RESUMO
INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Consenso , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Espanha , Equipe de Assistência ao Paciente , Técnica Delphi , Estadiamento de NeoplasiasRESUMO
Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurrent chemo-radiotherapy is the standard of care for LS-SCLC that is not surgically resectable, followed by prophylactic cranial irradiation (PCI) for patients without progression. For extensive-stage (ES)-SCLC, a combination of platinum and etoposide has historically been a mainstay of treatment. Recently, the efficacy of programmed death-ligand 1 inhibitors combined with chemotherapy has become the new front-line standard of care for ES-SCLC. Emerging knowledge regarding SCLC biology, including genomic characterization and molecular subtyping, and new treatment approaches will potentially lead to advances in SCLC patient care.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Etoposídeo/uso terapêutico , Platina/uso terapêutico , Seguimentos , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Central nervous system (CNS) dissemination is a severe complication in cancer and a leading cause of cancer-related mortality. Brain metastases (BMs) are the most common types of malignant intracranial tumors and are reported in approximately 25% of patients with metastatic cancers. The recent increase in incidence of BMs is due to several factors including better diagnostic assessments and the development of improved systemic therapies that have lower activity on the CNS. However, newer systemic therapies are being developed that can cross the blood-brain barrier giving us additional tools to treat BMs. The guidelines presented here focus on the efficacy of new targeted systemic therapies and immunotherapies on CNS BMs from breast, melanoma, and lung cancers.
Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Neoplasias Pulmonares , Melanoma , Segunda Neoplasia Primária , Encéfalo , Neoplasias Encefálicas/secundário , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Humanos , Neoplasias Pulmonares/patologia , Melanoma/patologiaRESUMO
OBJECTIVES: Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. MATERIALS AND METHODS: GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250â¯mg daily or gefitinib 250â¯mg daily plus olaparib 200â¯mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. RESULTS: Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3-13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1-14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00-1.92; pâ¯=â¯0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. CONCLUSIONS: The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination's safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Objetivos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , México , Mutação , Ftalazinas , Piperazinas , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , EspanhaRESUMO
PURPOSE: The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. METHODS: An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. RESULTS: 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. CONCLUSIONS: The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions.
Assuntos
Antineoplásicos/uso terapêutico , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Oncologia , Neoplasias/tratamento farmacológico , Sociedades Médicas , Humanos , Inquéritos e QuestionáriosRESUMO
The development of drugs with special mechanisms of action, such as tyrosine kinase inhibitors (TKIs), means that new clinical-molecular questions are being examined and this will help us to better select from the treatments available. In this study we review questions of survival and response to TKIs, attempting to distinguish prediction-and prognosis-related factors, at both the clinical and molecular levels. The evidence available today allows us to affirm that the benefits of TKI treatment occur regardless of the patient's status as a smoker, his/her gender or histological sub-type. Interestingly, in a subset analysis of ever-smokers, men with squamous cell histology derived a statistically significant survival benefit from erlotinib, a population that was previously thought not to benefit. The question of who should receive TKIs is still not completely resolved. Therefore, there should be an international effort to achieve a prognostic index, as has been done for lymphomas, that combines molecular and clinical factors. Such an index would classify patients into several sub-groups, defining the likelihood of non-response to TKIs.
Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfoma/tratamento farmacológico , Masculino , Prognóstico , Quinazolinas/uso terapêutico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition.