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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial(2021) BROSE, Marcia S.; ROBINSON, Bruce; I, Steven Sherman; KRAJEWSKA, Jolanta; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; HERNANDO, Jorge; FAORO, Leonardo; BANERJEE, Kamalika; OLIVER, Jennifer W.; KEAM, Bhumsuk; CAPDEVILA, JaumeBackground Patients with radioiodine-refractory differentiated thyroid cancer (DTC) previously treated with vascular endothelial growth factor receptor (VEGFR)-targeted therapy have aggressive disease and no available standard of care. The aim of this study was to evaluate the tyrosine kinase inhibitor cabozantinib in this patient population. Methods In this global, randomised, double-blind, placebo-controlled, phase 3 trial, patients aged 16 years and older with radioiodine-refractory DTC (papillary or follicular and their variants) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to oral cabozantinib (60 mg once daily) or matching placebo, stratified by previous lenvatinib treatment and age. The randomisation scheme used stratified permuted blocks of block size six and an interactive voice-web response system; both patients and investigators were masked to study treatment. Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors. Patients receiving placebo could cross over to open-label cabozantinib on disease progression confirmed by blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (confirmed response per Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population) and progression-free survival (time to earlier of disease progression per RECIST version 1.1 or death) in all patients (intention-to-treat [ITT] population), both assessed by BIRC. This report presents the primary objective response rate analysis and a concurrent preplanned interim progression-free survival analysis. The study is registered with ClinicalTrials.gov, NCT03690388, and is no longer enrolling patients. Findings Between Feb 27, 2019, and Aug 18, 2020, 227 patients were assessed for eligibility, of whom 187 were enrolled from 164 clinics in 25 countries and randomly assigned to cabozantinib (n=125) or placebo (n=62). At data cutoff (Aug 19, 2020) for the primary objective response rate and interim progression-free survival analyses, median followup was 6middot2 months (IQR 3middot4-9middot2) for the ITT population and 8middot9 months (7middot1-10middot5) for the OITT population. An objective response in the OITT population was achieved in ten (15%; 99% CI 5middot8-29middot3) of 67 patients in the cabozantinib group versus 0 (0%; 0-14middot8) of 33 in the placebo (p=0middot028) but did not meet the prespecified significance level (alpha=0middot01). At interim analysis, the primary endpoint of progression-free survival was met in the ITT population; cabozantinib showed significant improvement in progression-free survival over placebo: median not reached (96% CI 5middot7-not estimable [NE]) versus 1middot9 months (1middot8-3middot6); hazard ratio 0middot22 (96% CI 0middot13-0middot36; p<0middot0001). Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo, the most frequent of which were palmar-plantar erythrodysaesthesia (13 [10%] vs 0), hypertension (11 [9%] vs 2 [3%]), and fatigue (ten [8%] vs 0). Serious treatment-related adverse events occurred in 20 (16%) of 125 patients in the cabozantinib group and one (2%) of 62 in the placebo group. There were no treatment-related deaths. Interpretation Our results show that cabozantinib significantly prolongs progression-free survival and might provide a new treatment option for patients with radioiodine-refractory DTC who have no available standard of care.
- Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas(2021) PETENUCI, Janaina; GUIMARAES, Augusto G.; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; AFONSO, Ana Caroline F.; PEREIRA, Maria Adelaide A.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SOARES, Silvia C.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose L.; I, Roberto Lopes; DENES, Francisco T.; HOFF, Ana O.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and Methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.
- Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Results from the phase 3 COSMIC-311 trial.(2021) BROSE, Marcia S.; ROBINSON, Bruce; SHERMAN, Steven I.; JARZAB, Barbara; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; FAORO, Leonardo; BANERJEE, Kamalika; OLIVER, Jennifer; KEAM, Bhumsuk; CAPDEVILA, Jaume
- Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma(2021) TOYOSHIMA, Marcos Tadashi Kakitani; DOMINGUES, Regina Barros; SOARES, Ibere Cauduro; DANILOVIC, Debora Lucia Seguro; AMORIM, Larissa Costa; CAVALCANTE, Edla R. C.; ANTONACIO, Fernanda F.; ROITBERG, Felipe Santa Rosa; HOFF, Ana OliveiraCollision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient ' s death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.
- Valuable insights from real-life experiences of advanced thyroid cancer treatment with sorafenib in Latin America(2021) FARIAS, Evelin C.; HOFF, Ana Oliveira
- Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Updated results from the phase III COSMIC-311 trial and prespecified subgroup analyses by prior therapy(2021) CAPDEVILA, J.; ROBINSON, B.; SHERMAN, S. I.; JARZAB, B.; LIN, C-C.; VAISMAN, F.; HOFF, A. O.; HITRE, E.; BOWLES, D. W.; SEN, S.; PATEL, P.; OLIVER, J.; KEAM, B.; BROSE, M. S.
- SDHB large deletions are associated with absence of MIBG uptake in metastatic lesions of malignant paragangliomas(2021) PETENUCI, Janaina; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; GUIMARAES, Augusto G.; AFONSO, Ana Caroline F.; MOTA, Flavia T.; MAGALHAES, Aurea Luiza F.; COURA-FILHO, George B.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; MONTENEGRO, Fabio L. M.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose Luis; FERRARI, Marcela S. S.; BEZERRA NETO, Joao Evangelista; PEREIRA, Maria Adelaide A.; LATRONICO, Ana Claudia; FRAGOSO, Maria Candida B. V.; MENDONCA, Berenice B.; HOFF, Ana O.; ALMEIDA, Madson Q.
- Choosing Wisely for Thyroid Conditions: Recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism(2021) DORA, Jose Miguel; BISCOLLA, Rosa Paula Mello; CALDAS, Gustavo; CERUTTI, Janete; GRAF, Hans; HOFF, Ana O.; MAZETO, Glaucia M. F. S.; MAGALHAES, Patricia Kunzle Ribeiro; MESA JUNIOR, Cleo Otaviano; SCHEFFEL, Rafael Selbach; TEIXEIRA, Patricia de Fatima dos Santos; VAISMAN, Fernanda; VILLAGELIN, Danilo; MAIA, Ana LuizaObjective: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. Materials and methods: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. Results: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. Conclusion: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology.This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.
- Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer(2021) TAHARA, Makoto; KIYOTA, Naomi; HOFF, Ana O.; BADIU, Corin; OWONIKOKO, Taofeek K.; DUTCUS, Corina E.; SUZUKI, Takuya; REN, Min; WIRTH, Lori J.Background: Lung metastases may worsen overall survival (OS) in patients with radioiodine- refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). Patients and methods: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to openlabel lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. Results: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions >= 1.0 cm (n = 199), >= 1.5 cm (n = 150), >= 2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57-1.01; P = 0.0549). Median OS for lung metastases of >= 1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47 -0.85; PZ0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of >= 1.0 cm, >= 1.5 cm, >= 2.0 cm and <2.0 cm; median OS was shorter in the >= 2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1-49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of >= 1.0 cm after adjustment for baseline characteristics. Conclusions: Lenvatinib treatment resulted in longer OS in patients with lung metastases of >= 1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of >= 1.0 cm. (C) 2021 The Authors.