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1.
Pneumologie ; 75(9): 641-643, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34525486

RESUMO

Therapy of non-small cell lung cancer (NSCLC) should be based on biomarker test results in the palliative setting. To this end, testing of all patients in stage IV and in the future also in the earlier stages will be important. In a conference with the patronage of the German Cancer Society, the question of "reflex testing", i. e. independently of tumor stage, was discussed but not deemed to be acceptable. The current report summarizes the results of the consensus conference and discusses possible paths to efficent biomarker testing in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Consenso , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Cuidados Paliativos
2.
Nat Med ; 27(8): 1345-1356, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385702

RESUMO

Worldwide, lung cancer is the most common cause of cancer-related deaths. Molecular targeted therapies and immunotherapies for non-small-cell lung cancer (NSCLC) have improved outcomes markedly over the past two decades. However, the vast majority of advanced NSCLCs become resistant to current treatments and eventually progress. In this Perspective, we discuss some of the recent breakthrough therapies developed for NSCLC, focusing on immunotherapies and targeted therapies. We highlight our current understanding of mechanisms of resistance and the importance of incorporating genomic analyses into clinical studies to decipher these further. We underscore the future role of neoadjuvant and maintenance combination therapy approaches to potentially cure early disease. A major challenge to successful development of rational combination therapies will be the application of robust predictive biomarkers for clear-cut patient stratification, and we provide our views on clinical research areas that could influence how NSCLC will be managed over the coming decade.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Medicina de Precisão , Resistencia a Medicamentos Antineoplásicos , Humanos , Imunoterapia , Terapia de Alvo Molecular
3.
Nat Med ; 27(8): 1410-1418, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385708

RESUMO

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
4.
Nat Commun ; 12(1): 4852, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381028

RESUMO

Oncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Ubiquitina Tiolesterase/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiocinas/metabolismo , Regulação para Baixo , Humanos , Tolerância Imunológica , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Proteína Fosfatase 2C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina Tiolesterase/antagonistas & inibidores
5.
R I Med J (2013) ; 104(7): 36-41, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34437664

RESUMO

Lung cancer remains the most common cause of cancer-related deaths in the United States. Traditional treatment of non-small cell lung cancer has included surgical resection for suitable candidates with early stage (I/II) disease and various chemoradiotherapeutic regimens used for advanced disease, for which prognosis has been poor. Since the early 2000s, there has been a revolution in the diagnosis and treatment of non-small cell lung cancer driven by improved diagnostic techniques and therapies targeted to druggable oncogenic drivers or manipulation of the immunologic milieu in the tumor microenvironment. With this has come a need for frequently updated comprehensive data regarding response to treatment and acquired resistance to targeted therapies. In this article, we aim to provide a concise review of the state-of-the-art in lung cancer workup in 2021, with a focus on how molecular data now informs treatment decisions. With the burgeoning use of immunotherapeutic approaches, we will also discuss some of the complications seen, and briefly discuss their management.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral
6.
Lancet ; 398(10299): 535-554, 2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34273294

RESUMO

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide with an estimated 2 million new cases and 1·76 million deaths per year. Substantial improvements in our understanding of disease biology, application of predictive biomarkers, and refinements in treatment have led to remarkable progress in the past two decades and transformed outcomes for many patients. This seminar provides an overview of advances in the screening, diagnosis, and treatment of non-small-cell lung cancer and small-cell lung cancer, with a particular focus on targeted therapies and immune checkpoint inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/terapia , Humanos
7.
Lung Cancer ; 159: 34-41, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34304051

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most common cancers globally and has a 5-year survival rate ~20%. Immunotherapies have demonstrated long-term and durable responses in NSCLC patients, although they appear to be effective in only a subset of patients. A more comprehensive understanding of the underlying tumour biology may contribute to identifying those patients likely to achieve optimal outcomes. Profiling the tumour microenvironment (TME) has shown to be beneficial in addressing fundamental tumour-immune cell interactions. Advances in multiplexing immunohistochemistry and molecular barcoding has led to recent advances in profiling genes and proteins in NSCLC. Here, we review the recent advancements in spatial profiling technologies for the analysis of NSCLC tissue samples to gain new insights and therapeutic options for NSCLC. The combination of spatial transcriptomics combined with advanced imaging is likely to lead to deep insights into NSCLC tissue biology, which can be a powerful tool to predict likelihood of response to therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imuno-Histoquímica , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Microambiente Tumoral
8.
Crit Rev Oncol Hematol ; 164: 103417, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34242772

RESUMO

Non-small cell lung cancer (NSCLC) is of major concern for society as it is associated with high mortality and is one of the most commonly occurring of all cancers. Due to the number of mutational variants and general heterogeneity of this type of cancer, treatment using conventional modalities has been challenging. Therefore, it is important to have improved therapeutic treatments like immunotherapy, that can specifically treat the disease while causing minimal damage to healthy tissue and additionally provide systemic immunity. Cancer vaccines are an important element of cancer immunotherapy and have been approved for treatment of a limited number of cancers, including NSCLC. This article highlights scientific evidence for several therapeutic treatment strategies for NSCLC, alone or in combination, which offers new hope for those suffering. Although cancer vaccines have had some success as a monotherapy, their potential in a combination therapy needs to be critically analyzed for future applications.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia
9.
Ann Palliat Med ; 10(7): 7205-7213, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263627

RESUMO

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) is typically treated with concurrent chemoradiation (CRT). Excision Repair Cross-Complementing 1 (ERCC1) is a protein involved in DNA damage repair. The objective of this study was to assess whether higher tumoral ERCC1 expression would associate with worse clinical outcomes in NSCLC treated with CRT. METHODS: Twenty-five patients were included. Relative expression levels of messenger RNA (mRNA) for ERCC1 were measured with a quantitative reverse transcription polymerase chain reaction (qRT-PCR) and expressed as scaled ERCC1 mRNA gene expression value. Patients were followed every 3 months with history, physical exam, and imaging to assess clinical outcomes. We evaluated the associations between ERCC1, as well as other prognostic variables including stage, age, gender, race, histology, RT dose, performance status, and progression free survival (PFS) and overall survival (OS) with Kaplan-Meier method and Cox regression. RESULTS: Recursive partitioning analysis identified a GeneExp cutoff of 1.54. Higher ERCC1 expression was associated with worse PFS [hazard ratio (HR) =1.70, P=0.04] and trended towards worse OS (HR =1.53, P=0.11). Increasing tumor volume (HR =1.001, P=0.055), squamous cell (HR =7.86, P=0.008) and poorly differentiated histology (HR =5.25, P=0.06) also associated with worse OS. The cumulative incidence of local recurrence at 1 year trended higher with ERCC1 GeneExp ≥1.54 (78.1%) compared to ERCC1 GeneExp <1.54 (14.9%, P=0.08). Distant relapse at 1 year was 72% with tumor ERCC1 expression ≥1.54 and 52% with ERCC1 expression <1.54 (P=0.28). CONCLUSIONS: Higher ERCC1 expression by qRT-PCR appears to correlate with worse PFS in locally advanced NSCLC treated with CRT. However, the overall sample size of the population was small; thus, larger studies are warranted to integrate molecular biomarkers to identify patients who might benefit from treatment intensification.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico , Resultado do Tratamento
10.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208111

RESUMO

Anti-PD1/PD-L1 immunotherapy has emerged as a standard of care for stage III-IV non-small cell lung cancer (NSCLC) over the past decade. Patient selection is usually based on PD-L1 expression by tumor cells and/or tumor mutational burden. However, mutations in oncogenic drivers such as EGFR, ALK, BRAF, or MET modify the immune tumor microenvironment and may promote anti-PD1/PD-L1 resistance. In this review, we discuss the molecular mechanisms associated with these mutations, which shape the immune tumor microenvironment and may impede anti-PD1/PD-L1 efficacy. We provide an overview of the current clinical data on anti-PD1/PD-L1 efficacy in NSCLC with oncogenic driver mutation.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Mutação/genética , Oncogenes/genética , Animais , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-34300130

RESUMO

Routinely collected electronic healthcare data (rcEHD) have a tremendous potential for enriching pre-marketing evidence on target- and immunotherapies used to treat lung cancer (LC). A scoping review was performed to provide a structured overview of available rcEHD-based studies on this topic and to support the execution of future research by facilitating access to pertinent literature both for study design and benchmarking. Eligible studies published between 2016 and 2020 in PubMed and ISI Web of Science were searched. Data source and study characteristics, as well as evidence on drug utilization and survival were extracted. Thirty-two studies were included. Twenty-six studies used North American data, while three used European data only. Thirteen studies linked ≥1 data source types among administrative/claims data, cancer registries and medical/health records. Twenty-nine studies retrieved cancer-related information from medical records/cancer registries and 31 studies retrieved information on drug utilization or survival from medical records or administrative/claim data. Most part of studies concerned non-small-cell-LC patients (29 out of 32) while none focused on small-cell-LC. Study cohorts ranged between 85 to 81,983 patients. Only two studies described first-line utilization of immunotherapies. Results from this review will serve as a starting point for the execution of future rcEHD-based studies on innovative LC pharmacotherapies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/terapia , Atenção à Saúde , Eletrônica , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia
12.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207126

RESUMO

Although immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Estudos de Associação Genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Avaliação de Resultados da Assistência ao Paciente
13.
Crit Rev Oncol Hematol ; 165: 103431, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34324961

RESUMO

Stereotactic radiosurgery (SRS) in combination with immunotherapy (IT) is increasingly used in the setting of melanoma and non-small cell lung cancer (NSCLC) brain metastases (BM). The synergistic properties of this treatment combination are still not deeply understood. IT-SRS appropriate combination has been envisioned as a strategic point in patients' management. Authors performed a systematic review on current evidences up to December 2020. The impact of SRS-IT and different IT schedules on survival, local/distant intracranial control and toxicity, as well as predictive factors for relevant oncological and radiological outcomes has been analyzed. Authors retrieved 23 pertinent studies. Combining SRS with IT resulted in a significant improvement in OS and lesion response with no increase in radionecrosis, hemorrhage or other complications. The present review suggests that combining IT to SRS is safe and effective in providing a significant improvement in relevant clinical and radiological outcomes in melanoma and NSCLC BMs patients.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia , Estudos Retrospectivos
14.
J Thorac Cardiovasc Surg ; 162(3): 649-660.e8, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34144822

RESUMO

OBJECTIVE: Although previous studies have identified variation in quality lung cancer care, existing quality metrics may not fully capture the complexity of cancer care. The Thoracic Surgery Outcomes Research Network recently developed quality measures to address this. We evaluated baseline adherence to these measures and identified factors associated with adherence. METHODS: Patients with pathologic stage I and II non-small cell lung cancer from 2010 to 2015 were identified in the National Cancer Database. Patient-level and hospital-level adherence to 7 quality measures was calculated. Goal hospital adherence threshold was 85%. Factors influencing adherence were identified using multilevel logistic regression. RESULTS: We identified 253,182 patients from 1324 hospitals. Lymph node sampling was performed in 91% of patients nationally, but only 76% of hospitals met the 85% adherence mark. Similarly, 89% of T1b (seventh edition staging) tumors had anatomic resection, with 69% hospital-level adherence. Sixty-nine percent of pathologic stage II patients were recommended chemotherapy, with only 23% hospitals adherent. Eighty-three percent of patients had biopsy before primary radiation, with 64% hospitals adherent. Higher volume and academic institutions were associated with nonadherence to adjuvant chemotherapy and radiation therapy measures. Conversely, lower volume and nonacademic institutions were associated with inadequate nodal sampling and nonanatomic resection. CONCLUSIONS: Significant gaps continue to exist in the delivery of quality care to patients with early-stage lung cancer. High-volume academic hospitals had higher adherence for surgical care measures, but lower rates for coordination of care measures. This requires further investigation, but suggests targets for quality improvement may vary by institution type.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Fidelidade a Diretrizes/normas , Disparidades em Assistência à Saúde/normas , Neoplasias Pulmonares/terapia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Adolescente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lacunas da Prática Profissional/normas , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
15.
Theranostics ; 11(14): 7092-7109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093873

RESUMO

Background: Recent studies in non-small cell lung cancer (NSCLC) patients have demonstrated that first-line immunotherapy is associated with better therapeutic response than second-line treatment. So far, the mechanisms need to be explored. It prompted us to evaluate the association between first-line chemotherapy and subsequent immunotherapy in NSCLC as well as its underlying mechanisms at the genomic and transcriptomic level. Methods: We launched a prospective, observational clinical study, paired tumor biopsies before and after chemotherapy were collected from NSCLC patients without tyrosine kinase inhibitor (TKI)-related driver gene mutations. The analyses included genomic and transcriptional changes performed by next-generation sequencing (NGS)-based whole-exome sequencing (WES) and messager ribonucleic acid (mRNA) sequencing. Characteristic mutational alterations in 1574 genes were investigated based on mutational status, clinicopathological factors, and chemotherapy responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, neoantigen prediction and intratumoral heterogeneity evaluation were also performed. Results: Samples and information from 32 NSCLC patients without TKI-related driver gene mutations were obtained. We found that the total number of single nucleotide variants (SNV)/insertion-deletion (INDEL) mutations did not change significantly after chemotherapy. The tumor mutation burden (TMB) decreased significantly after chemotherapy in smoking patients and the decreased TMB correlated with a better survival of smoking patients. The change in copy number variations (CNVs) exhibited a decreasing trend during chemotherapy. Subsequent analysis at mRNA level revealed a significant decrease in the expression levels of genes related to antigen processing and presentation as well as other factors relevant for response to immunotherapy. Pathway enrichment analysis confirmed that the immune-related signaling pathways or biological processes were decreased after first-line chemotherapy. Conclusions: Our study presents an explanation for the unsatisfactory results of immunotherapy when given after chemotherapy, and suggests that first-line chemotherapy is able to influence the tumor microenvironment and decrease the efficacy of subsequent immunotherapy. The study was registered at ClinicalTrials.gov, number NCT03764917, and has completed enrolment; patients are still in follow-up.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Biópsia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores Enzimáticos/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Genômica , Humanos , Mutação INDEL , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Estudos Observacionais como Assunto , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , RNA-Seq , Fumantes , Microambiente Tumoral , Sequenciamento Completo do Exoma
16.
Crit Rev Oncol Hematol ; 163: 103378, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34087343

RESUMO

Treatment of locally advanced NSCLC (LA-NSCLC) is focused on multimodal strategy, including chemotherapy and radiotherapy (in combination or as alternative treatments), followed by surgery in selected cases. Recently, durvalumab consolidation after definitive chemo-radiation has shown a meaningful overall survival benefit. However, it is important to note that elderly patients represent a high proportion of NSCLC population and frailty and comorbidities can significantly limit treatment options. Indeed, elderly patients are under-represented in clinical trials and data to drive treatment selection in this category of patients are scanty. Available data, main issues and controversies on multimodal treatment in elderly LA-NSCLC patients will be reviewed in this paper.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia
17.
Lung Cancer ; 158: 60-73, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119934

RESUMO

The Middle East and Africa (MEA) region, a large geographical area, lies at the confluence of Asian, Caucasian and African races and comprises of a population with several distinct ethnicities. The course of management of non-small cell lung cancer (NSCLC) differs as per patients' performance status as well as stage of disease, requiring personalized therapy decisions. Although management of NSCLC has received a significant impetus in the form of molecularly targeted therapies and immune therapies in last few years, surgery remains gold standard for patients with early-stage disease. In case of unresectable disease, radiotherapy and chemotherapy are the primary management modalities. With newer therapies being approved for treatment of early stage disease, use of multi-disciplinary team (MDT) for comprehensive management of NSCLC is of prime importance. A group of experts with interest in thoracic oncology, deliberated and arrived at a consensus statement for the community oncologists treating patients with NSCLC in the MEA region. The deliberation was based on the review of the published evidence including literature and global and local guidelines, subject expertise of the participating panellists and experience in real-life management of patients with NSCLC. We present the proposed regional adaptations of international guidelines and recommends the MDT approach for management of NSCLC in MEA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Oncologistas , África/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Oriente Médio/epidemiologia
18.
Medicine (Baltimore) ; 100(26): e26488, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190175

RESUMO

BACKGROUND: The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed this meta-analysis to evaluate the prognostic significance of CONUT score in NSCLC patients. METHODS: A systematic literature review was conducted using PubMed, Embase, and the Cochrane Library databases. The hazard ratio (HR) and 95% confidence interval (CI) were extracted to assess the correlation between the CONUT score and the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), as well as the cancer-specific survival. RESULTS: A total of 11 studies with 3029 patients were included in the analysis. Pooled results indicated that a high CONUT score was positively correlated with poor OS (HR: 1.63, 95%CI: 1.40-1.88, P < .001) and shortened DFS/RFS (HR: 1.65, 95%CI: 1.35-2.01, P < .001), but no significant relationship with the cancer-specific survival (HR: 1.28, 95%CI: 0.60-2.73, P = .517) was identified. The negative effect of high CONUT score on the OS and DFS/RFS was detected in every subgroup with varying treatment methods, cancer stage, CONUT cut-off values, sample size, and analysis methods of HR. Additionally, preoperative high CONUT score was an independent predictor of postoperative complications (odds ratio: 1.58, 95%CI: 1.21-2.06, P = .001) in NSCLC. Last but not least, high CONUT score was not significantly correlated with the patients' sex, smoking status, cancer stage, lymphatic invasion, vascular invasion, pleural invasion, and pathological cancer type. CONCLUSION: These results demonstrate that high CONUT score is positively related to poor prognoses. The CONUT score may therefore be considered as an effective prognostic marker in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estado Nutricional , Complicações Pós-Operatórias/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco
19.
Theor Biol Med Model ; 18(1): 11, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078405

RESUMO

BACKGROUND: Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non-identifiable tumors as well as the future behavior of the cancerous disease. RESULTS: The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia , Modelos Teóricos , Carga Tumoral
20.
Medicine (Baltimore) ; 100(25): e26450, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160440

RESUMO

RATIONALE: The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. PATIENT CONCERNS: We described a 55-year-old man with good performance status (PS). DIAGNOSES: He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018. INTERVENTIONS: He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib. OUTCOMES: It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable. LESSIONS: This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.


Assuntos
Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimiorradioterapia/métodos , Resistencia a Medicamentos Antineoplásicos , Substituição de Medicamentos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada , Critérios de Avaliação de Resposta em Tumores Sólidos
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