Ifosfamide (IFO) and doxorubicin (DOX) dose-intensities seem related to overall survival in adult soft-tissue sarcoma (STS) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9581-9581
Author(s):  
G. F. Almeida ◽  
G. Castro ◽  
I. M. Snitcovsky ◽  
A. C. Bassani ◽  
M. E. Diz ◽  
...  

9581 Background: IFO/DOX dose intensities (DI) seem to impact on the outcome of STS. We explored retrospectively the relationship between DI and overall survival (OS) in STS. Methods: From Jan/00 to Jun/05, 70 untreated STS pts received IFO/DOX, 32 as neo/adjuvant and 38 in the palliative setting at our outpatient unit. Filgrastin was not mandatory. Median age 47 y (17–74 y), 44 male; mean tumor size 13.6 cm in the neo/adjuvant and 16.5 cm in the palliative group (p=0.202, t-test). Most frequent histologies: leiomyo (16 pts), synovial (13), malignant fibrous histiocytoma (8) and liposarcoma (8). 28 pts had lower/ 9 upper limb tumors, 9 retroperitoneal, 9 trunk, 6 mediastinal, 5 visceral and 4 head and neck. Kaplan-Meier survival curves were considered from diagnosis and compared by log-rank test. Results: For the 70 pts, the mean DI for IFO and DOX were 2.5±0.9 mg/m2/wk and 18.8±6.0 mg/m2/wk, respectively. There was no difference between neo/adjuvant and palliative IFO/DOX DI (p=0.314/p=0.247, respectively). With 19-mo median f-up, the median OS (mOS) was 43 mo in the neo/adjuvant group with an advantage for pts submitted to conservative surgeries (46.5 mo vs. 16.8 mo; HR 0.185, 95%CI 0.003–0.399, p=0.007) as well as in those diagnosed with tumors with less than 3 mitoses/10 HPF (48.3 mo vs. 18.8 mo; HR 0.272, 95%CI 0.058–0.871, p=0.031). No differences in mOS related to tumor size, margin status or primary sites were found. According to IFO DI, the mOS were 46.5 mo, not reached (NR), 14.5 mo and 43 mo for pts in the 1st and subsequent DI quartiles (chi-square test for trend, p=0.004). In the median f-up of 9.8 mo, pts in the palliative setting presented mOS 21.8 mo, superior in the lower grade subgroup (NR vs. 11.1 mo; HR 0.130, 95%CI 0.076–0.746, p=0.014) and in the STS not from extremities (40.9 mo vs. 10.8 mo; HR 2.152, 95%CI 0.959–5.137, p=0.063). According to IFO DI quartiles, we also found a direct correlation between mOS (11.3 mo, 19 mo, 45.1 mo, and NR) and DI (p=0.052), and similar trend was shown for DOX DI, with 11.3 mo, 10.3 mo, NR, and 40.9 mo mOS for the 1st, 2nd, 3rd and 4th quartiles (p=0.018). Conclusions: In these STS adult pts, we have found a relationship between IFO and DOX DI and OS. Further evaluations of more intensive chemotherapy schedules are warranted. No significant financial relationships to disclose.

2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background: Previous studies have demonstrated that microRNAs (miRNAs) played a crucial role in various diseases, including cancers. The aim of the study was to evaluate the clinical significance of miR-124 in patients with cholangiocarcinoma (CCA).Methods: The expression pattern of miR-124 was detected in CCA tissues using quantitative reserve transcription polymerase chain reaction (qRT-PCR). The correlation of miR-124 expression with clinicopathological features and overall survival of patients were explored using chi-square test, Kaplan-Meier methods and Cox regression analyses.Results: The miR-124 expression level was strong down-regulated in CCA tissues compared with normal para-cancerous tissues (P<0.001). Moreover, aberrant miR-124 expression was significantly associated with differentiation (P=0.045) and lymph node metastasis (P=0.040). In addition, Kaplan-Meier method and log-rank test revealed that patients with low miR-124 expression has a poorer overall survival compared with those with high miR-124 expression (P=0.002). Furthermore, multivariate analysis confirmed that miR-124 expression (P=0.006; HR=2.006; 95%CI: 1.224-3.289) was an independent prognostic indicator in CCA.Conclusions: Collectively, our results defined miR-124 expression plays important roles in CCA patients. MiR-124 expression might used as a valuable prognostic biomarker for patients with CCA.


2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background The study was designed to examine the reversion inducing cysteine rich protein with Kazal motifs (RECK) levels in patients with cholangiocarcinoma (CCA) and assess its role in CCA prognosis. Methods Quantitative real-time PCR (qRT-PCR) was used to determine the expression of RECK mRNA in 127 pairs of CCA samples and controls. Chi-square test was conducted to analyze the effects of clinical features on RECK expression. Kaplan-Meier curves were plotted to determine the overall survival rate of CCA patients with different RECK expression. The prognostic biomarkers for CCA patients were identified using the Cox regression analysis. Results Significantly down-regulated expression of RECK mRNA was determined in CCA tissues compared to noncancerous controls (P < 0.05). Chi-square test suggested reduced RECK expression was related with invasion depth (P = 0.026), differentiation (P = 0.025), lymphatic metastasis (P = 0.010) and TNM stage (P = 0.015). However, age, sex, tumor size and family history had no significant links with RECK expression (all, P > 0.05). The survival curves showed that patients with low RECK expression had a shorter overall survival rate than those with high RECK expression. Both the univariate analysis (P = 0.000, HR = 5.290, 95%CI = 3.195–8.758) and multivariate analysis (P = 0.000, HR = 5.376, 95%CI = 2.231–8.946) demonstrated that RECK was an independent biomarker for predicting the outcomes of CCA patients. Conclusions Taken together, the expression of RECK was down-regulated in CCA and it might be an efficient biomarker for CCA patients.


2020 ◽  
Vol 14 (8) ◽  
pp. 651-663
Author(s):  
Xueli Li ◽  
Wange Fan ◽  
Anhui Yao ◽  
Huiling Song ◽  
Yunxiao Ge ◽  
...  

Aim: In the present study, we studied the relationship between RELN and prognosis in glioma. Materials & methods: Expression profiles and methylation data of RELN were obtained from bioinformatic datasets. Correlations between RELN and clinicopathological features and overall survival were respectively assessed using chi-square test and Kaplan–Meier analysis. Results: RELN was downregulated in glioma, and its downregulation correlated well with glioma malignancy and overall survival. Meanwhile, hypermethylation of RELN was significantly correlated with low RELN expression. Additionally, gene set enrichment analysis demonstrated that low expression of RELN correlated with many key cancer pathways, possibly highlighting the importance of RELN in carcinogenesis of brain. Conclusion: RELN may serve as a potential prognostic marker and promising target molecule for new therapy of glioma.


2020 ◽  
Author(s):  
Zhong Dai ◽  
Ke-Qing Yao ◽  
Xing-Sheng Hu ◽  
Yi-Qun Li ◽  
Yu-Tao Liu ◽  
...  

Abstract Background: Rab25 was indicated to be involved in several human tumors. However, the clinical significance of Rab25 in hepatocellular carcinoma (HCC) was still unclear. The purpose of this study was to investigate the expression and prognostic value of Rab25 in HCC.Methods: The relative mRNA expression levels of Rab25 in HCC tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the relationship between Rab25 expression and clinical characteristics of patients. The prognostic value of Rab25 in HCC was estimated through Kaplan-Meier method and cox regression analysis.Results: Rab25 gene expression level was significantly higher in HCC tissues than that in normal tissues (P<0.001). Importantly, the increased Rab25 expression was closely associated with TNM stage (P=0.024), metastasis (P=0.022) and invasion classification (P=0.039). Moreover, patients with high Rab25 expression tended to have obviously shorter overall survival than those with low expression of Rab25 (log rank test, P<0.001) via Kaplan-Meier analysis. Univariate and multivariate cox regression analyses revealed that Rab25 was an independent prognostic factor of HCC.Conclusions: Rab25 is up-regulated in HCC and contributes to the progression of this tumor. What’s more, Rab25 may be a potential bio-marker for the prognosis of HCC.


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.


2012 ◽  
Vol 30 (21) ◽  
pp. 2684-2690 ◽  
Author(s):  
Rajul K. Jain ◽  
J. Jack Lee ◽  
Chaan Ng ◽  
David Hong ◽  
Jing Gong ◽  
...  

Purpose RECIST is used to quantify tumor changes during exposure to anticancer agents. Responses are categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Clinical trials dictate a patient's management options based on the category into which his or her response falls. However, the association between response and survival is not well studied in the early trial setting. Patients and Methods To study the correlation between response as quantified by RECIST and overall survival (OS, the gold-standard survival outcome), we analyzed 570 participants of 24 phase I trials conducted between October 2004 and May 2009, of whom 468 had quantifiable changes in tumor size. Analyses of Kaplan-Meier estimates of OS by response and null Martingale residuals of Cox models were the primary outcome measures. All analyses are landmark analyses. Results Kaplan-Meier analyses revealed strong associations between change in tumor size by RECIST and survival (P = 4.5 × 10−6 to < 1 × 10−8). The relationship was found to be near-linear (R2 = 0.75 to 0.92) and confirmed by the residual analyses. No clear inflection points were found to exist in the relationship between tumor size changes and survival. Conclusion RECIST quantification of response correlates with survival, validating RECIST's use in phase I trials. However, the lack of apparent boundary values in the relationship between change in tumor size and OS demonstrates the arbitrary nature of the CR/PR/SD/PD categories and questions emphasis placed on this categorization scheme. Describing tumor responses as a continuous variable may be more informative than reporting categoric responses when evaluating novel anticancer therapies.


2019 ◽  
Vol 130 (6) ◽  
pp. 1877-1888
Author(s):  
Mark G. Bigder ◽  
Sandeep Krishnan ◽  
E. Francis Cook ◽  
Anthony M. Kaufmann

OBJECTIVEPatients with multiple sclerosis (MS)–associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Margherita Ratti ◽  
Nicola Valeri ◽  
Jens Claus Hahne ◽  
Andrea Lampis ◽  
Michele Ghidini ◽  
...  

e15566 Background: Identification of prognostic biomarkers for gastric cancer (GC) patient selection is compelling to improve survival outcomes. Microsatellite instability (MSI) is related with a positive prognostic effect in GC, whereas perioperative chemotherapy resulted detrimental in this subgroup. In metastatic GC, immunotherapy with anti-PD1/PD-L1 drugs has shown promising results. Nevertheless, in early stages, data on the relation between MSI, clinic-pathological features, PD-L1 expression and overall survival (OS) remains sparse, especially in Western population. In our study, the prognostic role of MSI, clinic-pathological features and PD-L1 expression in a cohort of Italian GC patients was examined. Methods: CP data of 148 consecutive stage I-III GC pts resected in Cremona Institute between 2010 and 2014 (mostly chemo and/or radio-naive) were collected. MSI analysis was performed on tissue samples for all cases by polymerase chain reaction. PDL-1 expression, evaluated by immunohistochemistry, was assessed in MSI group. Differences between subgroups were evaluated with Chi-square test; Kaplan-Meier method and Long Rank test were used to calculate OS. Results: Female sex (p=0.012), earlier TNM stages (p=0.011) and limited nodal involvement (p=0.29) significantly correlated with MSI status. MSI is significantly associated with better prognosis, exhibiting an advantage of 28.6 months in OS compared with microsatellite stable subgroup (p<0.001). Most MSI patients expressed PD-L1. MSI patients without PD-L1 expression showed higher percentage of clinical features correlated with better prognosis compared with PD-L1 expressing MSI patients and MSS subgroup. Conclusions: MSI is an independent prognostic biomarker in GC and identifies a subset of patients with better OS and specific clinic-pathological features, including high percentage of PD-L1 expression. MSI could represent a promising biomarker to select patients for chemotherapy versus immunotherapy in non-metastatic disease.


2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Junjie Jiang ◽  
Hui-Ju Wang ◽  
Xiao-Zhou Mou ◽  
Huanqing Zhang ◽  
YiZhen Chen ◽  
...  

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.


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