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1.
Transl Lung Cancer Res ; 10(7): 3339-3350, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430371

RESUMO

Background: To describe the incidence and the clinical characteristics of oligometastatic non-small cell lung cancer (NSCLC) patients. Oligometastatic NSCLC is gaining recognition as a clinical condition with a different prognosis compared to multi metastatic disease. Usually, four different scenarios of oligometastatic disease can be described but not epidemiological data are available. To date, it is difficult to delineate an exhaustive epidemiological scenario because no uniform or shared definition of oligometastatic status exists, even though a recent consensus defined synchronous oligometastatic disease as having a maximum of 5 metastases in 3 different organs. Methods: A systematic review and a pooled analysis of literature were performed. Article selection was based on the following characteristics: focus on lung cancers; dealing with oligometastatic settings and providing a definition of oligometastatic disease; number of metastatic lesions with or without the number of organs involved; providing some incidence or clinical characteristics of oligometastatic NSCLC patients. Series focusing on a specific single metastatic organ were excluded. The research was launched in MEDLINE (OvidSP) in March 2020. Full articles were individually and collectively read by the authors according to the previous criteria. Each author inspected the reference list included in the eligible articles. If the selection criteria were recognized, the article was reviewed by all authors and then included. Data on patient clinical features were pooled together from 31 articles selected. Results: A total number of 31 articles have been selected for the analysis. The following variables were extracted from the publications: (I) number of metastases, (II) number of organs involved, (III) number of patients, (IV) number and percentage of males and females, (V) number and percentage of squamous and non-squamous histology, (VI) T and N status and/or stage of primary disease for oligometastatic setting. The data collected have been analyzed according to the oligometastatic setting. Conclusions: Oligometastatic status is globally identified as a different clinical condition from multi metastatic NSCLC, although the clinical characteristics were consistent in the general metastatic population, even with a lower-than-expected TN status. The brain and bones were the most frequent organs involved. Lacking consensus definition, these results must be interpreted cautiously and a prospective evaluation is urgently needed.

2.
Respir Med Res ; 80: 100845, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34242975

RESUMO

BACKGROUND: Immune checkpoints inhibitors (ICI) are becoming new standards of care for the treatment of non-small cell lung cancer (NSCLC), both as first (alone or in association with chemotherapy) and second line. However, no powerful predictive biomarker of therapeutic response to ICI has been found to date. It has been recently shown that microbiota composition could influence the ability of patients to respond to ICI. Indeed, the microbiota produces circulating metabolites that will subsequently act on immune system, the investigators hypothesized that plasma metabolic signature, reflecting a global microbiota function, could represent a predictive biomarker of response to ICI. METHODS: Monocentric prospective study. Primary objective is to identify baseline metabolic signature (metabolomics analysis by mass spectrometry) associated to ICI response. Secondary objectives are to link metabolic signature with microbiota composition (metagenomics analysis RNA 16S) and immune profile, and altogether with clinic response to ICI. The study will include 60 NSCLC patients treated by ICI in 1st, 2nd or 3rd line of treatment at the Grenoble Alpes University hospital (CHUGA) in 18 months. Patients that have received antibiotic or steroid treatment, 2 or 4 weeks before ICI initiation, respectively, will be excluded. Blood and feces will be collected prior to, at 2 months after ICI treatment initiation, and at 6 months or at progression. EXPECTED RESULTS: We expect to highlight a metabolic profile predictive of response to ICI. By identifying factors associated with early progression, we could avoid to treat potential non-responding patients. Moreover, by restoring a favorable microbiota, patients' ability to respond to these treatments might be restored.

3.
Cancers (Basel) ; 12(11)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33139612

RESUMO

Extended small cell lung cancer (ED-SCLC) is a very aggressive disease, characterized by rapid growth and an early tendency to relapse. In contrast to non-small cell lung cancer, no therapeutic innovation has improved survival in patients with ED-SCLC over the past 20 years. Recently, immunotherapy has shown an important role in the management of these patients, emerging as the treatment of first choice in combination with chemotherapy and completely changing the therapeutic paradigm. However, patients' selection for this strategy is still challenging due to a lack of reliable predictive biomarkers. Conversely, the immunotherapy efficacy beyond the first line is pretty disappointing and innovative chemotherapies or target agents seem to be more promising in this setting. Some of them are also under evaluation as an upfront strategy and they will probably change the treatment algorithm in the next future. This proposal provides a comprehensive overview of available treatment strategies for ED-SCLC patients, highlighting their strengths and weaknesses.

4.
Lung Cancer ; 140: 99-106, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911324

RESUMO

OBJECTIVES: Nivolumab is now a reference treatment for patients with advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. Little data are available on treatment approaches following discontinuation of nivolumab and on the interest of a second course of immunotherapy after nivolumab discontinuation. The aims of this study were to describe treatment pathways following nivolumab discontinuation and to describe survival following retreatment with immunotherapy. MATERIALS AND METHODS: The analysis includes all patients with NSCLC recorded in a national hospital database, starting nivolumab in 2015-2016. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Patients starting a second course of PD-1 inhibitor following nivolumab discontinuation were analysed according to the duration of their initial nivolumab treatment course. RESULTS: 10,452 patients were included (71 % men; mean age: 63.8 ± 9.6 years; squamous histology: 44 %). Median nivolumab treatment duration was 2.8 months [IQR :1.4-6.9]. Median OS was 11.5 months [95 %CI: 11.1-11.9]; 5118 (53.4 %) patients received post nivolumab therapy lines: 1517 (29.6 %) of these received a second course of PD-1 inhibitor, either after a treatment-free interval (resumption: n = 1127) or after intervening chemotherapy (rechallenge: n = 390). Median OS after nivolumab discontinuation was 15.0 months [13.9-16.7] in the resumption group and 18.4 months [14.8-21.9] in the rechallenge group. Median OS was significantly longer in patients with an initial nivolumab treatment duration ≥3 months. CONCLUSION: In this real-world setting, outcome after retreatment with a PD-1 inhibitor following a first course of nivolumab was significantly better in patients with a longer duration of initial nivolumab treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Retratamento/métodos , Idoso , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Front Med (Lausanne) ; 6: 233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737634

RESUMO

Non-small-cell lung cancers (NSCLC) represent 85% of all lung cancers, with adenocarcinoma as the most common subtype. Since the 2000's, the discovery of molecular alterations including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements together with the development of specific tyrosine kinase inhibitors (TKIs) has facilitated the development of personalized medicine in the management of this disease. This review focuses on the biology of molecular alterations in NSCLC as well as the diagnostic tools and therapeutic alternatives available for each targetable alteration. Rapid and sensitive methods are essential to detect gene alterations, using tumor tissue biopsies or liquid biopsies. Massive parallel sequencing or Next Generation Sequencing (NGS) allows to simultaneously analyze numerous genes from relatively low amounts of DNA. The detection of oncogenic fusions can be conducted using fluorescence in situ hybridization, reverse-transcription polymerase chain reaction, immunohistochemistry, or NGS. EGFR mutations, ALK and ROS1 rearrangements, MET (MET proto-oncogenereceptor tyrosine kinase), BRAF (B-Raf proto-oncogen serine/threonine kinase), NTRK (neurotrophic tropomyosin receptor kinase), and RET (ret proto-oncogene) alterations are described with their respective TKIs, either already authorized or still in development. We have herein paid particular attention to the mechanisms of resistance to EGFR and ALK-TKI. As a wealth of diagnostic tools and personalized treatments are currently under development, a close collaboration between molecular biologists, pathologists, and oncologists is crucial.

7.
Eur J Cancer ; 123: 28-35, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655358

RESUMO

INTRODUCTION: Synchronous oligometastatic non-small cell lung cancer (NSCLC) definition varies from 1 metastasis in 1 organ (tumour-node-metastasis 8 [TNM8]), 1-3 metastases (European Society for Medical Oncology [ESMO]), ≤3 metastases (including mediastinal nodes [MLN]) after systemic treatment to 3-5 metastases in ongoing trials. A single definition is however needed to design/compare trials. To assess oligometastatic NSCLC definitions used by clinical experts in daily practice and its evolution, we redistributed a 2012 case-based survey (Dooms, the World Congress of Lung Cancer 2013). METHODS: In December 2017, 10 real-life multidisciplinary team (MDT) discussed patients (good condition, no significant comorbidities, 18F-fluorodeoxyglucose positron emission tomography/brain magnetic resonance imaging staged, all < 5 metastases, 9/10 ≤ 3 metastases, oncogene-addicted or wild-type) were distributed to 33 international NSCLC experts involved in the European Organisation for Research and Treatment of Cancer oligometastatic NSCLC consensus group, questioning is this oligometastatic disease and if oligometastatic, which treatment proposal. The answers provided in 2017 were compared with the 2012 answers; real-life treatment and survival of the patients was added. RESULTS: Twenty-six of 33 experts (24 centres) replied: 8 medical oncologists, 7 pulmonologists, 7 radiation oncologists, 4 thoracic surgeons. Sixty-two percent of respondents discussed the cases with their MDT. One case had 100% oligometastatic consensus, and 3 cases had >90% consensus; the number of treatment proposals varied between 3 and 8. Radical treatment was more often offered in case of single metastasis or N0. Compared with 2012, there was a trend towards a more conservative oligometastatic definition and chemotherapy was more frequently included in the treatment proposal. CONCLUSIONS: Oligometastatic NSCLC definition was conservative. The number of organs, MLN status and radical treatment possibility seem to be components of daily practice oligometastatic definition.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/classificação , Neoplasias Pulmonares/classificação , Neoplasias das Glândulas Suprarrenais/classificação , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias Ósseas/classificação , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante , Consenso , Prova Pericial , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/secundário , Neoplasias Renais/terapia , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Imageamento por Ressonância Magnética , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/terapia , Pneumonectomia , Tomografia por Emissão de Pósitrons , Radiocirurgia
8.
J Thorac Oncol ; 14(12): 2109-2119, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31398540

RESUMO

INTRODUCTION: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process. METHODS: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting. RESULTS: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits. CONCLUSION: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Consenso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias
9.
J Thorac Oncol ; 14(12): 2053-2061, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31195177

RESUMO

INTRODUCTION: Synchronous oligometastatic (sOM) disease is an oncological concept characterized by a limited cancer burden. Patients with oligometastasis could potentially benefit from local radical treatments. Despite the fact that the sOM condition is well recognized, a universal definition, including a specific definition for NSCLC, is not yet available. The aim of this systematic review was to summarize the definitions of and staging requirements for use of the term synchronous oligometastatic in the context of NSCLC. METHODS: The key issue was formulated in one research question according to the population, intervention, comparator, and outcomes strategy. The question was introduced in MEDLINE (OvidSP). All articles dealing with sOM NSCLC and providing a definition of synchronous oligometastasis in NSCLC were selected and analyzed. RESULTS: A total of 21 eligible articles focusing on sOM NSCLC were retrieved and analyzed. In 17 studies (81%), patients had to be staged with magnetic resonance imaging or computed tomography of the brain, thoracic and abdominal computed tomography, and positron emission tomography. The total number of metastases allowed in the definitions ranged from one to eight, but in 38.1% of studies the maximum number was 5. Most of the publications did not define the number of involved organs or the maximum number of metastases per organ. For mediastinal lymph node involvement, only five articles (27.8%) counted this as a metastatic site. CONCLUSIONS: No uniform definition of sOM NSCLC could be retrieved by this systematic review. However, extended staging was mandated in most of the studies. An accepted oncological definition of synchronous oligometastasis is essential for patient selection to define prospective clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Resultado do Tratamento
10.
J Thorac Oncol ; 14(1): 130-134, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30217489

RESUMO

INTRODUCTION: Histologic transformation from NSCLC to SCLC is a mechanism of resistance in EGFR-mutant tumors but is also occasionally observed in nonmutated NSCLC. METHODS: We performed a multicenter retrospective collection of cases presenting between 2005 and 2017. The objectives were to analyze survival data and to define epidemiologic, clinical, treatment and histomolecular characteristics at both the time of diagnosis of NSCLC and of SCLC. RESULTS: Forty-eight EGFR-mutant NSCLC and 13 non-EGFR-mutant cases were registered. Most EGFR-mutant tumors retained the same EGFR mutation after transformation. The median time to SCLC transformation was shorter in the EGFR-mutant group than in non-EFGR mutants (16 months versus 26 months (p = 0.01)). Both tumors were responsive to platinum etoposide regimens (45% partial response for the EGFR-mutant group versus 40% for non-EFGR mutants). The median overall survival rates were 28 months in the EGFR-mutant group versus 37 months in the non-EFGR-mutant group, respectively. After transformation, the median overall survival was 9 months in the non-EGFR-mutant group versus 10 months in the EGFR-mutant group. CONCLUSIONS: Transformation into SCLC seems to occur more quickly in EGFR mutated tumors; however, once the tumor is transformed its survival and response to treatment seems comparable to that of classical SCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
11.
J Thorac Dis ; 10(Suppl 13): S1427-S1437, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29951294

RESUMO

Early non-small cell lung cancer (NSCLC) represents 16% of all new NSCLC at diagnosis with a 5-year survival rate of about 60%. Surgical intervention and adjuvant platinum-based chemotherapy represent the cornerstone treatments, but no significant advances have been achieved since several decades in term of relapse rate reduction or survival improvement. Immunotherapy represents an appealing strategy considering the acceptable toxicity profile but, despite the awesome changing recently introduced in the locally advanced and metastatic setting, its role in early NSCLC is not clear yet. In the past few years, two strategies have been investigated to improve the early NSCLC outcomes eliciting the anti-tumour immune response: tumour vaccines and adoptive cellular therapies. However, none of them provided convincing results. Preclinical and clinical data supported the prognostic role of immune checkpoints in resected NSCLC even if they did not show a clear predictive value for adjuvant treatment. However, some preliminary data about safety and efficacy of neo-adjuvant immune checkpoint inhibitors encourage further investigation of their potential role as monotherapy or as part of a multimodal strategy. Then, even if no significant progress has been done in early NSCLC treatment until today, checkpoint inhibitors can open the door to a new strategy in this setting.

12.
Lung Cancer ; 116: 15-24, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29413046

RESUMO

OBJECTIVES: The aim of the present study was firstly to assess in a clinical setting the yields of an amplicon-based parallel RNA sequencing (RNA-seq) assay for ALK fusion transcript variants detection in comparison with immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) in a selected population of ALK-positive and ALK-negative non-small cell lung cancer (NSCLC) cases, and secondly to evaluate the impact of the ALK variant on crizotinib efficacy. MATERIALS AND METHODS: The cohort used for the assessment of the RNA-seq assay comprised 53 samples initially diagnosed as being ALK-positive based on the results obtained by IHC and/or FISH, and 23 ALK-negative samples. A distinction was made between 'truly' IHC/FISH positive or 'truly' IHC/FISH negative samples, and those for which the IHC and/or FISH were equivocal (IHC) or borderline-positive (FISH). RESULTS: On the overall population, RNA-seq sensitivity (Se) and specificity (Spe) were of 80% and 100%, respectively when IHC and FISH were combined. For the 31 'truly positive' samples, Se and Spe of 100% were reached. An ALK status could be assigned by RNA-seq in 10/10 of the equivocal and/or borderline-positive IHC/FISH cases, 2/7 IHC/FISH discordant cases. When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants. CONCLUSION: RNA-seq detects ALK rearrangements with a high sensitivity and specificity using only 10 ng of RNA. It appears to be a promising rescue technique for non-clear-cut IHC/FISH cases and also offers a unique opportunity to identify ALK fusion variants and evaluate their predictive value for ALK inhibitors efficacy.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/farmacologia , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , RNA Neoplásico/genética , Análise de Sequência de RNA/métodos , Adulto Jovem
13.
J Med Case Rep ; 11(1): 183, 2017 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-28679408

RESUMO

BACKGROUND: Nivolumab, a monoclonal antibody targeting the programmed death-1 receptor, is indicated in locally advanced or metastatic non-small cell lung cancer, with progression after platinum-based chemotherapy. Up-to-now, few data are available concerning brain activity of this treatment and concomitant use of corticosteroids. CASE PRESENTATION: A 64-year-old caucasian man with a pulmonary adenocarcinoma associated with brain metastases received four courses of nivolumab in concomitance with a high dose of corticosteroids for his neurologic symptoms. He experienced a partial response in his brain and chest with an improvement in his general condition. Nivolumab was effective in shrinking symptomatic brain metastases, and metastases at other sites, in a patient with non-small cell lung cancer and first-line chemotherapy failure. The effect of nivolumab was obtained despite concomitant high-dose corticosteroid therapy. Combined nivolumab and high-dose corticosteroid therapy did not induce unexpected adverse events. CONCLUSION: Nivolumab and concomitant high-dose corticosteroid therapy was found to be efficient and well tolerated.


Assuntos
Adenocarcinoma/tratamento farmacológico , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Lung Cancer ; 89(3): 350-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26164208

RESUMO

OBJECTIVES: To analyze changes in pulmonary function and quality of life (QoL) at different time points after Stereotactic Ablative Radiotherapy (SABR) for early stage inoperable lung cancer, and potential correlations between radiation dose-volume parameters and pulmonary toxicity or changes in pulmonary function tests (PFT) and QoL. MATERIALS AND METHODS: From July 2012 to October 2013, 30 patients were enrolled in this prospective observational study. Complete PFT were performed and Lung Cancer Symptoms Scale (LCSS) questionnaire administered prior to SABR; all patients then underwent Computed Tomography (CT) scan and PFT at 45, 135, 225 and 315 days after SABR, together with LCSS questionnaire. Clinical lung toxicity and radiological toxicity (acute and late) were prospectively recorded by using the Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: A decline in Slow Vital Capacity (SVC), Forced Expiratory Volume in 1s (FEV1), Single-breath lung diffusing capacity (DLCO) and blood partial pressure of oxygen (PaO2) was seen at 135 days post-SABR. PaO2 values rescued to normal levels at 315 days. None of the baseline PFT parameters resulted to be associated with the occurrence of pulmonary toxicity or with late radiological changes. Mean V5, V10, and V20 and MLD2Gy were higher in patients who developed radiation pneumonitis, even if not significantly associated at Cox regression analysis. LCSS QoL showed a significant worsening of the single item fatigue at 135 days after SABR. CONCLUSIONS: A small (mean 10%) but significant decline in lung volumes and DLCO was recorded after SABR, with clinical impact of such change difficult to estimate in individual patients. Global QoL was not significantly impaired. Dose-volume parameters did not emerge as significantly predictive of any clinical, radiological or functional toxicity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Fatores de Risco , Resultado do Tratamento
15.
Expert Opin Pharmacother ; 14(5): 597-608, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23472711

RESUMO

INTRODUCTION: In the recent years, the growing attention to the molecular background of non-small-cell lung cancer (NSCLC) led to the identification of different molecular subtypes according to genetic abnormalities driving the disease development and progression. Whereas the addicted pathways were successfully inhibited (such as the mutant epidermal growth factor receptor), clinicians have witnessed a dramatic survival improvement. In this regard, the molecular portrait of adenocarcinoma was recently enriched by the identification of a specific patients' subgroup characterized by abnormalities in the anaplastic lymphoma kinase (ALK), with unclear prognostic features but impressive response to specific inhibitors. AREAS COVERED: In this article, updated data derived from the development and the use of crizotinib (the most advanced in development among tyrosine kinase ALK inhibitors) in comparison with standard second-line chemotherapy for patients affected by ALK-altered NSCLC are reviewed. EXPERT OPINION: Taking into account the available data, pretreated NSCLC patients carrying the ALK-translocation require a selected targeted therapy which significantly improves activity, efficacy and symptoms control versus chemotherapy. In this context, the identification of this disease entity and the availability of such impressive therapeutic targeting represent a further step toward the understanding of the molecular complexity behind the adenocarcinoma of the lung.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Perfilação da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Medicina de Precisão , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Quinase do Linfoma Anaplásico , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fenótipo , Valor Preditivo dos Testes , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Resultado do Tratamento
16.
Transl Lung Cancer Res ; 2(1): 23-39, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25806202

RESUMO

Targeted agents have completely changed cancer treatment strategy, leading it from a "one size fits all" approach to a customized therapy. In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming "druggable" only in this last period of time. Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell-cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization. Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis. Met amplification is also described to be linked to EGFR acquired resistance. Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment. This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation.

17.
Clin Lung Cancer ; 14(2): 139-48, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22868220

RESUMO

INTRODUCTION: To prospectively evaluate the frequency and spectrum of incidental findings (IF) in a 5-year lung cancer screening program with low-dose spiral computed tomography (CT) and to estimate the additional costs of their imaging workup incurred from subsequent radiologic follow-up evaluation. MATERIALS AND METHODS: A total of 519 asymptomatic volunteers were enrolled. All IFs were reported and were considered clinically relevant if they required further evaluations or with clinical implications if they required more than one additional diagnostic test for characterization or medical and/or surgical intervention. RESULTS: IFs were commonly found (59.2%, 307/519 participants at baseline and 5.3% per year at 5-year follow-up [123 participants of 2341 LDsCT exams performed during follow-up], with an overall rate of 26.3%). IFs were categorized as previously unknown clinically relevant in 52 (10.0%) individuals at baseline. Of these, 36 (6.9%) individuals had IFs with clinical implications (10 clinically relevant, of which 6 had clinical implications, detected during the subsequent 5-year follow-up). The most common recommendations were for additional imaging of the thyroid and kidneys. Additional imaging was mainly performed by ultrasound (43/68 [63.2%]). Subsequent surgical intervention resulted from these findings in 7 (1.5%) subjects. Six malignancies were diagnosed (rate, 0.2% per year). Costs of subsequent radiologic follow-up studies were calculated as €4644.56 [U.S. $6575.04] at baseline and €1052.30 [U.S. $1489.69] at 5-year follow-up (average added costs per participant €8.95 [U.S. $12.67] and €2.25 [U.S. $3.19], respectively). CONCLUSIONS: Low-dose spiral CT commonly detects IFs. Some of these require further investigations to assess their clinical relevance. Although such IFs add little clinical benefit to the screening intervention, moderate incremental costs are incurred based on additional radiologic procedures generated during short-term follow-up, given the potential for positive effects on patient care.


Assuntos
Detecção Precoce de Câncer , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Espiral/economia , Idoso , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Espiral/métodos
19.
Clin Cancer Res ; 15(3): 1039-45, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19188177

RESUMO

PURPOSE: The effect of translesion DNA synthesis system in conferring cellular tolerance to DNA-damaging agents has been recently described. DNA polymerase eta (Pol eta) is part of this machinery and in vitro models showed that it can overcome DNA damages caused by cisplatin and UV rays. The aim of the present study was to investigate the role of Pol eta mRNA expression levels in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Pol eta mRNA expression levels were evaluated by real-time PCR in (a) formalin-fixed paraffin-embedded biopsies of 72 NSCLC patients treated with platinum-based chemotherapy, (b) fresh snap-frozen surgical specimens of tumor and corresponding normal lung tissue from 50 consecutive patients not treated with perioperative or postoperative chemotherapy, and (c) five NSCLC cell lines. RESULTS: High Pol eta expression levels were strongly associated with shorter survival at both univariate (6.9 versus 21.1 months; P = 0.003) and multivariate (hazard ratio, 3.18; 95% confidence interval, 1.73-5.84; P = 0.008) analysis in the group of platinum-treated patients. By contrast, Pol eta expression was not significantly correlated with the prognosis in surgically resected patients (P = 0.54) and mRNA levels did not significantly differ in tumor versus normal lung (P = 0.82). Moreover, endogenous Pol eta mRNA expression was found to be inducible by cisplatin in three of five cell lines and significantly associated with in vitro sensitivity (P = 0.01). CONCLUSIONS: Taken together, these data indicate Pol eta as a predictive rather than prognostic marker worth of further investigation in NSCLC patients candidate to platinum-based chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Polimerase Dirigida por DNA/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , DNA Polimerase Dirigida por DNA/genética , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Resultado do Tratamento
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