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2.
Anticancer Res ; 40(10): 5895-5899, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988920

RESUMO

BACKGROUND: Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. PATIENTS AND METHODS: We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. RESULTS: We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. CONCLUSION: We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.


Assuntos
Neoplasias Pulmonares/radioterapia , Prognóstico , Radioterapia (Especialidade)/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos
4.
N Engl J Med ; 383(12): 1139-1148, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32877599

RESUMO

BACKGROUND: In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed. METHODS: We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached. RESULTS: The minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61). The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period. CONCLUSIONS: In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/uso terapêutico , Melanoma/tratamento farmacológico , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/genética , Análise de Sobrevida
5.
N Engl J Med ; 383(11): 1040-1049, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32905676

RESUMO

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Antagonistas de Receptores de Andrógenos/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Fadiga/induzido quimicamente , Fraturas Ósseas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Pirazóis/efeitos adversos
6.
Anticancer Res ; 40(10): 5529-5538, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988876

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is a unique subtype that lacks expression of several conventional biomarkers and has a higher incidence of lymph node invasion and distal metastasis among all breast cancers. Anoikis resistance is the fundamental reason behind tumor cells' survival without their attachment to the extracellular matrix and metastasis to distal organs. Therefore, finding novel anti-cancer drugs that can suppress anoikis resistance in cancer cells is critical for patients with TNBC. MATERIALS AND METHODS: Curcumol, a natural compound, was used to assess whether it can inhibit the anoikis resistance and affects cell mortality and motility of IV2-1 TNBC cells. RESULTS: Curcumol suppressed anoikis resistance and inhibited TNBC cell survival in suspension. Additionally, these anti-cancer effects induced by curcumol could be related to the YAP1/Skp2 molecular pathway. CONCLUSION: Curcumol is an effective Skp2-targeted therapy that attenuates anoikis resistance and metastasis in TNBC cells.


Assuntos
MicroRNAs/genética , Proteínas Quinases Associadas a Fase S/genética , Sesquiterpenos/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Anoikis/efeitos dos fármacos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
7.
Anticancer Res ; 40(10): 5735-5738, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988899

RESUMO

BACKGROUND/AIM: Surgical staging is paramount to treatment of primary bone sarcomas. Often, bone scintigraphy and/or positron emission tomography-computed tomography (PET-CT) are used to exclude skeletal metastases; however, skeletal metastases in chondrosarcoma are rare. The purpose of this study was to assess the utility of these staging methods in patients with chondrosarcoma. PATIENTS AND METHODS: We reviewed 138 (87 males, 51 female) patients, mean age 54±20 years, with a chondrosarcoma, who had completed a bone scintigraphy or PET/CT as part of surgical staging. Sensitivity, specificity, and positive/negative predictive value of the scans was calculated. RESULTS: Seventeen (12%) patients had a positive bone scintigraphy or PET-CT for skeletal metastases. In cases of bone scintigraphy (n=11), 6 were benign and 5 were skeletal metastases. In cases of PET-CT, 6 were skeletal metastases, 3 were positive and 3 benign. All positive cases regarded dedifferentiated chondrosarcoma. The overall sensitivity and specificity of a bone scan or PET-CT was 100% and 93.1%; with a positive and negative predictive value of 47.1% and 100%, respectively. CONCLUSION: Skeletal metastases at presentation of chondrosarcoma are rare and associated with dedifferentiated chondrosarcoma. Bone scintigraphy or PET-CT should only be performed in cases of high grade and dedifferentiated histology.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Condrossarcoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Cintilografia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Condrossarcoma/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada por Raios X
8.
Anticancer Res ; 40(10): 5743-5750, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988901

RESUMO

BACKGROUND/AIM: Angiosarcoma of primary gynecologic origin is an extremely rare and highly malignant tumor of endothelial origin with a 5-year survival rate of less than 35%. To date, only 61 cases have been described in the literature. The aim of this study was to present more cases and discuss potential therapy options. CASE REPORT: The following case series presents three cases of gynecologic angiosarcomas that were under therapy at the Charité - University medicine of Berlin from June 2014 to February 2018. RESULTS: Two of the cases deal with primary angiosarcomas of the uterus whereas the third case was diagnosed after the suspicion of a recurrence of a poorly differentiated squamous cell carcinoma of the cervix uteri. In case one a 75-year old patient with initial postmenopausal bleeding and a tumor mass of the uterus is described. After surgery a hemangiosarcoma of the uterus was confirmed. After two months the patient presented with a presacral peritoneal sarcomatosis. Chemotherapy of weekly paclitaxel was administered. Case two deals with a patient presenting with abdominal pain. A uterine sarcoma with infiltration of the parametry and angiosarcomatosis peritonei was diagnosed during an emergency laparotomy because of spontaneous peritoneal bleeding. Moreover, osseous metastasis was found. The patient underwent weekly paclitaxel. Due to tumor progression, chemotherapy was changed to doxorubicin and olaratumab and radiotherapy was induced. The patient died 33 months after initial diagnosis. Case three describes a 34-year old patient with suspected local recurrence of cervical cancer with infiltration of the bladder. During TURB an angiosarcoma was found. Following laparoscopy revealed peritoneal metastasis. The patient underwent weekly paclitaxel followed by a paclitaxel and pazopanib maintainance therapy which showed a regression. Due to progression afterwards, chemotherapy was changed to gemcitabine and docetaxel and gemcitabine monotherapy. The patient died 33 months after initial diagnosis. CONCLUSION: Even though there is no evidence on standard treatment of this extremely rare and aggressive tumor entity of the female genital tract the patients showed the longest stability of disease during chemotherapy with weekly paclitaxel.


Assuntos
Tratamento Farmacológico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Terapia Combinada , Feminino , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/cirurgia , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Laparotomia , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos
9.
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
10.
Anticancer Res ; 40(10): 5837-5844, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988913

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary tract. Venous migration, tumor thrombus and metastases are often seen in patients with RCC and are adverse prognostic factors. Intravascular tumor growth along the renal vein into the inferior vena cava occurs in up to 10% of all patients with RCC. Furthermore, extension of the tumor reaching the right atrium is detected in approximately 1% of all patients. Synchronous involvement of pulmonary arteries with tumor emboli is very rare and challenging. Management of metastatic RCC includes surgical resection of renal and metastatic lesions. We present 3 cases of patients with RCC tumor thrombus extending into the inferior vena cava (IVC) and with pulmonary emboli of the tumor thrombus into one of the branches of the main pulmonary artery. All the cases had simultaneous resection of the kidney tumor with the tumor thrombus and pulmonary lobectomy that included the tumor emboli with satisfactory outcome. CASE REPORT: We present a series of cases of RCC with tumor extension into the inferior vena cava (IVC) and with tumor emboli to the pulmonary arteries. Surgical procedure in all cases consisted of radical nephrectomy with IVC tumor thrombus resection, along with a thoracotomy with lung resection including the tumor emboli to one of the branches of the main pulmonary artery. Synchronous metastatic lesions were found on the liver in one case and contiguous extension of renal tumor to the pancreas in another. CONCLUSION: In patients with IVC thrombus with synchronous pulmonary artery tumor embolus, such as the cases presented in this series, a careful multidisciplinary management approach is preferable. Transplant technique used in our open approach minimizes complications, blood loss, and provides excellent visualization for abdominal vascular manipulation of IVC. This provides a potentially curable treatment option with acceptable survival rates.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nefrectomia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologia , Trombose Venosa/cirurgia
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(6): 869-875, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895200

RESUMO

OBJECTIVE: To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1. METHODS: The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability. RESULTS: The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells (P < 0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients (P < 0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells (P < 0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients (P < 0.05) in association with a poorer prognosis of the patients (P < 0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 (P < 0.05). CONCLUSIONS: miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.


Assuntos
Neoplasias da Mama , MicroRNAs/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica
12.
Medicine (Baltimore) ; 99(36): e22060, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899071

RESUMO

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Antimetabólitos Antineoplásicos , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas/métodos , Irinotecano/uso terapêutico , Japão/epidemiologia , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Oxaliplatina/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/métodos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
13.
Anticancer Res ; 40(9): 5229-5235, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878811

RESUMO

BACKGROUND/AIM: The prolactin receptor (PRLR) is implicated in the tumorigenesis of breast and prostate cancers where it drives cell proliferation, survival, and migration. LFA102 is a humanized monoclonal antibody against PRLR with promising preclinical antitumor activity. To determine the maximum tolerated dose or a recommended dose, and to delineate the pharmacokinetic profile of LFA102 in Japanese patients, we conducted a phase I study. PATIENTS AND METHODS: LFA102 was intravenously infused every 4 weeks to patients with advanced breast or castration-resistant prostate cancer, and the dose increased from 3 to 40 mg/kg. RESULTS: Fourteen patients were treated, and toxicities were reported in 9 (64%) patients. They were all grade 1 or 2, and the most frequently observed toxicity was nausea (3 patients, 21%). No dose-limiting toxicities were observed. LFA102 did not show antitumor activity as a single agent. CONCLUSION: Treatment with LFA102 was well tolerated.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias de Próstata Resistentes à Castração/etiologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
14.
Anticancer Res ; 40(9): 5277-5283, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878817

RESUMO

BACKGROUND/AIM: The treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has remained challenging. The effect of salvage chemotherapy (SCT) after nivolumab has been identified recently in other cancer types. The aim of this study was to examine the efficacy of SCT after nivolumab treatment in patients with R/M HNSCC. PATIENTS AND METHODS: A retrospective study was conducted at four institutions in Japan. Fifty-six patients were enrolled in the study. RESULTS: The overall survival (OS) in SCT patients was significantly longer than that in best supportive care (BSC) patients. In the SCT patients, the median OS, median progression-free survival (PFS) and objective response rate (ORR) were 7.3 months, 2.3 months and 36%, respectively. Prognostic factor for OS and ORR was performance score (PS) and previous radiation, respectively. CONCLUSION: SCT after nivolumab is associated with better clinical outcomes in patients with R/M HNSCC compared to those receiving BSC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Recidiva , Retratamento , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(33): e21775, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872077

RESUMO

BACKGROUND: Gastric cancer is a common gastrointestinal tumor, seriously threatening human health. Radical surgery is the preferred treatment for gastric cancer. However, due to the late diagnosis and postoperative recurrence and metastasis, the prognosis is dismal. In China, traditional Chinese medicine (TCM) has been used to treat gastric cancer for many years. The purpose of this study is to explore the efficacy and safety of Yiqi Huayu Jiedu decoction in the treatment of postoperative gastric caner. METHODS/DESIGN: 226 eligibility patients altogether will be randomly allocated to the treatment group and the control group at a ratio of 1:1. After enrollment, every patients will obtain 6 months of treatment, as well as 2 years of follow-up. At the end of this study, primary outcomes including 1-year progression-free survival rate, 2-year progression-free survival rate and disease-free survival, secondary outcomes containing tumor markers, TCM syndrome points, quality of life scale, imageological examination and the safety indicators will be assessed. DISCUSSION: This study will provide the evidence-based evidence for the efficacy of Yiqi Huayu Jiedu decoction reducing the risk of postoperative gastric cancer recurrence and metastasis, which will be beneficial to form the therapeutic regimen in postoperative gastric cancer with integrated TCM and Western medicine. TRAIL REGISTRATION: ChiCTR2000032802.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/prevenção & controle , Humanos , Metástase Neoplásica/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/cirurgia
16.
Nat Commun ; 11(1): 4301, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879317

RESUMO

Copy-number aberrations (CNAs) and whole-genome duplications (WGDs) are frequent somatic mutations in cancer but their quantification from DNA sequencing of bulk tumor samples is challenging. Standard methods for CNA inference analyze tumor samples individually; however, DNA sequencing of multiple samples from a cancer patient has recently become more common. We introduce HATCHet (Holistic Allele-specific Tumor Copy-number Heterogeneity), an algorithm that infers allele- and clone-specific CNAs and WGDs jointly across multiple tumor samples from the same patient. We show that HATCHet outperforms current state-of-the-art methods on multi-sample DNA sequencing data that we simulate using MASCoTE (Multiple Allele-specific Simulation of Copy-number Tumor Evolution). Applying HATCHet to 84 tumor samples from 14 prostate and pancreas cancer patients, we identify subclonal CNAs and WGDs that are more plausible than previously published analyses and more consistent with somatic single-nucleotide variants (SNVs) and small indels in the same samples.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA , Duplicação Gênica , Neoplasias Pancreáticas/genética , Neoplasias da Próstata/genética , Neoplasias da Mama/patologia , Conjuntos de Dados como Assunto , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Masculino , Taxa de Mutação , Metástase Neoplásica/genética , Neoplasias Pancreáticas/patologia , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/patologia , Análise de Célula Única , Sequenciamento Completo do Exoma
17.
Cancer Radiother ; 24(6-7): 559-566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32753240

RESUMO

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Algoritmos , Humanos , Metástase Neoplásica/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
18.
PLoS One ; 15(8): e0236570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764748

RESUMO

PURPOSE/OBJECTIVES: Recently a 1.5 Tesla MR Linac has been FDA approved and is commercially available. Clinical series describing treatment methods and outcomes for upper abdominal tumors using a 1.5 Tesla MR Linac are lacking. We present the first clinical series of upper abdominal tumors treated using a 1.5 Tesla MR Linac along with the acquisition of intra-treatment quantitative imaging. MATERIALS/METHODS: 10 patients with abdominal tumors were treated at our institution. Each patient enrolled in an IRB approved advanced imaging protocol. Both daily real-time adaptive and non-adaptive methods were used, and selection criteria are described. Adaptive plans were based on pre-beam motion-averaged or mid-position images derived from respiratory-correlated 4D-MRI. Quantitative intravoxel incoherent motion diffusion-weighted imaging and T2 mapping were acquired during plan adaptation. Real-time motion monitoring using cine MRI was performed during beam-on. RESULTS: Median patient age was 68.2, five patients were female. Tumor types included liver metastatic lesions from melanoma and sarcoma, primary liver hepatocellular carcinoma (HCC), and regional abdominal tumors included pancreatic metastatic lesions from renal cell carcinoma (RCC) along with two cases of recurrent pancreatic cancer. Doses included 30 Gy in 6 fractions, 33 Gy in 5 fractions, 50 Gy in 5 fractions, 45 Gy in 3 fractions, and 60 Gy in 3 fractions, depending on the location and clinical circumstances. Treatments were feasible and were successfully completed in all patients without significant acute toxicity, technical complications, or need for back up CT based treatment plans. CONCLUSIONS: We present a first clinical series of patients treated for pancreatic tumors, primary liver tumors, and secondary liver tumors with a 1.5 Tesla MR Linear accelerator using adapt-to-position and adapt-to-shape strategies. Treatments were well tolerated by all patients. Acquisition of fully quantitative MR imaging was feasible during the course of the treatment delivery workflow without extending overall treatment times.


Assuntos
Neoplasias Hepáticas/radioterapia , Metástase Neoplásica/radioterapia , Neoplasias Pancreáticas/radioterapia , Aceleradores de Partículas , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada
19.
Cancer Radiother ; 24(6-7): 567-575, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32814669

RESUMO

Synchronous metastatic breast cancer accounts for 5 to 6% of all breast cancers in Western countries, which corresponds to nearly 2500 new cases per year in France. Irradiation of the primary tumour in cases of metastatic disease at diagnosis was historically reserved for palliative indications. However, progress in systemic treatments, a better understanding of the biological basis of metastatic dissemination, the genesis of the concept of oligometastatic disease and ablative treatments directed towards metastases are revolutionizing the management of patients with de novo stage IV breast cancer. Survival of these patients has improved markedly over the years, and several studies have investigated the carcinological benefit of local treatment of the breast tumour in patients with advanced diseases at diagnosis. This article provides an update on the role of irradiation of the primary tumour in breast cancer with synchronous metastases, and discusses its interest through published or ongoing trials.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Neoplásica/radioterapia , Estudos Prospectivos , Estudos Retrospectivos
20.
Nature ; 585(7823): 113-118, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814895

RESUMO

Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.


Assuntos
Ferroptose , Linfa/metabolismo , Melanoma/patologia , Metástase Neoplásica/patologia , Animais , Sobrevivência Celular , Coenzima A Ligases/metabolismo , Feminino , Ferroptose/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Ferro/metabolismo , Masculino , Melanoma/sangue , Melanoma/metabolismo , Camundongos , Metástase Neoplásica/tratamento farmacológico , Ácido Oleico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Análise de Componente Principal
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