Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

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.

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Rab25 Acts as a Promising Novel Bio-Marker in the Prognosis of Patients with Hepatocellular Carcinoma

10.21203/rs.3.rs-43510/v1 ◽

2020 ◽

Author(s):

Zhong Dai ◽

Ke-Qing Yao ◽

Xing-Sheng Hu ◽

Yi-Qun Li ◽

Yu-Tao Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Value ◽

Cox Regression ◽

Rank Test ◽

Chi Square ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Square Test ◽

The Relationship

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.

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The Relationship Between microRNA-195 and the Prognosis of Cervical Cancer

10.21203/rs.3.rs-58914/v1 ◽

2020 ◽

Author(s):

Shuangqing Cao ◽

Lei Zheng

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Prognostic Value ◽

Cox Regression ◽

Rank Test ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Kaplan Meier ◽

Cancer Tissues ◽

The Relationship

Abstract Background: MicroRNA-195 (miR-195), a tumor suppressor, had reported to be involved in carcinogenesis and the progression of some cancers. However, the prognostic value of miR-195 in cervical cancer remained unclear. The purpose of this study was to detect the expression of miR-195 in cervical cancer tissues and to investigate its correlation with tumor progression and prognosis.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-195 in cervical cancer tissues and corresponding adjacent normal tissues. The relationship between miR-195 expression and clinical characteristics of patients was analyzed by chi-square test. Kaplan-Meier method was applied to compare the overall survival, and the prognostic value of miR-195 was estimated via cox regression analysis.Results: Compared with normal tissues, miR-195 expression was significantly down-regulated in cervical cancer tissues (P < 0.001). Importantly, decreased expression of miR-195 was closely associated with FIGO stage, lymph node metastasis and vascular invasion (P < 0.05). Additionally, Kaplan-Meier analysis indicated that patients with high miR-195 expression had obviously longer overall survival than those with low miR-195 expression (log rank test, P = 0.001). And miR-195 was an independent prognostic factor of cervical cancer patients via univariate and multivariate cox regression analyses.Conclusions: Decreased expression of miR-195 is associated with the progression of cervical cancer. And miR-195 may have potency to predict the prognosis of cervical cancer.

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Management of Atypical Cranial Meningiomas, Part 1

Neurosurgery ◽

10.1227/neu.0000000000000461 ◽

2014 ◽

Vol 75 (4) ◽

pp. 347-355 ◽

Cited By ~ 47

Author(s):

Sam Q. Sun ◽

Albert H. Kim ◽

Chunyu Cai ◽

Rory K.J. Murphy ◽

Todd DeWees ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Progression Free Survival ◽

External Beam Radiation ◽

Beam Radiation ◽

Free Survival ◽

Brain Invasion ◽

Predictors Of Recurrence ◽

Kaplan Meier ◽

The Impact

Abstract BACKGROUND: Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear. OBJECTIVE: To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study. METHODS: One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression. RESULTS: Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/EBRT (P = .8, P > .99). CONCLUSION: Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

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NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20180907 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 1

Author(s):

Ji-sheng Jing ◽

Hongbo Li ◽

Shun-cai Wang ◽

Jiu-ming Ma ◽

La-qing Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Survival Curve ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Kaplan Meier ◽

Tumor Tissues ◽

The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

Otolaryngology ◽

10.1177/0194599818804777 ◽

2018 ◽

Vol 160 (4) ◽

pp. 658-663 ◽

Cited By ~ 4

Author(s):

Phoebe Kuo ◽

Sina J. Torabi ◽

Dennis Kraus ◽

Benjamin L. Judson

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Maxillary Sinus ◽

Induction Chemotherapy ◽

Squamous Cell ◽

Cox Regression ◽

Rank Test ◽

Controlled Clinical Trial ◽

Log Rank Test ◽

Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

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Eight-Gene Metabolic Signature Related with Tumor-Associated Macrophages Predicting Overall Survival for Hepatocellular Carcinoma

10.21203/rs.3.rs-36554/v1 ◽

2020 ◽

Author(s):

Junyu Huo ◽

Yunjin Zang ◽

Hongjing Dong ◽

Xiaoqiang Liu ◽

Fu He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Analysis ◽

Risk Score ◽

Risk Group ◽

Cancer Genome ◽

Metabolic Reprogramming ◽

Tumor Associated Macrophages ◽

Kaplan Meier ◽

The Relationship

Abstract Background: In recent years, the relationship between tumor associated macrophages (TAMs) and solid tumors has become a research hotspot. The study aims at exploring the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma(HCC), in order to provide a new way of treatment for HCC.Materials and methods: The study selected 343 HCC patients with complete survival information(survival time >= 1month) in the Cancer Genome Atlas (TCGA) as the study objects. Kaplan-Meier survival analysis assisted in figuring out the relationship between macrophage infiltration level and overall survival (OS), and Pearson correlation test to identify metabolic reprogramming genes(MRGs) related to tumor macrophage abundance. Lasso regression algorithm were conducted on prognosis related MRGs screened by Univariate Cox regression analysis and Kaplan-Meier survival analysis to construct the riskscore, another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) were used for external validation regarding the prognostic signature.Results: A risk score composed of 8 metabolic genes can accurately predict the OS of training cohort(TCGA) and testing cohort(ICGC). It is important that the risk score could widely used for people with different clinical characteristics, and is an independent predictor independent of other clinical factors affecting prognosis. As expected, high-risk group exhibited an obviously higher macrophage abundance relative to low-risk group, and the risk score presented a positive relation to the expression level of three commonly used immune checkpoints(PD1,PDL1,CTLA4).Conclusion: Our study constructed and validated a novel eight‑gene signature for predicting HCC patients’ OS, which possibly contributed to making clinical treatment decisions.

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Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-020-07689-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiangye Liu ◽

Tingting Li ◽

Delong Kong ◽

Hongjuan You ◽

Fanyun Kong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Expression Profiles ◽

High Expression ◽

Rank Test ◽

Good Survival ◽

Alcohol Dehydrogenases ◽

Kaplan Meier ◽

Incidence And Mortality ◽

Prognostic Implications

Abstract Background Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

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Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21040 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21040-21040

Author(s):

R. Trujillo ◽

E. Gallego ◽

A. Márquez ◽

N. Ribelles ◽

J. Trigo ◽

...

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Phase Iii ◽

Rank Test ◽

Prognostic Effect ◽

Log Rank Test ◽

Kaplan Meier ◽

Phase Iii Trials ◽

Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

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Impact of dose-escalated radiation on overall survival in men with nonmetastatic prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.28 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 28-28

Author(s):

Anusha Kalbasi ◽

Jiaqi Li ◽

Abigail T. Berman ◽

Samuel Swisher-McClure ◽

Marc C. Smaldone ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

High Risk ◽

Standard Dose ◽

Low Risk ◽

External Beam Radiation ◽

Risk Category ◽

Beam Radiation ◽

Treatment Groups

28 Background: Infive publishedRCTs, dose-escalated external beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, the question of whether dose escalation improves overall survival (OS) remains unanswered. We examined OS among men with non-metastatic prostate cancer undergoing EBRT in the modern era. Methods: Using the National Cancer Database (NCDB), we conducted non-randomized comparative effectiveness studies of dose-escalated versus standard-dose EBRT in men diagnosed from 2004-2006 in three analytic cohorts defined by NCCN risk category: low- (N=12,848), intermediate- (N=14,966) or high-risk (N=14,587) prostate cancer. We categorized patients in each risk cohort into 2 treatment groups: standard-dose (68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT. The primary outcome was time to death from any cause, measured from diagnosis to NCDB date of death or end of follow-up (December 31, 2011). We compared OS between treatment groups in the three analytic cohorts using Cox proportional hazard models. Inverse probability weighted propensity score methods were used to balance differences between treatment groups in age, race, year of diagnosis, AJCC T- and N-stage, PSA, Gleason score, androgen deprivation therapy, IMRT use, comorbid disease, income, insurance, urban/rural location, facility type and facility volume. In secondary analyses, we evaluated dose response for survival by categorizing dose in approximately 2 Gy increments. Results: Median follow up for survivors was between 73 and 74 months in all three risk cohorts. Dose-escalated EBRT was associated with improved survival in the intermediate-risk (adjusted HR 0.81, 95% CI 0.77 and 0.85, p<0.0001) and high-risk groups (aHR 0.85, 95% CI 0.81 and 0.89, p<0.0001), but not the low-risk group (aHR 0.99, 95% CI 0.92-1.06, p=0.803). For every incremental ~2Gy increase in dose, there was a 9% (95% CI 6% – 11%, p<0.0001) and 7% (95% CI 3% - 10%, p=0.004) reduction in the hazard of death for intermediate- and high-risk patients, respectively. Conclusions: Dose-escalated EBRT is associated with improved survival in men with intermediate- and high-risk, but not low-risk, prostate cancer.

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AST-to-APOA ratio to predict overall survival in hepatocellular carcinoma receiving TACE.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16637 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16637-e16637

Author(s):

Yongjian Chen ◽

Xing Li ◽

Jie Chen ◽

Gang Qin ◽

Yidan Qiao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

Independent Predictor ◽

Group Versus ◽

Stage I ◽

Monocyte Count ◽

Validation Group ◽

Kaplan Meier ◽

Significant Difference

e16637 Background: Current guidelines lack definitive evidences about the predictive capability of clinical parameters for transcatheter arterial chemoembolization (TACE). The aim of this study was to comprehensively investigate the predictive factor among stage I-IV liver hepatocellular carcinoma (LIHC) patients after TACE. Methods: We investigated the clinical features of 211 stage I-IV patients with LIHC in discover group and 341 patients in validation group. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test. Results: Univariate Cox regression revealed that Monocyte count, TNM stage and AST-to-APOA ratio (AAR) were associated with unfavorable OS. AAR was identified as an independent predictor of OS using multivariate analysis. Kaplan-Meier curve demonstrated that patients with AAR < 50 displayed better prognosis. The median follow-up time was 17.1 (95%CI, 14.4 to 19.3) months, 3-year overall survival was 55.9% in the low AAR group versus 28.6% in the high AAR group, and there was significant difference in OS (Hazard ratio [HR] 0.47, 95%CI 0.33 to 0.67, P < 0.001). The AAR showed predictive ability for OS (12-month, AUC = 0.707). These findings were successfully validated in validation group (HR 0.62, 95%CI 0.46 to 0.84, P = 0.002; 12-month AUC = 0.636). Conclusions: AAR was an independent predictor among LIHC patients after TACE. Patients with lower AAR were optimal candidates for TACE.

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