FELIPPE LAZAR NETO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Human papillomavirus status and prognosis of oropharyngeal high-grade neuroendocrine carcinoma(2023) SOUSA, Luana G. de; NETO, Felippe Lazar; LAGO, Eduardo A. Dal; SIKORA, Andrew; HANNA, Ehab; MORENO, Amy; PHAN, Jack; GLISSON, Bonnie S.; BELL, Diana; FERRAROTTO, RenataBackground: The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established. Methods: Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models. Results: Thirty patients were included; most had a heavy (>= 10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was positive in 65% of tested samples (15/23). Of 24 patients treated with curative intent, the objective response rates was 90% (9/10) and 81% (17/21), respectively, for induction chemotherapy and definitive radiotherapy. During follow-up, 54% (13/24) recurred, mostly (11/13) at distant sites. Median overall survival (OS) was 46 months (95% CI, 14.3 -NA). OS was not associated with HPV status (HR 0.73, P = 0.6) or smoking (HR 1.16, P = 0.8). Among 63 patients with known HPV status after the literature review (19 HPV-and 44 HPV + ), HPV status remained unassociated with OS (P = 0.92). Conclusions: This is the largest retrospective cohort of oropharyngeal HG-NEC. Distant recurrence rate after curative treatment was high, suggesting that multimodality treatment including systemic therapy may benefit patients with locally advanced disease. HPV infection did not affect survival outcomes, therefore should not lead to therapy de-intensification for this histology.
- Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: an extracted individual patient data and trial-level meta-analysis(2024) CUNHA, Mateus Trinconi; GOUVEIA, Mariana Carvalho; LAZAR NETO, Felippe; TESTA, Laura; HOFF, Paulo Marcelo; AZAMBUJA, Evandro de; BONADIO, Renata ColomboBackground: Neoadjuvant immunotherapy (nIO) has emerged as a treatment option for stage II-III triple-negative breast cancer (TNBC). While randomised clinical trials (RCTs) demonstrated pathological complete response rate benefit to nIO added to chemotherapy, additional data on long-term outcomes is warranted. We performed this analysis to evaluate long-term efficacy outcomes of nIO in TNBC.Methods: We searched databases for RCTs evaluating nIO in early-stage TNBC. A meta-analysis of extracted individual patient data (EIPD) was performed to evaluate EFS and OS, with data from reported Kaplan-Meier plots. Additionally, we conducted a trial-level meta-analysis using fixed and random effects models.Results: The literature search resulted in four included RCTs with available EFS or OS (KEYNOTE-522, IMpassion031, I-SPY2 and GeparNuevo). EIPD showed that the addition of nIO to chemotherapy provides statistically significant benefits in EFS (HR 0.62, 0.50-0.76; p < 0.001) and OS (HR 0.62, 0.46-0.82, p < 0.001). Number needed to treat to avoid one EFS or OS event in 4 years was 9 and 14, respectively. Trial-level meta-analysis yielded similar results (EFS: HR 0.64, 0.51-0.79; OS: 0.57, 0.37-0.89).Conclusions: Results show that nIO combined with chemotherapy can provide significant EFS and OS benefits, supporting its use as standard treatment for early-stage TNBC.
- Mortality over time among COVID-19 patients hospitalized during the first surge of the pandemic: A large cohort study(2022) MARCILIO, Izabel; LAZAR NETO, Felippe; CORTEZ, Andre Lazzeri; MIETHKE-MORAIS, Anna; NOVAES, Hillegonda Maria Dutilh; SOUSA, Heraldo Possolo de; CARVALHO, Carlos Roberto Ribeiro de; LEVIN, Anna Sara Shafferman; FERREIRA, Juliana Carvalho; GOUVEIA, NelsonBackgroundCapacity strain negatively impacts patient outcome, and the effects of patient surge are a continuous threat during the COVID-19 pandemic. Evaluating changes in mortality over time enables evidence-based resource planning, thus improving patient outcome. Our aim was to describe baseline risk factors associated with mortality among COVID-19 hospitalized patients and to compare mortality rates over time. MethodsWe conducted a retrospective cohort study in the largest referral hospital for COVID-19 patients in Sao Paulo, Brazil. We investigated risk factors associated with mortality during hospitalization. Independent variables included age group, sex, the Charlson Comorbidity Index, admission period according to the stage of the first wave of the epidemic (early, peak, and late), and intubation. ResultsWe included 2949 consecutive COVID-19 patients. 1895 of them were admitted to the ICU, and 1473 required mechanical ventilation. Median length of stay in the ICU was 10 (IQR 5-17) days. Overall mortality rate was 35%, and the adjusted odds ratios for mortality increased with age, male sex, higher Charlson Comorbidity index, need for mechanical ventilation, and being admitted to the hospital during the wave peak of the epidemic. Being admitted to the hospital during the wave peak was associated with a 33% higher risk of mortality. ConclusionsIn-hospital mortality was independently affected by the epidemic period. The recognition of modifiable operational variables associated with patient outcome highlights the importance of a preparedness plan and institutional protocols that include evidence-based practices and allocation of resources.
- Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies(2023) NARAYANAN, Santhosshi; MORES, Aline Rozman de; COHEN, Lorenzo; ANWAR, Mohammed Moustapha; LAZAR, Felippe; HICKLEN, Rachel; LOPEZ, Gabriel; YANG, Peiying; BRUERA, EduardoPurpose of ReviewPatients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion.Recent FindingsOf 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design.Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.
- Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors(2023) SOUSA, Luana Guimaraes; MCGRAIL, Daniel J.; NETO, Felippe Lazar; LI, Kaiyi; MARQUES-PIUBELLI, Mario L.; FERRI-BORGOGNO, Sammy; DAI, Hui; MITANI, Yoshitsugu; BURR, Nicole Spardy; COOPER, Zachary A.; KINNEER, Krista; CORTEZ, Maria Angelica; LIN, Shiaw-Yih; BELL, Diana; NAGGAR, Adel El; BURKS, Jared; FERRAROTTO, RenataPurpose: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets. Experimental Design: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody-drug conjugate AZD8205 was tested in ACC patient-derived xeno-grafts (PDX). Results: RNA deconvolution revealed that most ACCs are immu-nologically ""cold,"" with approximately 30% being ""hot."" ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% com-plete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX. Conclusions: Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.