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1.
J Cancer Res Clin Oncol ; 146(10): 2681-2691, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449003

RESUMO

PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Panitumumabe/administração & dosagem , Resultado do Tratamento , Proteínas ras/genética
2.
Support Care Cancer ; 28(10): 4667-4675, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31955277

RESUMO

PURPOSE: Patients with advanced cancer often receive suboptimal end-of-life (EOL) care. Particularly males with advanced cancer are more likely to receive EOL care that is more aggressive, even if death is imminent. Critical factors determining EOL care are EOL conversations or advance care planning. However, information about gender-related factors influencing EOL conversations is lacking. Therefore, the current study investigates gender differences concerning the content, the desired time point, and the mode of initiation of EOL conversations in cancer patients. METHODS: In a cross-sectional study, 186 female and male cancer patients were asked about their preferences for EOL discussions using a semi-structured interview, focusing on (a) the importance of six different topics (medical and nursing care, organizational, emotional, social, and spiritual/religious aspects), (b) the desired time point, and (c) the mode of discussion initiation. RESULTS: The importance of EOL topics differs significantly regarding issue (p = 0.002, η2 = 0.02) and gender (p < 0.001, η2 = 0.11). Males wish to avoid the engagement in discussions about death and dying particularly if they are anxious about their end-of-life period. They wish to be addressed regarding the "hard facts" nursing and medical care only. In contrast, females prefer to speak more about "soft facts" and to be addressed about each EOL topic. Independent of gender, the majority of patients prefer to talk rather late: when the disease is getting worse (58%), at the end of their therapy, or when loosing self-sufficiency (27.5%). CONCLUSION: The tendency of patients to talk late about EOL issues increases the risk of delayed or missed EOL conversations, which may be due to a knowledge gap regarding the possibility of disease-associated incapability. Furthermore, there are significant gender differences influencing the access to EOL conversations. Therefore, for daily clinical routine, we suggest an early two-step, gender-sensitive approach to end-of-life conversations.


Assuntos
Planejamento Antecipado de Cuidados/normas , Neoplasias/psicologia , Assistência Terminal/psicologia , Estudos Transversais , Feminino , Identidade de Gênero , Humanos , Masculino
3.
Ann Oncol ; 29(10): 2076-2084, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137193

RESUMO

Background: The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease. The IMPULSE phase II study evaluated the efficacy and safety of lefitolimod as maintenance treatment in extensive-stage small-cell lung cancer (ES-SCLC) after objective response to first-line chemotherapy, an indication with a high unmet medical need and stagnant treatment improvement in the last decades. Patients and methods: 103 patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following four cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod maintenance therapy or local standard of care at a ratio of 3 : 2 until progression or unacceptable toxicity. Results: From 103 patients enrolled, 62 were randomized to lefitolimod, 41 to the control arm. Patient demographics and response patterns to first-line therapy were balanced. Lefitolimod exhibited a favorable safety profile and pharmacodynamic assessment confirmed the mode-of-action showing a clear activation of monocytes and production of interferon-gamma-induced protein 10 (IP-10). While in the intent-to-treat (ITT) population no relevant effect of lefitolimod on progression-free and overall survival (OS) could be observed, two predefined patient subgroups indicated promising results, favoring lefitolimod with respect to OS: in patients with a low frequency of activated CD86+ B cells (hazard ratio, HR 0.53, 95% CI: 0.26-1.08; n = 38 of 88 analyzed) and in patients with reported chronic obstructive pulmonary disease (COPD) (HR 0.48, 95% CI: 0.20-1.17, n = 25 of 103). Conclusions: The IMPULSE study showed no relevant effect of lefitolimod on the main efficacy end point OS in the ITT, but (1) the expected pharmacodynamic response to lefitolimod, (2) positive OS efficacy signals in two predefined subgroups and (3) a favorable safety profile. These data support further exploration of lefitolimod in SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunossupressores/uso terapêutico , Imunoterapia , Leflunomida/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Receptor Toll-Like 9/agonistas , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , Etoposídeo/administração & dosagem , Seguimentos , Humanos , Agências Internacionais , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Quimioterapia de Manutenção , Prognóstico , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida
4.
Ann Oncol ; 25(3): 707-711, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24504443

RESUMO

BACKGROUND: Evaluation of the SPIKES protocol, a recommended guideline for breaking bad news, is sparse, and information about patients' preferences for bad-news delivery in Germany is lacking. Being the first actual-theoretical comparison of a 'breaking bad news' guideline, the present study evaluates the recommended steps of the SPIKES protocol. Moreover, emotional consequences and quality of bad-news delivery are investigated. PATIENTS AND METHODS: A total of 350 cancer patients answered the MABBAN (Marburg Breaking Bad News Scale), a questionnaire representing the six SPIKES subscales, asking for the procedure, perception and satisfaction of the first cancer disclosure and patient's assign to these items. RESULTS: Only 46.2% of the asked cancer patients are completely satisfied with how bad news had been broken to them. The overall quality is significantly related to the emotional state after receiving bad news (r = -0.261, P < 0.001). Patients' preferences differ highly significantly from the way bad news were delivered, and the resulting rang list of patients' preferences indicates that the SPIKES protocol do not fully meet the priorities of cancer patients in Germany. CONCLUSIONS: It could be postulated that the low satisfaction of patients observed in this study reflects the highly significant difference between patients' preferences and bad-news delivery. Therefore, some adjunctions to the SPIKES protocol should be considered, including a frequent reassurance of listeners' understanding, the perpetual possibility to ask question, respect for prearrangement needs and the conception of bad-news delivery in a two-step procedure.


Assuntos
Neoplasias/diagnóstico , Neoplasias/psicologia , Relações Médico-Paciente , Revelação da Verdade , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Satisfação do Paciente , Prognóstico , Inquéritos e Questionários , Adulto Jovem
5.
Br J Radiol ; 75(899): 919-29, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12466260

RESUMO

Doppler ultrasound is a well established method for assessment of the portal venous system to detect the direction of portal blood flow. It is helpful for non-invasive diagnosis of intra-abdominal portosystemic shunts, especially in patients with cirrhosis. Less attention has been paid to other influences on portal venous flow, e.g. tricuspid regurgitation, increased hepatic out-flow resistance, respiratory cycle. The aim of this pictorial review is to describe the spectrum of physiological and pathological Doppler ultrasound flow patterns in the portal venous system.


Assuntos
Hepatopatias/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Cardiopatias/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Circulação Hepática , Fluxo Pulsátil
6.
Ultraschall Med ; 22(6): 289-92, 2001 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-11740698

RESUMO

Functional hyposplenia/asplenia is a severe longterm complication after allogeneic stemcell transplantation predominantly seen in patients who suffer from extensive chronic graft versus host disease (cGvHD). The risk of acquiring an overwhelming infection with encapsulated bacteria is ca. four fold increased in patients with functional hyposplenia/asplenia. Therefore follow up of patients who have received allogeneic blood stem cells (bone marrow or peripheral blood stem cells) should embrace screening for functional hyposplenia. When functional hyposplenia is diagnosed triple vaccination against streptococcus pneumonia, Haemophilus influenza type B and Meningococcus neisseria should be considered. Goldstandard in diagnosing functional hyposplenia is hepatosplenic scintigraphy. We present the case of 37 year old female in whom sonography was indicative of functional hyposplenia. The diagnosis was confirmed by scintigraphy. Sonography including color coded duplex sonography is a safe and cost saving procedure. Sensitivity, Specificity and predictive value of the following sonographic finding: a) decreasing splenic size and b) diminished or absent parenchymal blood flow are currently evaluated in a prospective study.


Assuntos
Transplante de Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Baço/diagnóstico por imagem , Baço/patologia , Adulto , Feminino , Humanos , Valor Preditivo dos Testes , Cintilografia , Sensibilidade e Especificidade , Transplante Homólogo , Ultrassonografia
7.
J Clin Ultrasound ; 29(9): 527-30, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11745865

RESUMO

We describe respiration-dependent reversed flow in the splenic vein detected by color Doppler sonography in 2 patients. In case 1, gray-scale sonography in a patient with liver cirrhosis and abdominal pain showed a hyperechoic, thickened colonic segment and diverticula, with increased echogenicity around the diseased colon. The liver was small, with a nodular surface and coarse echotexture. Doppler sonography of the portal and splenic veins showed a constant hepatopetal flow while the patient held her breath in midinspiration and a brief, transient color change restricted to the hilar splenic veins when the patient took a deep breath. In case 2, abdominal sonography in a patient with pneumonia and right-sided abdominal pain showed mural thickening of the appendix and left-sided pneumonic infiltration. The liver size and texture were normal. Color Doppler sonography of the portal and splenic veins showed a constant hepatopetal flow while the patient held his breath in midinspiration and a transient reversal of flow restricted to the splenic veins when the patient took a deep breath. Although the cause of this flow pattern is unclear, increased intra-abdominal pressure is a possible explanation.


Assuntos
Circulação Hepática/fisiologia , Veia Porta/fisiopatologia , Veia Esplênica/diagnóstico por imagem , Veia Esplênica/fisiopatologia , Ultrassonografia Doppler em Cores , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática/fisiopatologia , Masculino , Veia Porta/diagnóstico por imagem , Respiração
8.
J Clin Ultrasound ; 29(5): 294-7, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11486325

RESUMO

We report on 2 patients with hematologic diseases (1 follicular lymphoma and 1 myeloproliferative syndrome) and splenomegaly who had partial intrasplenic portosystemic shunting demonstrated by color Doppler sonography. Intrasplenic venous blood flow was in the normal direction at the hilum of the spleen but in a reversed direction at the periphery of the spleen. This type of reversed intrasplenic flow pattern results in portosystemic shunting and might be detected more frequently when careful color Doppler mapping of the entire splenic parenchyma is performed in patients with portal hypertension. The clinical significance of this phenomenon, however, is still unclear.


Assuntos
Baço/irrigação sanguínea , Esplenomegalia/diagnóstico por imagem , Feminino , Humanos , Linfoma Folicular/complicações , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Fluxo Sanguíneo Regional , Baço/diagnóstico por imagem , Esplenomegalia/etiologia , Ultrassonografia Doppler em Cores
9.
Ultraschall Med ; 21(1): 3-7, 2000 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-10746277

RESUMO

AIM: The aim of our study was to describe clinical data, frequency of the findings, sonographic patterns, confirmation of diagnosis, and differential diagnosis of focal echorich splenic lymphoma involvement. PATIENTS: During the last 20 years a focal splenic lesion was found in 178 patients with malignant lymphoma. Echorich splenic lesions were seen in 11 out of 178 cases (6.2%). METHODS: Splenic size, echomorphology of lesions, size and number of lesions, and presentation during sonographic follow-up examination were presented. RESULTS: Echorich infiltrates of the spleen were predominantly seen in patients with low grade Non-Hodgkin-Lymphoma (9 out of 11), the size of lesions mostly was less than 3 cm in diameter (9 out of 11), the underlying splenic size was over 8 x 20 cm in 9 out of 11 patients. Diagnosis was confirmed by sonographic follow-up (n = 11) and autopsy (n = 1). CONCLUSION: Echorich splenic lymphoma involvement is a rare event and is characterised by a variable presentation during follow-up. Up to date the clinic significance of our observation is still unclear.


Assuntos
Linfoma não Hodgkin/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Baço/diagnóstico por imagem , Neoplasias Esplênicas/diagnóstico por imagem , Idoso , Autopsia , Diagnóstico Diferencial , Seguimentos , Humanos , Linfoma/patologia , Linfoma não Hodgkin/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/patologia , Neoplasias Esplênicas/patologia , Tomografia Computadorizada por Raios X , Ultrassonografia
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