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Breast cancer (BC) is one of the most aggressive malignancies worldwide among females. Matrix metalloproteinases (MMPs), as the most abundant class of non-serine proteases present in invasive and metastatic tumors, can regulate a variety of alterations in the microenvironment during tumor progression. However, the differential expression of MMPs and its prognostic values in BC is yet to be elucidated. In this research, using the ONCOMINE dataset, The Cancer Genome Atlas, Breast Cancer Gene-Expression Miner v4.1 (Bc-GenExMiner), Kaplan-Meier Plotter and cBioPortal, the transcriptional MMPs and survival outcome data of patients with BC was compared. It was indicated that mRNA levels of MMP1/3/9/10/11/12/13 were increased compared with non-tumor tissues, whereas mRNA expression of MMP2/16/19/23B/28 was lower in BC tissues. Kaplan-Meier plots showed that high mRNA levels of MMP2/10/16/19/20/23B/27 in patients with BC were associated with better recurrence-free survival. In contrast, high MMP1/8/9/11/12 conferred worse RFS rate. Meanwhile, high transcription levels of MMP1/3/11/12/13 predicted shorter distant metastasis-free survival, while high levels of MMP1/12 demonstrated worse overall survival in patients with BC. From Bc-GenExMiner, it was indicated that high expression of MMP16/20 was correlated with better prognosis, while MMP1/9/11/12/13/14/15 exerted a negative effect on patient prognosis. The integrative bioinformatics analysis performed in the present study suggests that MMP1/9/12/16, compared with other MMPs, are potentially appropriate targets for targeted therapy in patients with BC.
RESUMO
OBJECTIVE: This study aimed to (a) assess the differences in the delineation of target volumes and organs-at-risk (OARs) by different physicians designing an intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and (b) analyze the impact of these differences on the treatment plan optimization. MATERIALS AND METHODS: The planning target volumes (PTVs) and OARs for radiotherapy were manually delineated from computed tomography images of a patient with NPC, and a standard delineation was determined using the STAPLE algorithm of ABAS software. IMRT was designed using one standard plan and 10 individual plans based on the same constraints and field conditions. The maximum/minimum ratio (MMR) of the PTV and OAR volumes and the coefficient of variation (CV) for the different groups were evaluated and compared to the volume of the standard contour. RESULTS: Significant differences were seen in the PTVs of the nasopharynx (PTVnx), neck lymph node (PTVnd) and the OARs manually delineated by different physicians. Compared to the standard plan, the mean dose-related parameters of various OARs in different individual plans were not significantly different, while that of most organs in different individual plans were reduced. However, a significant difference in the dose at each organ was noted in different individual plans. CONCLUSION: Significant differences were noted in the PTV and OAR delineations by different physicians in radiotherapy of NPC, and their dosimetric parameters were significantly different from the standard planned parameters. Therefore, multicenter trials should pay attention to the impact of these differences on the clinical evaluation.
Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Variações Dependentes do Observador , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Idoso , Humanos , Masculino , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Radioterapia de Intensidade Modulada/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To compare the clinical outcomes and toxicities of two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) for the treatment of children and adolescent nasopharyngeal carcinoma (NPC). METHODS: A total of 176 children with non-metastatic NPC treated at Sun Yat-sen University Cancer Center between October 2003 and September 2013 were included in this study. Of the 176 patients, 74 received 2D-CRT and 102 were treated with IMRT. The clinical outcomes and acute and late toxicities were determined and compared. RESULTS: The IMRT group achieved significantly higher overall survival (OS) (90.4% vs. 76.1% at 5 year, P = 0.007) and disease-free survival (DFS) (85.7% vs. 71.2%, P = 0.029) mainly due to an improvement in locoregional relapse-free survival (LRRFS) (97.9 vs. 88.3%, P = 0.049). After stratification by disease stage, IMRT provided significant benefits for patients with stage III-IV disease in terms of OS, LRRFS and DFS. Multivariate analyses indicated that the treatment group (2D-CRT vs. IMRT) was a prognostic factor for OS, LRRFS and DFS. A significant reduction in Grade 2-4 xerostomia (52.7 vs. 34.3%, P = 0.015) and hearing loss (40.5 vs. 22.5%, P = 0.010) was observed in patients treated by IMRT. CONCLUSION: IMRT provides better locoregional relapse-free survival and overall survival, especially in late-stage children and adolescent NPC patients, and is associated with a lower incidence of Grade 2-4 xerostomia as well as hearing loss compared with 2D-CRT. Distant metastasis remains a challenge in the treatment of children and adolescent NPC.
Assuntos
Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia de Intensidade Modulada , Adolescente , Carcinoma/epidemiologia , Carcinoma/patologia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: In the era of intensity-modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NAC) for locoregionally advanced nasopharyngeal carcinoma (NPC) is under-evaluated. The aim of this study was to compare the efficacy of NAC plus IMRT and concurrent chemoradiotherapy (CCRT) plus adjuvant chemotherapy (AC) on locoregionally advanced NPC. METHODS: Between January 2004 and December 2008, 240 cases of locoregionally advanced NPC confirmed by pathologic assessment in Sun Yat-sen University Cancer Center were reviewed. Of the 240 patients, 117 received NAC followed by IMRT, and 123 were treated with CCRT plus AC. The NAC + IMRT group received a regimen that included cisplatin and 5-fluorouracil (5-FU). The CCRT + AC group received cisplatin concurrently with radiotherapy, and subsequently received adjuvant cisplatin and 5-FU. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. RESULTS: The 5-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 78.0, 87.9, 79.0, and 69.8%, respectively, for the NAC + IMRT group and 78.7, 84.8, 76.2, and 65.6%, respectively, for the CCRT + AC group. There were no significant differences in survival between the two groups. In multivariate analysis, age (<50 years vs. ≥50 years) and overall stage (III vs. IV) were found to be independent predictors for OS and DFS; furthermore, the overall stage was a significant prognostic factor for DMFS. Compared with the CCRT + AC protocol, the NAC + IMRT protocol significantly reduced the occurrence rates of grade 3-4 nausea-vomiting (6.5 vs. 1.5%, P = 0.023) and leukopenia (9.7 vs. 0.8%, P = 0.006). CONCLUSIONS: The treatment outcomes of the NAC + IMRT and CCRT + AC groups were similar. Distant metastasis remained the predominant mode of treatment failure.