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IntroductionThere are many different chronic lymphoblastic leukemia (CLL) survival prediction models and scores. But none provide information on expression of immune-related genes in the CLL cells.MethodsWe interrogated data from the Gene Expression Omnibus database (GEO, GSE22762; Number = 151; training) and International Cancer Genome Consortium database (ICGC, CLLE-ES; Number = 491; validation) to develop an immune risk score (IRS) using Least absolute shrinkage and selection operator (LASSO) Cox regression analyses based on expression of immune-related genes in CLL cells. The accuracy of the predicted nomogram we developed using the IRS, Binet stage, and del(17p) cytogenetic data was subsequently assessed using calibration curves.ResultsA survival model based on expression of 5 immune-related genes was constructed. Areas under the curve (AUC) for 1-year survivals were 0.90 (95% confidence interval, 0.78, 0.99) and 0.75 (0.54, 0.87) in the training and validation datasets, respectively. 5-year survivals of low- and high-risk subjects were 89% (83, 95%) vs. 6% (0, 17%; p < 0.001) and 98% (95, 100%) vs. 92% (88, 96%; p < 0.001) in two datasets. The IRS was an independent survival predictor of both datasets. A calibration curve showed good performance of the nomogram. In vitro, the high expression of CDKN2A and SREBF2 in the bone marrow of patients with CLL was verified by immunohistochemistry analysis (IHC), which were associated with poor prognosis and may play an important role in the complex bone marrow immune environment.ConclusionThe IRS is an accurate independent survival predictor with a high C-statistic. A combined nomogram had good survival prediction accuracy in calibration curves. These data demonstrate the potential impact of immune related genes on survival in CLL.

Purpose: To establish a risk classification of de novo metastatic nasopharyngeal carcinoma (mNPC) patients based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET-CT) radiomics parameters to identify suitable candidates for locoregional radiotherapy (LRRT). Methods: In all, 586 de novo mNPC patients who underwent 18 F-FDG PET-CT prior to palliative chemotherapy (PCT) were involved. A Cox regression model was performed to identify prognostic factors for overall survival (OS). Candidate PET-CT parameters were incorporated into the PET-CT parameter score (PPS). Recursive partitioning analysis (RPA) was applied to construct a risk stratification system. Results: Multivariate Cox regression analyses revealed that total lesion glycolysis of locoregional lesions (LRL-TLG), the number of bone metastases (BMs), metabolic tumor volume of distant soft tissue metastases (DSTM-MTV), pretreatment Epstein–Barr virus DNA (EBV DNA), and liver involvement were independent prognosticators for OS. The number of BMs, LRL-TLG, and DSTM-MTV were incorporated as the PPS. Eligible patients were divided into three stages by the RPA-risk stratification model: M1a (low risk, PPS low + no liver involvement), M1b (intermediate risk, PPS low + liver involvement, PPS high + low EBV DNA), and M1c (high risk, PPS high + high EBV DNA). PCT followed by LRRT displayed favorable OS rates compared to PCT alone in M1a patients ( p 0.05). Conclusions: The PPS-based RPA stratification model could identify suitable candidates for LRRT. Patients with stage M1a disease could benefit from LRRT.

BackgroundTo build a predictive scoring model based on simple immune and inflammatory parameters to predict postoperative survival in patients with breast cancer.MethodsWe used a brand-new immuno-inflammatory index—pan-immune-inflammation value (PIV)—to retrospectively evaluate the relationship between PIV and overall survival (OS), and based on the results of Cox regression analysis, we established a simple scoring prediction model based on several independent prognostic parameters. The predictive accuracy of the model was evaluated and independently validated.ResultsA total of 1,312 patients were included for analysis. PIV was calculated as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). According to the best cutoff value of PIV, we divided the patients into two different subgroups, high PIV (PIV > 310.2) and low PIV (PIV ≤ 310.2), associated with significantly different survival outcomes (3-year OS, 80.26% vs. 86.29%, respectively; 5-year OS, 62.5% vs. 71.55%, respectively). Six independent prognostic factors were identified and used to build the scoring system, which performed well with a concordance index (C-index) of 0.759 (95% CI: 0.715–0.802); the calibration plot showed good calibration.ConclusionsWe have established and verified a simple scoring system for predicting prognosis, which can predict the survival of patients with operable breast cancer. This system can help clinicians implement targeted and individualized treatment strategies.

Abstract Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA

Abstract Background Early diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC. Methods Total RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2. Results There were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein–Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2. Conclusions The present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.

Abstract Background Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients. Methods This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival. Results Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS. Conclusions Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.

BackgroundUsing the current tumor lymph node metastasis (TNM) staging system to make treatment decisions and predict survival in patients with nasopharyngeal carcinoma (NPC) lacks sufficient accuracy. Patients at the same stage often have different survival prognoses.MethodsIn the current study 802 NPC patients who underwent concurrent radiotherapy and chemotherapy from January 2010 to December 2014 at Sun Yat-sen University Cancer Center in China were retrospectively assessed. The optimal cut-off points for skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) were determined via receiver operating characteristic curves. SMI-MLR (S-M) grade and a nomogram were developed and used as clinical indicators in NPC patients. The consistency index (C-index) and a calibration curve were used to measure the accuracy and discriminative capacity of prediction.ResultsThe predictive performance of S-M grade was better than that of TNM staging (C-index 0.639, range 0.578–0.701 vs. 0.605, range 0.545–0.665; p = 0.037). In multivariate analysis S-M grade, T stage, and N stage were independent prognostic factors. These three factors were then combined, yielding a nomogram with a C-index of 0.71 (range 0.64–0.77), indicating good predictive capacity.ConclusionWe developed and validated a prognostic parameter, S-M grade, which increased prediction accuracy significantly and can be combined with TNM staging to predict survival in patients with NPC undergoing concurrent chemoradiotherapy.

BackgroundThe present study aimed to construct a prognostic nomogram including Epstein-Barr virus DNA (EBV-DNA) and sarcopenia in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT).MethodsIn this retrospective analysis, we studied 1,045 patients with NPC who had been treated with CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography scans of the third cervical vertebrae. A new S-E grade was constructed using a receiver-operating characteristic (ROC) curve analyses determined cutoff values of sarcopenia and plasma EBV-DNA. The nomogram was developed base on the sarcopenia-EBV (S-E) grade and traditional prognostic factors. A calibration curve, time-dependent ROC, decision curve analysis, and the concordance index (C-index) determined the accuracy of prediction and discrimination of the nomogram, and were compared with TNM staging system and a traditional nomogram.ResultsPatient survival was significantly different when sarcopenia (P < 0.001) or EBV-DNA (P = 0.001) were used and they continued to be independent prognostic factors for survival upon univariate (P < 0.001, P = 0.002, respectively) and multivariate (P < 0.001, P = 0.015, respectively) analyses. Predicting overall survival (OS) was more accurate using the S-E grade than using TNM staging and sarcopenia or EBV-DNA alone. Nomogram B (model with sarcopenia) or nomogram A (model without sarcopenia) were then developed based on the identified independent prognostic factors. Comparing nomogram prediction with actual observation showed good agreement among the calibration curves for probability of 1-, 3-, and 5-year OS. Predicted survival (C-index = 0.77) of nomogram B was statistically higher than that of nomogram A (0.676, P = 0.020) and TNM staging (0.604, P < 0.001). Risk group stratification could distinguish between survival curves within respective TNM stages (all stages, P < 0.001; stage III, P < 0.001; stage IV, P = 0.002).ConclusionsThe sarcopenia-EBV DNA nomogram allowed more accurate prediction of prognosis for patients with NPC receiving CCRT.

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest identified member of the IQGAP family, may act as a crucial factor in cancer development and progression; however, its clinical value in breast cancer remains unestablished. We explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer.Methods: IQGAP3 mRNA and protein levels were detected in breast cancer cell lines and tumor tissues by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was also evaluated immunohistochemically in archived paraffin-embedded specimens from 257 breast cancer patients, and the associations between IQGAP3 expression level, clinical characteristics, and prognosis were analyzed. We assessed the relationship between IQGAP3 expression and sensitivity to radiation therapy which was determined by subgroup analysis.Results: IQGAP3 was significantly upregulated in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to controls. Additionally, high levels of IQGAP3 expression were detected in 110/257 (42.8%) of archived paraffin-embedded breast cancer specimens. High IQGAP3 expression level was significantly related to clinical stage (p = 0.001), T category (p = 0.002), N category (p = 0.001), locoregional recurrence (p = 0.002), distant metastasis (p = 0.001), and vital status (p = 0.001). Univariate and multivariate statistical analysis showed that IQGAP3 expression was an independent prognostic factor among all 257 breast cancer patients in our cohort (p = 0.003, p = 0.001). Subgroup analysis revealed IQGAP3 expression correlated with radioresistance and was also an independent predictor of radiotherapy outcome.Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy.

BackgroundTo compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Patients and MethodsOne thousand three hundred twenty four patients with newly-diagnosed NPC treated with IC+CCRT or IC+RT were enrolled. Progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRFS), and acute toxicities during radiotherapy were compared using propensity score matching (PSM). A nomogram was developed to predict the 3- and 5-year PFS with or without concurrent chemotherapy (CC).ResultsPSM assigned 387 patients to the IC+CCRT group and IC+RT group, respectively. After 3 years, no significant difference in PFS (84.7 vs. 87.5%, P = 0.080), OS (95.5 vs. 97.6%, P = 0.123), DMFS (89.7 vs. 92.8%, P = 0.134), or LRFS (94.0 vs. 94.1%, P = 0.557) was noted between the groups. Subgroup analysis indicated comparable survival outcomes in low-risk NPC patients (II–III with EBV DNA

Background: Given the growing evidence that sarcopenia is associated with toxicity and survival in various cancers, we investigated its significance in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). Methods: In this retrospective analysis, we studied 862 NPC patients who had received CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography (CT) simulation scans at the third cervical vertebral level. Receiver-operating characteristic curve analyses were used to determine the optimal cutoff values. Propensity score matching (PSM) was applied to develop comparable cohorts of patients with or without sarcopenia. Results: A total of 862 patients were included as the primary cohort, and 308 patients were matched and regarded as the matched cohort. In the primary cohort, the 5-year overall survival (OS), locoregional recurrence-free survival, and distant metastasis-free survival (DMFS) rates for the sarcopenia group versus non-sarcopenia group were 78.2% versus 93.6% ( p

Purpose: It was reported that the novel preoperative systemic immune-inflammation index (SII) can predict survival in cases of many malignant tumors. However, the prognostic significance of preoperative SII in breast cancer remains unclear. The purpose of this study was to investigate the relationship between SII and survival in breast cancer patients.Methods: Breast cancer patients (1,026) who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. The SII was determined using the following formula: neutrophil count × platelet count/lymphocyte count. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for SII. Propensity score matching (PSM) was applied to develop comparable cohorts of high SII group and low SII group.Results: A total of 1,026 patients were included as the primary cohort, and 894 patients were matched and regarded as the matched cohort. Patients were divided into two groups based on SII value: SII 601.7. In the primary cohort, the 5-years overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) rates for high SII group and low SII group were (85.6% vs. 91.3%, P = 0.016), (95.8% vs. 96.4%, P = 0.684), and (83.5% vs. 90.6%, P = 0.007), respectively. Univariate analysis showed that histological type, T stage, N stage, PR, HER2, Ki67, and SII all showed significant associations with OS; and histological type, T stage, N stage, and SII all showed significant associations with DMFS. Multivariate survival analysis revealed that SII can independently predict OS (P = 0.017) and DMFS (P = 0.007). Similar results were found in PSM cohort.Conclusions: Preoperative SII may be a reliable predictor of OS and DMFS in patients with operable breast cancer to provide personalized prognostication and assist in formulation of the clinical treatment strategy.

Purpose: Whether or not skeletal muscle mass (SMM) depletion, known as sarcopenia, has significant negative effects on the prognosis of patients with head and neck cancer (HNC) is both new and controversial. In this meta-analysis, we aimed to determine the prognostic significance of sarcopenia in HNC.Methods: We searched PubMed, the Cochrane Library, Embase, and Web of Science, which contain trial registries and meeting proceedings, to identify related published or unpublished studies. We used the Newcastle–Ottawa Scale (NOS) to appraise the risk of bias of the included retrospective studies. Pooled hazard ratios (HR) and the I2 statistic were estimated for the impact of sarcopenia on overall survival (OS) and relapse-free survival (RFS).Results: We analyzed data from 11 studies involving 2,483 patients (39.4% on average of whom had sarcopenia). Based on the univariate analysis data, the sarcopenia group had significantly poorer OS compared to the non-sarcopenia group [HR = 1.97, 95% confidence interval (CI): 1.71–2.26, I2 = 0%]. In the cutoff value subgroup, group 1, defined as skeletal muscle index (SMI) of 38.5 cm2/m2 for women and 52.4 cm2/m2 for men (HR = 2.41, 95% CI: 1.72–3.38, I2 = 0%), had much poorer OS. In the race subgroup, the results were consistent between the Asia (HR = 2.11, 95% CI: 1.59–2.81) and non-Asia group (HR = 1.92, 95% CI: 1.64–2.25). The sarcopenia group also had significantly poorer RFS (HR = 1.74, 95% CI: 1.43–2.12, I2 = 0%).Conclusions: Presence of pre-treatment sarcopenia has a significant negative impact on OS and RFS in HNC compared with its absence. Further well-conducted studies with detailed stratification are needed to complement our findings.

Background: To investigate the significance of the prognostic nutrition index (PNI) as a predictor of survival and guide for treating T1-2N1 breast cancer.Methods: Patients with T1-2N1 breast cancer (N = 380) who underwent a mastectomy at our center were studied. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm3). The cutoff for the PNI was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the PNI and the clinicopathologic characteristics were analyzed using Pearson's χ2 test. Survival curves were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model.Results: Subgroup analyses of patients with low PNI value (≤52.0) and high PNI value (>52.0) showed that a high PNI was significantly associated with HER2 status, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), and KI 67 status. The OS of patients with a high PNI was significantly better than that of patients with a low PNI. We then conducted subgroup analyses based on PNI and radiotherapy. Among patients who received radiotherapy, the OS of those with a high PNI was significantly better than that of patients with a low PNI. Among patients with a high PNI, the OS of those who received radiotherapy was better than that of the patients who did not receive radiotherapy. However, among the patients with a low PNI, the OS of those who received radiation was worse than that of patients who did not receive radiotherapy. The Kaplan–Meier survival analysis and the multivariate analysis of patients with T1-2N1 breast cancer who received radiotherapy showed PNI independently predicted OS.Conclusions: The preoperative PNI may be a reliable predictor of OS of patients with operable T1-2N1 breast cancer, with the capacity to provide a personalized prognosis and facilitate the development of clinical treatment strategies. However, radiotherapy did not achieve satisfactory outcomes in patients with PNI ≤52.0; thus, further studies on treatment optimization are needed.

Background: Nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) frequently develop low skeletal muscle mass (SMM), but, little is known about the impacts of low SMM on health-related quality of life (QOL).Methods: We retrospectively assessed 56 patients with locoregionally advanced NPC enrolled in a prospective trial. Low SMM was determined on routine computed tomography simulation (CT-sim) scans taken before radiotherapy, at the third cervical (C3) vertebral level with validated sex-specific cutoffs. QOL was assessed using the World Health Organization Quality of Life Questionnaire-100 at baseline and after 3 weeks. Pain was scored every 24 h using a numerical rating scale (NRS). Characteristics related to low SMM were identified by logistic regression. The chi-square test was used to examine the association of low SMM with QOL and pain.Results: Of the 56 participants (mean age 44.20 ± 10.93 years), over half (60.71%) developed low SMM. Patients with low SMM were more likely to be older (P = 0.035), male (P = 0.066), have a lower body-mass index (BMI; P = 0.091), and have a higher pain score (P = 0.001). Older age (hazard ratio [HR] = 1.788, P = 0.016), being male (HR = 3.145, P = 0.010), lower BMI (HR = 0.761, P = 0.033), and lower prognostic nutritional index (HR = 0.186, P = 0.034) were associated with higher risk of low SMM. Low SMM was associated with poorer baseline QOL scores (P = 0.072), especially in the physical domain (P = 0.002) and its three facets: pain (P = 0.003), energy (P = 0.021), and sleep (P = 0.007). Low SMM was also associated with significantly worse QOL scores (P = 0.006) at 3 weeks, especially in the physical (P = 0.002), psychological (P = 0.046), independence (P = 0.003), social domains (P = 0.023), and in general health condition (P = 0.043). For pain score, low SMM group had worse overall changes from baseline to week 3 (P = 0.011).Conclusions: The incidence of low SMM, as evaluated using routine CT-sim scans, is high in patients receiving CCRT for locoregionally advanced NPC. Low SMM results in poorer QOL and higher pain scores, which underscores the requirement for nutritional and functional interventions to address low SMM early in the treatment course.

Abstract Background We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). Methods A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM). Results In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer.Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients.Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score 30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score.Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists.

Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3+ immune cells and the relationship of both factors to survival in nasopharyngeal carcinoma (NPC) patients. A total of 209 NPC patients treated between 1991 and 2000 were included. Pairs of TMAs were immunohistochemically stained with PD-L1 and CD3. Survival analysis was evaluated according to PD-L1 status and the spatial distribution of CD3+ immune cells in the primary lesion microenvironment. PD-L1 staining was observed on tumor cells and tumor-infiltrating immune cells (TILs); however, PD-L1-positive immune cells were more common (98/209) than PD-L1-positive tumor cells (68/209). Limited numbers of intra-tumoral CD3+ T cells (median number: 20) were detected. Patients with higher CD3+ T cell infiltration, both intratumorally and peritumorally, had higher PD-L1 expression on tumor cells (both p < 0.001) and immune cells (p = 0.002 and p < 0.001, respectively). Increasing intratumoral CD3 infiltration was correlated with increased overall survival (OS) (p = 0.008) and disease-free survival (DFS) (p = 0.003). Nevertheless, patients with low levels of peritumoral TILs showed superior OS (p = 0.557) and DFS to those with higher levels of peritumoral TILs (p = 0.671). Moreover, type classification based on intratumoral CD3 infiltration and tumor cell PD-L1 expression was an independent prognostic factor for NPC patients. PD-L1 expression on tumor cells is a favorable prognosis factor in NPC patients with pre-existing intratumor-infiltrating lymphocytes.

Numerous studies have shown Kinesin family member 20A (KIF20A) may play a critical role in the development and progression of cancer. However, the clinical value of KIF20A in nasopharyngeal carcinoma (NPC) is unknown. Here, we investigated the expression pattern of KIF20A in NPC and its correlation with clinicopathological features of patients.Real-time PCR and Western blotting were used to quantify KIF20A expression in NPC cell lines and clinical specimens compared with normal controls. KIF20A protein expression was also examined in archived paraffin embedded tumor samples from 105 patients with pathologically confirmed NPC by immunohistochemistry (IHC). Statistical analyses were applied to assess the associations between KIF20A expression and the clinicopathological features and survival outcomes. Effects on migration and invasion were assessed by wound healing and transwell invasion assays after KIF20A silencing.KIF20A was significantly overexpressed at both the mRNA and protein levels in NPC cell lines and human tumor tissues. 45/105 (42.9%) of NPC specimens expressed high levels of KIF20A among the KIF20A detectable cases. Statistical analysis revealed that high KIF20A expression was significantly associated with gender (P = 0.046), clinical stage (P

The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients).The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

BACKGROUND: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. METHODS: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. RESULTS: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis) or patients with proximal gastric cancer (P=0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis). CONCLUSIONS: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

INTRODUCTION: Ki-67 expression is a biomarker for proliferation. Its prognostic value is recognized in breast cancer (BC) patients with negative axillary nodes, but is less clear in BC patients with positive axillary lymph nodes. METHODS: We retrospectively reviewed the medical records of 1131 Chinese BC patients treated from January 2002 to June 2007 and 450 patients met the inclusion criteria: positive nodes, adjuvant therapy, and complete biomarker profile (estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki-67). Univariate and multivariate regression analysis were used to correlate biomarkers and tumor characteristics with metastasis free survival (MFS) and overall survival (OS). RESULTS: Median follow-up time was 46 months (range 5-76 months). The Ki-67 expression was associated significantly with histological grade, ER, PR, HER2, and P53 status (P

OBJECTIVE: The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients. METHODS: The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival. RESULTS: Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5-168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values

It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P

BackgroundWhether the expression of Golgi phosphoprotein 3 (GOLPH3) correlates with esophageal cancer tumorigenesis is currently unclear. The aim of this study was to examine GOLPH3 expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance.MethodsDifferences in the expression of GOLPH3 at the mRNA and protein level were examined via quantitative reverse transcriptase PCR and western blotting, respectively. GOLPH3 expression levels in ESCC tissue were determined through immunohistochemistry, and were compared in accordance with specific clinicopathological features of the patients and tissue specimens. Factors associated with patient survival were also analyzed.ResultsA notably higher level of GOLPH3 expression was found in ESCC cell lines and tissues at both mRNA and protein levels. High expression of GOLPH3 in ESCC patients was positively associated with clinical stage, TNM classification, histological differentiation and vital status (all PConclusionsExperiments demonstrated potential involvement of GOLPH3 in the development, differentiation, and tumorigenesis of ESCC, and concludes the possibility of its use as a diagnostic and prognostic marker in patients with ESCC.