MARCO AURELIO VAMONDES KULCSAR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/28 - Laboratório de Cirurgia Vascular e da Cabeça e Pescoço, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/28 - Laboratório de Cirurgia Vascular e da Cabeça e Pescoço, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Long term toxicities after cisplatin-based concurrent chemoradiation in head & neck squamous cell carcinoma (HNSCC) disease-free patients: A cross-sectional study(2015) RIVELLI, T. G.; SIMAO, E. F.; MAK, M. P.; MARTINS, R. Eiras; TAKAHASHI, T. K.; MARINI, A. M.; ROITBERG, F. S. R.; MESQUITA, C.; KULCSAR, M. A. V.; CASTRO JR., G.- Survival predictors in patients with head and neck cancer treated with surgical resection(2017) FRANCO, R. C. D. O.; MATOS, L. L. De; CASTRO JUNIOR, G. De; KULCSAR, M. A. V.; MARTA, G. N.
- Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis(2016) CASTRONEVES, Luciana Audi de; NEGRAO, Marcelo Vailati; FREITAS, Ricardo Miguel Costa de; PAPADIA, Carla; LIMA JR., Jose Viana; FUKUSHIMA, Julia T.; SIMAO, Eduardo Furquim; KULCSAR, Marco Aurelio Vamondes; TAVARES, Marcos Roberto; JORGE, Alexander Augusto de Lima; CASTRO, Gilberto de; HOFF, Paulo Marcelo; HOFF, Ana OliveiraBackground: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. Methods: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. Results: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. Conclusions: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
- Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers(2020) MAK, Milena Perez; PASINI, Fatima Solange; DIAO, Lixia; GARCIA, Fabyane O. Teixeira; TAKAHASHI, Tiago Kenji; NAKAZOTO, Denyei; MARTINS, Renata Eiras; ALMEIDA, Cristiane Maria; KULCSAR, Marco Aurelio Vamondes; LAMOUNIER, Valdelania Aparecida; NUNES, Emily Montosa; SOUZA, Isabela Cristina de; GARCIA, Marcio Ricardo Taveira; AMADIO, Alex Vieira; SIQUEIRA, Sheila Aparecida C.; SNITCOVSKY, Igor Moyses Longo; SICHERO, Laura; WANG, Jing; JR, Gilberto de CastroBackground: Cisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers. Methods: This phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated. Results: Given significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival. Conclusions: VPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122).
- Phase II trial of valproic acid combined with cisplatin-based chemoradiation in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) patients (pts).(2017) MAK, Milena Perez; PASINI, Fatima Solange; DIAO, Lixia; GARCIA, Fabyane Oliveira Teixeira; TAKAHASHI, Tiago Kenji; AMADIO, Alex Vitorio; SIQUEIRA, Sheila Aparecida Coelho; SICHERO, Laura; SNITCOVSKY, Igor M. L.; KULCSAR, Marco Aurelio Vamondes; WANG, Jing; CASTRO, Gilberto
- Influence of time between surgery and postoperative radiation therapy and total treatment time in locoregional control of patients with head and neck cancer: a single center experience(2020) FRANCO, Rejane; MATOS, Leandro Luongo de; KULCSAR, Marco Aurelio Vamondes; CASTRO-JUNIOR, Gilberto de; MARTA, Gustavo NaderOBJECTIVE: This study aimed to evaluate the effect of the delay to initiate postoperative radiation therapy (RT) on locoregional control to head and neck squamous cell carcinoma patients. METHODS: Retrospective cohort study that included patients submitted to surgery followed by adjuvant RT (with/without chemotherapy). The time interval between surgery and RT was dichotomized by the receiver operating characteristics curve method at 92 days. Other possible sources of heterogeneity with potential impact on locoregional control were explored by regressive analysis. RESULTS: A total of 168 patients were evaluated. The median time for locoregional recurrence (LRR) was 29.7 months. The relapse-free survival rates were 66.4% and 75.4% for patients who initiated RT more than and within 92 postoperative days (p=0.377), respectively. Doses lower than 60Gy were associated with worse rates of locoregional control (HR=6.523; 95%CI:2.266-18.777, p=0.001). Patients whose total treatment time (TTT) was longer than 150 days had LRR rate of 41.8%; no patient with TTT inferior to 150 days had relapses (p=0.001). CONCLUSIONS: The interval between surgery and RT did not show influence on locoregional control rates. However, doses <60Gy and the total treatment time >150 days were associated with lower locoregional control rates.
- Cachexia in head and neck squamous cell carcinoma (HNSCC) patients (pts) after cisplatin-based chemoradiation (CRT): A cross-sectional study.(2019) CASTRO, Gilberto; NEVES, Willian das; RIVELLI, Thomas Giollo; SIMAO, Eduardo Furquim; MARTINS, Renata Eiras; KULCSAR, Marco Aurelio Vamondes
- 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.
conferenceObject Influence of time between surgery and postoperative radiation therapy in head and neck cancer(2020) FRANCO, R.; LEANDRO, D. M.; AURELIO, K. Marco; CASTRO JUNIOR, G. De; MARTA, G.