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1.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Yonsei Med J ; 61(10): 844-850, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975058

RESUMO

PURPOSE: We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. MATERIALS AND METHODS: We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. RESULTS: Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1-6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2-35.3), the median time to response was 1.9 months (range, 1.4-5.7). The median duration of response was not reached (range, 8.8-not reached). The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. CONCLUSION: In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Neoplasias do Endométrio , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos
3.
N Z Med J ; 133(1520): 50-60, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994593

RESUMO

AIM: Therapeutic lymphadenectomy remains the gold standard for surgical management of clinically evident regional cervical disease for cutaneous malignancy. However, international consensus on adequate lymphadenectomy is lacking. Attempts have been made to establish quality measures; suggested benchmarks for minimum and average nodal yield, as well as recurrence and complication rates have been quoted. We aim to compare our key performance indicators to those benchmarks published in the literature. METHODS: This is a retrospective observational study conducted with prospectively maintained data, over an 11-year period (2007-2018). RESULTS: Of 91 cervical lymphadenectomies included, mean nodal yield for ≤3 and ≥4 dissection levels were 19.7 and 38.7 respectively. We observed a combined locoregional recurrence rate of 25%. Subgroup analysis for melanoma (60) and cSCC (28) revealing regional nodal recurrence of 15% and 11%, respectively. We observed a 38.5% complication rate; however, less than 5.5% was considered grade IIIb/IIIb(d) [Clavein-Dindo]. Median follow-up of 19.3 months, five-year survivial rate of 38% and 32% for melanoma and cSCC, respectively. CONCLUSION: Our data indicates that we are meeting quality measures, set by higher volume centres. We believe that any surgeon with subspecialty training in head and neck surgery can meet quality measures with regards to cervical lymphadenopathy for cutaneous malignancy.


Assuntos
Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Pescoço/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Metástase Linfática/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Nova Zelândia/epidemiologia , Guias de Prática Clínica como Assunto , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Neoplasias Cutâneas/secundário , Cirurgiões/educação , Taxa de Sobrevida
4.
Anticancer Res ; 40(10): 5649-5657, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988889

RESUMO

BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67. MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of ≥5% nüclear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive. RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger. CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.


Assuntos
Carcinoma Ductal de Mama/genética , Fator de Transcrição GATA3/genética , Antígeno Ki-67/genética , Recidiva Local de Neoplasia/genética , Adulto , Biomarcadores Tumorais , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Intervalo Livre de Doença , Estrogênios/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Progesterona/genética , Prognóstico , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética
5.
Anticancer Res ; 40(10): 5715-5725, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988897

RESUMO

BACKGROUND/AIM: The platelet distribution width (PDW) and serum C-reactive protein (CRP) levels are known to be predictive of prognosis in various malignancies. Our aim was to determine whether combining PDW and serum CRP levels produces a prognostic indicator for esophageal cancer (EC) patients. PATIENTS AND METHODS: A total of 168 EC patients who underwent neoadjuvant therapy prior to esophagectomy were included in this study. RESULTS: We defined a combined PDW and CRP (CPC) score as follows: patients with both low pretherapeutic PDW (≤12.4 fl) and high postoperative serum CRP levels (≥0.5 mg/dl) were assigned a score of 2, while patients with one or neither of those were assigned a score of 1 or 0. A multivariable analysis showed that the CPC score was a significant risk factor for overall (p=0.006) and recurrence-free (p=0.004) survival. CONCLUSION: The CPC score is a strong prognostic indicator in EC patients.


Assuntos
Plaquetas/metabolismo , Proteína C-Reativa/metabolismo , Neoplasias Esofágicas/sangue , Prognóstico , Idoso , Plaquetas/patologia , Carcinoma de Células Escamosas , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Fatores de Risco
6.
Anticancer Res ; 40(10): 5739-5742, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988900

RESUMO

BACKGROUND/AIM: Locoregional recurrence (LRR) of breast cancer is reported to occur at a rate of 5%-15%. Wide excision of LRR is the recommended treatment, which can increase the probability of subsequent local control. Herein, we describe a surgical technique wherein a pedicled skin and subcutaneous flap close the skin defect after resection of a breast cancer LRR without use of a skin graft. PATIENTS AND METHODS: We reviewed four patients who underwent surgical resection using a pedicled rotation flap for chest wall recurrence after mastectomy. RESULTS: The surgical margin was set 2 cm apart from the tumor margin. After resection of tumor from the chest wall, we formed an adjacent pedicled flap and rotated the flap to the skin defect. There were no post-operative complications, including wound necrosis. CONCLUSION: Surgical resection with a pedicled rotation flap for post-mastectomy breast cancer LRR is a highly feasible way to achieve complete resection.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/efeitos adversos , Recidiva Local de Neoplasia/patologia , Retalhos Cirúrgicos , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Mamoplastia/métodos , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia
7.
Anticancer Res ; 40(10): 5823-5828, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988911

RESUMO

AIM: Our aim was to confirm the utility of Indocyanine green (ICG) fluorescence imaging for intraoperative detection of adrenal hepatocellular carcinoma (HCC) metastasis. CASE REPORT: An 83-year-old man with a right adrenal HCC metastasis was admitted after complete remission of primary HCC and a metachronous left adrenal metastasis. He was treated with ICG fluorescence-guided limited resection to preserve adrenal function. ICG was administered intravenously at a dose of 0.5 mg/kg, 6 days before the operation. After removal of the entire suspicious metastatic HCC, ICG fluorescence imaging clearly demonstrated two illuminated lesions. The lesions were separately resected using an energy device. Finally, there were no ICG fluorescent lesions which meant residual tumor. Histopathological examination confirmed adrenal metastasis of moderately differentiated HCC in the initial specimen and the additional resected specimens. Three months after the operation, adrenal function was well preserved without recurrence of HCC. CONCLUSION: ICG fluorescence imaging is essential for complete resection of adrenal HCC metastasis.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Imagem Óptica , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Verde de Indocianina/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
8.
Medicine (Baltimore) ; 99(38): e22238, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957367

RESUMO

BACKGROUND: Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma. METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis. RESULTS: These results obtained in this study will be published in a peer-reviewed journal. CONCLUSION: Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202080078.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Metanálise como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Revisões Sistemáticas como Assunto , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Lomustina/efeitos adversos , Lomustina/uso terapêutico , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
9.
Lancet Oncol ; 21(9): 1224-1233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888454

RESUMO

BACKGROUND: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer. METHODS: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m2 from day 1 to day 3]) or oral topotecan (2·3 mg/m2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02738346. FINDINGS: Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0-37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9-5·5 vs 2·7 months, 2·3-3·2; stratified hazard ratio 0·57, 90% CI 0·41-0·73; p=0·0041). The most frequent grade 3-4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group. INTERPRETATION: Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer. FUNDING: Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie).


Assuntos
Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Etoposídeo/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Topotecan/efeitos adversos
10.
Khirurgiia (Mosk) ; (8): 35-41, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32869613

RESUMO

OBJECTIVE: Optimization of diagnosis and treatment of patients with solitary fibrous tumor of pleura, analysis of overall survival and disease-free survival, predictors of recurrence. MATERIAL AND METHODS: There were 66 patients with solitary fibrous tumor of pleura (26 men and 40 women) aged 57.6 years (range 26-80 years). Asymptomatic course was found in 29 (44%) patients, various symptoms - in 37 (56%) patients. Thoracotomy was applied in 36 patients, thoracoscopy - in 30 patients. Immunohistochemical examination included analysis of definition of Stat6 expression. RESULTS: Benign variant of SFT was diagnosed in 50 (75.7%) patients, malignant variant - in 16 (24.3%) patients. STAT6 expression was observed in all cases. Postoperative morbidity was 9%, mortality - 1.6%. Recurrence was diagnosed in 2 (4%) patients with benign variant of disease and in 5 (31.2%) patients with malignant variant (2 of them died from progression of disease). Progression-free survival was 89.4%, overall survival - 95.4%. Predictors of recurrence are tumor dimension over 10 cm, necrosis and/or hemorrhagic component of tumor, mitotic count of at least four per 10 high-power fields. CONCLUSION. S: Olitary fibrous tumor of pleura is a rare mesenchymal fibroblastic neoplasm growing from submesothelial layer. Differential and preoperative morphological diagnosis of SFT is difficult and demands a special immunohistochemical examination with analysis of Stat 6 expression. Surgery is preferred for tumor de novo and recurrent neoplasm.


Assuntos
Recidiva Local de Neoplasia/patologia , Fator de Transcrição STAT6/biossíntese , Tumor Fibroso Solitário Pleural/diagnóstico , Tumor Fibroso Solitário Pleural/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Pleura , Tumor Fibroso Solitário Pleural/metabolismo , Tumor Fibroso Solitário Pleural/mortalidade , Análise de Sobrevida , Procedimentos Cirúrgicos Torácicos
11.
Yonsei Med J ; 61(9): 774-779, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882761

RESUMO

PURPOSE: Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS: We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS: The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION: Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.


Assuntos
Células Dendríticas/patologia , Histiócitos/patologia , Transtornos Histiocíticos Malignos/patologia , Sarcoma Histiocítico/patologia , Adulto , Criança , Sarcoma de Células Dendríticas Foliculares/epidemiologia , Sarcoma de Células Dendríticas Foliculares/patologia , Feminino , Transtornos Histiocíticos Malignos/epidemiologia , Sarcoma Histiocítico/epidemiologia , Histiocitose de Células de Langerhans/epidemiologia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Prevalência , República da Coreia/epidemiologia , Seul , Xantogranuloma Juvenil/epidemiologia , Xantogranuloma Juvenil/patologia
12.
PLoS One ; 15(8): e0236569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756596

RESUMO

BACKGROUND: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. METHODS: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. RESULTS: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). CONCLUSION: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Intervalo Livre de Progressão
14.
Lancet Oncol ; 21(9): 1155-1164, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32771088

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors combined with immunotherapy have shown antitumour activity in preclinical studies. We aimed to assess the safety and activity of olaparib in combination with the PD-L1-inhibitor, durvalumab, in patients with germline BRCA1-mutated or BRCA2-mutated metastatic breast cancer. METHODS: The MEDIOLA trial is a multicentre, open-label, phase 1/2, basket trial of durvalumab and olaparib in solid tumours. Patients were enrolled into four initial cohorts: germline BRCA-mutated, metastatic breast cancer; germline BRCA-mutated, metastatic ovarian cancer; metastatic gastric cancer; and relapsed small-cell lung cancer. Here, we report on the cohort of patients with breast cancer. Patients who were aged 18 years or older (or aged 19 years or older in South Korea) with germline BRCA1-mutated or BRCA2-mutated or both and histologically confirmed, progressive, HER2-negative, metastatic breast cancer were enrolled from 14 health centres in the UK, the USA, Israel, France, Switzerland, and South Korea. Patients should not have received more than two previous lines of chemotherapy for metastatic breast cancer. Patients received 300 mg olaparib in tablet form orally twice daily for 4 weeks and thereafter a combination of olaparib 300 mg twice daily and durvalumab 1·5 g via intravenous infusion every 4 weeks until disease progression. Primary endpoints were safety and tolerability, and 12-week disease control rate. Safety was analysed in patients who received at least one dose of study treatment, and activity analyses were done in the full-analysis set (patients who received at least one dose of study treatment and were not excluded from the study). Recruitment has completed and the study is ongoing. This trial is registered with ClinicalTrials.gov, NCT02734004. FINDINGS: Between June 14, 2016, and May 2, 2017, 34 patients were enrolled and received both study drugs and were included in the safety analysis. 11 (32%) patients experienced grade 3 or worse adverse events, of which the most common were anaemia (four [12%]), neutropenia (three [9%]), and pancreatitis (two [6%]). Three (9%) patients discontinued due to adverse events and four (12%) patients experienced a total of six serious adverse events. There were no treatment-related deaths. 24 (80%; 90% CI 64·3-90·9) of 30 patients eligible for activity analysis had disease control at 12 weeks. INTERPRETATION: Combination of olaparib and durvalumab showed promising antitumour activity and safety similar to that previously observed in olaparib and durvalumab monotherapy studies. Further research in a randomised setting is needed to determine predictors of therapeutic benefit and whether addition of durvalumab improves long-term clinical outcomes compared with olaparib monotherapy. FUNDING: AstraZeneca.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Adulto Jovem
15.
Lancet Oncol ; 21(9): 1234-1243, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32818466

RESUMO

BACKGROUND: Effective treatments for patients with cholangiocarcinoma after progression on gemcitabine-based chemotherapy are urgently needed. Mutations in the BRAF gene have been found in 5% of biliary tract tumours. The combination of dabrafenib and trametinib has shown activity in several BRAFV600E-mutated cancers. We aimed to assess the activity and safety of dabrafenib and trametinib combination therapy in patients with BRAFV600E-mutated biliary tract cancer. METHODS: This study is part of an ongoing, phase 2, open-label, single-arm, multicentre, Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAFV600E-mutated rare cancers. Patients were eligible for the biliary tract cancer cohort if they were aged 18 years or older, had BRAFV600E-mutated, unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received previous systemic treatment. All patients were treated with oral dabrafenib 150 mg twice daily and oral trametinib 2 mg once daily until disease progression or intolerance of treatment. The primary endpoint was the overall response rate, which was determined by Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat evaluable population, which comprised all enrolled patients regardless of receiving treatment who were evaluable (ie, had progression, began a new anticancer treatment, withdrew consent, died, had stable disease for 6 weeks or longer, or had two or more post-baseline assessments). The ROAR trial is registered with ClinicalTrials.gov, NCT02034110. These results are based on an interim analysis; the study is active but not recruiting. FINDINGS: Between March 12, 2014, and July 18, 2018, 43 patients with BRAFV600E-mutated biliary tract cancer were enrolled to the study and were evaluable. Median follow-up was 10 months (IQR 6-15). An investigator-assessed overall response was achieved by 22 (51%, 95% CI 36-67) of 43 patients. An independent reviewer-assessed overall response was achieved by 20 (47%, 95% CI 31-62) of 43 patients. The most common grade 3 or worse adverse event was increased γ-glutamyltransferase in five (12%) patients. 17 (40%) patients had serious adverse events and nine (21%) had treatment-related serious adverse events, the most frequent of which was pyrexia (eight [19%]). No treatment-related deaths were reported. INTERPRETATION: Dabrafenib plus trametinib combination treatment showed promising activity in patients with BRAFV600E-mutated biliary tract cancer, with a manageable safety profile. Routine testing for BRAFV600E mutations should be considered in patients with biliary tract cancer. FUNDING: GlaxoSmithKline and Novartis.


Assuntos
Neoplasias do Sistema Biliar/tratamento farmacológico , Imidazóis/administração & dosagem , Oximas/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Resultado do Tratamento
16.
Life Sci ; 258: 118152, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735881

RESUMO

AIMS: Cancer stem cells (CSCs) are the source of tumors and play a key role in the resistance of cancer to therapies. To improve the current therapies against CSCs, in this work we developed a novel system of electrospun polycaprolactone (PCL) nanofibers containing hydroxylated multi-walled carbon nanotubes (MWCNTs-OH) and all-trans retinoic acid (ATRA). MATERIALS AND METHODS: The nanofiber membranes were forged by electrospinning, and the physical and chemical properties of the nanofiber membranes were evaluated by scanning electron microscopy, XRD and Raman etc. The photothermal properties of nanofiber membranes and their effects on CSCs differentiation and cytotoxicity were investigated. Finally, the anti-tumor effect of nanofiber membranes in vivo was evaluated. KEY FINDINGS: The nanofibers formed under optimal conditions were smooth without beads. The nanofibrous membranes with MWCNTs-OH could increase temperature of the medium under near-infrared (NIR) illumination to suppress the viability of glioma stem cells (GSCs). Meanwhile, the added ATRA could further induce the differentiation of GSCs to destroy their stemness and reduce their resistance to heat treatment. Compared with no NIR irradiation, after 2min NIR irradiation, the membranes reduced the in-vitro viability of GSCs by 13.41%, 14.83%, and 26.71% after 1, 2, and 3 days, respectively. After 3 min daily illumination for 3 days, the viability of GSCs was only 22.75%, and similar results were observed in vivo. SIGNIFICANCE: These results showed efficiently cytotoxicity to CSCs by combining heat therapy and differentiation therapy. The nanofiber membranes if inserted at the site after surgical tumor removal, may hinder tumor recurrence.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Glioma/terapia , Nanofibras/uso terapêutico , Células-Tronco Neoplásicas/efeitos dos fármacos , Tretinoína/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Glioma/patologia , Humanos , Hipertermia Induzida/métodos , Masculino , Camundongos Endogâmicos BALB C , Nanofibras/química , Nanotubos de Carbono/química , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/patologia , Poliésteres/química , Poliésteres/uso terapêutico , Tretinoína/administração & dosagem
17.
Zhonghua Fu Chan Ke Za Zhi ; 55(8): 529-534, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32854477

RESUMO

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ,included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: (1) PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC (type Ⅱ) than those of low-grade (type Ⅰ) and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Receptor de Morte Celular Programada 1 , RNA Mensageiro/genética
18.
Anticancer Res ; 40(7): 3605-3618, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620600

RESUMO

Radiomics, an emerging field in radiation therapy, is hypothesized to improve classification of tumour risk and prognosis. Despite encouraging results, there are issues of practicality and interpretation of radiomic data. This study investigates the emerging role of radiomics in tumour risk classification and prognosis of breast and prostate cancer. A literature search was conducted using predefined terms to retrieve studies related to radiomics. Studies were evaluated and selected upon meeting the criteria defined. A total of 19 relevant publications were selected from 63 publications identified. Data from studies revealed significant area under the curve (AUC) values and high discriminative power. Significant AUC values for biochemical recurrence of disease and disease-free survival were reported for prognosis. Radiomics show promising potential in discriminating tumour risk and predicting prognosis of cancer using specified features. It is an alternative to conventional predictive tools and has the ability to improve with the use of existing tools.


Assuntos
Neoplasias/patologia , Neoplasias/radioterapia , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias/mortalidade , Prognóstico , Radioterapia/métodos , Risco
19.
Anticancer Res ; 40(7): 3733-3742, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620612

RESUMO

BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1/CD274) elicits T-cell anergy, leading to immune suppression. We aimed to determine the prognostic relevance of PD-L1 expression in the blood of breast cancer (BC) patients. MATERIALS AND METHODS: We measured PD-L1 mRNA expression in blood and tumor tissues of BC patients using RT-qPCR and a dataset from The Cancer Genome Atlas, and performed a survival analysis of PD-L1 expression in the blood of 330 BC patients. Flow cytometric analysis was performed using blood cells. RESULTS: No statistical difference in PD-L1 expression was seen between normal controls and BC in blood or tissues. There was a significant positive correlation between the PD-L1 expression levels in blood and tissues. Decreased PD-L1 expression in blood or tissues was associated with poor recurrence-free survival. PD-L1 is mainly expressed in polymorphonuclear leukocytes. CONCLUSION: Low expression of PD-L1 in the blood could serve as a biomarker of poor prognosis in BC patients.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Recidiva Local de Neoplasia/genética , RNA Mensageiro/genética , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Recidiva Local de Neoplasia/patologia , Prognóstico
20.
Anticancer Res ; 40(7): 3973-3981, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620640

RESUMO

BACKGROUND/AIM: HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. PATIENTS AND METHODS: After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. RESULTS: HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. CONCLUSION: Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Retratamento , Adulto Jovem
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