Independent Predictor Of Disease-free Survival Research Articles

Selective use of concurrent chemotherapy in elderly cervical cancer patients treated with definitive radiotherapy: experience from two institutions.

Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy.Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS).Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS.Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.

Predictors of survival in non-metastatic renal cell cancer after surgery: A retrospective analysis

Aim:To investigate the prognostic significance of clinical and pathological factors of non-metastatic renal cell cancer after surgery.Patients and methods:We conducted a retrospective cohort study based on the records of patients with non-metastatic renal cancer submitted to radical or partial nephrectomy between 2000 and 2015 in Salah-Azaiez Institute.Results:Median follow-up was 38 months (interquartile range: 20–64). Five-year overall and disease-free survival were 53.8% and 43.1%. In the multivariate setting, lymph node invasion (p = 0.01), clear cell renal carcinoma subtype (p = 0.014), and tumor necrosis (p = 0.009) were the only independent statistically significant predictors of disease-free survival, while Fuhrman grade (p = 0.025), clear cell renal carcinoma subtype (p = 0.044), and TNM stage (0.041) were the only factors correlated with overall survival.Conclusion:For patients with non-metastatic renal cell carcinoma, independent predictors of disease-free survival and overall survival were clear cell renal cell carcinoma, Fuhrman grade, TNM stage, lymph node invasion, and tumor necrosis. Such information could be used to guide the intensity of follow-up and identify high-risk patients who can be targeted for adjuvant therapy trials.

The combination of histone deacetylase and p53 expressions and histological subtype has prognostic implication in uterine leiomyosarcoma

To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients. The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients. Histone deacetylases 1-4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival. Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.

The Effect of Prognostic Factors and Adjuvant Radiotherapy on Survival in Patients with High-Grade Early-Stage Endometrial Cancer: A Retrospective Clinical Study

BackgroundThis retrospective clinical study aimed to investigate the effect of prognostic factors and adjuvant radiotherapy in patients with high-grade early-stage endometrial cancer on overall survival (OS) and disease-free survival (DFS).Material/MethodsThe medical records of patients diagnosed with high-grade, early stage (I or II) endometrial adenocarcinoma who had received adjuvant radiotherapy after surgery were reviewed.ResultsSeventy-nine patients included 39 patients (49.4%) with stage II endometrial cancer, 25 patients (31.6%) with histologic grade 3 tumors, and 47 patients (59.5%) with endometrial cancer showing lymphovascular space invasion (LVSI). There were 45 patients (57.0%) who received external pelvic radiotherapy with an average dose of 46.0 Gy (range, 11.2–50.4 Gy), and 34 patients (43.0%) received vaginal brachytherapy (VBT) with an average dose of 21.5 Gy (range, 10–36 Gy). Multivariate analysis showed that tumor stage (HR, 4.066; 95% CI, 1.227–13.467; p=0.022) and histologic grade (HR, 16.652; 95% CI, 4.430–62.589; p<0.001) were independent predictors for OS. Increased serum CA-125 levels (HR, 1.136; 95% CI, 0.995–1.653; p=0.047) and histologic grade (HR, 3.236; 95% CI, 1.107–15.156; p=0.015) were independent predictors for DFS. Adjuvant radiotherapy was not found to be significantly associated with improved OS (HR, 1.259; 95% CI, 0.518–3.058; p=0.612) or DFS (HR, 1.056; 95% CI, 0.994–1.123; p=0.078).ConclusionsThis retrospective study showed that in high-grade early-stage endometrial cancer treated with postoperative adjuvant radiotherapy, independent predictors for OS were tumor stage and grade. Adjuvant radiotherapy was not associated with improved OS or DFS.

Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling

Long noncoding RNA (lncRNA) MEG3 has been widely reported to be decreased in a growing list of primary human tumours and play a key role in tumour suppression. However, there are few reports about MEG3 expression and function in oesophagal squamous cell carcinoma (ESCC). Here, we found that MEG3 expression was significantly downregulated in tumour tissues, and its low expression was associated with large tumour size, lymph node metastasis and advanced clinical stage in ESCC patients. Univariate and multivariate analyses revealed low expression of MEG3 as an independent predictor for disease-free survival and overall survival. Cell experiments showed that MEG3 inhibited ESCC cell proliferation, migration and invasion. Subsequently, miR-4261 was identified and confirmed to be the target of MEG3, and MEG3 functions, at least in part, by targeting miR-4261. Additionally, Dickkopf-2 (DKK2), a Wnt/β-catenin signalling inhibitor, was identified to be a target of miR-4261. MEG3 interacted with miR-4261, derepressed DKK2 and blocked the Wnt/β-catenin signalling, thereby inhibiting tumourigenesis and progression in ESCC. In vivo experiments also confirmed this conclusion. Our study for the first time elaborated the critical role of MEG3-miR-4261-DKK2-Wnt/β-catenin signalling axis in ESCC, and MEG3 could represent a novel diagnostic and prognostic biomarker and therapeutic target in ESCC.

A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease-free survival in low-risk breast cancer patients.

A Disintegrin And Metalloprotease 23 (ADAM23), a member of the ADAM family, is involved in neuronal differentiation and cancer. ADAM23 is considered a possible tumor suppressor gene and is frequently downregulated in various types of malignancies. Its epigenetic silencing through promoter hypermethylation was observed in breast cancer (BC). In the present study, we evaluated the prognostic significance of ADAM23 promoter methylation for hematogenous spread and disease‐free survival (DFS). Pyrosequencing was used to quantify ADAM23 methylation in tumors of 203 BC patients. Presence of circulating tumor cells (CTC) in their peripheral blood was detected by quantitative RT‐PCR. Expression of epithelial (KRT19) or mesenchymal (epithelial‐mesenchymal transition [EMT]‐inducing transcription factors TWIST1,SNAI1,SLUG and ZEB1) mRNA transcripts was examined in CD45‐depleted peripheral blood mononuclear cells. ADAM23 methylation was significantly lower in tumors of patients with the mesenchymal CTC (P = .006). It positively correlated with Ki‐67 proliferation, especially in mesenchymal CTC‐negative patients (P = .001). In low‐risk patients, characterized by low Ki‐67 and mesenchymal CTC absence, ADAM23 hypermethylation was an independent predictor of DFS (P = .006). Our results indicate that ADAM23 is likely involved in BC progression and dissemination of mesenchymal CTC. ADAM23 methylation has the potential to function as a novel prognostic marker and therapeutic target.

Does Primary Tumor Side Matter in Patients with Metastatic Colon Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy?

Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed. A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p=0.007) and to have signet ring cell histology (17% vs. 4%, p=0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14months (95% confidence interval [CI] 10.5-17.5) and 36 months (95% CI 27.4-44.6), respectively, versus 16months (95% CI 11.0-21.0) and 69 months (95% CI 24.3-113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS. In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.

18F-FDG and 18F-FAMT PET-derived metabolic parameters predict outcome of oral squamous cell carcinoma

ObjectivesL-3-[18F]-Fluoro-α-methyl tyrosine (FAMT), an amino acid positron emission tomography (PET) tracer, complements [18F]-fluorodeoxyglucose (FDG) in the diagnosis of malignancies. We compared the predictive ability of FAMT PET versus FDG PET regarding metastatic oral squamous cell carcinoma (OSCC) outcomes for distant metastasis, including lymph node metastasis, and identified the relevant metabolic parameters for each.MethodsWe enrolled 160 patients with OSCC who underwent PET/computed tomography using FDG and FAMT before treatment. Outcomes were assessed using clinicopathological characteristics such as the standardized uptake value (SUVmax, SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis or total lesion retention. Univariate and multivariate Cox proportional hazards models were used to identify the independent predictors of disease-free survival (DFS) and overall survival (OS) during an average follow-up time of 1401.7 and 1646.0 days, respectively. Areas under the receiver operating characteristic curves were analyzed for the accuracy and predictive value of imaging parameters.ResultsClinical parameters (excluding age) and PET metabolic parameters were significantly associated with OS. Multivariate analysis showed that an infiltrative growth pattern [p = 0.034, hazard ratio (HR) = 2.30], and the FDG-measured SUVpeak (p = 0.045, HR = 2.45) were independent risk factors for DFS and that lymph node metastasis (p = 0.03, HR = 2.57) and the FAMT-measured MTV (p = 0.004, HR = 3.65) were independent risk factors for OS.ConclusionsIn patients with OSCC, FDG PET predicted DFS, whereas FAMT predicted OS. The two PET tracers, combined with clinical parameters, provide complementary, outcome-related diagnostic information in OSCC.

DNMT3A/3B overexpression might be correlated with poor patient survival, hypermethylation and low expression of ESR1/PGR in endometrioid carcinoma: an analysis of The Cancer Genome Atlas.

Background:DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer. ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors. However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively. The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR expression.Methods:The clinicopathologic information and RNA-Seq expression data of DNMT3A/3B of 544 endometrial cancers were derived from The Cancer Genome Atlas (TCGA) uterine cancer cohort in May 2018. RNA-Seq level of DNMT3A/3B was compared between these clinicopathologic factors with t-test or one-way analysis of variance.Results:DNMT3A/3B was overexpressed in endometrioid carcinoma (EEC) and was even higher in non-endometrioid carcinoma (NEEC) (DNMT3A, EEC vs. NEEC: 37.6% vs. 69.9%, t = −7.440, P < 0.001; DNMT3B, EEC vs. NEEC: 42.4% vs. 72.8%, t = −6.897, P < 0.001). In EEC, DNMT3A overexpression was significantly correlated with the hypermethylation and low expression of the ESR1 and PGR (P < 0.05). The same trend was observed in the DNMT3B overexpression subgroup. In the ESR1/PGR low-expression subgroups, as much as 83.1% of ESR1 and 59.5% of PGR were hypermethylated, which was significantly greater than the ESR1/PGR high-expression subgroups (31.3% and 11.9%, respectively). However, the above phenomena were absent in NEEC, while DNMT3A/3B overexpression, ESR1/PGR hypermethylation, and low ER/PR expression occurred much more often. In univariate analysis, DNMT3A/3B overexpressions were significantly correlated with worse prognosis. In multivariate analysis, only DNMT3A was an independent predictor of disease-free survival (P < 0.05).Conclusions:DNMT3A/3B expression increases progressively from EEC to NEEC and is correlated with poor survival. The mechanisms underlying low ER/PR expression might be distinct in EEC vs. NEEC. In EEC, methylation related to DNMT3A/3B overexpression might play a major role in ER/PR downregulation.

Neoadjuvant Chemotherapy Plays an Adverse Role in the Prognosis of Grade 2 Breast Cancer.

Background: The role of neoadjuvant chemotherapy (NAC) in the prognosis of breast cancer among patients with grade 2 tumors remains unclear. As such, we aimed to explore the relationships between NAC and survival outcomes among patients with grade 2 breast cancer.Materials and Methods: We collected data on 726 breast cancer patients with grade 2 tumors and at least 5-years of follow-up from the date of diagnosis. We then conducted survival analyses to examine the association between NAC and disease-free survival (DFS) and overall survival (OS). The role of NAC in prognosis was further examined in subgroup analyses, with patients stratified according to molecular subtypes, histological grade, ER status, PR status, HER2 status and Ki67 index. We also determined the main sites of local recurrence, as well as these organs involved in distant metastasis among patients receiving NAC. Finally, we analyzed independent predictive factors for DFS and OS using Cox regression analyses.Results: Among patients who received NAC, the prevalence of pathologic complete response (pCR) was 9.87% (23/233), with 32.6% of patients (76/233) experiencing partial response. Survival analyses demonstrated that NAC had an overall adverse effect on DFS and OS. Subgroup analyses showed that patients who received NAC had shorter DFS in all molecular subgroups of breast cancer, with exception of triple negative breast cancer (TNBC) patients. NAC was also associated with shorter OS among patients with histological grade of 2 and a low Ki67 index. The main recurrence site was the chest well, while distant metastasis occurred in the bone, liver and lung. In Cox regression analyses, we found that NAC was an independent predictor for DFS, but not for OS.Conclusions: NAC may have an adverse effect on breast cancer prognosis among patients with grade 2 tumors. These patients need not receive NAC, except when the patient has a strong desire for breast conservation, and this is unlikely to be achieved in the absence of NAC.

Cribriform pattern in lung invasive adenocarcinoma correlates with poor prognosis in a Chinese cohort

The 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification and the following 2015 WHO classification have both been validated for their predictive values of histologic subtypes for prognosis. We sought to investigate the clinicopathological and prognostic significance of the cribriform pattern in lung adenocarcinomas. Histologic subtypes were evaluated in 395 patients who underwent complete resection for invasive lung adenocarcinomas between 2011 and 2013. Cribriform pattern was correlated with clinicopathological factors as well as molecular and survival data. One hundred and thirty cases (33%) were present with cribriform pattern (5–100%; mean ± SD, 24% ± 22%). Thirty two (8%) of those were reclassified into cribriform predominant tumors. Presence of cribriform pattern (≥5%) was significantly associated with lymph/vascular invasion (P＜0.001), nodal positivity (P = 0.003), higher T stage(P = 0.005) and higher TNM stage (P = 0.001). Cribriform pattern (≥10%) was highly associated with worse disease-free survival (DFS) and overall survival (OS) (mean DFS: 42.6 months, P < 0.001; mean OS: 64.1 months, P = 0.012). The DFS or OS for cribriform predominant tumors was similar to that for solid or micropapillary tumors. In multivariate analysis, cribriform pattern (≥10%) or cribriform predominant subtype was an independent predictor for DFS. Cribriform pattern was a specific pattern compared to other acinar patterns, presenting with more aggressive behavior. Moreover, presence of cribriform pattern was a strong predictor for worse prognosis and should be considered a high grade pattern. Our study provides further evidence for cribriform pattern to be acknowledged as an independent subtype in the future classification.

Salvage Surgery for Recurrence after Radiotherapy for Squamous Cell Carcinoma of the Head and Neck.

Most studies that report on salvage surgery after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) are small and heterogeneous. Subsequently, some relevant questions remain unanswered. We specifically focused on (1) difference in prognosis per tumor subsite, corrected for disease stage, and (2) differences in prognosis after salvage surgery for local, regional, and locoregional recurrences. Retrospective analysis. Single-center study (2000-2016). Patients treated with salvage surgery for HNSCC recurrence after (chemo)radiotherapy. In total, 189 patients were included. Five-year overall survival (OS) was 33%, and median OS was 18 (95% confidence interval [CI], 11-26) months. Treatment-related mortality was 2%. Larynx carcinoma was associated with more favorable local (adjusted hazard ratio [HR] = 4.02; 95% CI, 1.46-11.10; P = .007) and locoregional control (adjusted HR = 5.34; 95% CI, 1.83-15.61; P = .002) than pharyngeal carcinoma. American Society of Anesthesiologists (ASA) score (≥3 vs 1-2: adjusted HR = 3.04; 95% CI, 1.17-7.91; P = .023), pT stage (3-4 vs 1-2: adjusted HR = 4.41; 95% CI, 1.65-11.82; P = .003), and salvage surgery for locoregional recurrences (locoregional vs local: adjusted HR = 3.81; 95% CI, 1.13-11.82; P = .021) were independent predictors for disease-free survival (DFS). Salvage surgery for larynx carcinoma, regardless of disease stage and other prognostic factors, results in more favorable loco(regional) control but not favorable DFS than pharyngeal carcinoma. The observed difference in DFS between salvage surgery for local and regional recurrences was not significant after correction for confounders. However, survival following salvage surgery for locoregional disease is significantly worse. For this subgroup, we propose to consider T status and comorbidity for clinical decision making, as high pT stage and ASA score are independent predictors for worse DFS.

Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy.

Gastric cancer (GC) is a leading cause of cancer-specific mortality with limited biologically informed treatments. The ataxia telangiectasia mutated (ATM) gene is critically involved in the repair of double-stranded DNA breaks and a component of DNA damage repair (DDR) pathways. Platinum salts are hypothesized to have increased efficacy in tumors deficient in DDR pathways. We sought to investigate an association between ATM status and response to XELOX in a homogenous first line GC patient cohort. A clinically annotated cohort of 137 Korean patients with advanced GC treated with first-line XELOX was retrospectively examined for ATM status by immunohistochemistry. Correlation between ATM expression and clinicopathologic variables was performed by two-tailed, unpaired t-tests and Fisher's exact tests. Kaplan-Meier survival analysis curves and Cox proportional hazards models were used to evaluate for independent predictors of disease-free survival (DFS) and overall survival (OS). Low ATM expression was observed in 19.0% (26/137) of patients and was not associated with clinicopathologic features or response rate to XELOX. Univariate, but not multivariable, logistic regression and Cox analysis identified ATM as an independent risk factor influencing OS and DFS. A higher ECOG score independently predicted worse survival [hazard ratio (HR) 2.96, P=0.016] and complete surgical resection independently protected against progression of disease (HR 0.69, P=0.007). Low ATM expression was not associated with increased response rates to XELOX in a single-institution cohort of advanced GC patients. Similarly, ATM status did not predict DFS or OS after platinum-based chemotherapy.

Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.

Increased expression of long non-coding RNA SNHG16 correlates with tumor progression and poor prognosis in non-small cell lung cancer

In this study, we report that lncRNA SNHG16 is upregulated in non-small cell lung cancer (NSCLC) tissues, and correlates with tumor size, TNM stage and lymph node metastasis. Kaplan-Meier analysis shows that the patients with high SNHG16 expression have poorer disease-free survival (DFS) and overall survival (OS) than the patients with low SNHG16 expression. Multivariate Cox regression analysis reveals that SNHG16 expression could be regarded as an independent predictor for DFS and OS in NSCLC patients. Cell experiments show that SNHG16 promotes NSCLC cell proliferation, migration and invasion. miR-146a is further identified and confirmed to be the target of SNHG16, and SNHG16 functions by targeting miR-146a. Subsequently, MUC5AC, a major mucin in the human respiratory tract correlated with post-operative metastasis and recurrence of NSCLC, is confirmed to be regulated by SNHG16 and miR-146a, and plays a positive role in promoting cell proliferation, migration and invasion, which might be involved in the oncogenic activity of SNHG16-miR-146a axis in NSCLC. Animal experiments also confirm these conclusions. Collectively, these results elucidate a potential mechanism underlying the carcinogenesis role of SNHG16 in NSCLC, and indicate that SNHG16 could act as a novel promising marker for prognosis, and a potential therapeutic target for NSCLC treatment.

Pre-treatment serum levels of soluble programmed cell death-ligand 1 predict prognosis in patients with hepatitis B-related hepatocellular carcinoma.

Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapy has shown promise in tumor immunotherapy. Our objectives were to measure pre-treatment serum-soluble PD-L1 (sPD-L1) levels and to assess the relationships between sPD-L1 levels and clinical characteristics, prognosis, and tumor tissue PD-L1 expression in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Pre-treatment serum sPD-L1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 81 patients with HBV-related HCC and compared to those in 49 healthy controls. The association between serum sPD-L1 levels and prognosis was assessed using survival analysis. The correlation between paired serum sPD-L1 levels and tumor PD-L1 expression (in resected tissue homogenates) was assessed in a separate group of 20 patients with HBV-related HCC. Median sPD-L1 concentration in patients with HBV-related HCC was 5.129 (range 0.140-12.391) ng/mL and in healthy controls was 0.836 (range 0.105-2.168) ng/mL (p < 0.001). On multivariate analysis, sPD-L1 levels were significant independent predictors of disease-free survival (hazard ratio [HR] 3.503; 95% confidence interval [CI], 1.559-7.871; p = 0.002) and overall survival (HR 3.399; 95% CI 1.308-8.831; p = 0.012). Positive correlation (r = 0.527, p = 0.017) between serum sPD-L1 and tumor PD-L1 expression was observed. Tumor expression of PD-L1 was significantly higher in those with serum sPD-L1 concentrations above vs. below the median level of 5.471ng/ml (p = 0.012). In patients with HBV-related HCC, serum sPD-L1 concentrations were elevated, and positively correlated with tumor PD-L1 expression. Lower pre-treatment serum sPD-L1 levels were predictors of more favorable disease-free and overall survival. Serum sPD-L1 testing has a potential role in HBV-related HCC disease assessment, systemic therapy choices and survival prediction.

Influence of Conversion and Anastomotic Leakage on Survival in Rectal Cancer Surgery; Retrospective Cross-sectional Study

BackgroundConversion and anastomotic leakage in colorectal cancer surgery have been suggested to have a negative impact on long-term oncologic outcomes. The aim of this study in a large Dutch national cohort was to analyze the influence of conversion and anastomotic leakage on long-term oncologic outcome in rectal cancer surgery. MethodsPatients were selected from a retrospective cross-sectional snapshot study. Patients with a benign lesion, distant metastasis, or unknown tumor or metastasis status were excluded. Overall (OS) and disease-free survival (DFS) were compared between laparoscopic, converted, and open surgery as well as between patients with and without anastomotic leakage. ResultsOut of a database of 2095 patients, 638 patients were eligible for inclusion in the laparoscopic, 752 in the open, and 107 in the conversion group. A total of 746 patients met the inclusion criteria and underwent low anterior resection with primary anastomosis, including 106 (14.2%) with anastomotic leakage. OS and DFS were significantly shorter in the conversion compared to the laparoscopic group (p = 0.025 and p = 0.001, respectively) as well as in anastomotic leakage compared to patients without anastomotic leakage (p = 0.002 and p = 0.024, respectively). In multivariable analysis, anastomotic leakage was an independent predictor of OS (hazard ratio 2.167, 95% confidence interval 1.322–3.551) and DFS (1.592, 1077–2.353). Conversion was an independent predictor of DFS (1.525, 1.071–2.172), but not of OS. ConclusionTechnical difficulties during laparoscopic rectal cancer surgery, as reflected by conversion, as well as anastomotic leakage have a negative prognostic impact, underlining the need to improve both aspects in rectal cancer surgery.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

ObjectivesThe optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages.MethodsWe performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2–IIA.ResultsFor patients with stage IA2–IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2–IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2–IIA.ConclusionsIn cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Comparison and validation of the value of preoperative inflammation marker-based prognostic scores in resectable pancreatic ductal adenocarcinoma.

PurposeWe aimed to compare and validate the prognostic value of inflammation-based prognostic scores for patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to establish a novel, effective nomogram incorporating inflammation-based prognostic scores to predict disease-free survival (DFS) in these patients.Patients and methodsClinicopathological characteristics and follow-up data were retrieved from our prospective database. A total of 420 patients with PDAC who underwent radical resection were evaluated between January 2007 and December 2016. Blood samples were obtained within 7 days prior to surgical intervention. Time-dependent receiver operating characteristic curves were generated to determine optimal cutoff values for independent prognostic factors. Nomograms for DFS were established based on multivariate Cox proportional hazard models, and the results were internally validated using bootstrap resampling.ResultsNeutrophil-lymphocyte ratio (NLR) >2.13 and platelet-lymphocyte ratio (PLR) >140 were independent prognostic factors for DFS and overall survival. Stratified analyses indicated that these associations were not present among patients with stage III disease. Independent predictors of DFS, including Eastern Cooperative Oncology Group performance status score, tumor stage, differentiation, adjuvant treatment, NLR, and PLR, were incorporated into two nomograms for prediction of DFS in a cohort of PDAC patients after curative surgery. The area under receiver operating characteristic curve of the nomogram including NLR and PLR (0.804) was higher than that without NLR and PLR (0.711). The bootstrap-corrected AUC for the model including NLR and PLR was 0.803, while that for the model without NLR and PLR was 0.711.ConclusionOur study demonstrates that high NLR and high PLR are important clinical predictors of poor survival in patients with resectable PDAC. Additionally, a nomogram including NLR and PLR can objectively and reliably predict DFS among patients with PDAC following curative surgery.

Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with Differentiated Thyroid Cancer.

Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC. A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs. >4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models. There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors >4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE] HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS, regardless of the presence of mETE within each size category (group 2 [≤4 cm with mETE] vs. group 1 [≤4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4 [>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For LRF and DMF, size but not mETE was also an independent risk factor. Tumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.