Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

BackgroundThe prognostic significance of vascular endothelial growth factor C (VEGF-C) expression in breast cancer (BC) patients remains controversial. Therefore, this meta-analysis was performed to determine the prognostic significance of VEGF-C expression in BC patients.ResultsThe present meta analysis totally included 21 eligible studies and 2828 patients with BC. The combined HRs were 1.87(95% CI 1.25–2.79, P = 0.001) for DFS and 1.96(95% CI 1.15–3.31, P = 0.001) for OS. The pooled HRs of non-Asian subgroup were 2.04(95%CI 1.36–3.05, P = 0.001) for DFS and 2.61(95%CI 1.51–4.52, P = 0.001) for OS, which were significantly higher than that of Asian subgroup. The funnel plot for publication bias was symmetrical. The further Egger''s test and Begg''s test did not detect significant publication bias (all P>0.05).ConclusionsThe present meta analysis strongly supported the prognostic role of VEGF-C expression for DFS and OS in BC patients, especially for patients in non-Asian countries. Furthermore, stratification by VEGF-C expression may help to optimize the treatments and the integrated managements for BC patients.     

Radiotherapy for locally advanced head and neck cancer in elderly patients: results and prognostic factors a single cohort

BackgroundThe objective of this study was to assess the treatment outcomes and prognostic factors of elderly patients with locally advanced head and neck cancer (LAHNC) undergoing radiotherapy (RT).Materials and methodsA retrospective cohort from a single institution, from 2000 to 2015, including patients older than 65 years old with LAHNC (stage III–IVa) treated by RT combined or not with chemotherapy (CRT). Univariate and multivariate analysis (MVA) were performed to identify prognostic factors associated with overall survival (OS), cancer-specific survival (CS), and locoregional control (LRC). A p-value < 0.05 was considered significant.Results220 patients with LAHNC and > 65 years of age were identified. The median follow-up was 3.8 years, the 3/5 years estimated OS, CS, and LRC rate was 40%/30%, 49%/34%, 76%/45%, respectively. In the univariate analysis, clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.035), Karnofsky performance status (KPS, 60–70, p = 0.03) and tumor site (other than vs. hypopharynx, p = 0.0001) were associated with lower OS. Patients with clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.015), N stage (N0/1 vs. N2/3, p = 0.04), (KPS 60–70, p = 0.04) and tumor site (other than vs. hypopharynx, p = 0.0001) had worst CS. For the LRC, clinical stage (III vs. IVa/b, p = 0.02), tumor stage (T1/2 vs. T3/4, p = 0.02), treatment type (CRT vs. RT, p = 0.02), RT technique (IMRT vs. 2DRT/3DRT, p = 0.0001), and tumor site (other than vs. hypopharynx, p = 0.02) were significant. In the MVA, KPS maintained significant for OS and CS. For LRC, clinical stage (Iva/b, p = 0.007), tumor stage (T3/4, p = 0.047) and radiotherapy technique other than IMRT (p = 0.0001) were significant.ConclusionThe OS, CS, and LRC were associated with several prognostic factors. The clinical performance was the main marker of OS and CS. Chemoradiation should be offered to selected elderly patients using IMRT to improve LRC.     

Association of Type 2 Diabetes Genetic Variants with Breast Cancer Survival among Chinese Women

ObjectiveTo evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC).MethodsIncluded in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models.ResultsDuring a median follow-up of 8.08 years (range, 0.01–16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05–1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28–3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04–20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups.ConclusionsOur study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism.     

Determinants of Long-Term Outcome in Patients Undergoing Simultaneous Resection of Synchronous Colorectal Liver Metastases

Background

It remains unclear which patients can benefit from simultaneous resection of synchronous colorectal liver metastases (SCRLMs). This study aimed to examine the prognostic value of patient- and tumor-related factors in predicting long-term outcomes of patients undergoing simultaneous resection of SCRLMs and to help patients select a suitable therapeutic regimen and proper surveillance.

Methods

Clinicopathological and outcome data of 154 consecutive SCRLM patients who underwent simultaneous resection between July 2003 and July 2013 were collected from our prospectively established SCRLM data and analyzed with univariate and multivariate methods, and the prognostic index (PI) was formulated based on the regression coefficients (β) of the Cox model. The patients were classified into high- and low-risk groups according to the PI value; the cut-off point was the third quartile.

Results

The 5-year overall survival rate was 46%, and the 5-year disease-free survival rate was 35%. Five factors were found to be independent predictors of poor overall survival (OS) by multivariate analysis: positive lymph node status, vascular invasion, BRAF mutation, the distribution of bilobar liver metastases (LMs) and non-R0 resection of LMs. Compared to low PI (≤5.978), high PI (>5.978) was highly predictive of shorter OS. Three factors were found to be independent predictors of poor disease-free survival (DFS) by multivariate analysis: tumor deposits, BRAF mutation and bilobar LM distribution. We also determined the PI for DFS. Compared to low PI (≤2.945), high PI (>2.945) was highly predictive of shorter DFS.

Conclusions

Simultaneous resection of SCRLM may lead to various long-term outcomes. Patients with low PI have longer OS and DFS, while those with high PI have shorter OS and DFS. Thus, patients with high PI may receive more aggressive treatment and intensive surveillance, This model needs further validation.     

Prognostic Significance of Combination of Preoperative Platelet Count and Neutrophil-Lymphocyte Ratio (COP-NLR) in Patients with Non-Small Cell Lung Cancer: Based on a Large Cohort Study

IntroductionThe aim of this study was to investigate the prognostic significance of the combination of the preoperative platelet count and neutrophil-lymphocyte ratio (COP-NLR) for predicting postoperative survival of patients undergoing complete resection for non-small cell lung cancer (NSCLC).MethodsThe preoperative COP-NLR was calculated on the basis of data obtained.Patients with both an increased platelet count (>30.0×10⁴ mm^-3) and an elevated NLR (>2.3) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively.ResultsA total of 1238 NSCLC patients were enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory variables selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to 2.200, P<0.001) and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001). In sub-analyses by tumor stage (I, II, IIIA), a significant association was found between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002, P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS). When the subgroup of patients with high-risk COP-NLR (score of 2) was analyzed, no benefit of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS).ConclusionsThe preoperative COP-NLR is able to predict the prognosis of patients with NSCLC and divide these patients into three independent groups before surgery. Our results also demonstrate that high-risk patients based on the COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted.     

Young Cervical Cancer Patients May Be More Responsive than Older Patients to Neoadjuvant Chemotherapy Followed by Radical Surgery

Objective

To evaluate the effects of age and the clinical response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer who received neoadjuvant chemotherapy followed by radical surgery.

Methods

A total of 1,014 patients with advanced cervical cancer who received NACT followed by radical surgery were retrospectively selected. Patients were divided into young (aged ≤35 years, n = 177) and older (aged >35 years, n = 837) groups. We compared the short-term responses and survival rates between the groups. The five-year disease-free survival (DFS) and overall survival (OS) rates were stratified by age, NACT response, and FIGO stage.

Results

The overall response rate was 86.8% in the young group and 80.9% in the older group. The young patients had an earlier FIGO stage (P<0.001), a higher rate of adenocarcinoma (P = 0.022), and more lymph node metastasis (P = 0.033) than the older patients. The presence of adenocarcinoma as the histological type (P = 0.024) and positive lymph node metastasis (P<0.001) were identified as independent risk factors for survival. When stratified by age and clinical response, young patients with no response to NACT had a worse clinicopathological condition compared with the other subgroups. Compared with non-responders, responders to NACT had a higher five-year DFS rate (80.1% versus 71.8%; P = 0.019) and OS rate (82.6% versus 71.8%; P = 0.003) among the young patients but not among the older patients.

Conclusions

Responders to NACT aged 35 years or younger benefitted the most from NACT, while the young non-responders benefitted the least. Age might represent an important factor to consider when performing NACT in patients with cervical cancer.     

Pathological stage,surgical margin and lymphovascular invasion as prognostic factors after salvage radiotherapy for post-prostatectomy relapsed prostate cancer — outcomes and optimization strategies

BackgroundSalvage radiotherapy (sRT) is the main potentially curative treatment after biochemical failure/locoregional relapse post-radical prostatectomy (RP). The aim of the study was to characterize the population who underwent sRT after RP at our Department, to understand the influence of several potential prognosis factors, and to determine possible optimization strategies.Materials and methodsWe retrospectively analyzed patients undergoing sRT at our department between 2012 and 2017, evaluating patient, tumor and treatment characteristics, restaging procedures and clinical outcomes — namely biochemical relapse-free survival (BC-RFS), clinical relapse-free survival (C-RFS), additional hormone therapy-free survival (HT-FS) and overall survival (OS). We assessed potential prognostic factors by univariate and multivariate models (MVA).ResultsWe included 277 patients (median age 68 years). Median pre-sRT PSA was > 0.5ng/mL in 54.9%. All underwent prostate bed irradiation. Pelvic lymph nodes were included in 9.7%. Outcome analysis was performed for 264 patients (35.6 months median follow-up). At 3 years, BC-RFS was 61.4%, C-RFS was 81.3%, HT-FS was 79.9% and OS was 96.6%. Most relapses occurred in regional lymph nodes only (47.9% patients who relapsed). On MVA, lymphovascular invasion, advanced pT-stages and negative margins negatively influenced BC-RFS (p = 0.029, p = 0.002 and p < 0.001) and HT-FS (p = 0.001, p = 0.029 and p = 0.002). C-RFS was worsened by lymphovascular invasion (p = 0.009) and negative margins (p = 0.015). These had no effect on OS. BC-RFS and HT-FS were improved when sRT started while PSA ≤ 0.5 ng/mL (p < 0.05).ConclusionLymphovascular invasion, higher pT-stages and negative margins negatively affected prognosis. An early start of sRT (PSA ≤ 0.5 ng/mL) predicted better BC-RFS and HT-FS.     

The Predictive Value of Serum Squamous Cell Carcinoma Antigen in Patients with Cervical Cancer Who Receive Neoadjuvant Chemotherapy followed by Radical Surgery: A Single-Institute Study

Objective

Neoadjuvant chemotherapy (NACT) could affect the levels of squamous cell carcinoma antigen (SCC-Ag). This study evaluates the predictive value of pre- and posttreatment SCC-Ag levels in patients with cervical cancer who were treated with NACT followed by radical surgery.

Methods

A total of 286 patients with Stage IB1-IIIB squamous cell carcinoma of the uterine cervix who were treated with NACT followed by radical hysterectomy were analyzed retrospectively. The relationship between SCC-Ag levels, the clinicopathologic parameters, the response to NACT and the three-year survival rate was investigated.

Results

The levels of SCC-Ag were elevated (>3.5 ng/mL) in 43.8% of patients before NACT, and 13.0% of patients after NACT. Pre- and posttreatment levels of SCC-Ag correlated with the response to NACT (P = 0.010, and P<0.001), deep stromal infiltration (P = 0.041, and P = 0.006), and lymph node status (P<0.001, and P<0.001). In the multivariate analysis, the elevated pretreatment level of SCC-Ag was demonstrated to be an independent risk factor for Lymph node metastases (P<0.001). Patients with both pre- and posttreatment SCC-Ag levels ≤3.5 ng/mL showed the best 3-year disease-free survival (DFS) and 3-year overall survival (OS) compared with patients with either pre- or posttreatment levels >3.5 ng/mL (P<0.001, and P<0.001, respectively). A multivariate analysis showed that posttreatment SCC-Ag levels were a strong independent predictor of OS (P = 0.001) and DFS (P = 0.012).

Conclusion

Elevated pretreatment levels of SCC-Ag (>3.5 ng/mL) indicated a poor response to NACT and a higher risk of lymph node metastases. Elevated posttreatment levels of SCC-Ag were correlated with poor DFS and OS.     

Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

Introduction

The locoregional recurrence (LRR) rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1–2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT).

Methods and Materials

In total, 390 patients with pT1-2N0M0 (n = 307) and pT1-2N1M0 (n = 83) breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.

Results

After a median follow-up period of 5.6 years (range, 0.6–11.3 years), 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS) rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01) and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04) were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03) was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.

Conclusion

Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

Consolidative mediastinal radiotherapy for advanced-stage classical Hodgkin lymphoma with bulky disease in patients who achieve complete response after chemotherapy in PET-CT era

BackgroundThe role of consolidation mediastinal radiotherapy (RT) for mediastinal bulky disease in advanced-stage classical Hodgkin lymphoma (cHL) is controversial in the positron emission tomography/computed tomography (PET-CT) era.Materials and methodsWe reviewed the medical charts of patients with advanced-stage (clinical stage IIX–IVX) cHL and mediastinal bulky that achieved a complete response after first line chemotherapy treatment between August 2010 and December 2020 and compared the results of those who received with those who did not receive consolidation mediastinal RT. Inclusion criteria required PET-CT imaging for staging and response assessment.ResultsWe included 115 patients; 91 received mediastinal RT and 24 did not. Patient’s characteristics were balanced between the two groups. The median age in patients that received and did not receive mediastinal RT was 28 years and 24.5 years, respectively. Median International Prognostic Score among patients that received and did not receive mediastinal RT was 2 and 2.5, respectively. Disease free survival (DFS) was statistically better in patients that received mediastinal RT (p = 0.013). Two-year DFS for patients that received and did not receive mediastinal RT was 95.2% [95% confidence interval (95% CI): 87.6–98.2%] and 76.4% (95% CI: 52.2–89.4%), respectively. Overall survival (OS) was not different between the two groups (p = 0.617). In multivariate analysis, not receiving mediastinal radiotherapy and only achieving partial response (vs. complete response) after 2 cycles of chemotherapy were factors predictive of lower DFS.ConclusionDFS, but not OS, was superior in patients that received mediastinal RT.     

Impact of Diabetes Mellitus on the Prognosis of Patients with Hepatocellular Carcinoma after Curative Hepatectomy

Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy. Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model. Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS. Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis.     

Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study

IntroductionWe previously reported that most patients with rheumatoid arthritis (RA) and moderate cardiovascular disease (CVD) risk according to the Systematic COronary Evaluation score (SCORE) experience carotid artery plaque. In this study, we aimed to identify patient characteristics that can potentially predict carotid plaque presence in women with RA and a concurrent low CVD risk according to the SCORE.MethodsA cohort of 144 women with an evaluated low risk of CVD (SCORE value of zero) was assembled amongst 550 consecutive patients with RA that underwent CVD risk factor recording and carotid artery ultrasound. Participants had no established CVD, moderate or severe chronic kidney disease, or diabetes. We assessed carotid plaque(s) presence and its associated patient characteristics.ResultsCarotid artery plaque was present in 35 (24.3%) of women with RA. Age, the number of synthetic disease-modifying agents (DMARDs) and total cholesterol concentrations were independently associated with plaque in multivariable stepwise backward regression analysis (odds ratio (95% confidence interval) = 1.15 (1.07 to 1.24), P <0.0001, 1.51 (1.05 to 2.17), P = 0.03 and 1.66 (1.00 to 2.73) P = 0.04), respectively). The area under the curve (AUC) of the receiver operating curve (ROC) for the association with plaque was 0.807 (P <0.0001), 0.679 (P = 0.001) and 0.599 (P = 0.08) for age, total cholesterol concentrations and number of synthetic DMARDs used, respectively. The optimal cutoff value in predicting plaque presence for age was 49.5 years with a sensitivity and specificity of 74% and 75%, respectively, and for total cholesterol concentration, it was 5.4 mmol/l with a sensitivity and specificity of 63% and 70%, respectively. The plaque prevalence was 37.5% in patients (n = 80; 55.6%) with age >49.5 years or/and total cholesterol concentration of >5.4 mmol/l, respectively, compared to only 7.8% in those (n = 64; 44.4%) with age ≤49.5 years or/and total cholesterol concentration of ≤5.4 mmol/l, respectively.ConclusionsApproximately one-third of women with RA who experience a low SCORE value and are aged >49.5 years or/and have a total cholesterol concentration of >5.4 mmol/l, experience high-risk atherosclerosis, which requires intensive CVD risk management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0576-7) contains supplementary material, which is available to authorized users.     

The effect of lymphadenectomy and radiotherapy on recurrence and survival in endometrial carcinoma. Experience in a population reference centre

Aim

To evaluate the effect of lymphadenectomy and/or radiotherapy on recurrence and survival patterns in endometrial carcinoma (EC) in a radiotherapy reference centre population.

Material and Methods

A retrospective population-based review was conducted on 261 patients with stages I–III EC. Univariate and multivariate analyses were carried out. Both recurrence and survival were analysed according to patient age, FIGO stage, tumour size, myometrial invasion, tumour grade, lymphadenectomy, external beam irradiation (EBI), and brachytherapy (BT).

Results

Median age: 64.8 years. Median follow-up: 151 months. The following treatments were administered: surgery, 97.32%; lymph-node dissection, 54.4%; radiotherapy, 162 patients (62%) (EBI and BT: 64.1%, BT alone: 30.2%, EBI alone: 5.6%).Twenty-six patients (9.96%) suffered loco-regional recurrence, whilst 27 (10.34%) suffered distant failure. The 5-year overall survival (OS) for all stages was 80.1%. The 5-year disease free survival (DFS) was 92.1% for all patients. The 10-year DFS was 89.9%.The independent significant prognostic factors for a good outcome identified through the multivariate analysis were: age <75 years (p = 0.001); tumour size ≤2 cm (p = 0.003); myometrial invasion ≤50% (p = 0.011); lymphadenectomy (p = 0.02); EBI (p = 0.001); and BT (p = 0.031).Toxicity occurred in 114 of the 162 patients who received radiotherapy (70.5%). The toxicity was mainly acute, and late in only 28.3% (n = 45) of cases. The majority experienced G1-2 toxicity, and only 3% of patients experienced G3 late toxicity (5/162).

Conclusions

Our results suggest that age <75 years, tumour size ≤2 cm, myometrial invasion ≤50%, lymphadenectomy, EBI, and BT, are predictors of a good outcome in EC.     

A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×10⁹/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×10⁹/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.     

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer

BackgroundRed cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT).Materials and methodsThis retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis.ResultsThe OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51–0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50–0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12–1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06–1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03–1.29, p = 0.012).ConclusionsIn the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.     

HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host’s immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3’UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3’UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3’UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3’UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3’UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38–0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26–0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19–5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16–6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3’UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.     

Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

ObjectiveRecently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor.MethodsEligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types.ResultsData from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02–4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67–2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09–2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28–4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441).ConclusionIn this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type.     

A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer

BackgroundSingle nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results.MethodsWe pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified.ResultsThree SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555–0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730–0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037–2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations.ConclusionRs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.