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1.
Eur Rev Med Pharmacol Sci ; 25(20): 6232-6244, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34730203

RESUMO

OBJECTIVE: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC. MATERIALS AND METHODS: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study. RESULTS: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001). CONCLUSIONS: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Taxa de Sobrevida
2.
Ann Oncol ; 30(8): 1232-1243, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31056702

RESUMO

BACKGROUND: Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy. METHODS: To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression. RESULTS: The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types. CONCLUSIONS: This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Testes Genéticos/normas , Instabilidade de Microssatélites , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , União Europeia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Oncologia/métodos , Oncologia/normas , Mutação , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Sociedades Médicas/normas
3.
Pathologica ; 110(1): 12-28, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30259910

RESUMO

Malignant pleural mesothelioma is a neoplasm characterized by a very poor prognosis and medico-legal implications. Diagnosis, prognosis and therapy are often challenging and include several issues. Cytological diagnosis is frequently the first step of the diagnostic process, and although its sensitivity may be somewhat lower, diagnostic criteria should be taken into account. When effusion cytology is inconclusive for the diagnosis, tissue biopsies should be taken. Even if the morphologic criteria for deciding whether a mesothelial proliferation is a benign or a malignant process have been defined, the separation of benign from malignant mesothelial proliferation is often a difficult problem for the pathologist, particularly on small biopsies. Thirdly, when the diagnosis is made, despite many efforts have been made to identify possible new biomarkers for early diagnosis, prognostic stratification and also predictive tools should be defined. Nowadays, the main prognostic parameter is still represented by the histological subtype, having the epithelioid MPM a better outcome than the sarcomatoid or biphasic MPM. A nuclear grading system have been also proposed to stratify patient outcome. Reliable predictive biomarkers are still lacking in MPM and a personalized therapeutic concept is eagerly needed. Mesothelioma occurs mostly as sporadic cancer and the main risk factor is asbestos exposure, but it also occurs among blood relatives suggesting possible increased genetic susceptibility besides shared exposures. Recently the study of genetic predisposition syndrome raised new aspect in the occurrence of mesothelioma cases.This review summarize these most important issues.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Biópsia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Mesotelioma Maligno , Gradação de Tumores , Neoplasias Pleurais/patologia , Prognóstico
5.
Eur J Surg Oncol ; 42(7): 919-25, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27005805

RESUMO

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Excisão de Linfonodo , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Biópsia de Linfonodo Sentinela , Análise de Sobrevida
7.
Pathologica ; 108(4): 164-168, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28195257

RESUMO

A pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas , Adenocarcinoma/terapia , Adenocarcinoma de Pulmão , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Ann Oncol ; 27(1): 42-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26483050

RESUMO

BACKGROUND: The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. MATERIALS AND METHODS: Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. RESULTS: Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%). CONCLUSIONS: Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems.


Assuntos
Neoplasias Colorretais/patologia , Linfonodos/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Resultado do Tratamento
9.
Pathologica ; 103(6): 325-30, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22558889

RESUMO

Data on 2436 primary breast carcinomas diagnosed between 1992 and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed to evaluate resection margins for conservative surgery or sentinel node status were excluded. Over time, there was a decrease in the use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2% in 1999, and 0% in 2005-2006. In the same period, the adoption of cytology and core biopsy for breast cancer diagnosis increased from 40% in 1992 to more than 90% since 1999. In an audited diagnostic activity on breast pathology, the routine use of frozen sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be limited to cases with inadequate pre-surgical sampling.


Assuntos
Neoplasias da Mama/diagnóstico , Secções Congeladas/estatística & dados numéricos , Secções Congeladas/tendências , Neoplasias da Mama/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias
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