ANA AMELIA FIALHO DE OLIVEIRA HOFF
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Comparison of Ga-68 PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases(2018) CASTRONEVES, Luciana Audi; COURA FILHO, George; FREITAS, Ricardo Miguel Costa de; SALLES, Raphael; MOYSES, Raquel Ajub; LOPEZ, Rossana Veronica Mendoza; PEREIRA, Maria Adelaide Albergaria; TAVARES, Marcos Roberto; JORGE, Alexander Augusto de Lima; BUCHPIGUEL, Carlos Alberto; HOFF, Ana OliveiraContext: Persistent disease after surgery is common in medullary thyroid cancer (MTC), requiring lifelong radiological surveillance. Staging workup includes imaging of neck, chest, abdomen, and bones. A study integrating all sites would be ideal. Despite the established use of gallium-68 (Ga-68) positron emission tomography (PET)/CT with somatostatin analogues in most neuroendocrine tumors, its efficacy is controversial in MTC. Objective: Evaluate the efficacy of Ga-68 PET/CT in detecting MTC lesions and evaluate tumor expression of somatostatin receptors (SSTRs) associated with Ga-68 PET/CT findings. Methods: Prospective study evaluating 30 patients with MTC [group 1 (n = 16), biochemical disease; group 2 (n = 14), metastatic disease]. Patients underwent Ga-68 PET/CT, bone scan, CT and ultrasound of the neck, CT of the chest, CT/MRI of the abdomen, and MRI of the spine. Ga-68 PET/CT findings were analyzed by disease site as positive or negative and as concordant or discordant with conventional studies. Sensitivity and specificity were calculated using pathological or cytological analysis or unequivocal identification by standard imaging studies. Immunohistochemical analysis of SSTRs was compared with Ga-68 PET/CT findings. Results: In both groups, Ga-68 PET/CT was inferior to currently used imaging studies except for bone scan. In group 2, Ga-68 PET/CT sensitivities were 56%, 57%, and 9% for detecting neck lymph nodes, lung metastases, and liver metastases, respectively, and 100% for bone metastases, superior to the bone scan (44%). Expression of SSTRs, observed in 44% of tumors, was not associated with Ga-68-DOTATATE uptake. Conclusions: Ga-68 PET/CT does not provide optimal whole-body imaging as a single procedure in patients with MTC. However, it is highly sensitive in detecting bone lesions and could be a substitute for a bone scan and MRI.
- Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma(2018) DANILOVIC, Debora Lucia Seguro; MELLO, Evandro Sobroza de; FRAZZATO, Eliana Salgado Turri; WAKAMATSU, Alda; JORGE, Alexander Augusto de Lima; HOFF, Ana Oliveira; MARUI, SuemiBackgroundNuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. MethodsCoding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. ResultsAlthough no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. ConclusionWe identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.
- Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on F-18-Fluoride PET/CT than on Ga-68-Dotatate PET/CT(2018) DUARTE, Paulo Schiavom; CASTRONEVES, Luciana Audi de; SADO, Heitor Naoki; SAPIENZA, Marcelo Tatit; HOFF, Ana Amelia Fialho de Oliveira; BUCHPIGUEL, Carlos AlbertoHerein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with F-18-fluoride (F-18-NaF) and Ga-68-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring. We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on F-18-NaF PET/CT than on Ga-68-dotatate PET/CT. This case illustrates that the F-18-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.
- Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer(2018) DANILOVIC, Debora L. S.; CASTRO JR., Gilberto; ROITBERG, Felipe S. R.; VANDERLEI, Felipe A. B.; BONANI, Fernanda A.; FREITAS, Ricardo M. C.; COURA-FILHO, George B.; CAMARGO, Rosalinda Y.; KULCSAR, Marco A.; MARUI, Suemi; HOFF, Ana O.Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC.
- Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden Two case reports(2018) MOTA, Jose Mauricio; SOUSA, Luana Guimaraes; BRAGHIROLI, Maria Ignez; SIQUEIRA, Luiz Tenorio; BEZERRA NETO, Joao Evangelista; CHAPCHAP, Paulo; HOFF, Ana A. de Oliveira; HOFF, Paulo M.Rationale: In the setting of metastatic or locally advanced adrenocortical carcinoma, a limited number of therapies are available and their efficacy is generally below modest. The backbone of treatment remains surgery, even for metastatic disease, whenever it is possible, and mitotane. Chemotherapy can be used with limited results. A small subset of patients with adrenocortical carcinoma may have high mutational burden and harbor mutations in mismatch-repair genes. Patientconcerns: We report a 40-year old and a 28-year-old female patients with metastatic adrenocortical carcinoma refractory to multiple treatments. Diagnosis: Next-generation sequencing detected high mutational burden (>10mutations/megabase) in both patients, one of them with MSH2 mutation. Interventions: They were treated with pembrolizumab (100 to 200mg every 3 weeks). Outcomes: The patient harboring a MSH2 mutation experienced a long-term complete response after pembrolizumab, while the patient with high mutational burden and absence of mismatch repair deficiency did not have any response. Lessons: To the best of our knowledge, this is the first report in the literature of a durable complete response after pembrolizumab in a patient with metastatic adrenocortical carcinoma. Differences in therapy sequencing, possibly abscopal effect related to multiple previous radiotherapy exposition, predictive values of high mutational burden and mutations in mismatch-repair genes are discussed.
- Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors(2018) KRAUSS, Tobias; FERRARA, Alfonso Massimiliano; LINKS, Thera P.; WELLNER, Ulrich; BANCOSS, Irina; KVACHENYUK, Andrey; HERAS, Karim Villar Gomez de las; YUKINA, Marina Y.; PETROV, Roman; BULLIVANT, Garrett; DUECKER, Laura von; JADHAV, Swati; PLOECKINGER, Ursula; WELIN, Staffan; SCHALIN-JANTTI, Camilla; GIMM, Oliver; PFEIFER, Marija; NGEOW, Joanne; HASSE-LAZAR, Kornelia; SANSO, Gabriela; QI, Xiaoping; UGURLU, M. Umit; DIAZ, Rene E.; WOHLLK, Nelson; PECZKOWSKA, Mariola; ABERLE, Jens; JR, Delmar M. Lourenco; PEREIRA, Maria A. A.; V, Maria C. B. Fragoso; HOFF, Ana O.; ALMEIDA, Madson Q.; VIOLANTE, Alice H. D.; OUIDUTE, Ana R. P.; ZHANG, Zhewei; RECASENS, Monica; DIAZ, Luis Robles; KUNAVISARUT, Tada; WANNACHALEE, Taweesak; SIRINVARAVONG, Sirinart; JONASCH, Eric; GROZINSKY-GLASBERG, Simona; FRAENKEL, Merav; BELTSEVICH, Dmitry; I, Viacheslav Egorov; BAUSCH, Dirk; SCHOTT, Matthias; TILING, Nikolaus; PENNELLI, Gianmaria; ZSCHIEDRICH, Stefan; DAERR, Roland; RUF, Juri; DENECKE, Timm; LINK, Karl-Heinrich; ZOVATO, Stefania; DOBSCHUETZ, Ernst von; YAREMCHUK, Svetlana; AMTHAUER, Holger; MAKAY, Ozer; PATOCS, Attila; WALZ, Martin K.; HUBER, Tobias B.; SEUFERT, Jochen; HELLMAN, Per; EKATERINA, Raymond H.; KUCHINSKAYA, Ekaterina; SCHIAVI, Francesca; MALINOC, Angelica; REISCH, Nicole; JARZAB, Barbara; BARONTINI, Marta; JANUSZEWICZ, Andrzej; SHAH, Nalini; YOUNG JR., William F.; OPOCHER, Giuseppe; ENG, Charis; NEUMANN, Hartmut P. H.; BAUSCH, BirkePancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were >= 2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off >= 2.8 cm, 44% and 91% for TVDT cut-off of <= 24 months). In 117 of 273 patients, PanNETs > 1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs < 2.8 cm vs >= 2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.