The Diagnostic Accuracy of Chest CT in the Detection of Tumor and Nodal Status in Non Small Cell Lung Carcinoma

At this time there is an increasing demand for an accurate pre operative staging in non small cell lung cancer. Chest Computed Tomography (CT) is one of the imaging modality of choice used for this purpose. This study evaluated the accuracy of the chest CT to determine the status of the tumor and nodules in non small cell lung cancer. During the years 1998 and 1999, a descriptive prospective study of 32 patients undergoing a contrast enhanced chest CT examination for non small cell lung cancer, stage I-IIIA, was conducted. Lobectomy, lymph nodes dissection and postoperative histo-pathological examination were done. CT findings were as follows: a sensitivity of 100%, a specificity of 25% and an accuracy of 60% in the detection of the nodule stage were found. In 17 patients with adenocarcinoma, the sensitivity, the specificity and the accuracy were 86.6%, 100% and 88.2% respectively. The diagnosis of all patients was confirmed histo-pathologically. Six patients with T2 and 26 patients with T3 were detected by chest CT; the accuracy of the tumor status was 93.7%, confirmed by surgical and histo-pathological examinations. It was concluded that the CT played an important role in determining the clinical stage of non small cell lung cancer. The specificity and accuracy were higher in adeno-carcinoma as compared with squamous cell carcinoma in detecting the nodal status

Review of the use of ceritinib, a newly approved anaplastic lymphoma kinase (ALK) inhibitor, in crizotinib-resistant anaplastic lymphoma kinase-rearranged non-small cell lung cancer

Lung cancer is one of the most prevalent cancers in the United States, and is the leading cause of death related to cancer. Non-small cell lung cancer is the most common subtype, with approximately 85% of diagnosed lung cancer being non-small cell lung cancer. Several genetic mutations exist in patients with non-small cell lung cancer, which allows for specialized targeted therapy. One such mutation, EML4-ALK fusion protein abnormalities, represents roughly 5% of non-small cell lung cancer patients, but the patient population in which it is most prevalent is young adults and those that don’t smoke or have a short history of smoking. Ceritinib (Zykadia), a newly approved ALK tyrosine kinase inhibitor, shows exceptional potency against ALK mutations, and shows promise in the ability to overcome resistance that develops during crizotinib (Xalkori) therapy. Several studies are currently underway that are further evaluating the effectiveness of ceritinib in different areas of treatment for ALK-rearranged non-small cell lung cancer

non-small cell lung cancer

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.O cancro é um problema mundial e, apesar dos avanços da ciência e medicina na compreensão da sua biologia e genética, é a segunda causa de morte. Durante muito tempo, o seu tratamento baseou-se na cirurgia, radioterapia e quimioterapia. Embora estas terapias tenham apresentado resultados positivos, apresenta taxas de sucesso variáveis devido à falta de especificidade e toxicidade sistémica inerente. A medicina de precisão introduz uma mudança de paradigma no campo médico, mostrando-se promissora no diagnóstico atempado, bem como na melhoria das condições de vida dos doentes com cancro. O objetivo é avaliar dados genéticos, estilo de vida e ambientais do paciente, com recurso a tecnologia de ponta, como testes moleculares e sequenciamento de última geração, para fornecer um diagnóstico preciso num estadio inicial, bem como um tratamento apropriado. Assim, a medicina de precisão pode permitir a prevenção de doenças e, ao mesmo tempo, reduzir os custos e efeitos colaterais da terapêutica. Atualmente, o campo com maior pesquisa e aplicação em medicina de precisão, é a oncologia. O cancro do pulmão é um exemplo proeminente do sucesso desta inovação no tratamento de tumores sólidos malignos. O cancro de pulmão é um grande problema de saúde pública, sendo a principal causa mundial de morte relacionada com o cancro. Isto deve-se a um diagnóstico em estadios avançados, em consequência da ausência de sintomas na fase inicial da doença, o que a torna muitas vezes incurável. Assim, a realização do perfil molecular é uma ferramenta ideal para o diagnóstico e deteção atempados. A caracterização molecular abrangente do cancro de pulmão expandiu a nossa perceção das origens celulares e vias moleculares afetadas em cada um dos subtipos. Além disso, muitas das alterações genéticas encontradas representam potenciais alvos terapêuticos (biomarcadores) para os quais novos fármacos estão em constante desenvolvimento. Esta monografia pretende dar uma visão geral da atual medicina de precisão no cancro, bem como as suas perspetivas futuras. Foi dado destaque ao cancro do pulmão, mais precisamente ao subtipo de cancro do pulmão de células não pequenas, devido à sua alta incidência e mortalidade.Cancer is a worldwide problem, and despite tremendous advances in science and medicine in the understanding of its biology and genetics, it is still a major cause of death. For a long time, surgery, radiotherapy, and chemotherapy were the most used approaches for cancer treatment. Even though these therapies have shown positive outcomes, variable success rates have been obtained due to their lack of specificity and inherent systemic toxicity. Precision medicine is a new, paradigm-shift approach in medical field that shows promise for improving many aspects of healthcare, both in terms of diagnosis and treatment of diseases. The goal of precision medicine is to use cutting-edge healthcare resources, such as molecular tests and next-generation sequencing to decipher patient's genomic, lifestyle, and environmental data, and thereby identify a precise diagnosis at an earlier stage, as wells as an appropriate treatment. In this way, precision medicine may allow the prevention of disease while also reducing the costs and side effects of therapy. Currently, oncology is the field with major research and application of precision medicine. A prominent example of the success of this innovation in treating solid tumour malignancies, is lung cancer. Lung cancer is a major public health concern, being the leading cause of cancer related mortality worldwide. The reason for this is the diagnosis at an advance stage, due to the absence of symptoms at early stages, which makes the disease often incurable. As such, molecular profiling isthe ideal tool for early diagnosis and detection. Comprehensive molecular characterization of lung cancer has expanded our understanding of the cellular origins and molecular pathways affected in each of the sub-types. Furthermore, many of these genetic alterations represent potential therapeutic targets (biomarkers) for which novel drugs are constantly under development. This monograph aims to give an overview of cancer precision medicine current state and future perspectives. A special focus was given to lung cancer, more precisely to the non-small cell lung cancer subtype, due to its high incidence and mortality

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine - a Phase I trial

Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine (R) Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20-50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP), overall survival (OS) and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs). Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21 days and only marginal accumulation. The tolerability profile was acceptable (all dose levels - all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%;>= grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%). Disease control rate, OS and TTP signaled a treatment effect. Conclusion: Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional dosing. Blood concentrations were consistent with anti-angiogenic or immune modulating pharmacologic properties of vinorelbine. Further studies are warranted to evaluate the safety and efficacy of this novel approach in specific patient populations

Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer

Objective: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Methods: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Results: Patients with pre-operative hypoalbuminemia

SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer

PET/CT in the Staging of the Non-Small-Cell Lung Cancer

Lung cancer is a common disease and the leading cause of cancer-related death in many countries. Precise staging of patients with non-small-cell lung cancer plays an important role in determining treatment strategy and prognosis. Positron emission tomography/computed tomography (PET/CT), combining anatomic information of CT and metabolic information of PET, is emerging as a potential diagnosis and staging test in patients with non-small-cell lung cancer (NSCLC). The purpose of this paper is to discuss the value of integrated PET/CT in the staging of the non-small-cell lung cancer and its health economics

Potential role of immunotherapy in advanced non-small-cell lung cancer

Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD- 1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.Pierre Fabr

Impact of tumor size on outcomes after anatomic lung resection for stage 1A non–small cell lung cancer based on the current staging system

ObjectiveAnatomic segmentectomy may achieve results comparable to lobectomy for early-stage non–small cell lung cancer. The 7th edition of the AJCC Cancer Staging Handbook stratified the previous T1 tumor designation into T1a and T1b subsets, which still define stage 1A node-negative non–small cell lung cancer. We are left to hypothesize whether this classification may aid in directing the extent of surgical resection. We retrospectively reviewed our anatomic segmentectomy and lobectomy management of stage 1A non–small cell lung cancer to determine differences in survival and local recurrence rates based on the new stratification.MethodsWe performed a retrospective review of 429 patients undergoing resection of pathologically confirmed stage 1A non–small cell lung cancer via lobectomy or anatomic segmentectomy. Primary outcome variables included mortality, recurrence, and survival. Recurrence-free and cancer-specific survivals were estimated using the Kaplan–Meier method.ResultsPatients undergoing segmentectomy were older than patients undergoing lobectomy (mean age 69.2 vs 66.8 years, P < .006). The mean preoperative forced expiratory volume in 1 second was significantly lower in the segmentectomy group than in the lobectomy group (71.8% vs 81.1%, P = .02). Mortality was similar after segmentectomy (1.1%) and lobectomy (1.2%). There was no difference in mortality, recurrence rates (14.0% vs 14.7%, P = 1.00), or 5-year cancer-specific survival (T1a: 90% vs 91%, P = .984; T1b: 82% vs 78%, P = .892) when comparing segmentectomy and lobectomy for pathologic stage 1A non–small cell lung cancer, when stratified by T stage.ConclusionsAnatomic segmentectomy may achieve equivalent recurrence and survival compared with lobectomy for patients with stage 1A non–small cell lung cancer. Prospective studies will be necessary to delineate the potential merits of anatomic segmentectomy in this setting