Impact of sustained viral response postcurative therapy of hepatitis C‐related hepatocellular carcinoma: a systematic review and meta‐analysis

Antiviral therapy with interferon based therapies (IBT) has shown potential in improving survival in patients who have undergone resection or locoregional therapy for hepatitis C‐associated hepatocellular carcinoma (HCV‐HCC). However, this benefit has not been definitively ascribed to sustained viral response (SVR). Since IBT has been replaced with new directly acting agents (DAA), which are more efficacious in the treatment of HCV, we sought to better determine the prognostic impact of SVR in HCV‐HCC. A systematic search of MEDLINE and EMBASE from inception through October 2015 was performed to identify studies that described the impact of presence of SVR in patients who underwent curative treatment of HCV‐HCC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated for recurrence‐free survival (RFS) and overall survival (OS) utilizing a random‐effects model. After reviewing 858 abstracts, ten studies which included a total of 1,794 patients were selected and data was extracted. Of these ten studies, the impact of SVR on RFS and OS was reported in eight and seven studies respectively. In a meta‐analysis which included 1,519 patients, SVR was associated with improved OS (HR 0.18; 95% CI 0.11–0.29, I² = 2%). We also found that SVR was associated with better RFS in a meta‐analysis (1,241 patients; HR 0.50; 95% CI 0.40–0.63, I² = 0). In conclusion, SVR is associated with improved OS and RFS in patients with HCV who have undergone resection or locoregional therapy for HCC. Newer DAA therapies which offer increased tolerability and viral eradication should be considered as adjunctive therapy.     

Gender differences in colorectal cancer survival: A meta‐analysis

A meta‐analysis was conducted to determine the influence of gender on overall survival (OS) and cancer‐specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer‐specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85–0.89) and CSS (HR = 0.92; 95% CI = 0.89–0.95) than males after meta‐analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.     

Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence‐free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non‐)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non‐academic hospitals were included. RFS and OS were analyzed with Kaplan‐Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five‐year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68‐1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64–1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three‐year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85–2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70–1.97)). Three‐year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11–3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12–3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.     

Impact of body mass index on clinical outcomes in triple-negative breast cancer

BACKGROUND:

Obesity is associated with poorer outcomes in patients with hormone receptor‐positive breast cancers. This association is not well established for women with triple‐negative breast cancers (TNBC). In this study, the prognostic effects of body mass index on clinical outcome were evaluated in patients with TNBC.

METHODS:

A retrospective study was conducted on 418 patients who were treated between July 1996 and July 2010 for TNBC. Recurrence‐free survival (RFS) and overall survival (OS) were evaluated in relation to body mass index (BMI) after controlling for clinically significant variables.

RESULTS:

One hundred twenty‐four patients (29.7%) were normal/underweight (BMI ≤24.9 kg/m²), 130 patients (31.1%) were overweight (BMI from 25 to 29.9 kg/m²), and 164 patients (39.2%) were obese (BMI ≥30 kg/m²). At a median follow‐up of 37.2 months, there were 105 recurrences (25.1%) and 87 deaths (20.8%). Compared with normal/underweight patients, the multivariate hazard ratio (HR) for RFS was 0.81 (95% confidence interval [CI], 0.49‐1.34) for obese patients. Similarly, OS was not associated with BMI category; obese patients had an HR of death of 0.94 (95% CI, 0.54‐1.64) compared with normal/underweight patients. A Cox regression analysis identified the receipt of chemotherapy (HR, 0.25; 95% CI, 0.12‐0.52), ductal histology (HR, 0.49; 95% CI, 0.25‐0.97), stage III disease (HR, 3.5; 95% CI, 1.35‐9.06), and increasing tumor size (HR, 1.19; 95% CI, 1.09‐1.3) as independent prognostic factors for OS.

CONCLUSIONS:

No significant relation between obesity and RFS or OS emerged in patients with TNBC after controlling for clinically significant factors. Cancer 2011;. © 2011 American Cancer Society.     

MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

Objective: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnosticand prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aimof the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety ofcarcinomas. Methods: Relevant studies were identified by searching PubMed and EMBASE. Data were extractedfrom studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS)in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios(HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. Results: A total of 15studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissuewas 1.89 (95% CI: 1.20-2.99, P =0.006), which could markedly predict poorer survival in general cancer. ForRFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR= 1.50, 95% CI: 1.10-2.05, P= 0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI:0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P = 0.015), with statistical significance; thepooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P =0.003) and2.61 (95% CI: 1.98-3.42, P<0.05), respectively. Conclusions: The results indicated that the miR-155 expressionlevel plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.     

Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study

Accumulating evidences indicate cancer-triggered inflammation plays a pivotal role in carcinogenesis. Systematic inflammatory response biomarkers are considered as potential prognostic factors for improving predictive accuracy in colorectal cancer (CRC). Preoperative neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte- to-monocyte ratio (LMR) were investigated and compared in 205 surgical CRC patients. ROC curve was applied to determine thresholds for four biomarkers, and their prognostic values were assessed using Kaplan–Meier curve, univariate and multivariate COX regression models. Moreover, a number of risk factors were used to form nomograms for evaluating risk of survival, and Harrell’s concordance index (c-index) was used to evaluate predictive accuracy. Results showed that elevated NLR was significantly associated with diminished recurrent-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in surgical CRC patients. Moreover, multivariate COX analysis identified elevated NLR as an independent factor for poor RFS (P < 0.001, HR 2.52, 95 % CI 1.65–3.83), OS (P < 0.001, HR 2.73, 95 % CI 1.74–4.29) and CSS (P < 0.001, HR 2.77, 95 % CI 1.72–4.46). Additionally, predictive nomograms including NLR for RFS, OS and CSS could be more effective in predicting RFS (c-index: 0.810 vs. 0.656), OS (c-index: 0.809 vs. 0.690) and CSS (c-index: 0.802 vs. 0.688) in surgical CRC patients, respectively. These findings indicate that preoperative elevated NLR can be considered as an independent prognostic biomarker for RFS, OS and CSS. Nomograms containing NLR provide improved accuracy for predicting clinical outcomes in surgical CRC patients under surgery resection.     

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta‐analysis

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme “HMG CoA reductase” and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta‐analysis of 10 studies, statin use was associated with improved recurrence‐free survival (RFS; HR 0.64; 95% CI 0.53–0.79, I² = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59–0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44–1.46). Statin users similarly showed improved overall survival in a meta‐analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44–0.99, I² = 89%). Statin users also had improved cancer‐specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46–1.06, I² = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence‐free survival. Statin users also had improved overall survival and cancer‐specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.     

High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL‐ and cisplatin‐induced apoptosis in human ovarian cancer cells

Dysregulated apoptotic pathways are regarded as major reasons for chemoresistance development as a particular challenge in ovarian cancer therapy. In search of molecular factors affecting human ovarian cancer cell apoptosis and, consequently, patient survival, we examined tumors of 103 platinum‐/taxane‐treated ovarian cancer patients by mRNA‐array hybridization, qPCR, and immunohistochemistry. We identified high expression of crystallin αB (CRYAB), a proposed negative regulator of tumor necrosis factor‐related apoptosis inducing ligand (TRAIL)‐mediated apoptosis. By Kaplan Meier analysis, this factor turned out to be significantly associated with poor patient outcome [overall survival (OS) p = 0.001, recurrence‐free survival (RFS) p = 0.003]. Elevated hazard ratios (HR) were estimated with regard to OS (HR = 2.11, 95% CI 1.10–4.06) and RFS (HR = 1.92, 95% CI 1.07–3.47) in multivariable analyses. These associations were confirmed in independent, publicly available mRNA data comprising 431 patients for OS (p < 0.001) and 413 for RFS (p < 0.001)_. Our findings were validated by studying apoptotic events in cultured human ovarian cancer cells which were stably transfected to express elevated CRYAB levels. These data emphasized the crucial role of CRYAB in human ovarian cancer biology since TRAIL‐ as well as cisplatin‐induced apoptosis was significantly impaired as a function of enhanced CRYAB expression. Taken together, we identified CRYAB as an independent biomarker for unfavourable outcome of human ovarian cancer patients. Since TRAIL is currently tested as anti‐cancer drug and large proportions of the present patient cohort displayed low CRYAB levels in their tumors, CRYAB may enable the selection of patient subgroups benefiting most from TRAIL‐containing therapy.     

Body mass index and mortality in patients with gastric cancer: a large cohort study

Background

The effects of obesity on prognosis in gastric cancer are controversial.

Aims

To evaluate the association between body mass index (BMI) and mortality in patients with gastric cancer.

Methods

A single-institution cohort of 7765 patients with gastric cancer undergoing curative gastrectomy between October 2000 and June 2016 was categorized into six groups based on BMI: underweight (<?18.5 kg/m²), normal (18.5 to?<?23 kg/m²), overweight (23 to?<?25 kg/m²), mildly obese (25 to?<?28 kg/m²), moderately obese (28 to?<?30 kg/m²), and severely obese (≥?30 kg/m²). Hazard ratios (HRs) for overall survival (OS) and disease-specific survival (DSS) were calculated using Cox proportional hazard models.

Results

We identified 1279 (16.5%) all-cause and 763 (9.8%) disease-specific deaths among 7765 patients over 83.05 months (range 1.02–186.97) median follow-up. In multivariable analyses adjusted for statistically significant clinicopathological characteristics, preoperative BMI was associated with OS in a non-linear pattern. Compared with normal-weight patients, underweight patients had worse OS [HR 1.42; 95% confidence interval (CI) 1.15–1.77], whereas overweight (HR 0.84; 95% CI 0.73–0.97), mildly obese (HR 0.77; 95% CI 0.66–0.90), and moderately obese (HR 0.77; 95% CI 0.59–1.01) patients had better OS. DSS exhibited a similar pattern, with lowest mortality in moderately obese patients (HR 0.58; 95% CI 0.39–0.85). Spline analysis showed the lowest all-cause mortality risk at a BMI of 26.67 kg/m².

Conclusion

In patients undergoing curative gastric cancer surgery, those who were overweight or mildly-to-moderately obese (BMI 23 to?<?30 kg/m²) preoperatively had better OS and DSS than normal-weight patients.

     

The impact of smoking on survival in renal cell carcinoma: a systematic review and meta-analysis

Epidemiological evidence suggests that cigarette smoking is the best-established risk factor for renal cell cancer (RCC). However, the effect of smoking on survival of RCC patients remains debated. We therefore conducted a meta-analysis to investigate the impact of smoking status on overall mortality (OM), disease-specific mortality (DSM), overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with RCC. We searched Medline, Embase, and the Cochrane Central Search Library for published studies that analyzed the effect of smoking on survival or mortality of RCC. We selected 14 articles according to predefined inclusion criteria. The smoking status was categorized into never smokers and ever smokers (former smokers and/or current smokers). Summary hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated with a fixed or random effects model. Overall, 14 studies including 343,993 RCC cases were accepted for meta-analysis. Ever smoking was significantly correlated with OM (HR 1.30, 95 % CI 1.07–1.58), while no associated with poorer DSM (HR 1.23, 95 % CI 0.96–1.57). Further analysis found current (HR 1.57, 95 % CI 1.20–2.06) but not former smoking (HR 1.14, 95 % CI 0.79–1.63) was associated with a significantly increased risk of OM. Meanwhile, current smoking was associated with poorer DSM (HR 1.50, 95 % CI 1.10–2.05) in subgroup analysis. Ever smoking was significantly associated with poorer OS (HR 1.45; 95 % CI 1.00–2.09) and poorer CSS (HR 1.01; 95 % CI 1.00–1.02), compared with never smokers. Current smoking was associated with poorer PFS (HR 2.94, 95 % CI 1.89–4.58). This review provides preliminary evidence that current smoking in a patient with RCC is associated with poorer survival, demonstrating active smoking to be an independent risk for prognosis of RCC. Smoking cessation should be recommended for RCC patients.     

Overall survival benefits for irinotecan‐containing regimens as first‐line treatment for advanced gastric cancer: An updated meta‐analysis of ten randomized controlled trials

The standard treatment for patients with advanced gastric cancer (AGC) is still debated, and the available data on the benefit of irinotecan‐containing regimen as first‐line treatment for those patients are controversial. We performed a systematic review and meta‐analysis of randomized controlled trials to determine the survival benefits of irinotecan‐containing regimens in this setting. A total of 1,837 patients from ten trials were included in the analysis. Our results showed that irinotecan‐containing regimens significantly improved overall survival [OS: hazard ratio (HR) 0.86, 95% CI = 0.78–0.94, p = 0.002] and progression‐free survival [HR = 0.82, 95% CI = 0.69–0.97, p = 0.026); however, the improvement of time to failure (HR = 0.90; 95% CI = 0.77–1.04, p = 0.15), 1‐year survival rate [1‐year SR: relative risk (RR) 1.10, 95% CI = 0.97–1.24, p = 0.13] and overall response rate (RR = 1.16, 95% CI = 0.91–1.49, p = 0.24] were nonsignificant. Equivalent frequencies of toxicities were found between the two groups excluding more Grade 3 or 4 fatigue (p = 0.001) in irinotecan‐containing regimens. This updated meta‐analysis provided strong evidence for a survival benefit of irinotecan‐containing regimen as first‐line treatment for AGC. A clear advantage of irinotecan‐containing over nonirinotecan‐containing regimen had not been established. These results should help to inform decisions about patient management and design of future trials.     

Overweight/obese status associates with favorable outcome in patients with metastatic nasopharyngeal carcinoma:a 10-year retrospective study

Background: Although the prognostic impact of body mass index (BMI) in patients with non?metastatic naso?pharyngeal carcinoma (NPC) had been extensively studied, its effect among metastatic NPC patients remains unknown. The purpose of this study was to evaluate the prognostic effect of BMI in patients with metastatic NPC. Methods: We retrospectively studied 819 patients who were diagnosed with distant metastasis from NPC and received treatment between 1998 and 2007. The patients were divided into three subgroups according to the World Health Organization classifications for Asian populations: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5–22.9 kg/m2), and overweight/obese (BMI ≥23.0 kg/m2). The associations of BMI with overall survival (OS) andprogression?free survival (PFS) were determined by Cox regression analysis. Results: Of the 819 patients, 168 (20.5%) were underweight, 431 (52.6%) were normal weight, and 220 (26.9%) were overweight/obese. Multivariate analysis adjusted for covariates showed that overweight/obese patients had a longer OS than underweight patients [hazard ratio (HR), 0.64; 95% confidence interval (CI), 0.49–0.84] and normal weight patients (HR, 0.72; 95% CI, 0.57–0.90); no significant difference in PFS was observed among these three groups (P = 0.407). Moreover, in stratified analysis, no statistically significant differences in the effect of overweight/obesestatus among different subgroups were observed. Conclusion: For patients with metastatic NPC, overweight/obese status was associated with longer OS but not longer PFS compared with underweight or normal weight status.     

Pathologic complete response in breast cancer patients receiving anthracycline‐ and taxane‐based neoadjuvant chemotherapy

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline‐ and taxane‐based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan‐Meier product‐limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence‐free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor‐positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49‐0.97) and OS (HR, 0.63; 95% CI, 0.41‐0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97‐1.68] and OS: HR, 1.32 [95% CI, 0.97‐1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.     

Prognostic role of neutrophil‐to‐lymphocyte ratio in colorectal cancer: A systematic review and meta‐analysis

The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.     

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15–1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03–1.65)). In hormone-receptor-negative (HR−) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80–1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24–2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82–2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63–2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29–1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.     

Prognostic value of phospho‐Akt in patients with non‐small cell lung carcinoma: A meta‐analysis

Previous studies have been inconsistent with respect to the reported associations between phospho‐Akt (p‐Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta‐analysis to assess the prognostic value of p‐Akt in patients with non‐small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random‐effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta‐analysis. p‐Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11–1.70; p < 0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19–1.75; p < 0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70–2.14; p = 0.48). The HR in cases of early stage disease (I–III) was 1.35 (95% CI: 1.08–1.69; p = 0.04); however, in cases of late stage disease (III–IV), the association became non‐significant (HR: 1.22, 95% CI: 0.64–2.33; p = 0.54). Our results suggest that there was a significantly inverse association between p‐Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early‐stage patients who underwent surgery.     

弥漫大B细胞淋巴瘤患者体质量指数对预后影响的Meta分析

目的:系统评价体质量指数（BMI）对弥漫大B细胞淋巴瘤（DLBCL）患者预后的影响。方法:计算机检索PubMed、Medline、Web of Science等数据库,按照纳入及排除标准筛选关于BMI与DLBCL患者预后关系的临床研究文献,采用RevMan 5.3软件对各研究的总生存（OS）、无进展生存（PFS）的风险比（ HR）及95%置信区间（95% CI）等数据进行分析,同时评估纳入文献质量、偏倚风险及异质性。 结果:共12篇文献纳入研究。Meta分析结果显示,与正常体质量（BMI 18.5~24.9 kg/m 2）患者相比,超重（BMI 25.0~29.9 kg/m 2）患者OS和PFS时间更长,但差异均无统计学意义（OS： HR=0.93,95% CI 0.78~1.11, P=0.42;PFS： HR=0.89,95% CI 0.67~1.20, P=0.45）;低体质量（BMI<18.5 kg/m 2）患者（OS： HR=1.97,95% CI 1.41~2.74, P<0.01;PFS： HR=1.89,95% CI 1.19~3.03, P<0.01）和肥胖（BMI≥30.0 kg/m 2）患者OS和PFS时间更短,但后者差异无统计学意义（OS： HR=1.15,95% CI 0.88~1.51, P=0.31;PFS： HR=1.32,95% CI 0.90~1.94, P=0.15）。漏斗图对称,纳入文献无发表偏倚。 结论:一定范围内BMI升高是DLBCL患者预后的保护性因素。     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

Prognostic significance of cyclooxygenase‐2 in cervical cancer: A meta‐analysis

Published data on the prognostic value of cyclooxygenase‐2 (COX‐2) overexpression in cervical cancer are conflicting and heterogeneous. We performed a meta‐analysis to more precisely estimate its prognostic significance. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effects. Twenty‐three studies with 1,477 cervical cancer patients were selected to evaluate the association between COX‐2 and overall survival (OS), disease‐free survival (DFS), response to chemoradiation (RC) and clinicopathological parameters. High COX‐2 expression predicted poor OS (HR: 2.53, 95% CI: 1.54–4.18), DFS (HR: 2.41, 95% CI: 1.58–3.69) and RC (OR: 3.03, 95% CI: 1.97–4.64). Subgroup analyses showed that COX‐2 overexpression was related significantly with poor OS in patients treated by chemoradiation or surgery, and in patients with squamous cell carcinoma, respectively. Besides, COX‐2 overexpression was related significantly with poor DFS in chemoradiation subgroup. Furthermore, COX‐2 overexpression was associated with poor RC in patients who received “FP” regimen or “P” regimen. Additionally, there were significant associations between COX‐2 expression and all clinicopathological parameters except tumor grade. The pooled ORs (95% CI) were as follows: 1.49 (1.09–2.04) for age, 1.77 (1.22–2.56) for lymph node metastasis, 1.04 (0.74–1.47) for tumor grade, 1.71 (1.12–2.64) for tumor size, 2.38 (1.28–4.45) for FIGO stage, 3.96 (2.32–6.77) for histological type, 2.45(1.10–5.42) for parametrical involvement. This meta‐analysis indicated that COX‐2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.     

Correlation between sex and efficacy of immune checkpoint inhibitors (PD‐1 and CTLA‐4 inhibitors)

Immune checkpoint inhibitors (ICIs) exert the antitumor efficacy depending on immune response, which is affected by sex difference, where both biological and sociological factors are involved. The role of sex in ICI trials has been overlooked. How sex correlates with ICI efficacy is incompletely understood. Clinical trials evaluating ICI versus other therapies in male and female patients were included. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression‐free survival (PFS) were used. Six thousand and ninety‐six patients from 11 trials were included. More improvement of OS was observed in males (HR, 0.62; 95% CI, 0.53–0.71; p < 0.001) treated with ICI versus controls than females (HR, 0.74; 95% CI, 0.65–0.84; p < 0.001). ICIs improved PFS more in males (HR, 0.57; 95% CI, 0.43–0.71; p < 0.001) than females (HR, 0.71; 95% CI, 0.52–0.91; p < 0.001). The sex difference had more effect on the overall survival in melanoma patients versus NSCLC patients. Overall survival of patients treated with CTLA‐4 inhibitor was more influenced by sex variable compared with PD‐1 inhibitors. A significant sex‐related efficacy difference was observed between female and male melanoma patients. Although male patients had longer OS and PFS than females when treated with ICIs versus controls, the difference was not significant. Sex difference should be more considered in future clinical trials, guidelines and clinical practice.