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1.
Eur J Cancer ; 190: 112947, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451182

RESUMO

The standard first-line treatment for non-oncogene driven metastatic non-small cell lung cancer (NSCLC) is an immune checkpoint inhibitor (ICI) based strategy. Although guidelines increasingly advise adding local radical treatment (LRT) to patients with synchronous oligometastatic (sOMD) NSCLC responding to systemic therapy, this recommendation is based on the studies without ICI. Furthermore, the majority of published oligometastatic studies were not on an intention-to-treat basis, resulting in selection bias. Moreover, staging Positron Emission Tomography-Computed Tomography (PET-CT) and brain imaging were often not mandatory and definitions of oligometastatic were heterogeneous. Therefore, this study focused on a single centre retrospective series, including all adequately staged patients with sOMD NSCLC according to the European Organisation for Research and Treatment of Cancer definition (maximum of 5 metastases in 3 organs) that were treated with induction (chemo)-ICI and compared outcomes to those treated with chemotherapy only, with and without LRT. The primary end-points were median progression-free survival (PFS) and overall survival (OS) for patients treated with induction (chemo)-ICI versus chemotherapy. Out of 68 included patients, 38 (56%) eventually received LRT. With a median follow-up of 26.7 months, the median PFS was 19.0 months for (chemo)-ICI (n = 18) versus 6.8 for chemotherapy-only (n = 50) (HR 0.5, p = 0.03), the median OS was 19.3 versus 15.7 months, respectively (HR 0.8, p = 0.4). In patients having received LRT, median PFS was 19.0 months for (chemo)-ICI versus 8.3 for chemotherapy-only (HR 0.6, p = 0.2). In conclusion, an ICI-based systemic treatment is feasible and may result in superior survival outcomes. This should be investigated in prospective trials. Strategies to improve response rates to systemic treatment are also needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Estudos Prospectivos , Análise de Intenção de Tratamento , Resultado do Tratamento , Imunoterapia/efeitos adversos
2.
Pharmacoepidemiol Drug Saf ; 32(10): 1161-1177, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37309816

RESUMO

INTRODUCTION: In recent years, the number of general practices contributing to the Clinical Practice Research Datalink (CPRD) database GOLD is decreasing. Therefore, for research questions addressing for instance novel treatments requiring up-to-date data, sample size will become an important consideration in study feasibility. In recent years, CPRD Aurum, containing information of practices that use EMIS software, has become an additional data source that is being used for CPRD studies. In order to establish whether Aurum is suited to act as data source for future studies in the field of lung cancer research, we aimed to compare characteristics between patients with lung cancer in Aurum and GOLD. METHODS: A retrospective study was performed comparing characteristics and overall survival (OS) of patients with lung cancer in Aurum and GOLD. To further evaluate similarity, hypothetical eligibility of these patients in Aurum and GOLD was compared for 11 randomized clinical trials (RCTs). RESULTS: Baseline characteristics registered in Aurum and GOLD were largely similar, with some clinically irrelevant differences for previous malignancies, deviant laboratory values and drug use. Median OS was 9.8 and 9.0 months for patients in Aurum and GOLD, respectively. Potential RCT eligibility varied between 49.4% and 79.5% and 49.1% and 78.1% for patients in Aurum and GOLD, respectively. Mortality rates and the comparison of the obtained HRs per hypothetical eligibility cohort per RCT were similar in Aurum and GOLD. CONCLUSION: This study showed that data of patients with lung cancer in Aurum and GOLD are largely comparable, suggesting that Aurum is suitable for future epidemiological lung cancer research.


Assuntos
Registros Eletrônicos de Saúde , Neoplasias Pulmonares , Humanos , Gerenciamento de Dados , Neoplasias Pulmonares/epidemiologia , Bases de Dados Factuais , Atenção Primária à Saúde , Reino Unido/epidemiologia
3.
JTO Clin Res Rep ; 4(4): 100481, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37035409

RESUMO

Introduction: EGFR tyrosine kinase inhibitor improved the survival of patients with metastatic EGFR mutation-positive (EGFRm+) NSCLC. Despite high response rates, resistance develops inevitably in every patient. In up to 13%, HER2 protein overexpression is found on progression. We hypothesized that dual blockade of EGFR and HER2 by osimertinib combined with trastuzumab-emtansine (T-DM1) could reinduce tumor responses. Methods: In this multicenter, single-arm, phase 1-2 study (NCT03784599), patients with EGFRm+ NSCLC, progressing on osimertinib and HER2 overexpression were included. Patients were treated with T-DM1 3.6 mg/kg (intravenously) every 3 weeks and osimertinib 80 mg once a day. Primary end points were objective response rate (ORR) at 12 weeks and safety. Responses were assessed every 6 weeks (Response Evaluation Criteria in Solid Tumors 1.1). Sample size was calculated using Simon's two-stage minimax design (H0 = 41%, H1 > 55%, 80% power, one-sided type I error 10%: a ORR 16 of 36 was needed to proceed to 58 patients). Results: From January 2019 to April 2021, 27 patients were enrolled. ORR after 12 weeks of treatment was 4% (1 of 27). Median progression-free survival was 2.8 months (95% confidence interval: 1.4-4.6 mo). Most frequent treatment-related adverse events of any grade were fatigue, diarrhea, and nausea, among these, grade 3 in four patients. There were no grade 4 or 5 therapy-related adverse events. Conclusions: TRAEMOS (Trastuzumab-Emtansine and Osimertinib) is the first trial combining T-DM1 and osimertinib in patients with EGFRm+ NSCLC to target HER2 overexpression at osimertinib resistance. Safety profile was favorable compared with cytotoxic chemotherapy; but treatment revealed limited efficacy. Further clinical evaluation of this regimen is not warranted.

6.
Ann Oncol ; 33(9): 893-908, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35777706

RESUMO

The standard of care for patients with stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by 1 year of adjuvant durvalumab. Despite the survival benefit granted by immunotherapy in this setting, only 1/3 of patients are alive and disease free at 5 years. Novel treatment strategies are under development to improve patient outcomes in this setting: different anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] antibodies after CCRT, consolidation immunotherapy after sequential chemoradiotherapy, induction immunotherapy before CCRT and immunotherapy concurrent with CCRT and/or sequential chemoradiotherapy. Cross-trial comparison is particularly challenging in this setting due to the different timing of immunotherapy delivery and different patients' inclusion and exclusion criteria. In this review, we present the results of clinical trials investigating immune therapy in unresectable stage III NSCLC and discuss in-depth their biological rationale, their pitfalls and potential benefits. Particular emphasis is placed on the potential mechanisms of synergism between chemotherapy, radiation therapy and different monoclonal antibodies, and how this affects the tumor immune microenvironment. The designs and questions tackled by ongoing clinical trials are also discussed. Last, we address open questions and unmet clinical needs, such as the necessity for predictive biomarkers (e.g. radiomics and circulating tumor DNA). Identifying distinct subsets of patients to tailor anticancer treatment is a priority, especially in a heterogeneous disease such as stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/métodos , Humanos , Fatores Imunológicos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Microambiente Tumoral
9.
Lung Cancer ; 155: 163-169, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33838467

RESUMO

OBJECTIVES: Monotherapy with pembrolizumab is the preferred first-line treatment for metastatic non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression ≥50 %, without targetable oncogenic drivers. Although targeted therapies are in development for patients with specific Kirsten rat sarcoma (KRAS) mutations, these are not available in daily care yet. It is not clear whether there is a difference in survival on first-line pembrolizumab for patients with a high PD-L1 status with or without a KRAS mutation. We aim to compare this survival based on real-world data. MATERIALS AND METHODS: This is a real-world retrospective population-based study using data from the Netherlands Cancer Registry. We selected patients with stage IV lung adenocarcinoma with PD-L1 expression ≥50 % diagnosed between January 2017 and December 2018, treated with first-line pembrolizumab. Patients with EGFR mutations, ALK translocations or ROS1 rearrangements were excluded. The primary outcome parameter was overall survival. RESULTS: 388 (57 %) of 595 patients had a KRAS mutation. KRAS was seen more frequently in women than in men (65 % versus 49 % respectively, p < 0.001). The median overall survival was 19.2 months versus 16.8 months for patients with and without KRAS mutation, respectively (p = 0.86). Multivariable analysis revealed WHO performance score, number of organs with metastases and PD-L1 percentage as independent prognostic factors. KRAS mutation status had no prognostic influence (hazard ratio = 1.03, 95 % CI 0.83-1.29). CONCLUSION: The survival of KRAS mutated versus KRAS wild-type lung adenocarcinoma patients, treated with first-line pembrolizumab monotherapy, is similar, suggesting that KRAS has no prognostic value with respect to treatment with pembrolizumab.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Anticorpos Monoclonais Humanizados , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Países Baixos , Prognóstico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
10.
Respir Med Res ; 78: 100788, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980653

RESUMO

PURPOSE: Anti Programmed Death-ligand (PD1/PD-L1) directed immune-checkpoint-inhibitors (ICI) are widely used to treat patients with advanced non-small cell lung cancer (NSCLC) who progress after first line chemotherapy. The best strategy after early progression under first line has not been specifically studied. PATIENTS AND METHODS: We conducted a multicenter, retrospective study including all consecutive NSCLC patients progressing within the first 3 months following introduction of first-line chemotherapy and being treated with second line ICI monotherapy or chemotherapy between March 2010 and November 2017. We analysed the clinicopathological data and outcome under second line chemotherapy vs. second line ICI: objective response rate (ORR), progression-free survival (PFS), overall survival (OS. RESULTS: We identified 176 patients with refractory disease, 99 who received subsequent immunotherapy and 77 undergoing chemotherapy. The 2 populations were comparable regarding the main prognostic criteria, median age was 60, main histology was adenocarcimoma (68.2%). PFS was not significantly different between both treatments 1.9 [1.8-2.1] versus 1.6 month [1.4-2.0] (P=0.125). Compared to chemotherapy, ICI treated patients had a superior OS (P=0.03) (Median [95% CI] OS 4.6 [2.8-6.7] versus 4.2 months [3.4-5.9] and a non-significant improvement in ORR (17.2% versus 7.9%, respectively, P=0.072). Poor performance status (ECOG PS≥2) and a higher number of metastatic sites (≥3) were associated with poorer prognosis. KRAS-mutated patients did not seem to benefit more from ICI than chemotherapy. CONCLUSIONS: ICI appears to be the preferred second-line treatment for patients who are refractory to first line chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Feminino , França , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
11.
Lung Cancer ; 140: 107-112, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911323

RESUMO

OBJECTIVE: Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials. MATERIALS AND METHODS: From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied. RESULTS: A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days. Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7-2.7; 1.3, 95 % CI 1.0-1.6 and 1.2, 95 % CI 1.1-1.4, respectively). CONCLUSIONS: Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + .


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Registros/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Prognóstico , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida
12.
Tijdschr Psychiatr ; 61(12): 884-890, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31907903

RESUMO

Approximately 40% of adolescents with obsessive-compulsive disorder (ocd) do not improve sufficiently from standard cognitive behavioral therapy, and are at risk for a chronic course of the symptomatology as well as stagnation in their development. There has hardly been any research into next step evidence-based treatments for adolescents with persevering ocd. We treated three adolescents with persevering ocd with an eight-day intensive, therapist-assisted exposure and response prevention (erp) in which family members were involved. Two out of the three patients showed an improvement in ocd-symptoms and for one of these two patients the symptoms went in full remission. These outcomes are promising, and these case studies prove that short erp therapy, which is more intensive and provides assisted erp, can be a possible second step in the treatment.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo/terapia , Adolescente , Feminino , Humanos , Resultado do Tratamento
13.
Cancer Treat Rev ; 71: 47-58, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30359792

RESUMO

Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment strategy of advanced non-small cell lung cancer (NSCLC) in first- and second-line setting improving the prognosis of these patients. However, the treatment landscape has been also drastically overturned with the advent of targeted therapies in oncogenic-addicted advanced NSCLC patients. Despite ICIs represent an active and new treatment option for a wide range of advanced NSCLC patients, the efficacy and the optimal place of ICI in the treatment strategy algorithm of oncogenic-addicted tumors remains still controversial, as only a minority of trials with ICI enrol oncogenic-addicted NSCLC patients previously treated with standard therapy. Therefore, there are still several open questions about ICI in oncogenic-driven NSCLC, such as the efficacy and toxicities, which need to be addressed before considering treatment with ICI as a standard approach in this population. It is in this framework, we provide a thorough overview on this currently controversial topic.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Proteínas Oncogênicas/genética , Quinase do Linfoma Anaplásico/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor ErbB-2/genética
14.
Lung Cancer ; 121: 76-81, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29858031

RESUMO

OBJECTIVES: Biological predisposition for specific metastatic organs might differ between molecular subgroups of lung cancer. We aimed to assess the association between molecular status and metastatic organs at diagnosis in a nationwide stage IV non-squamous non-small cell lung cancer ((ns)-NSCLC) cohort. METHODS: All ns-NSCLC from 2013 that were stage IV at diagnosis were identified from the Netherlands Cancer Registry, which records information on metastatic organs at diagnosis. Tumors were matched to the Dutch Pathology Registry (PALGA) from which data on molecular status established in routine practice was extracted. Four molecular subgroups (EGFR+, KRAS+, ALK+, triple-negative) were identified. For each metastatic organ, proportions of tumors metastasized to this organ were, per molecular subgroup, compared to triple-negative tumors by multivariable logistic regression analyses (adjusted odds ratios (OR) with 95% confidence intervals (CI)), taking clinicopathological variables into account. RESULTS: 160 EGFR+ (exon 19 del, exon 21 L858R), 784 KRAS+, 42 ALK+, and 1008 triple-negative tumors were identified. Most frequent metastatic organs were the bone (34%), pleura (24%), lung (23%), and brain (22%). Compared to triple-negatives, EGFR+ tumors had more often metastases to the bone (31.5 vs 53.8%; OR 2.55 (95% CI 1.80-3.62)) and pleura (24.1 vs 37.5%; OR 2.06 (1.42-2.98)), and less often to the brain (22.0 vs 12.5%; OR 0.53 (0.32-0.88)) and adrenal glands (19.1 vs 7.5%; OR 0.46 (0.28-0.75)). Compared to triple-negatives, KRAS+ and ALK+ tumors had at diagnosis metastasized more often to the lung (20.3 vs 26.7%; OR 1.40 (1.12-1.76)) and the liver (13.1 vs 23.8%; OR 2.07 (1.00-4.32)), respectively. CONCLUSION: NSCLC molecular status was associated with metastatic pattern at diagnosis. 54% of stage IV EGFR+ ns-NSCLC patients had bone metastases at diagnosis. These observational results are hypothesis generating, and call for a prospective study where EGFR+ patients are screened for bone metastases, and treated to prevent skeletal related events.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Genes erbB-1/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Países Baixos , Patologia Molecular , Sistema de Registros , Análise de Sobrevida
15.
Clin Cancer Res ; 23(15): 4251-4258, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28183714

RESUMO

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non-small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH.Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH-positive advanced NSCLC from four other hospitals were used for validation.Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC-positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH-positive but ALK-IHC-negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P = 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P = 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P = 0.01, respectively].Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy. Clin Cancer Res; 23(15); 4251-8. ©2017 AACR.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Adulto , Idoso , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/isolamento & purificação , Biópsia por Agulha Fina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Rearranjo Gênico/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Receptores Proteína Tirosina Quinases/administração & dosagem , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/isolamento & purificação
16.
J Intellect Disabil Res ; 60(2): 134-48, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26708920

RESUMO

BACKGROUND: Training support staff in dealing with challenging behaviour in clients with intellectual disabilities (ID) is needed. The goal of this study is to determine which elements need to be incorporated in a training on staff interactions with these clients, building upon a framework and an interpersonal model. As in functional analysis, this study tests the influence of client interpersonal behaviour, three types of staff reactions to challenging behaviour, two types of staff psychological resources and staff team climate on four styles of staff interpersonal behaviour. METHOD: A total of 318 support staff members completed a questionnaire on staff interpersonal behaviour for 44 clients with ID and challenging behaviour, as well as seven questionnaires on client interpersonal behaviour, staff emotions, attributions, self-efficacy, self-reflection, coping styles and team climate. The influence of these seven factors on four staff interpersonal behaviours was examined using multilevel multiple regression analysis. RESULTS: Friendly-warm and dominant client interpersonal behaviour had a significant positive impact on friendly and assertive control staff behaviour, respectively. Also, there was a strong influence of staff negative and positive emotions, as well as their self-efficacy, on most of the staff interpersonal behaviours. Staff self-reflection, insight and avoidance-focused coping style had an impact on some staff interpersonal behaviours. Staff team climate only predicted higher support-seeking staff behaviour. CONCLUSIONS: In conducting a functional analysis of staff interpersonal behaviour, the results of this study can be used both as a framework in staff-client interaction training and in clinical practice for treating challenging behaviour. The emphasis in training and practice should not only be on the bidirectional dynamics of control and affiliation between staff and clients, but also - in order of importance - on the impact of staff emotions, self-efficacy, self-reflection and insight, coping style, team climate and attributions on staff interpersonal behaviour.


Assuntos
Pessoal de Saúde/psicologia , Deficiência Intelectual/reabilitação , Comportamento Problema , Relações Profissional-Paciente , Adolescente , Adulto , Atitude do Pessoal de Saúde , Criança , Feminino , Pessoal de Saúde/educação , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Eur J Cancer ; 51(17): 2534-44, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26323530

RESUMO

PURPOSE: To analyse the prognostic impact on overall survival (OS) of single versus multiple organ metastases, organ affected, and local disease status in a population based stage IV non-small cell lung cancer (NSCLC) cohort. METHODS: In this observational study, data were analysed of all histologically confirmed stage IV NSCLC patients diagnosed between 1 January 2006 and 31 December 2012 registered in the Netherlands Cancer Registry. Location of metastases before treatment was registered. Multivariable survival analyses [age, gender, histology, M-status, local disease status, number of involved organs, actual organ affected] were performed for all patients and for an (18)fluorodeoxyglucose-positron emission tomography ((18)FDG-PET)-staged subgroup. RESULTS: 11,094 patients were selected: 60% male, mean age 65 years, 73% adenocarcinoma. Median OS for 1 (N = 5676), 2 (N = 3280), and ⩾ 3 (N = 2138) metastatically affected organs was 6.7, 4.3, 2.8 months, respectively (p < 0.001). Hazard ratio (HR) for 2 versus 1 organ(s) was 1.33 (p < 0.001), for ⩾ 3 versus 1 organ(s) 1.91 (p < 0.001). Results were confirmed in the (18)FDG-PET-staged cohort (N = 1517): patients with single organ versus 2 and ⩾ 3 organ metastases had higher OS (8.6, 5.7, 3.8 months, HR 1.40 and 2.17, respectively, p < 0.001). In single organ metastases, OS for low versus high TN-status was 8.5 versus 6.5 months [HR 1.40 (p < 0 .001)]. (18)FDG-PET-staged single organ metastases patients with low TN-status had a superior OS than those with high TN-status (11.6 versus 8.2 months, HR 1.62, p < 0.001). CONCLUSION: Patients with single organ metastases stage IV NSCLC have a favourable prognosis, especially in combination with low TN status. They have to be regarded as a separate subgroup of stage IV disease.


Assuntos
Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Idoso , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imagem Multimodal/estatística & dados numéricos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X
18.
Lung Cancer ; 84(1): 86-91, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24529684

RESUMO

OBJECTIVES: Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied. METHODS: In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected. RESULTS: 189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p=0.645). Mean time to brain metastases was 20.8 [± 12.0], 10.8 [± 9.8], 16.4 [± 10.2] months (EGFR+-KRAS+, p = 0.020, EGFR+-WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0-19.1], 7.6 [1.2-14.0], 10.7 [1.5-19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p=0.528). Mean time to development of metastatic bone disease was 13.4 [± 10.6], 23.3 [± 19.4], 16.4 [± 9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6-20.3], 9.0 [5.2-12.9], 3.2 [0.0-6.9] months (p = 0.010). Time to 1st SRE was not significantly different. CONCLUSIONS: Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Genes ras , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Respir Med Case Rep ; 5: 37-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-26029585

RESUMO

Lung transplantation is an accepted therapy for patients with end-stage lung disease and offers a major survival benefit in selected patients. The most important indications are chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis besides cystic fibrosis and pulmonary arterial hypertension. The incidence of lung cancer in patients after Ltx is 20-25 times higher than in the general population. Diagnosis is often difficult in IPF patients because of the diffuse lung abnormalities due to the underlying fibrosis. Moreover, the lung cancer may mimic a pulmonary infection. Symptoms are often aspecific, diagnosis is difficult, and prognosis is extremely poor. We describe three patients who were transplanted for idiopathic pulmonary fibrosis and who developed a primary lung cancer.

20.
Res Dev Disabil ; 31(3): 760-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20211538

RESUMO

Given that sexually offensive behavior on the part of people with intellectual disabilities has been identified as a significant problem, we developed a risk assessment questionnaire, that takes not only various static and dynamic factors into account but also environmental risk variables. Psychologists and staff members completed this Risk Inventarization Scale on Sexually Offensive Behavior of Clients with Intellectual Disabilities for 56 intellectually disabled clients with sexually offensive behavior problems. The scale contains static client variables (rated using two- or five-point likert scales and open questions) and both dynamic client and environmental variables (rated using a five-point Likert scale). Factor analyses of the dynamic client and environmental variables revealed three subscales: quality of supervision, offending behavior and emotional and social stability. Reliability analyses showed sufficient to good reliability for both the total scale (r=0.82) and the identified subscales (quality of guidance r=0.94; offending behavior r=0.75, and emotional and social stability r=0.58). Correlational analyses of the quality of guidance subscale showed high positive correlations with such static variables as values and norms, living conditions, and criminal offenses in early youth. Because both dynamic and environmental variables can be altered, the implications for treatment of the sexually offensive behavior of clients with intellectual disabilities are discussed further.


Assuntos
Exibicionismo/epidemiologia , Deficiência Intelectual/epidemiologia , Estupro/estatística & dados numéricos , Inquéritos e Questionários , Violência/estatística & dados numéricos , Adulto , Meio Ambiente , Exibicionismo/diagnóstico , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Medição de Risco , Fatores de Risco , Valores Sociais
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