Recurrence-free Survival Time Research Articles

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect

Objective: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance. Patients and Methods: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate. Results: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015). Conclusion: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

Impact of squamous and/or glandular differentiation on recurrence and progression following transurethral resection for non-muscle invasive urothelial carcinoma of bladder.

The aim of the present study was to investigate the impact of squamous and/or glandular differentiation on the recurrence and progression in patients with nonmuscle invasive urothelial carcinoma of bladder (NMIUCB) following transurethral resection (TURBT). A total of 869 patients with NMIUCB who had been treated with TURBT at The Second Hospital of Tianjin Medical University (Tianjin, China) between January 2006 and January 2011 were retrospectively selected for the present analysis. Associations among squamous and/or glandular differentiation with other clinical and pathological features were assessed by the χ2 test. Recurrence-free survival (RFS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed through a Cox's proportional hazards regression model. Among the 869 patients, 232 (26.7%) patients had squamous and/or glandular differentiation. High grade tumors were more common in patients with squamous and/or glandular differentiation compared with those with pure urothelial carcinoma of bladder (P<0.001). Associations between age (P=0.115), sex (P=0.184), tumor size (P=0.223), tumor multiplicity (P=0.108), pathological tumor stage (P=0.909) and squamous and/or glandular differentiation were not observed to be statistically significant. There was a significant tendency towards higher recurrence rate and shorter RFS time in patients with squamous and/or glandular differentiation. However, no statistically significant differences were observed in progression rate and PFS between the two groups. The multivariate Cox regression analysis, identified squamous and/or glandular differentiation as an independent prognostic predictor of recurrence (hazard ratio =1.46, 95% confidence interval=1.10–1.92, P=0.008). In the present study, the presence of squamous and/or glandular differentiation was associated with a higher recurrence rate and shorter RFS time in patients with NMIUCB. Squamous and/or glandular differentiation is therefore an independent prognostic predictor of recurrence.

Retrospective review of FOLFIRINOX in local advanced pancreatic cancer: Single institution experience.

e15714 Background: Although combination of fluorouracil, irinotecan, Leucovorin and oxaliplatin [FOLFIRINOX] significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine based on ACCORD trial, the efficacy and toxicities may be different in non-metastatic setting. We reviewed our institution’s experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC). Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with LAPC and receiving between June 2010 and July 2015, with at least one year of follow up from diagnosis, at University of Alabama at Birmingham. Results: Total of 41 patients with ECOG performance scale of 0 or 1, who underwent neoadjuvant chemotherapy with FOLFIRINOX were assessed for clinical and pathological characteristics. Median age was 61 years (range 38-81) with 23 (56.1%) males, 28 (68.3%) Caucasians and 16 (39.0%) underwent surgery (whipple operation) post-neoadjuvant. Median OS (time of diagnosis to last follow up/death) is 83.5 months for whole cohort, survival rates are 94.9% at 1 year, 58.4% at 2 year, and 33.3% at 5 year.Median OS for those who underwent surgical resection following the chemotherapy is 38.6 months; 100% at one year, 85.1% at 2 year, 55.3% at 5 year; while median OS for those who did not undergo surgery is 21.8 months; 91.7% at one year, 41.5% at 2 year, 20.7% at 5 years. Among those who underwent surgery, the median recurrence free survival (time from surgery to relapse/progression) is 19.9 months with liver being common recurrence site (81%). There was no post-operative mortality in 30 days. Grade 3-4 toxicity occurred in 46% ( vomiting (12%), fatigue (28%) and neutropenia (54%), febrile neutropenia (9%)). There is a significant difference between surgery and non-surgery groups (p = 0.012) for improved OS by log-rank test. Conclusions: Neoadjuvant FOLFIRINOX treatment associated with high response rates leading to surgical resection in our cohort. Patients who underwent neoadjuvant chemotherapy followed by resection for LAPC have statistically significant improved OS compared to those who did not.

A low serum Tat-interacting protein 30 level is a diagnostic and prognostic biomarker for hepatocellular carcinoma.

The present study aimed to evaluate the diagnostic and prognostic value of Tat-interacting protein 30 (HTATIP2/TIP30) levels alone and in combination with α-fetoprotein (AFP) for the evaluation of hepatocellular carcinoma (HCC) patients. ELISA and immunohistochemical measurements on the serum and tissue of HTATIP2/TIP30 protein from HCC patients and normal controls were made. Receiver operating characteristic (ROC) curve analyses of AFP and HTATIP2/TIP30 were performed, as well as logistic regression analysis of APF combined with HTATIP2/TIP30. Log-rank analysis was used to correlate the prognosis with various levels of HTATIP2/TIP30. HTATIP2/TIP30 levels were significantly lower in the HCC group compared with the control group (4.50±2.63 vs. 9.50±2.04 ng/ml, P<0.001). ROC analysis revealed an optimal cut-off point at 7.27 ng/ml HTATIP2/TIP30 for separating the HCC from the control groups. The sensitivity and specificity were 84.6 and 93.7% (P<0.001), respectively. ROC areas of HTATIP2/TIP30 (0.928, P<0.001) were significantly higher than those for AFP (P<0.001). The area under the curve of the HTATIP2/TIP30 and AFP combination was 0.950 (P<0.001). Log-rank tests revealed that the recurrence-free survival time of the group with HTATIP2/TIP30>5.71 ng/ml was significantly higher than that of the control group (P<0.001). This is the first study to demonstrate that HTATIP2/TIP30 levels in serum may be an effective biomarker for the diagnosis and prognosis of HCC.

Utilization and impact of adjuvant chemotherapy among patients with resected stage II colon cancer: a multi-institutional analysis

BackgroundThe use of chemotherapy among patients with stage II colon cancer is controversial. We aimed to define the utilization and factors associated with the receipt of chemotherapy and the impact of chemotherapy on long-term prognosis among a large, multiinstitutional cohort of patients. Materials and methodsWe identified 876 patients who underwent resection for stage II colon cancer between 2004 and 2013 at one of seven participating institutions. Overall survival (OS) and recurrence-free survival (RFS) time was calculated from the date of the index procedure to the date of death. ResultsA total of 163 patients (18.6%) received adjuvant chemotherapy and this utilization decreased over time (P = 0.003). Younger age (P < 0.001), margin positivity (odds ratio [OR], 12.16; 95% confidence interval [CI]: 2.57-57.52; P = 0.002), and the presence of perineural invasion (OR, 1.24; 95% CI: 1.07-1.44; P = 0.005) increased the likelihood of receiving chemotherapy. Receipt of chemotherapy was associated with improved median OS and RFS. After controlling for all factors, the addition of oxaliplatin to 5-fluorouracil did not affect survival, and there was no difference in OS (hazard ratio [HR], 0.74; 95% CI: 0.27-2.06; P = 0.57) or RFS (HR, 0.71; 95% CI: 0.32-1.58; P = 0.88) with adjuvant treatment, including for patients with high-risk features (OS—HR, 0.63; 95% CI: 0.33-1.19; P = 0.15; RFS—HR, 0.77; 95% CI: 0.32-1.86; P = 0.56). ConclusionsThe utilization of chemotherapy has declined over time after resection for stage II colon cancer. Chemotherapy was not independently associated with improved OS or RFS in this study group, including in patients with high-risk features. Future prospective studies should strive to identify the subset of stage II colon cancer patients that will benefit the most from the addition of adjuvant chemotherapy.

Long noncoding RNA LINC01296 is associated with poor prognosis in prostate cancer and promotes cancer-cell proliferation and metastasis.

Background/purposeLong noncoding RNAs (lncRNAs) have emerged as important regulators and biomarkers of tumor development and progression. This study investigated the clinical significance, biological functions, and underlying mechanisms of long intergenic non-protein-coding RNA 1296 (LINC01296) in prostate cancer.Materials and methodsLINC01296 expression in prostate cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between LINC01296 expression and clinicopathologic characteristics of prostate cancer was analyzed using Kaplan–Meier analysis and the Cox proportional-hazard model. Small interfering RNA was used to suppress LINC01296, and knockdown efficiency was examined by qRT-PCR. Cell Counting Kit 8 assay, colony-formation assay, migration and invasion assays, and Western blot assay were used to explore the role of LINC01296 in tumor progression further.ResultsLINC01296-expression level was higher in prostate cancer tissues and prostate cancer cells than in adjacent nontumor tissues and immortalized normal prostate stromal WPMY1 cells. LINC01296 expression was correlated with preoperative prostate specific antigen (P=0.002), lymph-node metastasis (P=0.035), Gleason score (P<0.001), and tumor stage (P=0.036). Patients with higher LINC01296 expression displayed advanced clinical features and shorter biochemical recurrence-free survival time than those with lower LINC01296 expression. Multivariate analysis showed that LINC01296 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Additionally, LINC01296 knockdown inhibited prostate cancer-cell proliferation, migration, and invasion, demonstrated in an in vitro study involving regulation of PI3K–Akt–mTOR signaling and epithelial–mesenchymal transition.ConclusionThe results demonstrated that LINC01296 is a novel molecule involved in prostate cancer development and progression, and thus is a potential biomarker of prognosis.

Hormone receptor status and survival of medullary breast cancer patients. A Turkish cohort.

Objectives:To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC).Methods:Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis.Results:Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05).Conclusion:Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma.

Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n=140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n=89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p=0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p<0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk.

The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma.

BackgroundLung adenocarcinoma (AD) is a common variant of non-small cell lung cancer (NSCLC). Programmed cell death protein 1/programmed cell death ligand 1 (PD1/PD-L1) are promising immunotherapy targets and its expression may be an important biomarker of predicting clinical response. In this study, we evaluated PD-L1 expression in conjunction with clinicopathological characteristics and outcomes in resected lung adenocarcinoma.ResultsThis study included 133 cases of lung adenocarcinoma. PD-L1 expression rate in lung adenocarcinoma was 16.5% at the mRNA level and 13.5% at the protein level, and the kappa coefficient of the two examination methods was 0.824 (P = 0.219, highly correlated). PD-L1 was highly expressed in male patients and smokers with lung adenocarcinoma (P = 0.019 and 0.002, respectively), while no associations were identified between PD-L1 expression and age, tumor size, clinical stage, positive pleural invasion, lymph node metastasis, or therapy methods. Overexpression of PD-L1 was a significant indicator of shorter recurrence free survival time and overall survival (P = 0.000 and 0.000, respectively). Multivariate analysis revealed that PD-L1 expression was an independent risk factor for poor recurrence free survival and overall survival (P = 0.009 and 0.016, respectively).Materials and MethodsExpression of PD-L1 was examined with immunohistochemistry, using the VENTANA PD-L1 (SP263) rabbit monoclonal antibody. mRNA levels of PD-L1 were evaluated using in situ hybridization.ConclusionsPD-L1 overexpression is more frequently observed in male patients and smokers in lung adenocarcinoma. PD-L1 expression is an indicator of worse prognosis in surgically resected lung adenocarcinoma patients.

High baseline levels of interleukin-8 in leukocytes and urine predict tumor recurrence in non-muscle invasive bladder cancer patients receiving bacillus Calmette–Guerin therapy: A long-term survival analysis

ABSTRACTBacillus Calmette–Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) can significantly reduce the risk of recurrence and progression. However, BCG therapy may fail in up to a half of treated patients and may also cause toxicities. Biomarkers to predict the effectiveness of BCG therapy are desired to pre-select patients for BCG therapy to maximize efficacy while avoid unnecessary toxicity. Twelve cytokines were measured in 100 blood and 112 urine samples using cytokine antibody array and correlated with recurrence-free survival in overall and BCG-treated NMIBC patients. Of the 12 cytokines, interleukin (IL) -2, IL-8, IL-10, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-γ were measurable in more than 30% of peripheral blood leukocyte (PBL) samples. Only IL-8 in PBL was found to be significantly associated with tumor recurrence, especially in those who receiving BCG therapy (hazard ratio [HR] = 4.24; 95% confidence interval [95%CI] = 1.65–10.88; p = 0.003). The median recurrence-free survival time for BCG-treated patients with high baseline IL-8 levels were much shorter than those with low IL-8 levels (7.9 vs. >78.4 mo, p = 0.004). Furthermore, consistent associations between urinary IL-8 levels and tumor recurrence in patients receiving BCG therapy were observed in 58 pre-BCG and 54 long-term post-BCG-treated urine samples (both p ≤ 0.005). High urinary baseline IL-8 level also predicted shorter time to tumor recurrence in NMIBC patients (both p ≤ 0.004). By using antibody array-based technology in two separate cohorts of NMIBC patients, we found that PBL and urinary baseline IL-8 levels were significantly associated with tumor recurrence after BCG therapy.

Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined. SUIT-2 pancreatic cancer cells were subcutaneously injected into nude mice alone or with PSCs and the size of the tumors was monitored. Kindlin-2 expression was observed in PDAC and the peritumoral stroma. Stromal kindlin-2 expression was associated with shorter recurrence-free survival time after R0 resection. Knockdown of kindlin-2 resulted in decreased proliferation, migration, and cytokine expression in PSCs. The PSC-induced proliferation and migration of pancreatic cancer cells were suppressed by kindlin-2 knockdown in PSCs. In vivo, co-injection of PSCs increased the size of the tumors, but this effect was abolished by kindlin-2 knockdown in PSCs. In conclusion, kindlin-2 in PSCs promoted the progression of pancreatic cancer.

Overexpression of HER-2 Protein is a High-Risk Factor for Patients with Surgically-Resected Stage T3 Gastric Adenocarcinoma.

Factors associated with tumor recurrence and death in stage T3-gastric adenocarcinoma (GA) after surgical resection remain unclear. In this study, we investigated whether patients with overexpression of epidermal growth factor receptor 2 (HER-2) comprised a high-risk group. The immunohistochemistry data of HER-2 protein expression from 633 surgically-resected T3-GA tissues were collected and then retrospectively analyzed by Chi-square test, Kaplan-Meier curve, and log rank test as well as univariate and multivariate analyses. Patients with HER-2 overexpression had increased recurrence rates and decreased median recurrence free survival times (MRFST) compared to those with low expression of HER-2 (76.3% vs. 65.4%, p = 0.004; and 18 vs. 26 months, p = 0.002, respectively). Conversely, overall survival rates and median overall survival times (MOST) were decreased in these patients (23.3% vs. 35.7%, p = 0.001 and 26 vs. 36 months, p = 0.001, respectively). HER-2 overexpression, lymph node metastasis (pN1-pN3), distant metastasis, and R1 resection margin were identified as independent prognostic factors for shorter MRFST and MOST in patients with surgically-resected T3-GA. Overexpression of HER-2 is a simple and reliable predictor for increased recurrence and poorer survival in patients with T3-GA following surgical resection. As such, these patients may benefit from trastuzumabbased therapy.

Recurrence and survival factors analysis of 171 cases of sacral chordoma in a single institute.

To evaluate postoperative recurrence, survival and metastasis results and related factors of sacral chordoma. Between 1978 and 2013, a total of 171 patients with sacral chordoma were diagnosed at our institution and 162 cases underwent operation. The clinical characteristics, treatment and outcomes of all these patients were reviewed. The 3-year recurrence free survival rate was 83.1%. The median recurrence free survival time was 73±7.8months. Tumor level in sacrum and surgical margin were significant factors influencing recurrence. Recurrence was significant factor influencing metastasis. One hundred and fifty-seven cases were followed up for an average of 55.6months. 135 cases (86%) survived, 37 cases (23.6%) developed recurrence, and 17 cases (10.8%) developed metastasis. The overall 5- and 10-year survival rate was 88.3% and 59.6%, respectively. Age (p=0.037) and metastasis (p=0.001) were significant factors influencing survival. The 3-year recurrence free survival rate was 80.1%. The median recurrence free survival time was 69±12.7months. Tumor level in sacrum (p=0.035) and surgical margin (p=0.009) were significant factors influencing recurrence. Seventeen cases (10.8%) had metastasis. Recurrence (p=0.016) was significant factors influencing metastasis. Sacral chordoma tended to occur in elderly male patients and locate below sacral 3 level. The recurrence rate was high, especially for tumor above sacral 3 level. Wide surgical margin is very important for good local control. The patients with metastasis had poor prognosis.

Assessment value of preoperative platelet-lymphocyte ratio in the prognosis of patients with gastric mixed adenoneuroendocrine carcinoma

To explore the prognostic assessment value of preoperative blood platelet-lymphocyte ratio (PLR) in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) treated with radical surgery. Clinical and pathological data of 84 gMANEC patients who underwent radical resection from 2006 to 2016 in Department of Gastric Surgery, Fujian Medical University Union Hospital were analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PLR for predicting prognosis. The Cox proportional hazards regression model was used to identify prognostic factors of gMANEC. All the patients underwent D2 lymph node dissection, including 26 cases of distal subtotal gastrectomy and 58 cases of total gastrectomy. The postoperative pathological TNM stage system(pTNM) demonstrated that the patients of stage I(, II(, and III( were 9(10.7%), 14(16.7%), and 61(72.6%) cases, respectively. The median follow-up time was 40(3 to 96) months. The recurrence rate was 41.7%(35/84). The median time to recurrence was 10 (1 to 40) months, and 82.9%(29/35) patients experienced recurrence within the first 2 years after operation. The median overall survival time was 27(3 to 39) month, and the median recurrence-free survival time was 21 (1 to 96) months. The 1-, 3-, and 5-year overall survival(OS) rates were 87.6%, 56.6%, and 47.4%, respectively, and the 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 70.5%, 50.7%, and 44.9%, respectively. The best cutoff value of the PLR for predicting prognosis was 133 through ROC curve, which categorized all the patients into low PLR group (≤133) comprising 28 patients and high PLR group (>133) comprising 56 patients. The tumor recurrence rate was significantly higher in high PLR group (50.0%, 28/56) than that in low PLR group(25.0%, 7/28)(P=0.028). The live metastasis rate was significantly higher in high PLR group(35.7%, 20/56) than that in low PLR group(10.7%, 3/28)(P=0.015). Cox regression analysis showed that only pTNM stage (P=0.003) was independent prognostic factors of OS, while both pTNM stage (P=0.000) and blood PLR (P=0.015) were independent prognostic factors of RFS. gMANEC patients with high preoperative PLR tend to present recurrence and metastasis, especially to present live metastasis, so they should be kept under surveillance more frequently after surgery.

SCLCの予後に対する異なる放射線療法の組み合わせ方案の影響【JST・京大機械翻訳】

Objective To investigate the effects of different chemoradiotherapy (CRT) schemes on the prognosis of extensive-stage small-cell lung cancer (SCLC). Methods A retrospective analysis was performed in 322 patients with extensive-stage SCLC who were admitted to our hospital from 2011 to 2015.All patients received standard EP/CE (etoposide+ cisplatin/carboplatin) chemotherapy. According to RECIST criteria, the efficacy of chemotherapy was divided into complete response, partial response, stable disease, and progressive disease (PD). A total of 232 patients without PD after chemotherapy were enrolled as subjects and divided into radiotherapy group (n=187) and non-radiotherapy group (n=45). The patients undergoing radiotherapy were further divided into early radiotherapy group (before 3 cycles of chemotherapy, n=65) and late radiotherapy group (after 3 cycles of chemotherapy, n=122), or concurrent CRT group (n=45) and sequential CRT group (n=142). The survival rates were analyzed using the Kaplan-Meier method. Between-group comparison was made by log-rank test. The Cox regression model was used for multivariate prognostic analysis. Results In all the patients, the median overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) time was 13.2, 8.7, and 14.6 months, respectively. The non-radiotherapy group had significantly shorter median OS, PFS, and LRFS time than the radiotherapy group (8.7 vs. 15.0 months, P=0.00; 5.6 vs. 9.8 months, P=0.00; 5.9 vs. 19.2 months, P=0.00). There were no significant differences in median OS, PFS, or LRFS time between the early radiotherapy group and the late radiotherapy group (15.4 vs. 14.6 months, P=0.720; 8.0 vs. 10.8 months, P=0.426; 19.2 vs. 18.1 months, P=0.981). The concurrent CRT group had significantly longer median OS time than the sequential CRT group (19.4 vs. 13.8 months, P=0.036), while there were no significant differences in median PFS or LRFS time between the two groups (10.8 vs. 9.8 months, P=0.656; 19.8 vs. 17.8 months, P=0.768). Generally, patients undergoing radiotherapy had increased incidence rates of adverse reactions than those without radiotherapy (P=0.038). However, the incidence rates of grade ≥3 adverse reactions were similar between the two groups (P=0.126). Conclusions In the treatment of extensive-stage SCLC, thoracic radiotherapy improves the treatment outcomes without increasing the incidence rates of severe adverse reactions. When to receive radiotherapy has nothing to do with the prognosis. Concurrent CRT may further improve the treatment outcomes, which still needs further studies. Key words: Carcinoma, small cell lung/radiotherapy; Carcinoma, small cell lung/chemotherapy; Radiochemotherapy, concurrent; Radiochemotherapy, sequential; Prognosis

Downregulation of mir-23b in plasma is associated with poor prognosis in patients with colorectal cancer.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs have potential as cancer biomarkers. The main objective of the present study was to assess the effect of miRNA-23b (miR-23b) expression in plasma on the diagnosis and prognosis of colorectal cancer (CRC). Reverse transcription-quantitative polymerase chain reaction (PCR) was used to measure miR-23b expression levels, and methylation-specific PCR was used to test the promoter methylation status. Subsequently, the expression level of miR-23b in plasma samples was compared between CRC patients and healthy control individuals. The miR-23b expression levels were significantly lower in CRC cells and primary CRC tissues than in nonmalignant colorectal tissues (P<0.001). It was also shown that miR-23b expression is downregulated by promoter methylation and can be restored by demethylation agent treatment. miR-23b was significantly decreased in plasma samples from CRC patients compared with the healthy control individuals (P<0.001). The value of the area under the receiver operating characteristic curve was 0.842 (sensitivity, 84.38%; specificity, 77.08%; 95% confidence interval, 0.763-0.922). Low plasma miR-23b expression was significantly associated with clinical stage, tumor depth, distant metastasis and tumor recurrence. CRC patients with low miR-23b expression in plasma exhibited a shorter recurrence-free survival time and poorer overall survival rate. The present results suggested that the downregulation of miR-23b in the plasma has the potential to be a diagnostic and prognostic biomarker in CRC.

Paraoxonase 3 inhibits cell proliferation and serves as a prognostic predictor in hepatocellular carcinoma.

Paraoxonase 3 (PON3) exerts prominent anti-inflammation and anti-oxidation properties mainly at the cellular level, and is primarily expressed in the liver. However, its role in HCC remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of PON3 in HCC. PON3 mRNA and protein levels were respectively determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) of tissue microarray. We found that PON3 was downregulated in most HCCs. Kaplan-Meier and log-rank test showed that PON3 downregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in all HCC patients, especially early-stage HCC patients. Cox regression analysis revealed that the PON3 downregulation was an independent risk factor for RFS and OS. Gain- and loss-of-function experiments revealed that PON3 suppressed cell proliferation in vivo and in vitro, which was attributed to its cell-cycle arrest effect. In addition, microarray analysis showed that some pro-proliferative genes were elevated when PON3 was knockdown, and these genes possibly involved in the underlying mechanisms. In conclusion, our studies reveal the cell proliferation inhibitory function of PON3 and offer a potential prognostic predictor and therapeutic target for HCC.

Immune signature of urothelial cancer associated with grade, recurrence, and invasion

BackgroundUrothelial carcinoma (UC) is one of most common genitourinary malignancy and the spectrum of disease ranges from in situ lesions to muscle-invasive cancers. The non–muscle-invasive lesions have tendency to recur or progress to muscle-invasive disease. The study of the immune profile may identify immune determinants associated with high-grade, recurrence, and invasion in patients with UC. MethodsPathway-focused RT2 profiler arrays were used to screen patients with UC for dysregulation of candidate genes of Th1-Th2-Th3 and NFκB pathways, which were then validated by real-time polymerase chain reaction on tumor samples and correlated with grade, recurrence, and invasion of tumors to identify their role in predicting behavior of the tumor. The cytokines found associated with recurrence were then validated in urine of patients with UC. ResultsIFNγ, IL2, IL4, IL10, IL17, CCL7, CTLA4, and SPP1 of the cytokine pathway and TLR4, TLR3, RELA, NFκB1, and MYD88 of the NFκB pathway were found differentially expressed in patients with urothelial cancer by array and quantative real-time polymerase chain reaction. Among these, IL10 and SPP1 were found consistently up-regulated in high-grade, invasive, and recurrent cases and up-regulated IL10 and CTLA4 were found associated with a short recurrence-free survival time (P = 0.001 and P = 0.065). Urinary IL10 concentration was significantly higher in both patients with cancer and cystitis compared with healthy controls, but the difference in concentration between patients with cancer and cystitis patients was not statistically significant. However, urinary CTLA4 concentrations were found to be significantly higher in urothelial cancer patients compared with healthy controls and cystitis cases and found to be associated with poor recurrence-free survival. ConclusionThe study indicates that high urinary CTLA4 concentration raises the index of suspicion of recurrence in a known case of urothelial cancer and may be used as a surveillance marker.

High Tumor Vascular Endothelial Growth Factor Expression Is Associated With Poorer Clinical Outcomes in Resected T3 Gastric Adenocarcinoma.

To investigate the clinical and prognostic significance of high vascular endothelial growth factor (VEGF) expression in resected T3 gastric adenocarcinoma (GA). Data of VEGF expression on 453 patients with resected T3 GA were collected from a single institute in Fuzhou, China. VEGF expression in the resected tumor tissues was evaluated by immunohistochemistry (IHC). Associations between VEGF expression outcomes and prognosis were investigated using by the χ(2) test, Kaplan-Meier plus log-rank test, and univariate and multivariate Cox models. In total, 48.6% (220/453) patients had low VEGF expression (IHC score ≤2+). Patients with high VEGF expression (IHC>2+; 233/453, 51.4%) had significantly poorer median recurrence-free survival time (20 vs 55 months, P < 001) and median overall survival time (28 vs 58 months; P < 001) than patients with low VEGF. High VEGF was associated with higher overall recurrence (68.2% vs 51.4%, P = 2.675 × 10(-4)), poorer overall survival (27.5% vs 47.3%, P = 1.719 × 10(-5)), and increased risk of recurrence (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.33-2.19; P = 2.43 × 10(-5)) and death (HR, 1.80; 95% CI, 1.41-2.3; P = 2.19 × 10(-6)). High VEGF expression is associated with a higher risk of recurrence and shorter survival in resected T3 GA. These findings may provide a foundation for evaluating VEGF-targeted molecular therapies in T3 GA.

Transurethral electric resection plus arterial catheterization chemotherapy for T2a bladder carcinoma

Clinical data of 23 patients with T2a bladder cancer admitted from March 2008 to August 2013 were retrospectively analyzed. Among 23 patients, 11 cases were treated with transurethral resection (TURBT) plus arterial catheterization chemotherapy (study group) and 12 cases were treated with radical cystectomy (control group). The overall survival time and recurrence free survival time of two groups were compared. Patients in study group were followed up for 20-68 months, recurrence occurred in 5 cases (5/11), including 4 cases of invasive recurrence; patients in control group were followed up for 2~86 months, 1 case had superficial recurrent and underwent TURBT, 2 cases dead due to bladder tumor. During the course of chemotherapy, the main adverse effects were digestive reaction (7/11), fever (4/11), bone marrow suppression (2/11), symptomatic treatment was given, which was tolerated. There were no significant differences in overall survival time and recurrence free survival time between two groups (P>0.05). The quality of life of study group was better than that of control group (P<0.05). It is suggested that the arterial interventional chemotherapy combined with transurethral resection for T2a stage invasive bladder cancer has a certain curative effect with the advantage of preservation of bladder function and higher quality of life. Key words: Urinary bladder neoplasms; Drug therapy, interventional; Prognosis