Prognostic Value of Plasma Epstein–Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era

This study aimed to evaluate the prognostic value of plasma Epstein–Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level <4000 copies/mL, patients with an EBV DNA ≥4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68–84]) versus (93%, 95% CI [90–96], P < 0.001), DMFS (83%, 95% CI [76–89]) versus (97%, 95% CI [94–99], P < 0.001), and OS (85%, 95% CI [78–92]) versus (98%, 95% CI [95–100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80–6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036–3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647–14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701–8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252–5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.     

Plasma Epstein–Barr Viral Deoxyribonucleic Acid Predicts Worse Outcomes in Pediatric Nonmetastatic Nasopharyngeal Carcinoma Patients: An Observational Study of 89 Cases in an Endemic Area

To evaluate the clinical significance of pretreatment levels of plasma Epstein–Barr virus DNA (pEBV DNA) on prognoses in pediatric nasopharyngeal carcinoma (NPC) patients.Eighty-nine patients aged 21 years old or younger with nonmetastatic NPC were evaluated to determine the effect of pEBV DNA levels on progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS). Survival probabilities in patient groups that were segregated by clinical stage or pEBV DNA load (low or high) were compared.The median pretreatment concentrations of pEBV DNA were 3440 copies/mL in 35 patients with stage III disease and 14,900 copies/mL in 50 patients with stage IV disease (P = 0.059). The median concentration of pEBV DNA was 34,500 copies/mL in 17 patients with relapse, which was higher than the concentration in 72 patients without relapse, who had a median level of 4985 copies/mL (P = 0.057). Further study showed that pretreatment pEBV DNA load was an independent prognostic indicator in pediatric NPC patients. High pEBV DNA was associated with adverse clinical outcomes, including PFS [3-year PFS rate = 80.5% versus 95.8%, hazard ratio (HR) = 5.00, 95% confidence interval (CI) = 1.00–25.00; P = 0.050], DMFS (3-year DMFS rate = 80.5% versus 95.8%, HR = 5.20, 95% CI = 1.04–26.00; P = 0.045), and OS (3-year OS rate = 82.9% versus 95.8%, HR = 5.41, 95% CI = 1.08–27.22; P = 0.040).Pretreatment pEBV DNA load was an independent prognostic indicator for PFS, DMFS, and OS in pediatric patients with NPC. Prospective studies, however, are needed to validate these results.     

The Prognosis of Nasopharyngeal Carcinoma Involving Masticatory Muscles: A Retrospective Analysis for Revising T Subclassifications

This work is a retrospective study of magnetic resonance imaging (MRI) and T-stage subclassifications of nasopharyngeal carcinoma (NPC) involving the masticatory muscles (MMs). We examined how involvement of MMs influences the clinical T-stage classifications and the survival outcomes of NPC patients.MRI data as well as the medical records from 816 NPC patients were analyzed retrospectively. All cases were restaged according to the seventh edition of American Joint Committee on Cancer staging system criteria. The overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed by the Kaplan–Meier method, and their survival outcomes between different degrees of MM involvement and different T classifications were compared by using the log-rank test. All statistical analyses were conducted on SPSS 18.0 software. P > 0.05 was considered significant.Of the 816 NPC patients analyzed, 283 (34.68%) had tumors that involved MMs. All of those 283 patients involved the medial pterygoid muscle, and 125 cases (15.32%) involved the lateral pterygoid muscle. Multivariate analysis identified MM involvement as an independent prognostic factor for patient''s OS (P = 0.007) and LRFS (P = 0.024). MM involvement significantly correlated with a lower OS and LRFS (P < 0.01). In addition, compared with concurrent involvement of the medial and lateral pterygoid muscle, the medial pterygoid muscle involvement correlated with a higher OS and LRFS (P < 0.05). Among NPC patients, T-classifications 1 to 4 usually predicted the ultimate OS, LRFS, and DMFS (P > 0.1), unless the cancer involved the lateral pterygoid muscle.NPC involving the lateral pterygoid muscle presents a worse survival outcome than that involving the medial pterygoid muscle. Any cancer involving the lateral pterygoid muscle should be classified in a higher T-stage subclassification.     

Prognostic value of lactate dehydrogenase for melanoma patients receiving anti-PD-1/PD-L1 therapy: A meta-analysis

Background:Several studies indicate the level of pretreatment lactate dehydrogenase (LDH) may be associated with the prognosis of patients receiving immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) which had been reported to dramatically improve the survival of patients with advanced or metastatic melanoma; however, no consensus has been reached because the presence of controversial conclusions. This study was to perform a meta-analysis to comprehensively explore the prognostic values of LDH for melanoma patients receiving anti-PD1/PD-L1 monotherapy.Methods:A systematic electronic search in the databases of PubMed, EMBASE and the Cochrane library was performed to identify all related articles up to April, 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained to assess the prognostic values of pretreatment LDH in blood for overall survival (OS) and progression-free survival (PFS).Results:A total of 22 eligible studies involving 2745 patients were included. Of them, 19 studies with 20 results assessed the OS and the pooled analysis showed that an elevated pretreatment LDH level was significantly associated with a worse OS (HR = 2.44; 95% CI: 1.95–3.04, P < .001). Thirteen studies reported PFS and meta-analysis also revealed that a higher pretreatment LDH level predicted a significantly shorter PFS (HR, 1.61; 95% CI, 1.34–1.92; P < .001). Although heterogeneity existed among these studies, the same results were acquired in subgroup analyses based on sample size, country, study design, cut-off of LDH, type of PD-1/PD-L1 inhibitors and statistics for HRs (all HRs > 1 and P < .05).Conclusion:This meta-analysis suggests LDH may serve as a potential biomarker to identify patients who can benefit from anti-PD-1/PD-L1 and then schedule treatments.     

Prognostic value of the systemic inflammation response index in human malignancy: A meta-analysis

Background:This meta-analysis aimed to evaluate the prognostic value of the systemic inflammation response index (SIRI) in malignancy based on existing evidence.Methods:We searched for relevant literature published in the electronic databases PubMed, Web of Science, Cochrane Library, and Embase before April 10, 2020. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated and pooled to evaluate the relationship between SIRI and malignancy outcomes.Results:We included 14 articles, describing 6,035 patients. Our findings revealed that patients with high SIRI had worse overall survival (OS) (HR = 2.20, 95% CI: 1.85–2.62, P < .001), disease-free survival (DFS) (HR: 1.92, 95% CI: 1.49–2.48, P < .001), time-to-progression (TTP) (HR: 2.00, 95% CI: 1.55–2.58, P < .001), progression-free survival (PFS) (HR: 1.73, 95% CI: 1.38–2.16, P < .001), cancer-specific survival (CSS) (HR: 3.57, 95% CI: 2.25–5.68, P < 0.001), disease-specific survival (DSS) (HR: 1.99, 95% CI: 1.46 - 2.72, P < .001), and metastasis-free survival (MFS) (HR: 2.26, 95% CI: 1.28–3.99, P = .005) than patients with low SIRI. The correlation between SIRI and OS did not change in a subgroup analysis. Meta-regression indicated that heterogeneity may be related to differences in primary therapy strategies. Sensitivity analysis suggested that our results were reliable.Conclusions:SIRI could be used as a useful predictor of poor prognosis during malignancy treatment.     

Prognostic Significance of Hypoxia-Inducible Factor Expression in Renal Cell Carcinoma: A PRISMA-compliant Systematic Review and Meta-Analysis

The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis.PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed.A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898–2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595–2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675–1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667–3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566–1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206–3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629–3.407, P = 0.000).The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.     

Prognostic Value and Grading of MRI-Based T Category in Patients With Nasopharyngeal Carcinoma Without Lymph Node Metastasis Undergoing Intensity-Modulated Radiation Therapy

We investigated the prognostic value and gradation of the T category in N0 nasopharyngeal carcinoma (NPC) patients undergoing magnetic resonance imaging (MRI) and intensity-modulated radiotherapy (IMRT).A total of 749 patients were retrospectively reviewed, and a total of 181 N0 NPC patients were included in this retrospective study. All patients were restaged according to the 7th edition of the American Joint Committee on Cancer staging system. The following endpoints were estimated: overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS).The 5-year survival rates for T1 to T4 were: OS (97.3%, 100.0%, 86.1%, and 82.8%; P = 0.007), PFS (94.6%, 96.9%, 76.5%, and 76.7%; P = 0.002), LRFS (98.5%, 100.0%, 92.2%, and 86.7%; P < 0.001), and DMFS (97.3%, 96.9%, 85.5%, and 85.7%; P = 0.042), respectively. Pairwise comparisons showed that the OS, PFS, and LRFS rates were significantly poorer in the advanced T categories (T3 and T4) than the early ones (T1 and T2), and no significant differences between T1 and T2, and T3 and T4 were found. In Cox''s proportional hazard analysis, T category was found to be an independent prognostic factor only for PFS (P = 0.003). According to the primary tumor extent, we then graded all 181 N0 patients into 3 groups: group 1, early T category (n = 107); group 2, low-risk advanced T category (n = 35); and group 3, high-risk advanced T category (n = 39). The 5-year survival rates for the 3 groups were: OS (98.1%, 94.1%, and 76.3%; P < 0.001), PFS (95.3%, 88.2%, and 66.2%; P < 0.001), LRFS (99.0%, 97.0%, and 83.4%; P < 0.001), and DMFS (97.2%, 91.1%, and 80.4%; P = 0.002). The 5-year OS, PFS, and LRFS rates of group 3 differed significantly from those of groups 1 and 2, and a significant difference was observed in the DMFS rate only between groups 3 and 1. In Cox''s proportional hazard analysis, the 3-grade T category was an independent prognostic factor for OS (P = 0.002), PFS (P < 0.001), and LRFS (P = 0.002).The 3-grade T category, using MRI according to the site of invasion, has prognostic value for the outcome of IMRT treatment in N0 NPC, and could aid in developing individualized treatment strategies.     

Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy

It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3–4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan–Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03–3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08–2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.     

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80–0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80–0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08–1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91–1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82–1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63–1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.     

Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung Cancer Patients

Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated.We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of clinicopathologic information in postoperative mu agonists group and no mu agonists group was analyzed by χ² test. Univariate and multivariate Cox regression analysis were conducted and represented as hazards ratio and 95% confidence interval form. The primary endpoint was OS and secondary endpoint was DFS.This retrospective study included 984 consecutive NSCLC patients who underwent surgery between January 2006 and December 2011. No significant difference existed between postoperative mu agonists usage group and no mu agonists usage group in clinicopathologic information except operation type (P = 0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95% CI 1.197–1.916, P = 0.001) and shorter DFS (HR 1.415, 95% CI 1.123–1.781, P = 0.003) in the multivariate Cox regression model. For the patients who received postoperative chemotherapy or radiotherapy postoperative mu agonists also predict shorter survival (HR 1.437, 95% CI 1.041–1.982, P = 0.027). Subgroup analysis showed that administration of postoperative mu agonists was related to shorter OS, especially in males, more smoking, poor differential degree, bilobectomy or pneumonectomy, and stage III subgroup, respectively.Administration of postoperative mu agonists was related to shorter OS and DFS for the NSCLC patients who underwent surgery.     

Treatment and Prognoses in Patients With Primary Gastrointestinal Stromal Tumors ≥10?cm: A Single-Institution Experience in China

Data on treatments and specific outcomes of primary gastrointestinal stromal tumors (GISTs) ≥10 cm are limited. We here report the treatments and survival outcomes concerning a subgroup of primary giant GISTs.Data of 83 consecutive patients with primary GISTs ≥10 cm in a single institution were retrospectively collected. Fifty-eight patients underwent surgery before imatinib mesylate (IM) treatment (Group A), 10 underwent surgical resection following IM therapy (Group B), whereas 15 patients took IM as drug therapy alone (Group C).The baseline clinical characteristics were similar among the 3 groups. However, a lower proportion in Group A had metastatic disease at the time of diagnosis or surgery compared with Groups B and C (8.6% vs 40.0% vs 40.0%, P < 0.05). The median follow-up duration was 21.5 months. No statistically significant differences were observed on progression-free survival (PFS) among the groups. However, patients in Group B showed significantly better overall survival (OS) compared with those in Group C (P = 0.044). Multivariate analysis showed that patients treated with adjuvant IM were associated with better PFS (hazard ratio [HR] 3.01; 95% confidence interval [CI] 1.13–7.97; P = 0.027) and OS (HR 29.11; 95% CI 3.32–125.36; P = 0.004). The subgroup with mitotic count >10/50 high-power fields (HPF) showed worse PFS (HR 3.50; 95% CI 1.19–10.25; P = 0.022) and OS (HR 20.04; 95% CI 1.67–143.79; P = 0.018) than that of mitotic count ≤5/50 HPF.Clinical treatment patterns for primary giant GISTs are different, and the outcomes of different interventions vary. The optimal treatments for these subgroup of patients still require further long-term investigation. Moreover, mitotic count and adjuvant IM are closely associated with PFS and OS in giant GISTs.     

The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC: A meta-analysis

Whether programmed death-ligand 1 (PD-L1) expression could predict the outcome of tyrosine kinase inhibitor (TKI) treatment and prognosis of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) is remaining controversial.Potential studies were search from PubMed, Embase, and Web of Science databases. Pooled odds ratio of objective response rate was used to describe the relationship between PD-L1 expression and primary resistance to EGFR-TKIs. Pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were included to assess the effects of PD-L1 status on the outcome of EGFR-TKI treatment and survival of EGFR-mutant NSCLCs.Eighteen eligible studies (1986 EGFR-mutant NSCLCs) were included in this meta-analysis. Positive PD-L1 expression correlated with lower objective response rate of EGFR-TKI treatment (odds ratio [95% confidence interval {CI}] = 0.52 [0.28–0.98], P = .043), while PFS (adjusted HR [95% CI] = 1.49 [0.96–1.89], P = .332) and OS (HR [95% CI] = 1.24 [0.70–2.20], P = .456) of EGFR-TKI treatment did not correlated with PD-L1 status. Furthermore, PD-L1 expression was not a predictive biomarker for the OS (HR [95% CI] = 1.43 [0.98–2.08], P = .062) in overall EGFR-mutant cohort.Positive PD-L1 expression indicated a higher incidence of primary resistance, but did not correlate with the PFS or OS of EGFR-TKI therapy. In addition, PD-L1 expression was unlikely a predictive biomarker for prognosis of EGFR-mutant NSCLCs.     

Risk factors for postoperative pneumonia and prognosis in lung cancer patients after surgery: A retrospective study

Postoperative pneumonia (POP) is one of the most frequent complications following lung surgery. The aim of this study was to identify the risk factors for developing POP and the prognostic factors in lung cancer patients after lung resection.We performed a retrospective review of 726 patients who underwent surgery for stages I–III lung cancer at a single institution between August 2017 and July 2018 by conducting logistic regression analysis of the risk factors for POP. The Cox risk model was used to analyze the factors influencing the survival of patients with lung cancer.We identified 112 patients with POP. Important risk factors for POP included smoking (odds ratio [OR], 2.672; 95% confidence interval [CI], 1.586–4.503; P < .001), diffusing capacity for carbon monoxide (DLCO) (40–59 vs ≥80%, 4.328; 95% CI, 1.976–9.481; P < .001, <40 vs ≥80%, 4.725; 95% CI, 1.352–16.514; P = .015), and the acute physiology and chronic health evaluation (APACHE) II score (OR, 2.304; 95% CI, 1.382–3.842; P = .001). In the Cox risk model, we observed that age (hazard ratios (HR), 1.633; 95% CI, 1.062–2.513; P = .026), smoking (HR, 1.670; 95% CI, 1.027–2.716; P = .039), POP (HR, 1.637; 95% CI, 1.030–2.600; P = .037), etc were predictor variables for patient survival among the factors examined in this study.The risk factors for POP and the predictive factors affecting overall survival (OS) should be taken into account for effective management of patients with lung cancer undergoing surgery.     

Clinical Significance of Preoperative Serum High Density Lipoprotein Cholesterol Levels in Soft Tissue Sarcoma

The prognostic value of lipid profile remains unclear in soft tissue sarcoma. The aim of the present study was to validate the prognostic value of preoperative plasma lipid profile (high density lipoprotein-cholesterol [HDL-C], low density lipoprotein-cholesterol [LDL-C], cholesterol, and triglycerides) levels on disease-free survival (DFS) and overall survival (OS) in soft tissue sarcoma (STS) patients undergoing extensive and radical surgical resection.The preoperative plasma lipid profile levels of 234 STS patients, who were operated on between 2000 with 2010, were retrospectively evaluated. Kaplan-Meier curves and multivariate Cox proportional models were calculated for DFS and OS.In univariate analysis, a decreased HDL-C level was significantly associated with decreased OS (hazard ratio [HR], 3.405; 95% confidence interval (CI), 1.445–8.021, P = 0.005) and remained significant in the multivariate analysis (HR, 5.615; 95% CI, 1.243–25.378, P = 0.025). Patients with HDL-C < 1.475 mmol/L showed a median OS of 71 months. In contrast, patients with HDL-C ≥1.475 mmol/L had a median OS of 101 months. In univariate analysis, a decreased HDL-C level was significantly associated with decreased DFS (HR, 2.085; 95% CI, 1.271–3.422, P = 0.004) and remained significant in the multivariate analysis (HR, 1.808; 95% CI, 1.118–2.924, P = 0.016). Patients with HDL-C <1.475 mmol/L presented with a median DFS of 47 months, whereas patients with HDL-C ≥1.475 mmol/L had a median DFS of 78 months. In univariate analysis and multivariate analyses regarding OS and DFS, there was no significant association between the groups in terms of LDL-C, CHO and TG.Our study investigated the potential prognostic utility of preoperative plasma HDL-C levels as an independent factor in STS patients who had undergone radical surgical resection.     

Prognostic Effect of Pretreatment Serum Carcinoembryonic Antigen Level: A Useful Tool for Prediction of Distant Metastasis in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision

Many studies have reported the prognostic value of pretreatment serum carcinoembryonic antigen (pre-CEA) levels on colorectal cancer outcomes. However, controversy remains concerning the significance of pre-CEA levels in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Our aim in this study was to investigate the prognostic role of the pre-CEA level in patients with locally advanced rectal cancer undergoing neoadjuvant CRT followed by total mesorectal excision (TME).A total of 419 patients with stages II and III rectal cancer treated with neoadjuvant CRT followed by TME with available pre-CEA data were included. The outcomes studied were 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Optimal pre-CEA cutoff values to predict DMFS were determined based on current smoking history.The median pre-CEA level of smokers was 3.8 ng/mL, and that of nonsmokers was 2.8 ng/mL (P < 0.01). Pre-CEA levels of 6.6 ng/mL for nonsmokers and 11.4 ng/mL for smokers were determined to best separate patients on the basis of time to distant metastasis by using log-rank statistics. The pre-CEA level was associated with DMFS (hazard ratio = 1.743, 95% confidence interval = 1.129–2.690, P = 0.01). The pre-CEA level was not associated with LRFS or DFS.The pre-CEA level appears to be a significant preoperative prognostic factor. Moreover, it is as valuable as any known pathologic factor. Future studies evaluating oncologic outcomes should take into consideration the pre-CEA level.     

Refusal of cancer-directed surgery in male breast cancer

It has been reported that some male breast cancer patients may refuse the recommended surgery, but the incidence rate in the United States is not clear. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with the rejection of such cancer-directed surgery.We collected data on 5860 patients with male breast cancer (MBC) from the Surveillance, Epidemiology, and End Results database, including 50 patients refusing surgery as recommended. Kaplan–Meier survival analysis and Cox proportional hazard regression were used to identify the effects of refusing surgery on cancer-specific survival (CSS) and overall survival (OS). The association between acceptance or rejection of surgery and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age, race, clinical characteristics, and radiation.Of the 5860 patients identified, 50 (0.9%) refused surgery. Old age (≥65: hazard ratio [HR]: 3.056, 95% confidence interval [CI]: 1.738–5.374, P < .0001), higher AJCC stage (III: HR: 3.283, 95% CI: 2.134–5.050, P < .0001, IV: HR: 14.237, 95% CI: 8.367–24.226, P < .0001), progesterone receptor status (negative: HR: 1.633, 95% CI: 1.007–2.648, P = .047) were considered risk factors. Compared with the surgery group, the refusal group was associated with a poorer prognosis in both OS and CSS (χ² = 94.81, P < .001, χ² = 140.4, P < .001). Moreover, significant differences were also observed in OS and CSS among 1:3 matched groups (P = .0002, P < .001).Compared with the patients undergoing surgery, the patients who refused the cancer-directed surgery had poor prognosis in the total survival period, particularly in stage II and III. The survival benefit for undergoing surgery remained even after adjustment, which indicates the importance of surgical treatment before an advanced stage for male breast cancer patients.     

Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer

To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.     

The Clinical Utility of Plasma Epstein–Barr Virus DNA Assays in Nasopharyngeal Carcinoma: The Dawn of a New Era?: A Systematic Review and Meta-Analysis of 7836 Cases

In this study, we assessed the potential of plasma Epstein–Barr virus (EBV) DNA assays to predict clinical outcomes in a large sample of nasopharyngeal carcinoma (NPC) patients and proposed a risk stratification model based on standardized EBV DNA load monitoring.We conducted a meta-analysis of 14 prospective and retrospective comparative studies (n = 7 836 patients) to evaluate the correlation between pretreatment plasma EBV DNA (pre-DNA), midtreatment plasma EBV DNA (mid-DNA), posttreatment plasma EBV DNA (post-DNA), the half-life value of plasma EBV DNA clearance rate (t_1/2), and clinical outcomes. Our primary endpoint was overall survival (OS). Our secondary endpoints were progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS).High pre-DNA, detectable mid-DNA, detectable post-DNA, and slow EBV DNA clearance rates were all significantly associated with poorer OS, with hazard radios (HRs) equal to 2.81, 3.29, 4.26, and 3.58, respectively. Pre-DNA, mid-DNA, and post-DNA had the same effects on PFS, DMFS, and LRFS.Plasma EBV DNA assays are highly prognostic of long-term survival and distant metastasis in NPC patients. Based on the results of this meta-analysis, we propose a 4-grade systematic risk stratification model. Given the inherent limitations of the included studies, future well-designed randomized clinical trials are required to confirm to the findings of this analysis and to contribute to the development of individualized treatment strategies for NPC patients.     

Uracil-tegafur vs fluorouracil as postoperative adjuvant chemotherapy in Stage II and III colon cancer: A nationwide cohort study and meta-analysis

We conducted a population-based cohort study enrolling patients with Stage II and III colon cancer receiving postoperative adjuvant chemotherapy with uracil and tegafur (UFT) or fluorouracil (5-FU) from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the current study were disease-free survival (DFS) and overall survival (OS). Hazard ratios (HRs) were calculated by multivariate Cox proportional hazard regression models. We compared our effectiveness results from the literature by meta-analysis, which provided the best evidence. Severe adverse events were compared in meta-analysis of reported clinical trials. In the nationwide cohort study, UFT (14,486 patients) showed DFS similar to postoperative adjuvant chemotherapy (adjusted HR 1.037; 95% confidence interval [CI] 0.954–1.126; P = .397) and OS (adjusted HR 0.964; 95% CI 0.891–1.041; P = .349) compared with the 5-FU (866 patients). Our meta-analysis confirmed the similarity of effectiveness and found the incidence of leucopaenia was statistically significantly reduced in UFT (risk ratio 0.12; 95% CI 0.02–0.67; I² = 0%). Through our analysis, we have confirmed that UFT is a well-tolerated adjuvant therapy choice, and has similar treatment efficacy as 5-FU in terms of DFS and OS in patients with Stage II and III colon cancer.