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1.
APMIS ; 128(1): 3-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628675

RESUMO

Biliary tract cancers (BTC) are a rare heterogeneous disease group with a dismal prognosis and limited treatment options. The mutational landscape consists of genetic aberrations both shared by and characteristic for anatomical location. Here, we present exome sequencing data on 22 genes from a phase 2 trial using a clinically validated panel used in patients with colorectal cancer. A total of 56 patients were included in a one-armed phase 2 trial investigating the treatment combination of capecitabine, gemcitabine, oxaliplatin, and cetuximab. Tissue DNA yield and quality allowed analysis of 30 patients on our panel including 22 genes. ARID1A (33%) and TP53 (33%) were found to be most frequently mutated followed by KRAS mutations found in 20% of the patients. Mutational aberrations in ARID1A were found more prevalent than expected, whereas TP53 and KRAS were in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis. Our panel is clinically validated and suitable for a high volume of samples to detect mutations in patients with BTC. However, it is reasonable to assume that the clinical utility could be optimized in this patient group by extending the panel to include BTC specific mutations with potential therapeutic consequences such as IDH1/2, FGFR fusions, ERBB3, and BRCA1/2.


Assuntos
Neoplasias dos Ductos Biliares/genética , Exoma , Mutação , Adulto , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Inclusão em Parafina , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de DNA , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , beta Catenina/genética
2.
N Engl J Med ; 381(25): 2416-2428, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31851799

RESUMO

BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida
3.
Zhonghua Zhong Liu Za Zhi ; 41(12): 937-942, 2019 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-31874552

RESUMO

Objective: To explore the effect of nutritional status pre-and during chemoradiotherapy on the prognosis of patients with limited- stage small cell lung cancer (LS-SCLC). Methods: We retrospectively collected medical records of 172 LS-SCLC patients undergoing concurrent chemoradiotherapy in our hospital from 2000 to 2014, with 126 males and 46 females. The data of complete blood count and hepatic and renal function were collected before initial treatment, before radiotherapy, 4 weeks during radiotherapy, and 1 month after complete of treatment. The prognostic nutritional index(PNI)was calculated. Kaplan-Meier method was used to calculate the survival rate. Log-rank test was performed used to compare the survival differences between groups. Multivariate prognostic analysis was performed using Cox regression model. Results: The median overall survival (OS) was 21 months, with median progression-free survival (PFS) of 11 months. At the beginning of treatment, patients with pre-treatment PNI ≥ 53 had significantly superior OS (median 37 vs 15 months, P=0.001) and PFS (median 16 vs 10 months, P=0.017). Patients with pre-treatment hemoglobin ≥140 g/L and <140 g/L had an median OS of 32 months and 17 months (P=0.019), and median PFS of 16 months and 9 months (P=0.040), respectively. During chemoradiation, patients with elevated hemoglobin had similar median OS compared with those had decreased hemoglobin (27 vs 18 months, P=0.063, but superior median PFS (15 vs 9 months, P=0.017). Multivariate analysis revealed that prophylactic cranial irradiation, pre-treatment hemoglobin ≥140 g/L, and pretreatment PNI ≥53 were independent predictors of OS and PFS in patients with LS-SCLC. Conclusion: Pre-treatment nutritional status and the changes of nutritional status during chemoradiotherapy is significantly associated with the prognosis of patients with limited-stage small cell lung cancer. The patients with better pre-treatment nutritional status have a better prognosis.


Assuntos
Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Estado Nutricional , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/química , Quimiorradioterapia , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Taxa de Sobrevida
4.
Medicine (Baltimore) ; 98(52): e18344, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876708

RESUMO

BACKGROUND: Approximately 80% to 90% of patients with low-risk rhabdomyosarcoma can be cured. However, cured patients often face long-term complications associated with the treatment. An important factor in the treatment plan is the dose of cyclophosphamide administered because the dose can have both acute and long-term side effects. It is therefore essential to investigate whether the dose can be reduced without a negative effect on treatment outcome. The ARST0331 trial revealed that drastically reducing the cyclophosphamide dose to 4.8 g/m negatively affected treatment outcomes. The current study aims to determine whether reducing the cyclophosphamide dose to 10.8 g/m while introducing a new drug, irinotecan, can prevent the negative effect on treatment outcome. We also aim to investigate whether the reduced cyclophosphamide dose results in a decrease in infertility, one of the long-term complications of this treatment. METHODS: The subjects are patients with stage 1 group III rhabdomyosarcoma (excluding those with orbital group III N0 and NX) or patients with stage 3 group I and II low-risk subset B embryonal rhabdomyosarcoma who will alternately undergo VAC 1.2 treatment (vincristine, actinomycin D, cyclophosphamide 1.2 g/m) and VI treatment (vincristine, irinotecan). The effectiveness and safety of this treatment regimen will be assessed. Data will be presented at international conferences and will be published in peer-reviewed journals. DISCUSSION: This study is significant because it aims to establish that the use of irinotecan in patients with low-risk subset B embryonal rhabdomyosarcoma (aged 30 or younger) allows the dose of cyclophosphamide to be reduced and is associated with few short-term adverse effects and long-term complications. The open-label and single-arm design of this study may be a limitation. TRIAL REGISTRATION AND ETHICAL APPROVAL: The trial registration number is jRCTs051180200 (Japan Registry of Clinical Trials). The study protocol was approved by the institutional review board at each of the participating centers and the data will be presented at international conferences and published in peer-reviewed journals.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Irinotecano/administração & dosagem , Rabdomiossarcoma/tratamento farmacológico , Vincristina/administração & dosagem , Adulto , Protocolos Clínicos , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Estadiamento de Neoplasias , Rabdomiossarcoma/patologia , Resultado do Tratamento , Vincristina/uso terapêutico
5.
Anticancer Res ; 39(11): 6217-6222, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704850

RESUMO

BACKGROUND/AIM: Elderly cancer patients are more prevalent and require special attention. This study focused on the outcome of elderly (≥65 years) rectal cancer patients treated with tri-modality therapy. PATIENTS AND METHODS: A total of 105 patients receiving neoadjuvant radio-chemotherapy and resection for locally advanced rectal cancers were retrospectively evaluated. Nine characteristics were analyzed for loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) including tumor location, gender, age, performance status, radiotherapy technique, primary tumor/lymph node categories, downstaging and histological grading. RESULTS: The 5-year rates of LRC, MFS and OS were 91%, 78% and 87%, respectively. Radio-chemotherapy was not completed in 12 patients (11%) due to toxicity; 18 patients (17%) experienced grade 3 toxicities. A total of 29 patients (28%) had surgical complications. On multivariate analyses, MFS was significantly associated with downstaging (p=0.003) and OS with lower histological grade (p=0.013). CONCLUSION: Tri-modality therapy resulted in promising outcomes and was tolerated reasonably well by elderly patients. Prognostic factors were identified that may help personalize future treatment.


Assuntos
Neoplasias Retais/terapia , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Avaliação de Estado de Karnofsky , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Complicações Pós-Operatórias , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
6.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
7.
Anticancer Res ; 39(11): 6265-6271, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704856

RESUMO

BACKGROUND/AIM: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. RESULTS: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. CONCLUSION: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.


Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Japão , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(44): e17748, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689828

RESUMO

BACKGROUND: Previous evidence directly evaluating the efficacy and safety of abiraterone and enzalutamide treatment for castration-resistant prostate cancer (CRPC) is limited. We aim to include more randomized controlled trials (RCTs) to comprehensively assess the efficacy and safety of abiraterone and enzalutamide treatment. METHODS: PubMed, Embase, and ClinicalTrial.gov were systematically searched. Pooled hazard ratios (HRs) were calculated using Stata 12.0 software. The comparison of the prostate-specific antigen (PSA) response rate and adverse events (AEs) between the treatment and control groups were performed using RevMan 5.3 software. RESULTS: Eight eligible RCTs with 6,490 patients were selected. Pooled HRs were 0.72 for overall survival, 0.45 for radiographic progression-free survival (rPFS), and 0.36 for PSA PFS. abiraterone and enzalutamide could significantly increase the PSA response rate OR = 8.67, 95%CI 4.42-17.04) and any AE occurrence (OR = 1.98, 95%CI 1.46-2.68). The treatment group had more occurrence of fatigue (OR = 1.34, 95%CI 1.20-1.49), back pain (OR = 1.15, 95%CI 1.01-1.15), hot flush (OR = 1.76, 95%CI 1.50-2.06), diarrhea (OR=1.22, 95%CI 1.07-2.40) and arthralgia (OR = 1.34, 95%CI 1.16-1.54). Particularly, AEs of special interest including any grade hypertension (OR = 2.06, 95%CI 1.71-2.47), hypokalemia (OR = 1.80, 95%CI 1.42-2.30) and fluid retention or edema (OR = 1.38, 95%CI 1.17-1.63) also occurred less in the control group. Moreover, a higher incidence of high-grade hypertension (OR = 2.60, 95%CI 1.79-3.79) and extremity pain (OR = 4.46, 95%CI 2.81-7.07) was observed in the treatment group. CONCLUSION: The survival benefits of abiraterone and enzalutamide for CRPC were evident and promising, while the risk of AE occurrence was also acceptably higher in the treatment group than in the placebo group.


Assuntos
Androstenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/uso terapêutico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(45): e17832, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702638

RESUMO

INTRODUCTION: The prognosis for recurrent intrahepatic cholangiocarcinoma with bone metastasis remains dismal and its treatment poses a challenge for oncologists. To date, only 2 cases were reported in which pembrolizumab, an agent against programmed cell death protein-1 (PD-1), combined with chemotherapy led to a complete response. The safety and efficacy of nivolumab-based immunotherapy combined with lenvatinibin intrahepatic cholangiocarcinoma is unknown. PATIENT CONCERNS: A 40-year-old female was identified as having a lesion of 7.0 cm in diameter in the right lobe of the liver. In addition, calculi in the main and left hepatic bile ducts as well as the gallbladder were found. DIAGNOSIS: Based on the results of imaging studies and tumor biomarker level, the patient was initially diagnosed as having intrahepatic cholangiocellular carcinoma and cholelithiasis, after which surgery was performed. The pathological examination confirmed that the tumor was cholangiocarcinoma. Adjuvant chemotherapy was administered after surgery. However, the patient developed recurrent lesions at the 5th month after surgery, and the cholangiocarcinoma expanded to the right thoracic vertebral pedicle (T7-8) at the 6th month. INTERVENTIONS: The patient underwent percutaneous microwave ablation after recurrence in the liver was identified. After that, the patient received nivolumab plus lenvatinib. OUTCOMES: The lesions in the liver decreased in size and disappeared after treatment with nivolumab plus lenvatinib. Additionally, the metastases in the right thoracic vertebral pedicle were stable after 9 months of therapy. LESSONS: Immunotherapy has revolutionized the treatment of non-small-cell lung cancer, melanoma, and advanced renal cell carcinoma. In this case, the patient achieved an excellent radiological and symptomatic response after receiving nivolumab plus lenvatinib combination therapy. Patients suffering from cholangiocarcinoma with dMMR status and a high tumor mutation burden (TMB) may have a consistent eutherapeutic effect with anti-PD-1-directed treatment.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Colangiocarcinoma/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Ablação por Radiofrequência , Análise de Sobrevida , Resultado do Tratamento
10.
Medicine (Baltimore) ; 98(45): e17872, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702654

RESUMO

RATIONALE: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) is a rare type of soft tissue sarcomas (STS), especially in infants, with poor prognosis. It is a so-called "small round cell" sarcoma, and has many features of Ewing sarcoma, but lacks rearrangements in EWSR1. The diagnosis and treatment of this kind of STS remains challenging. BCOR genetic abnormalities have been found in some Ewing-like sarcomas. PATIENT CONCERNS: This report presents an ELS case of a female infant, who was 2 months old when initially diagnosed, with the clinical stage of IIIA (G2T2N0M0). Histologic findings revealed an undifferentiated neoplasm composed of small round tumor cells with round, open chromatic nuclei, and scant cytoplasm in a sheet growth pattern. Fluorescence in situ hybridization (FISH) analysis showed absence of EWSR1 and ETV6 gene rearrangement. Molecular genetic testing found no established variants of clinical significance but variants of unknown significance in APC, KMT2D, and MSH6 were detected. Immunostaining revealed that the tumor cells were positive for TLE1 and BCOR, and negative for cytokeratin (AE1/AE3), Desmin, CD45, S100, CD31, HMB45, and SATB2. INI-1 was retained. DIAGNOSIS: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) INTERVENTIONS:: After initial diagnosis, the patient received 4 cycles of combination chemotherapy for 2 months. Radical amputation of left upper extremity was performed 3 months after diagnosis. Postoperative chemotherapy was continued for 6 cycles. OUTCOMES: The patient died of intracranial metastasis with hemorrhage in 13 months after initial diagnosis, 5 months after the last cycle of chemotherapy. LESSONS: ELS in infancy is extremely rare and has a poorer prognosis than Ewing sarcoma or infantile fibrosarcoma. APC and MSH6 variation might be related with the disease progression and predict a poorer prognosis. This rare case promotes better understanding of the disease and suggests a promising role for the combination chemotherapy regimen in treating infantile ELS. Importantly, it brings to light the possibility of intracranial metastasis, which requires proactive screening for timely detection.


Assuntos
Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Evolução Fatal , Feminino , Antebraço/diagnóstico por imagem , Humanos , Lactente , Sarcoma/diagnóstico por imagem , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética , Ultrassonografia Doppler em Cores , Vincristina/uso terapêutico
11.
Anticancer Res ; 39(11): 5867-5877, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704811

RESUMO

BACKGROUND/AIM: The aim of this study was to examine clonal heterogeneity, to test the utility of liquid biopsy in monitoring disease progression and to evaluate the usefulness of ex vivo drug screening in a BRAF L597Q-mutated colorectal cancer (CRC) patient developing metastases during adjuvant therapy. MATERIALS AND METHODS: Next generation sequencing (NGS) and droplet digital PCR (ddPCR) were performed in samples from tumor tissues and liquid biopsies. Live cancer cells from a metastatic lesion were used in ex vivo drug sensitivity assays. RESULTS: We found evidence of continued dependence of MEK/MAPK pathway activation, but different activating mutations in primary tumor and metastases. Liquid biopsy based BRAF L597Q ddPCR testing was a sensitive personalized biomarker predicting the rise of clinically aggressive metastatic disease. Ex vivo drug sensitivity assays with BRAF L597Q mutated cells showed response to MEK/MAPK targeted therapies. CONCLUSION: The rare BRAF L597Q mutation may be associated with aggressive tumor behavior in CRC. Liquid biopsy can be used to capture clinically relevant tumor features.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/secundário , MAP Quinase Quinase 1/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Mutação , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Capecitabina/administração & dosagem , Evolução Clonal , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MAP Quinase Quinase 1/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxaliplatina/administração & dosagem , Prognóstico
12.
Anticancer Res ; 39(11): 6097-6105, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704837

RESUMO

BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common in the world and its prevalence is rapidly increasing. Jagged-1-activated Notch signaling by apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) promotes CRC, and high expression of Jagged-1 is associated with poor prognosis. However, its clinical implication is unknown. The aim of this study was to investigate the clinical role of Jagged-1-activated Notch signaling by APEX1. MATERIALS AND METHODS: The 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the anti-cancer efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. Tissue from CRC patients was analyzed to assess the clinical specificity of Jagged-1 activated by APEX1. RESULTS: The half-maximal inhibitory concentration (IC50) in cells co-expressing APEX1 and Jagged-1 cells was higher than that in cells expressing only APEX1. These results indicated that the simultaneous expression of APEX1 and Jagged-1 might be associated with chemoresistance toward 5-FU, oxaliplatin, and irinotecan. Analysis of tissue from CRC patients revealed that high expression of Jagged-1 was associated with a statistically significantly low response to chemotherapy. CONCLUSION: Overexpression of Jagged-1 by APEX1 might serve as a predictor of response to chemotherapy and of poor prognosis, and moreover may be a therapeutic target for chemotherapy of advanced CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína Jagged-1/metabolismo , Receptor Notch1/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Proteína Jagged-1/genética , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Prognóstico , Receptor Notch1/genética , Estudos Retrospectivos , Taxa de Sobrevida , Células Tumorais Cultivadas
13.
N Engl J Med ; 381(20): 1929-1939, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722153

RESUMO

BACKGROUND: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation. METHODS: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival. RESULTS: A total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery. CONCLUSIONS: In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Paclitaxel/administração & dosagem , Qualidade de Vida , Reoperação , Análise de Sobrevida
14.
Gan To Kagaku Ryoho ; 46(11): 1791-1793, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748495

RESUMO

A 65-year-old woman was diagnosed with simultaneous hepatic metastasis of rectal cancer with portal venous tumor thrombi(Vp3)that developed in the bifurcation of the portal vein. Four days from the first visit, abdominal dynamic contrastenhanced CT image on the portal venous phase shows that the tumor thrombi progressed in the main trunk of the portal vein (Vp4). We decided that it was a condition of oncologic emergency and initiated FOLFOXIRI plus BV therapy. After 12 courses, tumor shrinkage and regression of the portal venous tumor thrombi were achieved, but conversion surgery was impossible because the collateral circulation of the hepatic portal region remained. The treatment target was changed to the extension of the survival period. The initiation and reinitiation of FOLFOXIRI plus BV therapy and maintenance of 5-FU/l-LV plus BV therapy contributed to disease control in 24 months and survival period of 36months.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas , Neoplasias Retais , Trombose Venosa , Idoso , Camptotecina/análogos & derivados , Feminino , Fluoruracila , Hepatectomia , Humanos , Leucovorina , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organoplatínicos , Veia Porta , Neoplasias Retais/complicações , Neoplasias Retais/tratamento farmacológico , Trombose Venosa/etiologia
16.
Bull Cancer ; 106(11): 983-999, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31587802

RESUMO

INTRODUCTION: Osteosarcoma is the most common malignant bone tumor before 25 years of age. Response to neoadjuvant chemotherapy determines continuation of treatment and is also a powerful prognostic factor. There are currently no reliable ways to evaluate it early. The aim is to develop a method to predict the chemotherapy response using radiomics from pre-treatment MRI. METHODS: Clinical characteristics and MRI of patients treated for local or metastatic osteosarcoma were collected retrospectively in the Rhône-Alpes region, from 2007 to 2016. On initial MRI exams, each tumor was segmented by expert radiologist and 87 radiomic features were extracted automatically. Univariate analysis was performed to assess each feature's association with histological response following neoadjuvante chemotherapy. To distinguish good histological responder from poor, we built predictive models based on support vector machines. Their classification performance was assessed with the area under operating characteristic curve receiver (AUROC) from test data. RESULTS: The analysis focused on the MRIs of 69 patients, 55.1% (38/69) of whom were good histological responders. The model obtained by support vector machines from initial MRI radiomic data had an AUROC of 0.98, a sensitivity of 100% (IC 95% [100%-100%]) and specificity of 86% (IC 95% [59.7%-111%]). DISCUSSION: Radiomic based on MRI data would predict the chemotherapy response before treatment initiation, in patients treated for osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Aprendizado de Máquina , Imagem por Ressonância Magnética , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Adolescente , Análise de Variância , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , França , Humanos , Lactente , Recém-Nascido , Masculino , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
17.
J Surg Oncol ; 120(7): 1096-1101, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31592538

RESUMO

BACKGROUND: Goblet cell carcinoid (GCC) tumors of the appendix are a rare malignancy. We aim to examine the overall survival per stage and the relationship between different treatment modalities and outcomes for patients with GCC tumors of the appendix. METHODS: We identified patients with GCC tumors of the appendix from the National Cancer Database. The main outcome was overall patient survival and cox proportional hazard models were used to ascertain predictors of survival. RESULTS: There were 2552 patients identified. The median age of diagnosis was 57 (interquartile range: 49-65) and 52.3% of patients were female. The 5-year survival for Stage I disease was 91.1% (95% confidence interval [CI]: 82.2%-95.7%), for Stage II disease was 90.5% (95% CI: 85.8%-93.7%), for Stage III disease was 57.0% (95% CI: 45.0%-67.3%), and for Stage IV disease was 18.9% (95% CI: 9.3%-31.0%). In a Cox proportional hazard model, older age (hazard ratio [HR]: 1.1; 95% CI: 1.03-1.12; P < .001), lymph node metastasis (HR: 6.9; 95% CI: 2.76-17.01; P < .001), and positive surgical margins (HR: 2.9; 95% CI:1.13-7.26; P = .003) were associated with worse overall survival for Stages I to III disease while only older age (HR: 1.03; 95% CI: 1.002-1.06; P = .04) was associated with worse overall survival for Stage IV disease. CONCLUSIONS: Patients with GCC tumors of the appendix who have the nonmetastatic disease have a high 5-year survival. We have identified several prognostic factors for GCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apendicectomia/mortalidade , Neoplasias do Apêndice/mortalidade , Tumor Carcinoide/mortalidade , Recidiva Local de Neoplasia/mortalidade , Idoso , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
19.
Gan To Kagaku Ryoho ; 46(10): 1531-1535, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631134

RESUMO

We investigated the incidence of thromboembolism in patients receiving combination chemotherapy with bevacizumab (BV)for colorectal cancer and examined its association with clinical factors. Between July 2007 and April 2014, 250 patients with colorectal cancer received combination chemotherapy with BV. Thromboembolism occurred in 24 cases(9.6%). Five predictive risk factors(platelet count B350,000/µL, hemoglobin <10 g/dL, leukocyte count>11,000/mL, body mass index B25.3 kg/m2, and D-dimer B1.44 µg/mL)were set based on a previous report, and the corresponding number of risk factors for thromboembolism and incidence of thromboembolism were examined. The results of multivariate analysis showed that the occurrence of 3 or more risk factors conferred a significant risk for the incidence of thromboembolism. Due to the increased risk of developing thromboembolism in such patients, special attention during management is required.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais , Tromboembolia , Tromboembolia Venosa , Bevacizumab , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia Combinada , Humanos , Fatores de Risco
20.
Gan To Kagaku Ryoho ; 46(10): 1565-1567, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631140

RESUMO

Neoadjuvant chemotherapy(NAC)is a promising approach for the improvement of gastric cancer treatment outcome. S-1 plus cisplatin(SP)or S-1 plus oxaliplatin (SOX)is generallythe first choice of NAC regimen. We experienced that NAC with ramucirumab(RAM)plus paclitaxel(PTX)was effective in locallyadvanced gastric cancer, but that with SOX was ineffective. A 68-year-old man developed locallyadvanced gastric cancer and received NAC with SOX, which was stopped because of tumor enlargement. The patient was then given NAC with RAM plus PTX, which was effective and enabled radical excision. Anti-angiogenic agents maycause wound healing complications, which mayincrease the risk of leakage. However, he was discharged without postoperative complications. Therefore, RAM plus PTX can be a promising NAC regimen for locallyadvanced gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Neoplasias Gástricas , Idoso , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Humanos , Masculino , Paclitaxel , Neoplasias Gástricas/tratamento farmacológico
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