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1.
Anticancer Res ; 40(4): 2359-2364, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234938

RESUMO

BACKGROUND: The aim of the present study was to evaluate the clinical impact of the perioperative use of antiplatelet/anticoagulation therapy for postoperative bleeding after esophagectomy for esophageal cancer. PATIENTS AND METHODS: Patients were selected from the medical records of consecutive patients who were diagnosed with primary esophageal adenocarcinoma or squamous cell carcinoma and who underwent complete resection at Yokohama City University from January 2005 to September 2018. The patients were divided into the antiplatelet/anticoagulation treatment group and the non-treatment group. We compared the safety and feasibility of esophagectomy between two groups. RESULTS: One hundred and twenty-two patients underwent esophagectomy for esophageal cancer and were analyzed in the present study. Among them, 18 (14.8%) received anti-thrombotic therapy (anticoagulation group). The incidence of postoperative bleeding in patients overall was 8.2% (10/122). The incidence of postoperative bleeding in the anticoagulation group was 22.2% (4/18), while that in the non-anticoagulation group was 5.8% (6/104). Preoperative anticoagulation therapy was identified as a significant independent risk factor for postoperative bleeding (hazard ratio=4.673, 95% confidence interval=1.170-18.519; p=0.029). CONCLUSION: The perioperative use of anti-thrombotic therapy was a significant risk factor for postoperative bleeding after esophagectomy for esophageal cancer. Thus, when patients receive perioperative antiplatelet/anticoagulation treatment, careful attention is required after esophagectomy due to their increased risk of postoperative bleeding.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Complicações Pós-Operatórias/diagnóstico , Hemorragia Pós-Operatória/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Esofagectomia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/etiologia , Fatores de Risco
2.
Medicine (Baltimore) ; 99(9): e19295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118743

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Compostos de Platina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidrocarbonetos Aromáticos com Pontes/normas , Quimiorradioterapia/normas , Quimiorradioterapia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/normas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Taxoides/normas , Texas , Resultado do Tratamento
3.
Zhonghua Zhong Liu Za Zhi ; 42(2): 139-144, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135649

RESUMO

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.


Assuntos
Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Antineoplásicos/uso terapêutico , Quimiorradioterapia , Relação Dose-Resposta à Radiação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Prognóstico , Dosagem Radioterapêutica , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Estudos Retrospectivos
4.
Anticancer Res ; 40(2): 965-975, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014941

RESUMO

BACKGROUND/AIM: A standard treatment recommendation for advanced stage gastroesophageal cancer is still missing. PATIENTS AND METHODS: We retrospectively analyzed clinical data of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2001 and 2017 at the Vienna General Hospital, Austria. RESULTS: Administration of systemic therapy was positively associated with overall survival (OS) (469 days vs. 185 days; p<0.001), while palliative gastrectomy or radiotherapy showed no correlation. OS was significantly longer in patients receiving capecitabine/oxaliplatin (XELOX) vs. leucovorin/5-FU/oxaliplatin (FOLFOX) (600 days vs. 327 days, p<0.05). Comparison of doublet vs. triplet chemotherapies showed no difference in OS, but triplet chemotherapy resulted in more adverse events. The anti-HER2-antibody trastuzumab doubled OS (836 days vs. 399 days, p=0.053). CONCLUSION: Capecitabine may be preferably used over infused 5-FU and doublet chemotherapy over triplet chemotherapy in the first-line palliative setting of advanced gastroesophageal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Cuidados Paliativos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Cuidados Paliativos/métodos , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
5.
Oncology ; 98(5): 289-294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097933

RESUMO

INTRODUCTION: Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma. Similarly, irinotecan-based therapy has marginal efficacy. We combined irinotecan plus a fluoropyrimidine with an anti-PD-1 antibody, nivolumab, with hopes of having a higher advantage for patients. OBJECTIVES: Primary objective was to assess safety judged by toxicities, dose delays, or dose reductions. Secondary endpoints included the assessment of response, overall survival (OS), and progression-free survival (PFS). METHODS: We treated 15 patients with this combination during July 2017 to April 2019. Patients were included if they had follow-up at our institution. RESULTS: Median doses given were nivolumab 240 mg + irinotecan 120 mg/m2 + 5-FU 2,000 mg/m2 over 46-48 h (or capecitabine 1,250 mg/m2/day; 7 days on, 7 days off) given every 2 weeks. Median age of the patients was 55 years, and all patients had an ECOG performance status of 0-1. The patients had a median of 1 prior therapy. Slightly over half of the patients had PD-L1 expression. The median number of cycles was 7. Five patients (33%) had a dose delay or dose adjustment. The most common reason for dose delay or adjustment was grade 2 fatigue. Disease control (response or stability) on first scan was 73.3% (n = 11). Median PFS and OS for the entire group was 7 and 13.3 months, respectively. CONCLUSION: In this small cohort of patients, we conclude that this combination is quite feasible and resulted in prolonged stability in some patients. Further development of this regimen is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Irinotecano/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/patologia
6.
Crit Rev Oncol Hematol ; 147: 102883, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32014674

RESUMO

Endoscopic resection (ER) combined with adjuvant therapy appears to be a new treatment for esophageal squamous cell cancers (ESCC) invading to deep mucosa (pT1a-m3) or submucosa (pT1b). Adjuvant therapy can take the form of esophagectomy or chemoradiotherapy (CRT), but it is unclear which treatment is better. This review is to explore the outcomes of adjuvant therapy between esophagectomy and CRT for the treatment of pT1a-m3/pT1b ESCC after ER. Ten relevant studies with a total of 285 patients were included. The reported 5-year overall survival rates ranged between 90-100 % for ER-esophagectomy and 75-85 % for ER-CRT. ESCC with the invasion of ≥ sm2 combined with lymphovascular involvement was associated with a high-risk of relapse in patients receiving ER-CRT, but not in ER-esophagectomy. In conclusion, patients with a high-risk of relapse should be treated with ER-esophagectomy; ER-CRT may be used as an alternative treatment for patients with a nonhigh risk of relapse.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(3): e18892, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011517

RESUMO

RATIONALE: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. PATIENT CONCERNS: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis. DIAGNOSES: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation. INTERVENTIONS: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic. OUTCOMES: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019. LESSONS: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Tegafur/uso terapêutico , Carcinoma de Células Pequenas/cirurgia , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Irinotecano/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Salvação
8.
Medicine (Baltimore) ; 99(7): e18332, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049776

RESUMO

BACKGROUND: Patients with advanced gastric or gastro-oesophageal junction cancer (GC/GEJC) that fail to respond to prior chemotherapy have poor clinical prognosis. Lately, many trials have paid much attention on the oncological outcomes of immune checkpoint inhibitors (ICI). A new therapy based on programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has recognized as promising prospects for advanced GC/GEJC. We assessed efficacy and safety of PD-L1 antibody versus chemotherapy alone in previously treated non-small cell lung cancer. METHODS: Computerized literature search was done on the published trials in: Pubmed, Embase, Cochrane library updated on June 2019. Randomized controlled trials were selected investigating chemotherapy plus PD-1/PD-L1 versus chemotherapy alone. RESULTS: Three randomized controlled trails were included. The pooled analysis of overall survival (OS) was longer with anti-PD1/PD-L1 than with chemotherapy alone in the OS (OR = 0.66, 95%CI = 0.47-0.92, P = .02) and sub-group OS of GEJC (OR = 0.73, 95%CI = 0.58-0.93, P = .01). Whereas, there is no significant difference in progression-free survival (OR = 0.93, 95%CI = 0.62-1.39, P = .72). The pooling adverse events (AE) data did not achieve advantage in the PD-1/PD-L1 targeted agents (OR = 0.53, 95%CI = 0.13-2.10, P = .36), the same as the treatment-related AE of grade 3 to 5 (OR = 0.53, 95%CI = 0.16-1.74, P = .30). CONCLUSIONS: Treatment of patients with advanced GC/GEJC with PD-1/PD-L1 targeted did result in an improvement in some but not all survival endpoints. Moreover, it had a comparable toxicity profile as compared with chemotherapy alone. More well designed studies are needed to develop a database of all anti-PD1/PD-L1 sub-groups and their individual impact on the differing anti-PD1/PD-L1 treatments.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento
10.
Cancer Treat Rev ; 84: 101950, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918022

RESUMO

Recent advances in our understanding of the molecular biology of gastric and oesophageal cancers have shown that gastroesophageal adenocarcinoma should be considered as one disease spectrum. Clinical management of these cancers is challenging, with poor outcomes in both early and late disease settings. Certain molecular subsets of gastroesophageal adenocarcinoma demonstrate features that suggest immunotherapy could be an effective treatment. Immunogenetic markers, including mismatch repair deficiency, PD-L1 status and tumour infiltrating lymphocytes influence overall prognosis. They may also determine the response to adjuvant and neoadjuvant conventional chemotherapy. Initial results from immunotherapy trials for gastroesophageal cancer have however been mixed, with poor overall responses in the first- and second-line settings. This review aims to discuss how better understanding of these immune and genetic interactions may lead to better selection of patients for conventional and immune based therapies, and therefore improve patient outcomes. We also discuss the challenges in implementing this new understanding in routine practice, and the current limitations of immune based treatments for gastroesophageal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Antígenos de Neoplasias/imunologia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Quimioterapia Adjuvante , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/imunologia , Humanos , Fenômenos Imunogenéticos , Linfócitos do Interstício Tumoral/imunologia , Complexo Principal de Histocompatibilidade/genética , Complexo Principal de Histocompatibilidade/imunologia , Instabilidade de Microssatélites , Terapia Neoadjuvante , Seleção de Pacientes , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
11.
Medicine (Baltimore) ; 99(1): e18691, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895837

RESUMO

RATIONALE: Apatinib has been proven to significantly prolong the survival of the patients with advanced chemotherapy-refractory gastric cancer. To date, studies on apatinib plus S-1 as first-line palliative therapy for metastatic gastroesophageal junction (GEJ) cancer are rare. PATIENT CONCERNS: A 61-year-old female patient was admitted with dysphagia, significant loss of body weight, and poor performance status. DIAGNOSES: Endoscopic biopsy revealed the diagnosis of poorly-differentiated GEJ adenocarcinoma, and the patient was clinically staged as T3NxM1G3 (IVB). INTERVENTIONS: She had received 4 cycles of palliative therapy using oral apatinib (425 mg daily) plus S-1 (40 mg twice daily for 4 weeks, with a 2-week drug-free interval), followed by maintenance low-dose apatinib (250 mg daily) plus S-1 at the same dosage thereafter. OUTCOMES: Her progression-free survival was nearly 5 months, and the overall survival was >11 months up to now. The adverse events were tolerable. LESSONS: Apatinib plus S-1 might be an alternative option for late-stage GEJ cancer. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Piridinas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Combinação de Medicamentos , Junção Esofagogástrica , Feminino , Humanos , Pessoa de Meia-Idade , Ácido Oxônico , Tegafur
12.
Cancer Sci ; 111(4): 1103-1112, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981293

RESUMO

The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pre-therapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4+ lymphocytes (with/without Foxp3 expression), CD8+ lymphocytes (with/without PD-1 expression), monocytes (CD14+ ) and macrophages (CD86+ , CD163+ and CD206+ ) by multiplex immunohistochemistry (IHC). The number of tumor-infiltrating CD206+ macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD-1) was not associated with clinico-pathological features. The high infiltration of CD163+ or CD206+ macrophages was significantly associated with poor pathological response to NAC (P = 0.0057 and 0.0196, respectively). Expression of arginase-1 in CD163+ macrophages tended to be higher in non-responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5-year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long-term survival in EC patients.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Terapia Neoadjuvante , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores Tumorais/sangue , Biópsia , Linhagem da Célula/efeitos dos fármacos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fatores de Transcrição Forkhead/sangue , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/sangue , Receptor de Morte Celular Programada 1/genética , Receptores de Superfície Celular/sangue , Microambiente Tumoral/efeitos dos fármacos
13.
Int J Cancer ; 146(7): 1889-1901, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31340065

RESUMO

The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010-2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83-1.02; TTF: HR 0.92, 95%CI 0.82-1.04) but significantly more grade 3-5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Cuidados Paliativos/métodos , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Países Baixos/epidemiologia , Sistema de Registros/estatística & dados numéricos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Trastuzumab/uso terapêutico , Falha de Tratamento
14.
Clin Nucl Med ; 45(2): 127-128, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876811

RESUMO

Paclitaxel-ramucirumab chemotherapy is indicated in second line of metastatic gastroesophageal junction cancer (mGEJC) after progression under platinum-5-FU chemotherapy. Nevertheless, the reported common response after treatment is only partial within series. To date, only 1 case report of negative posttreatment FDG PET/CT was published without baseline examination from RAINBOW trial. We illustrated the interest of FDG PET/CT to evaluate treatment especially paclitaxel-ramucirumab with 2 examples of complete metabolic responses in 2 patients having different HER2 biomarker profiles of mGEJC. As illustrated, FDG PET/CT emerges as a useful approach for therapeutic assessment of targeted drugs in mGEJC.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/diagnóstico por imagem , Fluordesoxiglucose F18 , Paclitaxel/farmacologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico
15.
BMJ Case Rep ; 12(12)2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843780

RESUMO

Acute gastrointestinal (GI) immune-related adverse events (irAE) are commonly reported by patients with cancer undergoing treatment with immune checkpoint inhibitors (CPI); however chronic irAEs are rare. We present a case of a 71-year-old woman with metastatic gastro-oesophageal junction (GOJ) adenocarcinoma who developed delayed-onset chronic intestinal pseudo-obstruction (CIPO) while receiving second-line pembrolizumab. Repeated CT scans of the abdomen/pelvis found no small bowel obstruction, and evaluations for bowel inflammation, infection and paraneoplastic syndrome were negative. Bowel rest and glucocorticoids were associated with transient symptom resolution; however, symptoms recurred within 1 month. The patient was ultimately supported with total parenteral nutrition and intestinal motility agents. After 4 months, the GOJ cancer remained stable with no signs of progression. As CPI use expands, the incidence of rare irAEs, such as CIPO, may increase.


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Pseudo-Obstrução Intestinal/induzido quimicamente , Adenocarcinoma/diagnóstico por imagem , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Esofágicas/diagnóstico por imagem , Junção Esofagogástrica , Feminino , Humanos , Pseudo-Obstrução Intestinal/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/tratamento farmacológico , Ultrassonografia
16.
Gan To Kagaku Ryoho ; 46(11): 1753-1755, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748486

RESUMO

A 79-year-old woman had recurrence in the mediastinal lymph node 6 months after curative resection of advanced esophageal cancer(pStage Ⅲ). After radiation therapy and 12 courses of chemotherapy with docetaxel, new recurrent tumors progressed in the mediastinum and apical region of the left lung, and her performance status(PS)deteriorated to grade 3. Alternate-day, low-dose S-1 chemotherapy was started at a dose of 60mg/day. Tumors decreased in size within 6 months, and her PS improved from grade 3 to 0. She had been treated for 33 months without severe adverse events until disease progression. So far, we have experienced in clinical practices that the alternate-day S-1 administration was tolerable for patients who were unfit for the standard daily administration. Alternate-day, low-dose S-1 administration may be a sustainable and effective option in S-1 chemotherapy in patients with recurrent esophageal cancer with impaired PS.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Esofágicas , Recidiva Local de Neoplasia , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel , Combinação de Medicamentos , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Linfonodos , Mediastino
17.
Medicine (Baltimore) ; 98(47): e18054, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764833

RESUMO

BACKGROUND: Current therapeutic options have limited efficacy for patients with advanced gastric or gastroesophageal junction cancer. Immune checkpoint inhibition now has been increasingly used in advanced gastric or gastroesophageal junction cancer therapy. To further understand the efficacy and safety of anti-programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) agents is critical for clinical practice. We conducted this systematic review and meta-analysis to assess the benefit and risk of PD-1 and PD-L1 inhibitors. METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science online databases were searched up to Jun 16, 2019. Primary outcomes were overall survival (OS), progression-free survival (PFS). Second outcomes were objective response rate (ORR), disease control rate (DCR) and adverse events. RESULTS: Six studies were assessed for inclusion in the final synthesis, of which 5 were eligible for meta-analysis. Compared with chemotherapy, the pooled hazard ratio (HR) for OS and PFS was, respectively, 1.01 (95% confidence interval [CI]: 0.88-1.15, P = .93) and 1.58 (95% CI: 1.38-1.81, P < .001) after treatment with PD-1/PD-L1 inhibitors. In patients treated with anti-PD-1/PD-L1 agents, the pooled ORR was 9.9% (95% CI: 4.4%-15.5%) and the pooled DCR was 30.8% (95% CI: 21.8%-39.9%). Sub-analysis for treatment related adverse events indicated that fatigue was the most common toxicity in anti-PD-1/PD-L1 therapy (incidence 10.6%, 95% CI: 5.6%-15.6%). CONCLUSION: PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric or gastroesophageal junction cancer patients. However, single-agent PD-1/PD-L1 inhibitor did not result in a relative improvement in OS and PFS compared with chemotherapy in the treatment of patients with advanced gastric or gastroesophageal junction cancer. Further randomized clinical trials are warranted to confirm our findings.


Assuntos
Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Humanos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
18.
Medicine (Baltimore) ; 98(40): e17164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577707

RESUMO

INTRODUCTION: The PD-1 inhibitors have shown good response in the treatment for many types of malignant tumors, but as monotherapy for advanced esophageal squamous carcinoma, the objective response rate is low. Here we report a case of the patient with advanced esophageal squamous cell carcinoma (ESCC) showing a completely response to nivolumab combined with a small molecule multi-target tyrosine kinase inhibitor (TKI) anlotinib. PATIENT CONCERNS: A 61-year-old male was put under a surgery as the response to the diagnosis of ESCC in March 2014. The post-operative follow-up in March 2018 suggested a recurrence based on imagological findings, and symptoms such as shortness of breath and cough were also observed in October 2018. DIAGNOSIS: The patient was diagnosed as advanced metastatic ESCC in October 2018. INTERVENTIONS: Radical resection and esophagogastrostomy under aortic arch with left thoracotomy was performed in March 2014. As a treatment against the post-surgical recurrence, 4 courses of paclitaxel combined with nedaplatin was administered in April 2018 with an outcome of PR, followed by a combined administration of Nivolumab and anlotinib in November 2018. OUTCOMES: Chest CT during a 3-month follow-up revealed the disappearance of all the metastases, and no adverse effect was observed during the treatment. CONCLUSION: The combined treatment of nivolumab and anlotinib is likely to be considered as an optional management of advanced ESCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Indóis/uso terapêutico , Nivolumabe/uso terapêutico , Quinolinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
19.
Anticancer Res ; 39(10): 5675-5682, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570466

RESUMO

BACKGROUND/AIM: This study explored the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and use of antibiotics in advanced esophageal squamous cell carcinoma (ESCC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Patients were enrolled from two referral centers in Taiwan. Clinical benefit was defined as complete response, partial response, or a stable disease for ≥6 months via Response Evaluation Criteria In Solid Tumors 1.1. Clinicopathological factors' impact on overall survival (OS) and progression-free survival (PFS) was analyzed via Cox proportional hazards model. RESULTS: Forty-nine patients were enrolled. The median PFS and OS were 1.8 and 6.1 months, respectively. The median NLR at baseline was 6.40, and 21 patients received antibiotics. Both high NLR and use of antibiotics were associated with inferior PFS (p=0.028 and p<0.001, respectively) and OS (p<0.001 and p<0.001, respectively) in multivariate analysis. CONCLUSION: High NLR and use of antibiotics were associated with inferior survival in advanced ESCC patients receiving ICIs.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taiwan
20.
BMC Cancer ; 19(1): 1004, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655563

RESUMO

BACKGROUND AND OBJECTIVES: The survival rate of patients with advanced oesophageal cancer is very low and can vary significantly, even among patients with the same TNM stage. It is important to look for indicators that are economical and readily available to predict overall survival. The aim of this study was to determine whether lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) could be potential predictors of survival in patients with advanced oesophageal squamous cell carcinoma (ESCC) undergoing concurrent chemoradiotherapy. METHODS: Differences in survival among 204 patients with advanced oesophageal cancer who underwent concurrent chemoradiotherapy were collected and analysed. Univariate and multivariate COX regression analyses were used to investigate the association between blood inflammatory markers and patient survival before treatment. RESULTS: Univariate COX regression analyses showed that a history of alcohol use, neutrophil count, LMR, NLR, tumour length, and N stage were significantly associated with the survival of tumour patients receiving concurrent chemoradiotherapy. Multivariate COX regression analysis showed that NLR and LMR were predictors of outcome in tumour patients receiving chemoradiotherapy. According to receiver operating characteristic (ROC) curve analysis, the AUC of LMR and NLR was 0.734 and 0.749, and the best cutoff point for LMR and NLR was 3.03 and 2.64, respectively. CONCLUSIONS: LMR and NLR can be used to predict the survival of patients with advanced oesophageal cancer receiving concurrent chemoradiotherapy, thereby providing clinicians with suggestions for further treatment options.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/tratamento farmacológico , Linfócitos/patologia , Monócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Área Sob a Curva , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
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