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1.
Clin. transl. oncol. (Print) ; 24(4): 681-692, abril 2022. tab
Artigo em Inglês | IBECS | ID: ibc-203772

RESUMO

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.


Assuntos
Humanos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/terapia , Diagnóstico , Terapêutica
2.
Clin Transl Oncol ; 24(4): 681-692, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35320504

RESUMO

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.


Assuntos
Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/terapia
3.
Clin Transl Gastroenterol ; 11(6): e00162, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32568477

RESUMO

INTRODUCTION: To date, we do not know the best therapeutic scheme in locally advanced rectal cancer when patients are older or have comorbidities. METHODS: In 2009, we established a prospective treatment protocol that included short-course preoperative radiotherapy (RT) with standard surgery +/- chemotherapy in frail patients, mostly older than 80 years or with comorbidities. RESULTS: We included 87 patients; the mean follow-up was 43.5 months (0.66-106.3). Disease-specific survival and disease-free survival at 36 months were 86.3% and 82.8%; at 60 months, they were 78.2% and 78%, respectively, with a local recurrence rate of 2.5%. The rate of late radiotoxicity was 9% in the form of sacral insufficiency fracture and small bowel obstruction with one death. The interval before surgery varied according to the involvement of the mesorectal fascia, but it was less than 2 weeks in 45% of cases. The rate of R0 was 95%. Surgical complications included abdominal wound dehiscence (3.5%), anastomotic leak (2.4%), and reoperations (11.5%). Downstaging was observed in 51% of the cases, regardless of the interval before surgery. DISCUSSION: Therapeutic outcomes in our group of elderly patients and/or patients with comorbidities with neoadjuvant short-course RT are such as those of the general population treated with neoadjuvant RT-chemotherapy, all with acceptable toxicity. Therefore, this treatment scheme, with short-course preoperative RT, would be the most appropriate in this group of patients.


Assuntos
Adenocarcinoma/terapia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Radioterapia Conformacional , Neoplasias Retais/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Intervalo Livre de Doença , Idoso Fragilizado , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Protectomia , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X
4.
Clin Colorectal Cancer ; 17(2): e323-e329, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29551560

RESUMO

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B). RESULTS: Forty-nine patients were included: 25 in arm A and 24 in arm B. The median follow-up was 26.07 months (95% confidence interval [CI], 18.44-31.73 months). Progression-free survival (PFS) rate at 6 months was 40.00% (95% CI, 21.28%-58.12%) in the axitinib arm versus 8.33% (95% CI, 1.44%-23.30%) in the placebo arm (P = .0141). The median PFS was statistically significantly longer in the axitinib group than in the placebo group (4.96 vs. 3.16 months; hazard ratio, 0.46; 95% CI, 0.25-0.86; P = .0116). Median overall survival was also longer in the axitinib arm but did not reach statistical significance (27.61 vs. 19.99 months; hazard ratio, 0.68; 95% CI, 0.31-1.48; P = .3279). Grade 3 to 4 treatment-related toxicities were experienced by 7 patients (28%) in cohort A and 1 patient (4%) in cohort B (P = .0488). The most frequent grade 3 to 4 treatment-related toxicities were hypertension, diarrhea, and asthenia. There were no toxic deaths. The study was prematurely closed because of slow recruitment. CONCLUSIONS: In our study, maintenance treatment with axitinib monotherapy showed a significant increase in PFS and a good safety profile. Axitinib should be further explored as a possible option for first-line chemotherapy maintenance treatment in patients with mCRC.


Assuntos
Antineoplásicos/uso terapêutico , Axitinibe/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão
5.
Lancet Oncol ; 17(10): 1386-1395, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27575023

RESUMO

BACKGROUND: Cancer of unknown primary ranks in the top ten cancer presentations and has an extremely poor prognosis. Identification of the primary tumour and development of a tailored site-specific therapy could improve the survival of these patients. We examined the feasability of using DNA methylation profiles to determine the occult original cancer in cases of cancer of unknown primary. METHODS: We established a classifier of cancer type based on the microarray DNA methylation signatures (EPICUP) in a training set of 2790 tumour samples of known origin representing 38 tumour types and including 85 metastases. To validate the classifier, we used an independent set of 7691 known tumour samples from the same tumour types that included 534 metastases. We applied the developed diagnostic test to predict the tumour type of 216 well-characterised cases of cancer of unknown primary. We validated the accuracy of the predictions from the EPICUP assay using autopsy examination, follow-up for subsequent clinical detection of the primary sites months after the initial presentation, light microscopy, and comprehensive immunohistochemistry profiling. FINDINGS: The tumour type classifier based on the DNA methylation profiles showed a 99·6% specificity (95% CI 99·5-99·7), 97·7% sensitivity (96·1-99·2), 88·6% positive predictive value (85·8-91·3), and 99·9% negative predictive value (99·9-100·0) in the validation set of 7691 tumours. DNA methylation profiling predicted a primary cancer of origin in 188 (87%) of 216 patients with cancer with unknown primary. Patients with EPICUP diagnoses who received a tumour type-specific therapy showed improved overall survival compared with that in patients who received empiric therapy (hazard ratio [HR] 3·24, p=0·0051 [95% CI 1·42-7·38]; log-rank p=0·0029). INTERPRETATION: We show that the development of a DNA methylation based assay can significantly improve diagnoses of cancer of unknown primary and guide more precise therapies associated with better outcomes. Epigenetic profiling could be a useful approach to unmask the original primary tumour site of cancer of unknown primary cases and a step towards the improvement of the clinical management of these patients. FUNDING: European Research Council (ERC), Cellex Foundation, the Institute of Health Carlos III (ISCIII), Cancer Australia, Victorian Cancer Agency, Samuel Waxman Cancer Research Foundation, the Health and Science Departments of the Generalitat de Catalunya, and Ferrer.


Assuntos
Metilação de DNA , Epigênese Genética , Neoplasias Primárias Desconhecidas/genética , Receptores ErbB/genética , Feminino , Humanos , Masculino , Neoplasias Primárias Desconhecidas/classificação , Neoplasias Primárias Desconhecidas/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
6.
J Peripher Nerv Syst ; 21(3): 134-41, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27282616

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse event. Nutritional status can become impaired in cancer patients, potentially contributing to neuropathy's evolution. Our aim was to evaluate serum micronutrients and prealbumin in a cohort of 113 solid-cancer patients receiving platinum and taxane compounds during the development and recovery of neuropathy, up to 1 year after finishing treatment. CIPN was graded according to Total Neuropathy Score(©) and NCI.CTCv3 at T0 (baseline), T1 (1-3 months), and T12 (12 months) after chemotherapy. CIPN was classified as asymptomatic (< grade 2) or symptomatic (≥2). CIPN recovery was defined as ≥1 grade improvement at T12. Symptomatic CIPN developed in 52% of patients. Symptomatic patients presented a higher increase in TNSc (p < 0.001), in TNSr(©) (p < 0.001), and decrease in sural (p < 0.001) and radial nerve conduction (p < 0.001). No significant differences with any of the micronutrients were observed along T0-T1 period between severity or chemotherapy groups. By T12, symptomatic patients without recovery had a decrease in vitamin E levels (p = 0.019) and prealbumin (p = 0.062) compared with those symptomatic that improved. A correlation between the variation of vitamin E and prealbumin at T0-T1 (r = 0.626, p = 0.001) and T1-T12 (r = 0.411, p = 0.06) was observed. After chemotherapy treatment, the improvement of patients displaying symptomatic neuropathy is related to vitamin E and prealbumin serum levels. Our results suggest that nutritional status can play a role in CIPN recovery.


Assuntos
Antineoplásicos/efeitos adversos , Micronutrientes/sangue , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pré-Albumina/metabolismo , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
7.
BMC Cancer ; 15: 59, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25886275

RESUMO

BACKGROUND: To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate. METHODS: A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m(2)/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery. RESULTS: Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables. CONCLUSION: BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00847119 . Trial registration date: February 18, 2009.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante/métodos , Neoplasias Retais/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Neoplasias Retais/patologia , Análise de Sobrevida , Resultado do Tratamento
8.
Rev Enferm ; 30(3): 29-30, 2007 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-17474369

RESUMO

An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion.


Assuntos
Analgesia Controlada pelo Paciente/instrumentação , Elastômeros , Prótese do Joelho , Desenho de Equipamento , Humanos , Consentimento Livre e Esclarecido
9.
Rev. Rol enferm ; 30(3): 189-190, mar. 2007. ilus, tab
Artigo em Es | IBECS | ID: ibc-053491

RESUMO

El infusor LV (ILV) consiste en una bomba de infusión que puede administrar medicamentos por vía intravenosa, epidural, subdural o cualquier vía raquídea, y subcutánea. Su finalidad se basa en la administración de medicamentos tales como drogas oncológicas y/o analgésicas por medio de infusión continua


An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion


Assuntos
Humanos , Analgesia Controlada pelo Paciente/instrumentação , Elastômeros , Prótese do Joelho , Desenho de Equipamento , Consentimento Livre e Esclarecido
10.
Dis Colon Rectum ; 49(4): 478-84, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16450212

RESUMO

PURPOSE: This study analyzes the results of a follow-up policy in colorectal cancer at our institution and evaluates the possible benefit provided by each test performed. PATIENTS AND METHODS: Six hundred nineteen patients who had radical surgery and adjuvant treatment for colorectal cancer were followed up with a protocol that included carcinoembryonic antigen testing and clinical examination every three months for the first two years, every four months in the third year, and every six months in the fourth and fifth years. Chest X-ray and colonoscopy were performed yearly for five years and abdominal ultrasound was done every six months for the first three years and yearly afterward. Abdominopelvic computerized tomography was performed yearly for the first two years in cases with rectal cancer. If relapse was detected, all operable cases underwent surgery if possible. RESULTS: Between 1993 and 1999, 619 patients were followed-up. Mean follow-up was 66.9 months. Two hundred eight relapses were detected, 83.6 percent in the first three years and 73 (35.1 percent) underwent surgical resection. Carcinoembryonic antigen testing detected 44.2 percent of recurrences and 31.9 percent of them were operated on. Imaging techniques detected a lower percentage of recurrences (18.7 percent) but were more often resectable: 52 percent and 60 percent of the recurrences detected by computerized tomography and chest X-ray, respectively, underwent surgery. Median overall survival of patients with resected relapse was 62 months, significantly higher than those who were not operable (12.4 months). CONCLUSION: Imaging techniques in the surveillance of resected colorectal cancer contribute to early detection of relapse with a high proportion of operable metastatic disease.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Vigilância da População , Adulto , Idoso , Diagnóstico por Imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento
11.
Anticancer Res ; 22(5): 2877-84, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12530011

RESUMO

BACKGROUND: To assess if surgical manipulation increases peripheral blood cancer cells dissemination in early stage (I and II) breast cancer patients. PATIENTS AND METHODS: We analyzed 64 patients using RT-PCR for cytokeratin-19 as a marker for peripheral blood breast cancer cell dissemination. Peripheral blood was obtained at 4 different time-points (24 hours before and after surgery, one week and one month later). RESULTS: RT-PCR was positive in 14 (24%) out of 59 evaluable patients. Circulating cells were detected in 4 out of 14 patients before surgery (7%) while in the remaining 10, the positivity was observed after surgery (17%). The percentage of patients with occult breast cancer cells increased significantly after surgery (p = 0.01). CONCLUSION: 1) 7% of early breast cancer patients had circulating tumor cells before surgery. 2) After surgery tumor cells were detected in 17% of patients. 3) Surgery significantly increased the presence of occult breast cancer cells. 4) The clinical significance of occult breast cancer cells should be tested within a larger clinical trial trying to assess their role as an independent prognostic factor.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Queratinas/genética , Inoculação de Neoplasia , Células Neoplásicas Circulantes/metabolismo , RNA Mensageiro/sangue , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Queratinas/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
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