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1.
J Eur Acad Dermatol Venereol ; 36 Suppl 1: 53-58, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34855244

RESUMO

It is well known that organ transplant recipients are prone to develop non-melanoma skin cancers, particularly cutaneous squamous cell carcinoma (cSCC). This is explained by the long-term use of immunosuppressants and thus the decrease of the immunosurveillance that protects from developing malignant tumours. Solid organ transplant recipients (SOTRs) are 65-250 times more likely to develop cSCC compared to the general population (Am J Transplant 2017; 17: 2509). Moreover, in these patients cSCCs follow a more aggressive course. Close follow-up and regular skin check-ups by a dermatologist are, therefore, crucial in the management of these patients. When detected early, cSCC can be easily and effectively treated by a simple excision. However, when advanced, outcomes are poor. Immune checkpoints inhibitors (ICIs) have been recently added to our arsenal and represent a breakthrough, having proved to be effective in achieving long-term responses. We, hereby, present two cases of difficult-to-treat cSCCs in renal transplanted patients.


Assuntos
Carcinoma de Células Escamosas , Transplante de Rim , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas/cirurgia , Humanos , Transplante de Rim/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico
2.
Qual Life Res ; 28(3): 663-676, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30511255

RESUMO

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.


Assuntos
Avaliação Geriátrica/métodos , Nível de Saúde , Diferença Mínima Clinicamente Importante , Neoplasias/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/patologia , Medição da Dor/métodos , Inquéritos e Questionários
3.
Ann Oncol ; 29(9): 1987-1994, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29905766

RESUMO

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.


Assuntos
Assistência ao Convalescente/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Neoplasias/diagnóstico , Assistência ao Convalescente/normas , Idoso , Idoso de 80 Anos ou mais , Bélgica , Tomada de Decisão Clínica , Feminino , Humanos , Masculino , Programas de Rastreamento/normas , Oncologia/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Qualidade de Vida
4.
Neurochirurgie ; 63(4): 297-301, 2017 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28882604

RESUMO

INTRODUCTION: Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined. METHOD: We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery. RESULTS: Five patients from 19 to 70 years of age (median, 37years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26months [8-90]). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 ± 5; range 12-24) of temozolomide (150-200mg/m2/day, 5days/28days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity. CONCLUSION: Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Astrocitoma/tratamento farmacológico , Astrocitoma/cirurgia , Dacarbazina/análogos & derivados , Neoplasias da Medula Espinal/tratamento farmacológico , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Astrocitoma/diagnóstico por imagem , Quimioterapia Adjuvante , Dacarbazina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico por imagem , Temozolomida , Adulto Jovem
5.
J Nutr Health Aging ; 20(1): 60-70, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26728935

RESUMO

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.


Assuntos
Avaliação Geriátrica , Hospitais , Programas de Rastreamento , Neoplasias/terapia , Idoso , Idoso de 80 Anos ou mais , Bélgica , Feminino , Serviços de Saúde para Idosos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Inquéritos e Questionários
6.
Clin Microbiol Infect ; 21(1): 35-42, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25636925

RESUMO

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.


Assuntos
Farmacorresistência Bacteriana , Otite Média/epidemiologia , Otite Média/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Antibacterianos/farmacologia , França/epidemiologia , Humanos , Incidência , Testes de Sensibilidade Microbiana , Otite Média com Derrame/microbiologia , Vacinas Pneumocócicas , Sorogrupo
7.
Diabetes Obes Metab ; 15 Suppl 3: 89-97, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24003925

RESUMO

This review focuses on genes that control ß-cell targeting in autoimmune, type 1-dependent, diabetes (T1D) and on insulin as the major autoantigen recognized by T lymphocytes throughout the disease process. T1D associates with multiple gene variants. Beyond genes that predispose to general failure of immune tolerance to self, loci identified by the analysis of crosses between non-obese diabetic (NOD) and conventional mouse strains harbour genes that control ß-cell targeting or the deviation of autoimmunity towards other tissues. We report here the role of genes encoding co-activation molecules involved in the activation of T lymphocytes, ICOS and ICOS ligand (B7RP1). NOD mice which are deficient in either of these two molecules are protected from diabetes, but instead develop a neuromuscular autoimmune disease. We also report the characterization in humans of T lymphocytes that are specific for major ß-cell autoantigens, especially insulin. This opens the way towards new bioassays in the diagnosis of autoimmunity and towards autoantigen-specific immunotherapy in T1D. In order to develop a new preclinical model of T1D that would allow testing insulin epitopes to induce immune tolerance in vivo, we developed a mouse that is deficient in endogenous major histocompatibility complex class I and class II genes and deficient for the two murine insulin genes and that express human class I, class II and insulin genes.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Células Secretoras de Insulina/imunologia , Linfócitos T/fisiologia , Animais , Autoimunidade/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Humanos , Tolerância Imunológica/genética , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos NOD
8.
Ann Oncol ; 24(5): 1306-12, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23293115

RESUMO

BACKGROUND: To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS: Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS: One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION: Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.


Assuntos
Avaliação Geriátrica , Serviços de Saúde para Idosos , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos de Viabilidade , Feminino , Humanos , Masculino , Programas de Rastreamento , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias/cirurgia , Estudos Prospectivos , Inquéritos e Questionários
9.
Acta Clin Belg ; 67(3): 226-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22897075

RESUMO

We describe the case of a 54-year old woman with breast cancer who was treated by vancomycin for febrile neutropenia due to a methicillin-resistant Staphyloccocus epidermidis infection of a surgically implanted catheter. She developed an hypersensitivity reaction to vancomycin associating neutropenia, fever, skin rash and elevated liver enzymes following re-challenge with vancomycin after having been misdiagnosed with septic thrombophlebitis. Following this re-challenge, neutrophils count fell dramatically but promptly resolved after cessation of vancomycin.


Assuntos
Antibacterianos/efeitos adversos , Exantema/induzido quimicamente , Febre/induzido quimicamente , Neutropenia/induzido quimicamente , Vancomicina/efeitos adversos , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Feminino , Humanos , Pessoa de Meia-Idade
10.
Vaccine ; 30(38): 5666-74, 2012 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-22776213

RESUMO

AIM: Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation. METHODS: BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively. RESULTS: AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2, Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells. CONCLUSIONS: In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Hipersensibilidade/terapia , Imunoglobulina G/administração & dosagem , Imunoterapia/métodos , Doenças Respiratórias/terapia , Administração Sublingual , Animais , Anticorpos Monoclonais/administração & dosagem , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/imunologia , Feminino , Humanos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Pletismografia Total , Resultado do Tratamento
11.
J Oncol ; 2012: 801306, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22481934

RESUMO

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials. Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals. Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1-31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7-39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment. Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

12.
J Hand Surg Am ; 37(5): 1024-32, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22480501

RESUMO

PURPOSE: Radiocapitellar arthroplasty has been proposed as a reconstructive option for combined radial head and capitellar deficiency. The purpose of this study was to assess the impact of radiocapitellar replacement on elbow kinematics. We hypothesized that with the medial collateral ligament (MCL) intact, radiocapitellar arthroplasty would replicate normal kinematics, and that a radiocapitellar arthroplasty would more closely approximate normal kinematics than an elbow with a deficient lateral column or with a deficient MCL. METHODS: We tested 7 cadaveric arms in an upper extremity joint simulator. Each arm underwent computed tomographic scanning to aid implant size selection and computer-assisted implant insertion. We obtained kinematic data using an electromagnetic tracking system during elbow flexion. The capitellar and radial head implants were placed through an extended lateral epicondylar osteotomy. We sectioned the anterior bundle of the MCL, leaving the flexor-pronator mass intact. Outcomes of interest were varus-valgus and rotational kinematics of the ulnohumeral joint. RESULTS: The radiocapitellar arthroplasty showed no difference in kinematics compared with the postosteotomy control. The MCL-deficient elbow showed more valgus angulation and more external ulnar rotation than the control or radiocapitellar arthroplasty in the pronated, valgus loaded position. The deficient lateral column demonstrated increased external ulnar rotation kinematics during active elbow flexion. CONCLUSIONS: Radiocapitellar arthroplasty can restore normal elbow kinematics with the MCL intact. If the MCL is deficient, radiocapitellar arthroplasty does not restore normal kinematics. CLINICAL RELEVANCE: Radiocapitellar arthroplasty should be considered in cases of lateral column deficiency because it maintains normal elbow kinematics during active motion. Whereas radiocapitellar arthroplasty improves the stability of the MCL-deficient elbow with deficiency of the lateral column, reconstruction of the MCL may further improve normal kinematics.


Assuntos
Artroplastia/métodos , Articulação do Cotovelo/fisiopatologia , Articulação do Cotovelo/cirurgia , Rádio (Anatomia)/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Cadáver , Ligamentos Colaterais/fisiopatologia , Ligamentos Colaterais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/fisiopatologia , Amplitude de Movimento Articular , Rotação , Tomografia Computadorizada por Raios X
13.
Rev Med Brux ; 30(5): 488-95, 2009.
Artigo em Francês | MEDLINE | ID: mdl-19998794

RESUMO

Comprehensive geriatric assessment (CGA) represents a multidisciplinary comprehensive evaluation of an older individual's functional status, comorbid medical conditions, cognition, psychological state, social support, nutritional status, and a review of the patient's medications. Initially, the use of a CGA in the care of older patients with cancer was based on an extrapolation of its ability to predict morbidity and mortality in the general geriatric population. More recently, however, accumulating data show the benefits of using a CGA particularly in patients with cancer to predict morbidity and mortality. Prospective trials evaluating the utility of a CGA to guide interventions to improve the quality of cancer care in older adults are justified.


Assuntos
Geriatria/estatística & dados numéricos , Neoplasias/epidemiologia , Idoso , Transtornos Cognitivos/complicações , Comorbidade , Humanos , Neoplasias/complicações , Neoplasias/terapia , Avaliação Nutricional , Estado Nutricional , Comportamento Social , Apoio Social
14.
Acta Clin Belg ; 62(4): 223-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17849693

RESUMO

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Interleucina-2/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Bélgica , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
15.
Lung Cancer ; 38(2): 111-21, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12399121

RESUMO

The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/tratamento farmacológico , Mesotelioma/imunologia , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Doxorrubicina/administração & dosagem , Humanos , Mesotelioma/patologia , Prognóstico , Resultado do Tratamento
16.
Rev Mal Respir ; 15(5): 633-41, 1998 Oct.
Artigo em Francês | MEDLINE | ID: mdl-9834991

RESUMO

The role of chest irradiation in the treatment of small cell lung cancer remains controversial. Two meta-analyses have shown a significant improvement of survival when this therapy is associated to chemotherapy but the controlled studies individually lead to contradictory conclusions. We have performed qualitative and quantitative evaluation of the literature on this topic in order to try to clarify this problem. On 15 published trials, 8 only give sufficient data allowing a meta-analysis. This does not show that chest irradiation improves statistically significantly survival in comparison to chemotherapy alone (odds ratio = 0.82; 95% CI: 0.63-1.07). The qualitative evaluation has been performed with the Chalmers and ELCWP scales. The scores obtained by both methods are highly correlated. There is no significant difference between the scores obtained by studies showing a survival improvement with irradiation or by negative studies. Very few trials report important criteria like definition of the primary end-point or the a priori estimate of the population size, attesting important methodological deficiencies. In conclusion, the quantitative aggregation of studies seems difficult to interpret because of the non optimal quality of the studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Quimioterapia Adjuvante , Humanos , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Análise de Sobrevida
17.
Rev Pneumol Clin ; 54(3): 119-22, 1998 Jul.
Artigo em Francês | MEDLINE | ID: mdl-9769997

RESUMO

The role of maintenance chemotherapy in the treatment of small cell lung cancer remains controversial. We have collected the arguments in favor of that approach by performing a quantitative and qualitative overview of the studies published on this topic in the French and English literatures since 1980. On the thirteen prospective randomized trials reported, six demonstrated a significant survival advantage in favor of maintenance, no difference was observed in 6 and 1 study had a significant survival advantage for no maintenance. Due to the heterogeneity of the study designs and to the lack of published data, no meta-analysis could be performed. A qualitative overview of the different trials showed that the quality scores of the positive trials was similar to the negative ones, allowing us to conclude that they could be considered at the same level. No negative trial with a similar design can be opposed to each particular positive trial that is thus not conterbalanced. Moreover the trials not in favor of maintenance could be falsely negative by a lack of power, the publications mentioning no statistical consideration. There are thus a series of arguments in favor of maintenance chemotherapy for small-cell lung cancer, which require to be confirmed by randomised trials of adequate quality.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Am J Hum Genet ; 62(4): 824-33, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9529364

RESUMO

Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription factor involved in renal and gonadal development, are found in most patients with Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with pseudohermaphroditism and/or Wilms tumor (WT). Most mutations in DDS patients lie in exon 8 or exon 9, encoding zinc finger 2 or zinc finger 3, respectively, with a hot spot (R394W) in exon 9. We analyzed a series of 24 patients, 10 with isolated DMS (IDMS), 10 with DDS, and 4 with urogenital abnormalities and/or WT. We report WT1 heterozygous mutations in 16 patients, 4 of whom presented with IDMS. One male and two female IDMS patients with WT1 mutations underwent normal puberty. Two mutations associated with IDMS are different from those described in DDS patients. No WT1 mutations were detected in the six other IDMS patients, suggesting genetic heterogeneity of this disease. We analyzed genotype/phenotype correlations, on the basis of the constitution of a WT1 mutation database of 84 germ-line mutations, to compare the distribution and type of mutations, according to the different symptoms. This demonstrated (1) the association between mutations in exons 8 and 9 and DMS; (2) among patients with DMS, a higher frequency of exon 8 mutations among 46, XY patients with female phenotype than among 46,XY patients with sexual ambiguity or male phenotype; and (3) statistically significant evidence that mutations in exons 8 and 9 preferentially affect amino acids with different functions.


Assuntos
Proteínas de Ligação a DNA/genética , Bases de Dados Factuais , Transtornos do Desenvolvimento Sexual/genética , Genes do Tumor de Wilms , Neoplasias Renais/genética , Mutação , Fatores de Transcrição/genética , Tumor de Wilms/genética , Sequência de Aminoácidos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Dados de Sequência Molecular , Fenótipo , Síndrome , Proteínas WT1
19.
Lung Cancer ; 19(2): 141-51, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9567251

RESUMO

Maintenance chemotherapy after induction therapy is a controversial topic in small cell lung cancer. We carried out a critical review of the literature on this topic. Since 1980, 13 randomized trials have been published. One shows a statistically significant difference in survival in favor of maintenance, five obtain some survival advantages in subgroups of patients, one shows a significantly shorter survival with maintenance and in six studies, there is no difference between both arms. A quantitative overview or meta-analysis was unpracticable because of the lack of data for calculation of the odds ratio in the publications and because of the heterogeneity of the studies' designs. A qualitative overview was carried out using two scales: the Chalmers scores and the European Lung Cancer Working Party (ELCWP) score. Correlation between both scores was excellent. There was no significant difference in quality scores with both methods between negative trials and those who showed some survival advantage for survival. The overall quality of the publications was not good, with important methodological aspects missing, such as a clear definition of the primary objective or an a priori estimate of the sample size necessary to conduct the trial. We concluded that maintenance chemotherapy could have some indications and that good quality trials, as reflected by very high quality scores, need to be carried out in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Taxa de Sobrevida
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