solids was a frequent abnormality in patients with end-stage cystic fibrosis, with a dramatic delay after surgery in almost all patients. These results emphasize the need for early management of such patients by dietary manipulation or prokinetic medications.


Assuntos
Fibrose Cística/fisiopatologia , Fibrose Cística/cirurgia , Esvaziamento Gástrico/fisiologia , Gastroparesia/diagnóstico por imagem , Transplante de Pulmão/fisiologia , Adolescente , Adulto , Fibrose Cística/complicações , Dietoterapia , Feminino , Gastroparesia/etiologia , Gastroparesia/terapia , Transplante de Coração-Pulmão/fisiologia , Humanos , Masculino , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Cintilografia/métodos
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