Intergroup Exemestane Study mature analysis: overall survival data

Abstract PURPOSE Antidepressant drugs have shown anti-tumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level. METHODS Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time-frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival data and the log-rank test was performed for comparisons. RESULTS Four hundred four patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N=46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in overall survival between those patients who had taken antidepressants at some point in their disease course and those who had not (p=0.356). These data were confirmed in a multivariate analysis including age, Karnofsky performance status, gender, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (p=0.315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (p=0.639). CONCLUSIONS This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.

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Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients

Journal of International Medical Research ◽

10.1177/0300060520981539 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098153

Author(s):

Qing Bi ◽

Yang Liu ◽

Tao Yuan ◽

Huizhen Wang ◽

Bin Li ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Survival Data ◽

Tumor Infiltrating Lymphocytes ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Whole Exome ◽

Cancer Genome Atlas ◽

Infiltrating Lymphocytes

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

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Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada

JCO Oncology Practice ◽

10.1200/jop.19.00719 ◽

2020 ◽

Vol 16 (5) ◽

pp. e425-e432 ◽

Cited By ~ 1

Author(s):

Todd A. Yezefski ◽

Dan Le ◽

Leo Chen ◽

Caroline H. Speers ◽

Shasank Chennupati ◽

...

Keyword(s):

Colorectal Cancer ◽

British Columbia ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Systemic Therapy ◽

Survival Data ◽

De Novo ◽

Tumor Resection ◽

Care Utilization ◽

Western Washington

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada’s single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

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Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy

Integrative Cancer Therapies ◽

10.1177/1534735421995256 ◽

2021 ◽

Vol 20 ◽

pp. 153473542199525

Author(s):

Shih Ming Tsao ◽

Tz Chin Wu ◽

JiZhen Chen ◽

Feichi Chang ◽

Thomos Tsao

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Survival Data ◽

Treatment Initiation ◽

Checkpoint Inhibitors ◽

Neutrophil To Lymphocyte Ratio ◽

Advanced Lung Cancer ◽

Control Group ◽

Lymphocyte Ratio ◽

Astragalus Polysaccharide

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in patients with cancer receiving immunotherapy. Recent studies have shown that a high NLR was associated with a poor response and decreased survival. However, there is no intervention to reverse abnormally high NLR and improve clinical outcomes. Astragalus polysaccharide injection (PG2) is an immunomodulatory therapy for cancer-related fatigue. This study aimed to examine whether PG2 might normalize the NLR and affect the overall survival of patients with lung cancer treated with immunotherapy. Materials and Methods: We retrospectively examined the medical records of patients with lung cancer treated with immune checkpoint inhibitors (ICIs) between October 1, 2015 and November 30, 2019. All patients received ICI combination chemotherapies, and some similarly received PG2 (Control vs PG2). The NLR was assessed before treatment and 6 weeks after ICI initiation, and the survival data was collected at least 4 years after treatment initiation for the first enrolled patient. Results: Fifty-three patients were included. Six weeks after ICI initiation, 91.3% of the patients in the PG2 group exhibited a predefined “Decrease or no change” in the NLR, which was 28% higher than that in the Control group (63.3%) ( P = .028). The NLR significantly decreased by 31.60% from baseline in the PG2 group ( P = .012), whereas it increased by 5.80% in the Control group ( P = .572). Six weeks after ICI treatment initiation, both groups had a median NLR of 3.73, and the overall survival was also similar (PG2 vs Control, 26.1 months vs 25.4 months, respectively); however, the PG2 group had a higher median baseline NLR than the Control group (PG2 vs Control, 4.51 vs 2.81, respectively). Conclusion: This study demonstrated that PG2 could normalize the NLR in patients with lung cancer receiving ICI combination treatments.

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CURE OF THREE PATIENTS WHO HAD SKELETAL METASTASES IN DISSEMINATED NEUROBLASTOMA

PEDIATRICS ◽

10.1542/peds.41.1.47 ◽

1968 ◽

Vol 41 (1) ◽

pp. 47-51

Author(s):

Douglas Reilly ◽

Mark E. Nesbit ◽

William Krivit

Keyword(s):

Overall Survival ◽

Survival Data ◽

Specific Treatment ◽

Skeletal Metastases ◽

University Of Minnesota ◽

Term Survival ◽

Long Term Survival ◽

Skeletal Involvement ◽

The University

The long-term survival of three children with disseminated skeletal metastases due to neuroblastoma is reported. These three patients are added to eight other patients reported in the literature who have survived longer than 2 years after the development of their metastatic osseous lesions. A review of the cases did not reveal a specific treatment regime which provided the success in these cases. The presence of skeletal involvement, therefore, should not indicate a hopeless prognosis. A review of 33 patients with neuroblastoma at the University of Minnesota from 1956-1966 is also given to provide overall survival data.

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Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma

10.1101/2021.03.04.433896 ◽

2021 ◽

Author(s):

Shunya Ohmura ◽

Aruna Marchetto ◽

Martin F. Orth ◽

Jing Li ◽

Susanne Jabar ◽

...

Keyword(s):

Overall Survival ◽

Ewing Sarcoma ◽

Survival Data ◽

Therapeutic Target ◽

Prognostic Biomarker ◽

Specific Inhibitor ◽

Cell Cycle Checkpoint ◽

Regulatory Subunit

Purpose: Ewing sarcoma (EwS) is a highly aggressive bone- or soft tissue-associated malignancy mostly affecting children, adolescents, and young adults. Although multimodal therapies have strongly improved patients′ overall survival over the past decades, the development of prognostic biomarkers for risk-based patient stratification and more effective therapies with less adverse effects is stagnating. Thus, new personalized medicine approaches are urgently required. Experimental design: Gene expression data of EwS and normal tissues were crossed with survival data to identify highly overexpressed, prognostically relevant, and actionable potential targets. RNA-interference and dose-response assays as well as tissue-microarray analyses were carried out to explore the functional role and druggability of a prominent candidate gene in vitro and in vivo, and to validate its suitability as a prognostic biomarker. Results: Employing a multilayered screening approach, we discover ribonucleotide reductase regulatory subunit M2 (RRM2) as a promising therapeutic target and prognostic biomarker in EwS. Through analysis of two independent EwS patient cohorts, we show that RRM2 mRNA and protein overexpression is associated with an aggressive clinical phenotype and poor patients′ overall survival. In agreement, RRM2 silencing as well as pharmacological inhibition by the specific inhibitor triapine (3-AP) significantly reduces EwS growth in vitro and in vivo. Furthermore, we present evidence that pharmacological RRM2 inhibition by triapine can overcome chemoresistance against doxorubicin or gemcitabine, and synergize with cell cycle checkpoint inhibitors (CHEK1 or WEE1). Conclusions: Based on the aggressive phenotype mediated by and the druggability of RRM2 our results provide a translational rationale for exploiting RRM2 as a novel therapeutic target in EwS and prompt further clinical investigations.

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Establishment and Validation of an MTORC1 Signaling-Related Gene Signature to Predict Overall Survival in Patients with Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/6299472 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Zheng Yao ◽

Song Wen ◽

Jun Luo ◽

Weiyuan Hao ◽

Weiren Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Decision Tree ◽

Survival Data ◽

Cox Regression ◽

Gene Signature ◽

Related Gene ◽

Cox Regression Analysis ◽

Cancer Hallmarks ◽

Mtorc1 Signaling

Background. Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. Methods. The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. Results. Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. Conclusions. The present study may contribute to the improvement of current prognostic systems for patients with HCC.

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Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in 27 Cases

Frontiers in Oncology ◽

10.3389/fonc.2021.732782 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhiyang Zhang ◽

Penglian Gao ◽

Zhengqi Bao ◽

Linggong Zeng ◽

Junyi Yao ◽

...

Keyword(s):

Overall Survival ◽

Distant Metastasis ◽

Survival Data ◽

Tumor Size ◽

Lymphovascular Invasion ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Molecular Characteristics ◽

Clinicopathologic Features ◽

Ki 67

ObjectiveClear cell carcinoma (CCC) of the endometrium is an uncommon yet aggressive tumor. Few cohort studies are reporting the overall survival time of CCC patients. This study aimed to retrospectively analyze the clinicopathologic features, molecular characteristics and survival data of 27 endometrial CCC patients to improve the understanding of CCC.MethodsThe clinicopathologic features, molecular characteristics and survival data total of 27 CCC patients admitted to the BBMU affiliated hospital (Anhui, China) between January 2005 and December 2018 were retrospectively analyzed. Kaplan-Meier method was used to analyze the prognosis-related factors.ResultsThe median age of the patients was 60 years (range; 39 to 81 years). The average tumor size was 3.8 cm (range; 0.8 to 13.0cm). Myometrial infiltration greater than 50% was reported in 55.6% of the patients, while the Ki-67 index greater than 50% was reported in 70.4% of the patients. The patients’ FIGO (2009) surgical stages were as follows: 18 I, 3 II, 4 III, and 2 IV. Besides, 7 (25.6%) patients had lymphovascular invasion, 3 (11.1%) patients with distant metastasis, including 1 patient with bone metastasis, and 2 with liver metastasis. Adjuvant treatment included 7 with chemotherapy alone, 9 with radiotherapy alone, and 9 with both radiotherapy and chemotherapy. The median overall survival time from the time of CCC diagnosis was 56 months. ER and PR showed negative expression and P16 showed patchy immunostaining. 18 (63%) cases showed Napsin A positive expression. Loss of MSH2, MSH6 and PTEN were seen in 5, 4 and 7 cases respectively. All cases showed HER-2/nue negative expression.ConclusionCCC is a rare and invasive tumor. Age of diagnosis, FIGO stage, tumor size, myometrial infiltration, lymphovascular invasion, distant metastasis, Ki-67 index and P53 expression are important indicators to evaluate patient’s prognosis (P = 0.048, P < 0.001, P = 0.016, P = 0.043, P = 0.001, P < 0.001, P = 0.026, and P = 0.007, respectively). CCC has a worse prognosis than endometrioid carcinoma (P = 0.002), and there is no significant difference when compared with uterine papillary serous carcinoma (P = 0.155).

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Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

Cancer Control ◽

10.1177/1073274818778001 ◽

2018 ◽

Vol 25 (1) ◽

pp. 107327481877800 ◽

Cited By ~ 4

Author(s):

Xi Liu ◽

Lei Chen ◽

Tao Zhang

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Survival Data ◽

Methylation Status ◽

Lung Squamous Cell Carcinoma ◽

Prognostic Indicator ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Recurrence Free Survival ◽

Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

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