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1.
Support Care Cancer ; 31(12): 653, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878140

RESUMO

Cancer patients seeking emergency care can be vulnerable in increasingly overcrowded Emergency Departments and timely delivery of care is often aspirational rather than reality in many acute care systems. Ambulatory emergency care and its various international models are recognized as contributing to the safety and sustainability of emergency care services. This schema can logically be extended to the emergency oncology setting. The recent proliferation of immune checkpoint inhibitors (ICIs) has led to another opportunity for the management of oncologic complications in the ambulatory emergency care setting. More nuanced risk stratification of currently perceived high-risk toxicities may also afford the opportunity to personalize acute management. Virtual wards, which predominantly provide virtual monitoring only, and hospital at home services, which provide more comprehensive in-person assessment and interventions, may be well suited to supporting care for ICI toxicity alongside hospital-based assessment. Emergency management guidelines for immune-mediated toxicities will increasingly need to be both pragmatic and deliverable, especially as larger numbers of patients will present outside cancer centers. Identifying and modelling those suitable for emergency ambulatory care is integral to achieving this.


Assuntos
Serviços Médicos de Emergência , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Oncologia , Hospitais , Assistência Ambulatorial
2.
Int J Clin Pract ; 74(1): e13436, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31633264

RESUMO

Ambulatory emergency oncology The challenges of emergency oncology alongside its increasing financial burden have led to an interest in developing optimal care models for meeting patients' needs. Ambulatory care is recognised as a key tenet in ensuring the safety and sustainability of acute care services. Increased access to ambulatory care has successfully reduced ED utilisation and improved clinical outcomes in high-risk non-oncological populations. Individualised management of acute cancer presentations is a key challenge for emergency oncology services so that it can mirror routine cancer care. There are an increasing number of acute cancer presentations, such as low-risk febrile neutropenia and incidental pulmonary embolism, that can be risk assessed for care in an emergency ambulatory setting. Modelling of ambulatory emergency oncology services will be dependent on local service deliveries and pathways, but are key for providing high quality, personalised and sustainable emergency oncology care. These services will also be at the forefront of much needed emergency oncology to define the optimal management of ambulatory-sensitive presentations.


Assuntos
Assistência Ambulatorial , Serviços Médicos de Emergência , Oncologia , Neoplasias/terapia , Assistência Ambulatorial/organização & administração , Serviços Médicos de Emergência/organização & administração , Humanos , Modelos Organizacionais , Neoplasias/complicações
3.
Br J Nurs ; 26(10): S4-S12, 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28541108

RESUMO

Quick access to toxicity management information ensures timely access to steroids/immunosuppressive treatment for cancer patients experiencing immune-related adverse events, thus reducing length of hospital stays or avoiding hospital admission entirely. This article discusses a project to add a QR (quick response) code to a patient-held immunotherapy alert card. As QR code generation is free and the immunotherapy clinical management algorithms were already publicly available through the trust's clinical network website, the costs of integrating a QR code into the alert card, after printing, were low, while the potential benefits are numerous. Patient-held alert cards are widely used for patients receiving anti-cancer treatment, and this established standard of care has been modified to enable rapid access of information through the incorporation of a QR code.


Assuntos
Acesso à Informação , Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Fatores Imunológicos/efeitos adversos , Internet , Neoplasias/tratamento farmacológico , Smartphone , Algoritmos , Gestão da Informação em Saúde , Humanos , Aplicativos Móveis , Enfermagem Oncológica
4.
Br J Cancer ; 115(10): 1193-1200, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27711083

RESUMO

BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. RESULTS: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/patologia , Terapia Combinada/métodos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Radiossensibilizantes/uso terapêutico , Radioterapia/métodos
5.
Oncologist ; 21(3): 301-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26921289

RESUMO

Remarkable progress has been made over the past decade in cancer medicine. Personalized medicine, driven by biomarker predictive factors, novel biotherapy, novel imaging, and molecular targeted therapeutics, has improved outcomes. Cancer is becoming a chronic disease rather than a fatal disease for many patients. However, despite this progress, there is much work to do if patients are to receive continuous high-quality care in the appropriate place, at the appropriate time, and with the right specialized expert oversight. Unfortunately, the rapid expansion of therapeutic options has also generated an ever-increasing burden of emergency care and encroaches into end-of-life palliative care. Emergency presentation is a common consequence of cancer and of cancer treatment complications. It represents an important proportion of new presentations of previously undiagnosed malignancy. In the U.K. alone, 20%-25% of new cancer diagnoses are made following an initial presentation to the hospital emergency department, with a greater proportion in patients older than 70 years. This late presentation accounts for poor survival outcomes and is often associated with poor patient experience and poorly coordinated care. The recent development of acute oncology services in the U.K. aims to improve patient safety, quality of care, and the coordination of care for all patients with cancer who require emergency access to care, irrespective of the place of care and admission route. Furthermore, prompt management coordinated by expert teams and access to protocol-driven pathways have the potential to improve patient experience and drive efficiency when services are fully established. The challenge to leaders of acute oncology services is to develop bespoke models of care, appropriate to local services, but with an opportunity for acute oncology teams to engage cancer care strategies and influence cancer care and delivery in the future. This will aid the integration of highly specialized cancer treatment with high-quality care close to home and help avoid hospital admission.


Assuntos
Serviços Médicos de Emergência , Neoplasias/mortalidade , Neoplasias/terapia , Serviço Hospitalar de Oncologia , Medicina de Precisão , Humanos , Prognóstico , Reino Unido
6.
Postgrad Med J ; 92(1093): 649-652, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27170310

RESUMO

BACKGROUND: Following the National Chemotherapy Advisory Group report, calling for better management of patients with cancer admitted acutely to hospital, Clatterbridge Cancer Centre, with Merseyside and Cheshire Cancer Network, implemented an acute oncology service (AOS) for the region's seven acute trusts. STUDY DESIGN: We prospectively collected data on all referrals from March 2010 to December 2012, seen by the seven local teams within the cancer network. RESULTS: Over 7000 patient-episodes were analyzed. We found an AOS has the greatest impact on reducing hospital stay of patients admitted with complications of cancer treatment, compared with patients presenting with cancer symptoms, or those presenting with a new cancer as an emergency. Also an AOS significantly reduces the mortality rate of patients admitted with complications of cancer treatment, compared with patients presenting with cancer symptoms, either of a known cancer or those patients presenting with a new cancer as an emergency. CONCLUSIONS: Our network establishment of an AOS has had a positive impact on the quality of care cancer patients receive, in addition to saving local trusts valuable bed days, due to the overall reduction in hospital stay. This study also highlights deficiencies in the cancer journeys of certain patients with cancer, such as patients who present with a new cancer as an emergency admission, or patients unable to be discharged due to a lack of community resources. Such analysis is important in highlighting where the AOS can concentrate resources and collaborate with other healthcare professionals, especially within the local community.

7.
Clin Med (Lond) ; 15(4): 382-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26407392

RESUMO

Radiotherapy is an effective treatment modality and an essential tool in the management of cancer. As the incidence of malignant disease rises it is inevitable that physicians will increasingly encounter patients who have presented acutely and require radiotherapy or with a complication from irradiation. This paper explores the basic principles of radiotherapy tailored to the perspective of the acute medical physician and how to manage acute complications. We also discuss the role of radiotherapy in the acutely ill patient and define the need for radiotherapy pathways to ensure that patients receive treatment in a timely manner.


Assuntos
Neoplasias/radioterapia , Cuidados Paliativos/métodos , Humanos , Fatores de Tempo
8.
World J Surg Oncol ; 12: 235, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-25070647

RESUMO

Calcifying fibrous tumors (CFT) are rare benign tumors. They usually affect children and young adults and the incidence is equal in males and females. The usual clinical presentation is that of a painless mass. A computed tomography scan typically reveals a well-demarcated calcified lesion. CFT usually presents as a solitary mass and the commonest sites of occurrence are in soft tissues, the pleura, or the peritoneum. Multifocal occurrences at the same site have also been reported. The first case of CFT was reported in 1988. We present a rare case of multiple calcifying fibrous tumors at multiple sites in the same patient. To the best of our knowledge, this is the first ever reported case of multifocal CFT atsix different anatomical sites in one patient.


Assuntos
Calcinose/diagnóstico , Neoplasias de Tecido Fibroso/diagnóstico , Adulto , Calcinose/cirurgia , Humanos , Masculino , Neoplasias de Tecido Fibroso/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X
9.
Int Immunol ; 24(7): 409-15, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22366043

RESUMO

CD56+ T cells were studied in samples of peripheral blood from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients compared with healthy controls. Relative numbers of CD56+CD3+ cells were increased in NSCLC (P = 0.001) and SCLC (P = 0.002) compared with normal subjects but their ability to respond to activation by up-regulating CD25 or producing IFN-γ were both significantly impaired. Expression of the killer-immunoglobulin-like receptor CD158a was significantly lower on CD56+CD3+ cells in SCLC than controls and also in early stage compared with late stage NSCLC patients. Mean levels of CD158e were higher in NSCLC patients than controls. CD158e levels on CD56+CD3+ cells were increased in the presence of its ligand HLA-Bw4 compared with controls. Although the precise role of CD56+CD3+ cells is not clear, they appear to be functionally impaired in lung cancer, which may have implications for a reduction of direct or indirect anti-tumour responses.


Assuntos
Complexo CD3/imunologia , Antígeno CD56/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Células Cultivadas , Antígenos HLA-B/metabolismo , Humanos , Interferon gama/metabolismo , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Estadiamento de Neoplasias , Receptores KIR2DL1/metabolismo
10.
Lancet Oncol ; 13(11): 1161-70, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23078958

RESUMO

BACKGROUND: Many patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients. METHODS: TOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050. FINDINGS: Between April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2-4·2, vs placebo, 3·6 months, 3·2-3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81-1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63-0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05-1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups. INTERPRETATION: Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival. FUNDING: Cancer Research UK, Roche.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Receptores ErbB , Cloridrato de Erlotinib , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Resultado do Tratamento
11.
Clin Med (Lond) ; 23(6): 571-581, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38065597

RESUMO

Acute oncology services (AOS) manage acute cancer-related presentations alongside acute medical teams. This study assessed AOS provision against national peer review measures and the burden of acute cancer-related admissions. The 2022 Society for Acute Medicine Benchmarking Audit surveyed UK hospitals, collecting hospital-level and patient-level data for all medical admissions over a 24-h period. Logistic regression models were constructed to identify differences in patient outcomes for cancer-related admissions. Most hospitals (n=120 or 91.6%) reported having an AOS. There was heterogeneity in AOS provision, with many failing to meet peer-review measures. Of the 7,116 patients, 542 (7.6%) were cancer-related admissions. Cancer-related admissions had greater clinical acuity (p<0.05), length of stay (p<0.001) and 14-day mortality (adjusted odds ratio (OR)=3.54, 95% confidence interval (CI): 2.41-5.22, p<0.001) compared with other medical admissions. Increasing availability of AOS with integration of ambulatory pathways are vital next steps to improving care for acute cancer-related admissions.


Assuntos
Benchmarking , Neoplasias , Humanos , Hospitalização , Auditoria Médica , Neoplasias/terapia , Reino Unido
12.
Immunology ; 133(1): 94-104, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21342183

RESUMO

Frequencies of natural killer (NK) cells from patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) did not differ from healthy controls. A higher proportion of NK cells from NSCLC patients expressed the killer immunoglobulin-like receptor (KIR) CD158b than in controls (P = 0.0004), in the presence or absence of its ligand, HLA-C1. A similar result was obtained for CD158e in the presence of its ligand HLA-Bw4 in NSCLC patients (P = 0.003); this was entirely attributable to the Bw4I group of alleles in the presence of which a fivefold higher percentage of CD158e(+) NK cells was found in NSCLC patients than controls. Proportions of CD158b(+) NK cells declined with advancing disease in NSCLC patients. Expression of NKp46, CD25 and perforin A, and production of interferon-γ following stimulation with interleukin-12 and interleukin-18, were all significantly lower in NK cells from NSCLC patients than in controls. Both NK cell cytotoxicity and granzyme B expression were also reduced in lung cancer patients. Increased inhibitory KIR expression would decrease NK cell cytotoxic function against tumour cells retaining class I HLA expression. Furthermore, the reduced ability to produce interferon-γ would restrict the ability of NK cells to stimulate T-cell responses in patients with lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Receptores KIR2DL3/biossíntese , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Separação Celular , Citocinas/imunologia , Citocinas/metabolismo , Citometria de Fluxo , Imunofluorescência , Humanos , Imunofenotipagem , Neoplasias Pulmonares/patologia , Receptores KIR/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Health Expect ; 14(4): 383-96, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21029286

RESUMO

BACKGROUND: Influential views on how to protect patient autonomy in clinical care have been greatly shaped by rational and deliberative models of decision-making. OBJECTIVE: Our aim was to understand how the general principle of respecting autonomy can be reconciled with the local reality of obtaining consent in a clinical situation that precludes extended deliberation. METHOD: We interviewed 22 patients with intraocular melanoma who had been offered cytogenetic tumour typing to indicate whether the tumour was likely to shorten life considerably. They were interviewed before and/or up to 36 months after receiving cytogenetic results. Patients described their decision-making about the test and how they anticipated and used the results. Their accounts were analysed qualitatively, using inconsistencies at a descriptive level to guide interpretative analysis. RESULTS: Patients did not see a decision to be made. For those who accepted testing, their choice reflected trust of what the clinicians offered them. Patients anticipated that a good prognosis would be reassuring, but this response was not evident. Although they anticipated that a poor prognosis would enable end-of-life planning, adverse results were interpreted hopefully. In general, the meaning of the test for patients was not separable from ongoing care. CONCLUSION: Models of decision-making and associated consent procedures that emphasize patients' active consideration of isolated decision-making opportunities are invalid for clinical situations such as this. Hence, responsibility for ensuring that a procedure protects patients' interests rests with practitioners who offer it and cannot be delegated to patients.


Assuntos
Tomada de Decisões , Consentimento Livre e Esclarecido , Melanoma/diagnóstico , Pacientes , Autonomia Pessoal , Neoplasias Uveais/diagnóstico , Adulto , Idoso , Citogenética , Feminino , Genótipo , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Prognóstico
14.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-33709965

RESUMO

Paraneoplastic neurological syndromes (PNS) are a group of rare and severe immune-mediated disorders that affect the nervous system in patients with cancer. The best way to diagnose a paraneoplastic neurological disorder is to identify anti-onconeural protein antibodies that are specifically associated with various cancers. The aim of this multicentric study was to clinically and immunologically characterize patients with PNS and study their association with cancer. Patients suspected to have PNS were enrolled from various clinical centres and were characterized immunologically. This study population consisted of 112 patients. Onset of PNS was mainly subacute (76 %). PNS patients had various neurological disorders and symptoms. PNS developed before the diagnosis of cancer in 28 definite PNS patients and in six suspected PNS patients. The most frequent autoantibodies detected in PNS patients were anti-Hu and anti-Yo. One definite PNS patient with cerebellar syndrome had anti-Tr antibody and seven patients had atypical antibodies. The literature associates these antibodies with various neurological disorders and cancers. Our observations confirm the important role of autoantibodies in PNS and their importance for the early diagnosis of cancer in PNS patients.


Assuntos
Autoanticorpos/imunologia , Imunofenotipagem , Neoplasias/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/patologia , Sistema Nervoso/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/epidemiologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Ratos
15.
Clin Cancer Res ; 15(1): 274-83, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19118055

RESUMO

PURPOSE: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood. EXPERIMENTAL DESIGN: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals. RESULTS: Expression profiling revealed multiple chromogranin transcripts were readily induced on REST depletion, most notably SCG3 was induced >500-fold. The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022). CONCLUSIONS: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.


Assuntos
Biomarcadores Tumorais/sangue , Cromograninas/sangue , Neoplasias Pulmonares/sangue , Tumores Neuroendócrinos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Impressões Digitais de DNA , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
17.
J Clin Oncol ; 23(27): 6674-81, 2005 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-16170175

RESUMO

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.


Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia de Salvação , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalos de Confiança , Feminino , Humanos , Lipossomos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
19.
Health Technol Assess ; 19(47): 1-134, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26134145

RESUMO

BACKGROUND: Lung cancer is the second most diagnosed cancer in the UK. Over 70% of lung cancers are non-small cell lung cancers (NSCLCs). Patients with stage III or IV NSCLC may be offered treatment to improve survival, disease control and quality of life. One-third of these patients receive further treatment following disease progression; these treatments are the focus of this systematic review. OBJECTIVES: To appraise the clinical effectiveness and cost-effectiveness of erlotinib [Tarceva(®), Roche (UK) Ltd] and gefitinib (IRESSA(®), AstraZeneca) compared with each other, docetaxel or best supportive care (BSC) for the treatment of NSCLC after disease progression following prior chemotherapy. The effectiveness of treatment with gefitinib was considered only for patients with epidermal growth factor mutation-positive (EGFR M+) disease. DATA SOURCES: Four electronic databases (EMBASE, MEDLINE, The Cochrane Library, PubMed) were searched for randomised controlled trials (RCTs) and economic evaluations. Manufacturers' evidence submissions to the National Institute for Health and Care Excellence were also considered. REVIEW METHODS: Outcomes for three distinct patient groups based on EGFR mutation status [EGFR M+, epidermal growth factor mutation negative (EGFR M-) and epidermal growth factor mutation status unknown (EGFR unknown)] were considered. Heterogeneity of the data precluded statistical analysis. A de novo economic model was developed to compare treatments (incremental cost per quality-adjusted life-year gained). RESULTS: Twelve trials were included in the review. The use of gefitinib was compared with chemotherapy (n = 6) or BSC (n = 1), and the use of erlotinib was compared with chemotherapy (n = 3) or BSC (n = 1). One trial compared the use of gefitinib with the use of erlotinib. No trials included solely EGFR M+ patients; all data were derived from retrospective subgroup analyses from six RCTs [Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer 2012;75:82-8, V-15-32, Tarceva In Treatment of Advanced NSCLC (TITAN), BR.21, IRESSA Survival Evaluation in Lung cancer (ISEL) and IRESSA NSCLC Trial Evaluating REsponse and Survival versus Taxotere (INTEREST)]. These limited data precluded conclusions regarding the clinical effectiveness of any treatment for EGFR M+ patients. For EGFR M- patients, data were derived from the TArceva Italian Lung Optimization tRial (TAILOR) trial and Docetaxel and Erlotinib Lung Cancer Trial (DELTA). Retrospective data were also derived from subgroup analyses of BR.21, Kim et al., TITAN, INTEREST and ISEL. The only statistically significant reported results were for progression-free survival (PFS) for TAILOR and DELTA, and favoured docetaxel over erlotinib [TAILOR hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.06 to 1.82; DELTA HR 1.44, 95% CI 1.08 to 1.92]. In EGFR unknown patients, nine trials (INTEREST, IRESSA as Second-line Therapy in Advanced NSCLC - KoreA, Li, Second-line Indication of Gefitinib in NSCLC, V-15-32, ISEL, DELTA, TITAN and BR.21) reported overall survival data and only one (BR.21) reported a statistically significant result favouring the use of erlotinib over BSC (HR 0.7, 95% CI 0.58 to 0.85). For PFS, BR.21 favoured the use of erlotinib when compared with BSC (HR 0.61, 95% CI 0.51 to 0.74) and the use of gefitinib was favoured when compared with BSC (HR 0.82, 95% CI 0.73 to 0.92) in ISEL. Limitations in the clinical data precluded assessment of cost-effectiveness of treatments for an EGFR M+ population by the Assessment Group (AG). The AG's economic model suggested that for the EGFR M- population, the use of erlotinib was not cost-effective compared with the use of docetaxel and compared with BSC. For EGFR unknown patients, the use of erlotinib was not cost-effective when compared with BSC. CONCLUSIONS/FUTURE WORK: The lack of clinical data available for distinct patient populations limited the conclusions of the assessment. Future trials should distinguish between patients with EGFR M+ and EGFR M- disease. FUNDING: The National Institute for Health Research Health Technology Assessment programme.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/economia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/economia , Quinazolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Custo-Benefício , Intervalo Livre de Doença , Cloridrato de Erlotinib/efeitos adversos , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Quinazolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Eur J Cancer ; 51(3): 271-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25542058

RESUMO

BACKGROUND: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. SETTINGS: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. RESULTS: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. INTERPRETATION: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.


Assuntos
Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Doenças Raras/terapia , Humanos , Cooperação Internacional , Neoplasias/epidemiologia , Parcerias Público-Privadas/organização & administração , Doenças Raras/epidemiologia , Projetos de Pesquisa
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