Independent Factor For Overall Survival Research Articles

Prognostic factors in pediatric pneumococcal meningitis patients in mainland China: a retrospective multicenter study.

Background: Prognosis of pneumococcal meningitis (PM) remains very poor, especially in less developed countries. Currently, few multi-centric studies on pediatric PM have been reported in mainland China.Objectives: This study aimed to explore the correlation of clinical and laboratory findings with complications and prognosis in pediatric PM.Methods: The pediatric PM patients were retrospectively recruited from ten pediatric tertiary hospitals across China between January 2013 and June 2018. Clinical, biochemical, and microbiological data and follow-up information were collected. Predictive factors for complications and prognostic factors for overall survival (OS) and sequelae-free survival (SFS) were analyzed.Results: A total of 132 pediatric PM patients were included. Seventy-one patients had complications, 25 patients died, and 39 patients had neurological sequelae. Multivariate logistic regression suggested that age less than 28 months (adjusted OR=2.654, 95%CI=1.067–6.600, P=0.036) and lower white blood cells in blood (aOR=3.169, 95%CI=1.395–7.202, P=0.006) were associated with high risk of complications. Multivariate Cox’s proportional hazard regression suggested that age less than 28 months (aHR=6.479, 95%CI=1.153–36.404, P=0.034), coma (aHR=9.808, 95%CI=2.802–34.323, P=0.000), and non-adjuvant steroid therapy (aHR=4.768 95%CI=1.946–11.678, P=0.001) were independent prognostic factors for poor OS; coma (aHR=5.841, 95%CI=2.652–12.864, P=0.000), septic shock on admission (aHR=2.949, 95%CI=1.049–8.290, P=0.040), and lower glucose level in cerebrospinal fluid (CSF) (aHR=2.523, 95%CI=1.336–4.765, P=0.004) were independent prognostic factors for poor SFS.Conclusion: Age, coma, and adjuvant steroid therapy were independent factors for OS, while coma, septic shock on admission, and lower glucose level in CSF were independent factors for SFS in pediatric PM patients. These factors might be used to identify PM patients with poor prognosis and guide individual treatment.

C-MYC expression in T (III/IV) stage oral squamous cell carcinoma (OSCC) patients.

Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma.Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters.Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P<0.001), American Joint Committee on Cancer (AJCC) stage (P<0.0001), and tumor differentiation (P=0.0025) were independent factors for overall survival in patients with OSCC except for c-MYC expression (P>0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan–Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270).Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).

Patients With Malignant Lymphoma and HIV Infection Experiencing Remission After First-Line Treatment Have an Excellent Prognosis

BackgroundMalignant lymphoma is still the leading cause of death among AIDS-related diseases. Patients and MethodsWe performed a retrospective analysis of 50 HIV-positive lymphoma patients. The median interval between HIV and malignant lymphoma diagnosis was 4 years. Eight patients (16%) had Hodgkin lymphoma and 42 (84%) non-Hodgkin lymphoma. Among non-Hodgkin lymphoma patients, diffuse large B-cell lymphoma (n = 18, 42%), Burkitt lymphoma (n = 11, 26%), and plasmoblastic lymphoma (n = 5, 12%) were the most frequent entities. ResultsLymphoma was treated according to standard protocols. Forty-four patients (88%) received combination antiretroviral therapy, 2 (4%) were not treated, and in 4 (8%) the HIV treatment status was not clarified. Response to first-line therapy was complete response (CR) in 24 (56%), partial response (PR) in 15 (35%), and stable disease in 1 (2%). Three patients (7%) developed progressive disease, and 9 (18%) experienced relapse after CR or PR. At a median observation period of 31 (range, 0.4-192) months, the 1-, 2-, and 5-year overall survival was 87%, 79%, and 76%, respectively. At univariate analysis, remission status after first-line treatment was predictive of outcome, as the 2-year overall survival was 95%, 66%, and 0 for patients with CR, with PR, and with progressive disease (P < .001). Results of the multivariate analysis revealed lactate dehydrogenase concentration at lymphoma diagnosis (P = .046) and relapse (P = .050) to be independent factors for overall survival. ConclusionFirst-line treatment of lymphoma in HIV positive patients is crucial. Patients who experienced and maintained a first CR had a favorable prognosis.

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma.

AimsBecause the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck.Methods and resultsNinety‐eight treatment‐naive head and neck cancer specimens were immunohistologically stained for SMO, GLI‐1, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI‐1 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI‐1 expression (ρ = 0.258, P = 0.010) in univariate and multivariate analysis (P = 0.007, t = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32–0.98; P = 0.044) and disease‐free survival (HR = 0.53; 95% CI = 0.30–0.95; P = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30–1.05; P = 0.072) and disease‐free survival (HR = 0.53; 95% CI = 0.28–1.02; P = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24–0.98; P = 0.043) and disease‐free survival (HR = 0.45; 95% CI = 0.22‐0.96; P = 0.037).ConclusionAlthough it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.

CircLMTK2 acts as a novel tumor suppressor in gastric cancer.

Recently, circRNAs have been found to play regulatory roles in cancer. In the present study, we aimed to investigate the characteristics and effect of circLMTK2, and its potential role as a novel biomarker in cases of gastric cancer (GC). About 111 pairs of clinical tissues from patients were collected for circLMTK2 expression investigation. Afterward, the relationship of circLMTK2 expression level and clinical features, such as survival, tumor size and so on, were analyzed, along with a multivariate Cox hazards analysis. Finally, malignant biological properties, like cell viability and mobility, were explored in cell line MGC-803. We found that circLMTK2 was a stable circRNA generated from the back-spliced Exon 10 and Exon 11 of the LMTK2 gene in GC cells. CircLMTK2 expression was significantly down-regulated in gastric carcinoma tissue specimens (P<0.001) compared with its expression in paired normal tissues. Furthermore, a Kaplan–Meier analysis revealed that lower levels of circLMTK2 expression were associated with decreased overall survival (OS) (P<0.001), and a multivariate Cox hazards analysis showed that high circLMTK2 expression was an independent factor for OS. Afterward, overexpression of circLMTK2 was performed in gastric cancer cell line MGC-803, and results indicated that malignant biological properties were inhibited by circLTMK2 overexpression. The present study showed the first evidence that circLMTK2 was down-regulated in GC, suggesting it as a novel biomarker for prognosis, and also as a therapeutic target in treatment of GC.

Additional prognostic value of metabolic parameters measured by dual time point pretreatment F-18 FDG PET/CT in patients with intrahepatic cholangiocarcinoma.

e15598 Background: The aim of this retrospective study was to determine whether delayed glucose metabolism assessed by dual time point F-18 FDG PET/CT provides additional prognostic information independent of established prognostic factors in patients with intrahepatic cholangiocarcinoma (IHCC). Methods: We reviewed retrospectively the medical records of 96 patients (men 57, women 39, mean age 66 ± 10 years) with pathologically proven IHCC. They underwent dual time point F-18 FDG PET/CT as part of a pretreatment workup from July 2012 to December 2017. For the analysis, patients were classified by age, sex, stage, serum CA19-9, early SUVmax (eSUV), delayed SUVmax (dSUV), delta SUVmax (ΔSUV, difference between early and delayed SUVmax) and histopathology (pCEA, p53, Ki-67 index). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier with log-Rank test and Cox’s proportional-hazard regression methods. Results: Median survival for all 96 study subjects was 303 days and median SUVmax was 7.2 (range: 2.5 – 21.7). The survival was found to be significantly related to eSUV ( p &lt; 0.0001), age ( p = 0.017), LN metastasis ( p = 0.03) and p53 index ( p = 0.04) and multivariate analysis study revealed that the patients with a higher SUVmax ( p = 0.0001, 95%CI = 1.80 to 5.89, HR = 3.26), prescence of LN metastasis ( p = 0.031), higher age ( p = 0.044) and a higher p53 index ( p = 0.007) showed worse overall survival. In addition, we carried out a subgroup analysis targeting the 55 patients with delayed SUVmax to evaluate a prognostic value of delayed image parameter. In univariate analysis, dSUV (cut-offvalue 7.3, p = 0.0006) and ΔSUV (cut-off value 3.2, p = 0.035), age ( p &lt; 0.0001) and sCA19-9 ( p = 0.018) showed significant correlation and dSUV was an independent factor of overall survival in multivariate analysis. ( p = 0.014, 95%CI = 1.30 to 10.7, HR = 3.74) And then, we analyzed combinations of eSUV, dSUV and ΔSUV each other to evaluate additional prognostic information. The result revealed that higher dSUV ( p = 0.0001, AUC = 0.68) and ΔSUV ( p = 0.0002, AUC = 0.71) showed a poorer overall survival although the eSUV of IHCC was low. Conclusions: Higher delayed SUVmax and ΔSUVmax on pretreatment dual time point F-18 FDG PET/CT can predict poorer survival and additional information of risk stratification in patients with IHCC.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

Comparisons of survivals and toxicities between young and elderly patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy

ObjectiveTo compare the survivals and toxicities of young and elderly patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy (CCRT). Materials and methodsPatients with cervical cancer treated with radiotherapy or CCRT between January 2010 and December 2015 in our institute were reviewed. A dose of 50.4 Gy in 28 fractions was delivered to the pelvis with intensity modulated radiation therapy. In addition, a dose of 30–36 Gy in 5–7 fractions was prescribed to point A with brachytherapy. Weekly cisplatin was the first-line regimen of concurrent chemotherapy. Comparisons were made between patients in the young group (<60 years) and those in the elderly group (≥70 years) with multivariate analysis and propensity score matching. ResultsThere were 991 patients in the young group and 70 patients in the elderly group. The median follow-up period was 30.2 months. In multivariate analysis, age was an independent factor of overall survival (OS, hazard ratio, HR 1.99, p = 0.014), but it was not significant in predicting disease-free survival (DFS, HR 1.41, p = 0.179) and cancer-specific survival (CSS, HR 1.38, p = 0.332). After propensity score matching, 64 pairs of patients were selected. The 3-year OS, DFS, and CSS rates in the young and elderly groups were 86.5% and 73.9% (p = 0.280), 74.6% and 75.4% (p = 0.744), and 87.9% and 81.7% (p = 0.967), respectively. Significant differences between the young and elderly groups were observed in grade 3 and above chronic toxicities (2.9% and 8.6%, p = 0.027) and grade 3 and above chronic gastrointestinal toxicities (2.4% and 8.6%, p = 0.009). ConclusionAfter definitive radiotherapy or CCRT, the DFS and CSS of elderly patients with cervical cancer were similar to those in young patients. Elderly patients experienced more chronic toxicities than did young patients.

The DNA methylation profile of non-coding RNAs improves prognosis prediction for pancreatic adenocarcinoma

BackgroundCompelling lines of evidence indicate that DNA methylation of non-coding RNAs (ncRNAs) plays critical roles in various tumour progression. In addition, the differential methylation of ncRNAs can predict prognosis of patients. However, little is known about the clear relationship between DNA methylation profile of ncRNAs and the prognosis of pancreatic adenocarcinoma (PAC) patients.MethodsThe data of DNA methylation, RNA-seq, miRNA-seq and clinical features of PAC patients were collected from TCGA database. The DNA methylation profile was obtained using the Infinium HumanMethylation450 BeadChip array. LASSO regression was performed to construct two methylation-based classifiers. The risk score of methylation-based classifiers was calculated for each patient, and the accuracy of the classifiers in predicting overall survival (OS) was examined by ROC curve analysis. In addition, Cox regression models were utilized to assess whether clinical variables and the classifiers were independent prognostic factors for OS. The targets of miRNA and the genes co-expressed with lncRNA were identified with DIANA microT-CDS and the Multi-Experiment Matrix (MEM), respectively. Moreover, DAVID Bioinformatics Resources were applied to analyse the functional enrichment of these targets and co-expressed genes.ResultsA total of 4004 CpG sites of miRNA and 11,259 CpG sites of lncRNA were screened. Among these CpG sites, 8 CpG sites of miRNA and 7 CpG sites of lncRNA were found with regression coefficients. By multiplying the sum of methylation degrees of the selected CpGs with these coefficients, two methylation-based classifiers were constructed. The classifiers have shown good performance in predicting the survival rate of PAC patients at varying follow-up times. Interestingly, both of these two classifiers were predominant and independent factors for OS. Furthermore, functional enrichment analysis demonstrated that aberrantly methylated miRNAs and lncRNAs are related to calcium ion transmembrane transport and MAPK, Ras and calcium signalling pathways.ConclusionIn the present study, we identified two methylation-based classifiers of ncRNA associated with OS in PAC patients through a comprehensive analysis of miRNA and lncRNA profiles. We are the first group to demonstrate a relationship between the aberrant DNA methylation of ncRNAs and the prognosis of PAC, and this relationship would contribute to individualized PAC therapy.

Characteristics, treatment patterns, prognostic determinants and outcome of peripheral T cell lymphoma and natural killer/T cell non-Hodgkin Lymphoma in older patients: The result of the nationwide multi-institutional registry Thai Lymphoma Study Group

IntroductionPeripheral T cell NHL (PTCL) and natural killer/T cell NHL (NKTCL) are relatively rare disorders. Data on clinical presentation, treatment and outcome are limited especially in older age groups. MethodsWe identified 127 patients with PTCL and NKTCL, excluding cutaneous T/NK cell lymphoma, aged over 60 years old from Thailand nationwide multicenter registry. ResultsOf 127 patients, median age of diagnosis was 67 years old. Patients aged older than 75 years old had similar characteristics to younger (60–74 years old) but higher comorbidity index. Seventy-nine patients (62.2%) received intensive/definite multi-agent chemotherapy, however, the proportion was significant lower in older patients (70.4% vs 34.5%, p < .001). After a median follow up duration of 17.3 months, 2-year progression free survival and overall survival were 38.1% and 48.5%. Univariate and multivariable analysis demonstrated older age, poor performance status and absence of definite multi-agent chemotherapy were associated with inferior survival. Definite multi-agent lymphoma specific chemotherapy was an independent factor for overall survival after adjustment for age, comorbidity index, performance status and prognostic index for T cell lymphoma. ConclusionDespite overall poor prognosis of PTCL and NKTCL in older adults, chemotherapy could result in objective response and long-term survival in selected patients of this vulnerable age group thus emphasizing the importance of comprehensive geriatric evaluation.

Prognostic significance of metabolic parameters measured by 18F-FDG PET/CT in limited-stage small-cell lung carcinoma.

Metabolic parameters measured by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) are important prognostic factors in several types of cancers. We evaluated the predictive value of tumor metabolic parameters measured by 18F-FDG PET/CT in limited-disease small-cell lung cancer (LD-SCLC). This retrospective study included 30 LD-SCLC patients who underwent standard chemotherapy after radiotherapy with 18F-FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and blood glucose-corrected values were used to evaluate metabolic parameters in primary tumors. For the median follow-up of 41.1 months, median overall survival (OS) was 75.0months [95% confidence interval (CI) 20.9-129.1 months], and median progression-free survival (PFS) was 9.5months (95% CI 6.8-12.1months). Two-year OS was 78.6%, and PFS was 32.7%. OS analysis indicated that MTV and TLG were significant predictors of OS following standard treatment. High glucose-corrected SUVmax (glu-SUVmax) was related to shorter median PFS. On multivariate analysis, MTV was an independent factor of OS, and glu-SUVmax was significantly related to PFS. MTV and glu-SUVmax measured on pretreatment 18F-FDG PET/CT were independent prognostic factors for LD-SCLC patients after chemoradiotherapy with curative intent. These metabolic markers need validation in larger prospective studies but may be useful in the clinical care of LD-SCLC patients.

Predictive factors of early recurrence after R0 resection of hilar cholangiocarcinoma: A single institution experience in China.

Prediction of early postoperative recurrence is of great significance for follow‐up treatment. However, there are few studies available that focus on high‐risk factors of early postoperative recurrence or even the definition the exact time of early recurrence for hilar cholangiocarcinoma. Thus, we aimed to examine the optimal cut‐off value for defining the early in patients with R0 resection of hilar cholangiocarcinoma and to investigate prognostic factors associated with early recurrence. Two hundred and fifty‐eight patients with R0 resection of hilar cholangiocarcinoma between 2000 and 2015 were included. The minimum P value approach was used to define the optimal cut‐off of early recurrence. The prognostic factors associated with early recurrence were investigated. The optimal cut‐off value for dividing patients into early and non‐early recurrence groups after R0 resection of hilar cholangiocarcinoma was 12 months. Sixty‐two patients were recorded as early recurrence, and the remaining 196 patients were labeled as non‐early recurrence. Multivariate logistic regression analysis indicated lymph node metastasis (OR = 2.756, 95% CI 1.409‐5.393; P = 0.003), poor differentiation (OR = 1.653; 95% CI 1.040‐2.632; P = 0.034), increased postoperative CA 19‐9 levels (OR = 1.965, 95% CI 1.282‐3.013; P = 0.002), neutrophil‐to‐lymphocyte ratio > 3.41 (OR = 5.125, 95% CI 2.419‐10.857; P < 0.001) and age > 60 years (OR = 2.018, 95% CI 1.032‐3.947; P = 0.040) were independent determinants of early and non‐early recurrence. Poor differentiation (HR = 2.609, 95% CI 1.600‐4.252; P < 0.001), Bismuth classification type III/IV (HR = 2.510, 95% CI 1.298‐4.852; P = 0.006) and perineural invasion (HR=2.380, 95% CI 1.271‐4.457; P = 0.007) were independent factors of overall survival in the subgroup of patients who developed early recurrence. The optimal cut‐off value for dividing early recurrence after R0 resection of hilar cholangiocarcinoma was 12 months. Tumor differentiation, Bismuth classification, and perineural invasion were independent factors of overall survival in the subgroup of patients with early recurrence. Patients with risk factors should be monitored closely after curative surgery.

MDR1 gene polymorphism correlated with pathological characteristics and prognosis in patients with primary hepatocellular carcinoma receiving interventional therapy.

The aim of this study was to explore the relationship of multidrug resistance gene 1 (MDR1) C1236T and C3435T single nucleotides polymorphisms (SNPs) with hepatocellular carcinoma (HCC) pathological features and prognosis. A total of 143 patients with HCC were treated with transcatheter arterial chemoembolization. Moreover, 251 controls were included in the study. C1236T and C3435T single nucleotide polymorphisms (SNPs) were detected by PCR-RFLP. Association of C1236T and C3435T SNPs with HCC was analyzed subsequently. There was no significant difference in genotypes distribution between HCC group and control group (P>0.05), indicating comparability. Among patients with portal vein tumor thrombus, the CC+CT genotype of C1236T locus was significantly higher than that of TT genotype (P=0.031). The median progression-free survival after interventional therapy for patients with C3435T genotype T (TC+TT) and C genotype (CC) was 36 and 18 months, respectively. CC and TC+TT genotype patients with C1236T loci showed statistically significant differences in tumor size stratification (χ=4.006, P=0.045). When tumor diameter was less than 5 cm, 5-10 cm, and more than 10 cm, the mean survival time of C and T genotypes was decreased gradually. The logistic regression model suggested that lesion size, blood volume value, and permeability surface value were influential factors for response to chemoradiotherapy (all P<0.05). Univariate analysis showed that postoperative chemotherapy, portal vein tumor thrombus, and capsular invasion were correlated with overall survival in patients with HCC. Cox proportional hazard model showed that postoperative chemotherapy, capsule invasion, and portal vein tumor thrombus were independent factors of overall survival after interventional therapy in patients with HCC (all P<0.05). C1236T genotype may predict changes in pathological features of patients with HCC to a certain extent, and C3435T SNP can be used as one of the prognostic factors of HCC. Postoperative chemotherapy and portal vein tumor thrombus are independent factors of overall survival in patients with HCC.

03:36 PM Abstract No. 320 Survival analysis of patients with hepatitis c and hepatocellular carcinoma receiving interventional oncology therapies and direct-acting antivirals with 12-week sustained viral response

To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C (HCV) viral infections treated by interventional oncology (IO) therapies. Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at a single institution with HCC treated by IO. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. 478 patients met inclusion criteria (mean age 63.7±9.5 yrs, 79% male). IO treatments include catheter-directed therapies (CDT) (n=252, 53%), ablation (n=123, 26%) and combination locoregional therapy (Combo LRT) (n=103, 22%). Of the HCC patients treated by IO, 292 (59%), 95 (33%) and 64 (67%) IO patients had HCV, received DAA and achieved SVR12 respectively. Of the patients receiving DAA therapy, 19 (21%) had HCC occurrence and 34 (49%) had recurrence following completion of DAA therapy. Median overall survival (OS) of the cohort was 26.7 mo (95% CI: 21.9-29.9 mo). OS for CDT, ablation and Combo LRT was 19.7 mo (CI: 16.5-22.8), 37.3 mo (CI: 30.7-49.9) and 29.3 mo (CI: 24.2-38.0) respectively (p<0.0001). OS in IO patients with HCV was 30.7 mo (CI: 24.2-35.2) vs 22.2 mo in non-HCV patients (CI: 17.8-27.8, p=0.03). IO patients with HCV who received DAA had higher survival (49.2 mo, CI: 36.5-not reached) vs those that did not receive DAA (18.5 mo, CI: 14.1-25.3, p<0.0001). In IO patients with HCV and SVR12 after DAA, OS was 71.8 mo (CI: 42.3-not reached) vs 26.7 mo (CI: 15.9-31.1) in the non-SVR12 group (p<0.0001). Multivariable analysis (MVA) revealed AJCC, Child-Pugh Score and tumor size to be independent factors for OS in the entire cohort (p<0.05). Within the HCV subgroup, significant factors were receiving ablation vs CDT and receiving DAA therapy (p<0.05). Significant factors in patients receiving both DAA and IO therapies were MELD score and SVR12 status (p<0.05). DAA therapy and achieving SVR12 is associated with higher OS in patients with HCV and HCC treated with Interventional Oncology therapies. This analysis supports the importance of treating HCV to SVR12 as part of HCC management.

Association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma treated with non-operative therapy

Objective: To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy. Methods: The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis. Results: The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (HR=0.64, P=0.026). The prognosis of patients in the late group of neutrophils to the lowest (HR=1.38, P=0.038) was poor compared with the early group. Furthermore, stratified by treatment methods, the overall survival of two groups showed statistically significant difference only in patients received concurrent chemoradiation. The mortality risk in the late group was higher than that in the early group (HR=3.53, P=0.010). Conclusion: The time of neutrophils to the lowest is an independent prognosis factor for non-operative treated ESCC patients. The prognosis of patients in the early group is better than that in the late group.

Liver resection for recurrent hepatocellular carcinoma after radiofrequency ablation therapy.

Although radiofrequency ablation (RFA) is an effective local treatment of hepatocellular carcinoma (HCC), local recurrence is relatively frequent. We aimed to elucidate the validity of salvage liver resection for recurrent HCC after RFA. Patients who underwent liver resection for recurrent HCC after RFA (LR after RFA) and those who underwent second liver resection for recurrent HCC (second LR) were included. The short-term outcomes were compared between the two groups. The survival rates between the two groups were compared after propensity-score matching to adjust for the variables, including patient background, liver function, and tumor status. Major resection was frequently carried out in the LR after RFA group, but there was no significant difference both in operative data and complication rate between LR after RFA (n = 54) and second LR (n = 266) groups. After a median follow-up period of 1.8years (range, 0.2-10.5), the median overall survival was 4.4years (95% confidence interval [CI], 2.2 - not applicable) and 5.6years (95% CI, 4.5-7.3; P = 0.023) in the LR after RFA group (n = 54) and second LR group (n = 54), respectively, and recurrence-free survival was 1.3years (0.4-2.2) and 1.2years (0.5-1.8, P = 0.469), respectively. The only independent factor for overall survival of the LR after RFA group was local recurrence (hazard ratio, 2.73; 1.06-9.00). Salvage liver resection of recurrent HCC after RFA could be recommended due to the safety of the procedure, especially in patients without local tumor progression after RFA.

A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse.

Purpose: Although osteosarcoma patients receive a standardized treatment, metachronous metastatic relapse still impairs the overall survival (OS). This study aimed to explore the clinicopathological features and prognostic factors of osteosarcoma patients with metachronous metastatic relapse.Patients and methods: We retrospectively analyzed 59 patients, between January 1st, 2004 and December 31st, 2013. Employed Chi-square test to recognize the differences in clinicopathological characteristics between early and late metastatic patients, and the differences between shorter and longer survival patients. Used the Kaplan-Meier method to evaluate the survival data, cox step proportional hazard test to analyze the prognostic factors associated with OS.Results: We found that early metastatic patients were prominently correlated with the male, tumor size ≥8 cm, histological grade G2, Enneking stages II, anatomic location of the distal femur, pathological of conventional types, and elevated alkaline phosphatase (ALP) level at diagnosis, (p<0.05). In parallel, the shorter survival patients were primarily linked to tumor size ≥8 cm, histological grade G2, Enneking stages II, early metastasis, multiple pulmonary metastases, lack of curative treatment after metastasis, increased level of ALP at diagnosis and LDH after metastasis, (p<0.05). The univariate analyses of the prognostic factors showed that patients who had these clinicopathological characteristics, such as male, tumor size ≥8 cm, Enneking stage IIB, multiple pulmonary metastases, lack of curative treatment after metastasis, the elevated ALP at diagnosis, elevated ALP and LDH after metastasis, had a worse OS in osteosarcoma patient with metachronous metastatic relapse, (p<0.05). The multivariate analyses showed that tumor size, type of metastasis and ALP level at diagnosis were independent factors for OS in osteosarcoma patient with metachronous metastatic relapse (p<0.05).Conclusion: These results indicated that osteosarcoma patients with metachronous metastatic relapse have special features which might be utilized to effectively predict the likelihood of early metastatic relapse and the prognosis.

Development and Validation of a Prognostic Nomogram in AFP-negative hepatocellular carcinoma.

The aim of this study is to establish and validate an effective prognostic nomogram in patients with AFP-negative hepatocellular carcinoma (HCC). The nomogram was based on a primary cohort that consisted of 419 patients with clinicopathologically diagnosed with HCC, all the data was gathered from 2008 to 2014 in Sun Yat-sen University Cancer Center. All the model factors were determined by univariate and multivariate Cox hazard analysis. The concordance index (C-index) and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram, and compared with the TNM staging systems on HCC. Internal validation was assessed. An independent validation cohort contained 150 continuous patients from 2014 to 2015. Independent factors for overall survival (OS) were body mass index (BMI), tumor stage, distant metastases, HBs Ag, lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), and albumin (ALB), which were all contained into the nomogram. The calibration curve for probability of OS showed good agreement between prediction by nomogram and actual observation. The C-index of nomogram was 0.807 (95% CI: 0.770-0.844), which was superior to the C-index of AJCC TNM Stage (0.697). The AUC was 0.809(95%CI: 0.762-0.857). In the validation cohort, the nomogram still gave good discrimination (C-index: 0.866, 95% CI: 00.796-0.936; AUC: 0.832, 95%CI: 0.747-0.917) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively. The proposed nomogram presents more accurate and useful prognostic prediction for patients with AFP-negative HCC.

Establishment of inflammation biomarkers-based nomograms to predict prognosis of advanced colorectal cancer patients based on real world data.

PurposeTo establish three novel prognostic nomograms with inflammatory factors for advanced colorectal cancer (ACRC), right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) according to real world data.Materials and methodsACRC patients receiving medicine therapy from January 1st, 2005 to September 31th, 2015 in Sun Yat-sen University Cancer Center were enrolled. Inflammatory indicators such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were analyzed for establishing nomograms predicting overall survival (OS). Concordance index (C-index) determined predictive accuracy and discriminative ability.ResultsOur study selected 807 ACRC patients, 29.6% RSCC and 70.4% LSCRC. Median OS was 23.36 months. Patients at lower level of NLR, PLR, CEA, CA 19–9, LDH and CRP showed longer OS (P < 0.001). For all patients, pathological grade (P = 0.018), treatments (P = 0.042), sidedness (P = 0.003), NLR (P < 0.001), CA 19–9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.0012) contributed to OS independently. For RSCC, pathological grade (P = 0.022), CA 19–9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.001) were significantly related with OS. For LSCRC patients, treatments (cetuximab vs chemotherapy: P = 0.008; bevacizumab vs chemotherapy: P = 0.166), NLR (P < 0.001), CA 19–9 (P = 0.030) and LDH (P < 0.001) were independent factors for OS. Final models showed acceptable internal validity with C-indexes of 0.687, 0.697 and 0.667 in all, RSCC and LSCRC patients.ConclusionsInflammatory factors enrolled in the proposed nomograms showed accurately individualized prognostic prediction, and prognostic factors for RSCC and LSCRC were different.

Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma of cervix after definitive radiotherapy or concurrent chemoradiotherapy

BackgroundConcurrent chemoradiotherapy (CCRT) is effective in the treatment of locally advanced cervical squamous cell carcinoma (SCC). However, whether treatment outcomes of cervical adenocarcinoma are equivalent to SCC after CCRT has been a topic of debate.MethodsMedical records of cervical cancer patients treated with definitive radiotherapy or CCRT in our institute from January 2011 to December 2014 were reviewed. Patients were treated with intensity modulated radiation therapy combined with intracavitary brachytherapy. Weekly cisplatin was the first line regimen of concurrent chemotherapy. The treatment outcomes of patients with SCC and adenocarcinoma were compared with a multivariate Cox regression model, and log-rank method before and after propensity score matching (1:1).ResultsA total of 815 patients with stage IB-IVA cervical cancer were included, with 744 patients in the SCC group and 71 patients in adenocarcinoma group. The median follow-up period was 36.2 months (range, 1.0–76.2 months). The 3-year overall survival (OS), disease-free survival (DFS), pelvic control and distant control rates of patients in the SCC group and adenocarcinoma group were 85.2 and 75.4% (p = 0.005), 77.5 and 57.3% (p < 0.001), 89.0 and 74.0% (p = 0.001) and 86.0 and 74.4% (p = 0.011), respectively. After multivariate analysis, histology was an independent factor of OS (p = 0.003), DFS (p < 0.001), pelvic control (p = 0.002) and distant control (p = 0.003). With propensity score matching, 71 pairs of patients were selected. After matching, the OS (p = 0.017), DFS (p = 0.001), pelvic control (p = 0.015) and distant control (p = 0.009) of patients with adenocarcinoma were poorer than those of patients with SCC. In subgroup analysis, patients with adenocarcinoma had significantly worse OS and DFS compared with patients with SCC, regardless of treatment with radiotherapy alone or CCRT.ConclusionThe present study demonstrated that patients with adenocarcinoma of the cervix had poorer OS and DFS than patients with SCC, regardless of treatment with radiotherapy alone or CCRT. New treatment approaches should be considered for cervical adenocarcinoma.