Duration of Chemotherapy for Small Cell Lung Cancer: A Meta-Analysis

Background

Maintenance chemotherapy is widely provided to patients with small cell lung cancer (SCLC). However, the benefits of maintenance chemotherapy compared with observation are a subject of debate.

Methodology and Principal Findings

To identify relevant literature, we systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. Eligible trials included patients with SCLC who either received maintenance chemotherapy (administered according to a continuous or switch strategy) or underwent observation. The primary outcome was 1-year mortality, and secondary outcomes were 2-year mortality, overall survival (OS), and progression-free survival (PFS). Of the 665 studies found in our search, we identified 14 relevant trials, which together reported data on 1806 patients with SCLC. When compared with observation, maintenance chemotherapy had no effect on 1-year mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.66–1.19; P = 0.414), 2-year mortality (OR: 0.82; 95% CI: 0.57–1.19; P = 0.302), OS (hazard ratio [HR]: 0.87; 95% CI: 0.71–1.06; P = 0.172), or PFS (HR: 0.87; 95% CI: 0.62–1.22; P = 0.432). However, subgroup analyses indicated that maintenance chemotherapy was associated with significantly longer PFS than observation in patients with extensive SCLC (HR, 0.72; 95% CI: 0.58–0.89; P = 0.003). Additionally, patients who were managed using the continuous strategy of maintenance chemotherapy appeared to be at a disadvantage in terms of PFS compared with patients who only underwent observation (HR, 1.27; 95% CI: 1.04–1.54; P = 0.018).

Conclusions/Significance

Maintenance chemotherapy failed to improve survival outcomes in patients with SCLC. However, a significant advantage in terms of PFS was observed for maintenance chemotherapy in patients with extensive disease. Additionally, our results suggest that the continuous strategy is inferior to observation; its clinical value needs to be investigated in additional trials.     

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Backgrounds

It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.

Methods

Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.

Results

A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.

Conclusions

For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.     

XRCC3 Thr241Met Polymorphism and Clinical Outcomes of NSCLC Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis

Introduction

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

Methods

A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099–2.072, P_{heterogeneity}  = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651–1.356, P_{heterogeneity}  = 0.112) or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539–1.710, P_{heterogeneity}  = 0.198). Additionally, no evidence of publication bias was observed.

Conclusions

This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.     

Prognostic Value of Human Equilibrative NucleosideTransporter1 in Pancreatic Cancer Receiving Gemcitabin-Based Chemotherapy: A Meta-Analysis

Background

The potential prognostic value of human equilibrative nucleoside transporter1 in pancreatic cancer receiving gemcitabine-based chemotherapy is variably reported.

Objective

The objective of this study was to conduct a systematic review of literature evaluating human equilibrative nucleoside transporter1 expression as a prognostic factor in pancreatic cancer receiving gemcitabine-based chemotherapy and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods

Related studies were identified and evaluated for quality through multiple search strategies. Only studies analyzing pancreatic cancer receiving gemcitabine-based chemotherapy were eligible for inclusion. Data were collected from studies comparing overall, disease-free and progression-free survival (OS, DFS and PFS) in patients with low human equilibrative nucleoside transporter1 levels and those having high levels. The hazard ratio (HR) and its 95% confidence interval (95%CI) were used to assess the strength of associations. Hazard ratios greater than 1 reflect adverse survival associated with low human equilibrative nucleoside transporter1 levels.

Results

A total of 12 studies (n = 875) were involved in this meta-analysis (12 for OS, 5 for DFS, 3 for PFS). For overall and disease-free survival, the pooled HRs of human equilibrative nucleoside transporter1 were significant at 2.93 (95% confidence interval [95% CI], 2.37–3.64) and 2.67 (95% CI, 1.87–3.81), respectively. For progression-free survival, the pooled HR in higher human equilibrative nucleoside transporter1 expression in pancreatic cancer receiving gemcitabine-based chemotherapy was 2.76 (95% CI, 1.76–4.34). No evidence of significant heterogeneity or publication bias was seen in any of these studies.

Conclusion

These results support the case for a low human equilibrative nucleoside transporter1 level representing a significant and reproducible marker of adverse prognosis in pancreatic cancer receiving gemcitabine-based chemotherapy.     

Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer

Background

To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum).

Patients and methods

This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints.

Results

Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007).

Conclusions

This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.     

Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

Objective

The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.

Methods

A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.

Results

A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.

Conclusion

CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.     

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

Background

The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.

Methods

Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.

Results

There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.

Conclusion

The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.     

Overall Survival Benefits for Combining Targeted Therapy as Second-Line Treatment for Advanced Non-Small-Cell-Lung Cancer: A Meta-Analysis of Published Data

Background

Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results

Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95%CI: 0.82–0.99, p = 0.024), PFS (HR 0.83, 95%CI: 0.72–0.97, p = 0.018), and ORR (OR 1.35, 95%CI 1.01–1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.

Conclusions

With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.     

Icotinib Is an Active Treatment of Non-Small-Cell Lung Cancer: A Retrospective Study

Background

Icotinib hydrochloride is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with preclinical and clinical activity in non-small cell lung cancer (NSCLC). This retrospective analysis was performed to assess the efficacy of icotinib on patients with non-small-cell lung cancer (NSCLC).

Methods

82 consecutive patients treated with icotinib as first (n = 24) or second/third line (n = 58) treatment at three hospitals in Nanjing were enrolled into our retrospective research. The Response Evaluation Criteria in Solid Tumors (RECIST) was used to evaluate the tumor responses and the progression-free survival (PFS) and overall survival (OS) was evaluated by the Kaplan-Meier method.

Results

Median PFS was 4.0 months (95% CI 2.311–5.689). Median OS was 11.0 months (95% CI 8.537–13.463) in this cohort. Median PFS for first and second/third line were 7.0 months (95% CI 2.151–11.8) and 3.0 months (95% CI 1.042–4.958), respectively. Median OS for first and second/third line were 13.0 months (95% CI 10.305–15.695) and 10.0 months (95% CI 7.295–12.70), respectively. In patients with EGFR mutation (n = 19), icotinib significantly reduced the risk of progression (HR 0.36, 95% CI 0.18–0.70, p = 0.003) and death (HR 0.10, 95% CI 0.02–0.42, p = 0.002) compared with those EGFR status unknown (n = 63). The most common adverse events were acne-like rash (39.0%) and diarrhea (20.7%).

Conclusions

Icotinib is active in the treatment of patients with NSCLC both in first or second/third line, especially in those patients harbouring EGFR mutations, with an acceptable adverse event profile.     

Tumor Site- and Stage-Specific Associations between Allelic Variants of Glutathione S-Transferase and DNA-Repair Genes and Overall Survival in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Chemotherapy

Introduction

Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.

Material and Methods

We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis.

Results

The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR  = 1.38, 95% CI  = 1.02–1.87), and rectal cancer patients had the poorest survival among them (HR  = 1.87, 95% CI  = 1.18–2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR  = 1.69, 95% CI  = 1.06–2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR  = 2.60, 95% CI  = 1.19–5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR  = 2.77, 95% CI  = 1.25–6.17).

Conclusion

The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.     

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.     

Prognostic Significance of COX-2 Immunohistochemical Expression in Colorectal Cancer: A Meta-Analysis of the Literature

Background

Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial.

Methods

Electronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed.

Results

We performed a meta-analysis of 23 studies (n  =  4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio]  =  1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR  =  1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer.

Conclusions

Cox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified.     

No Survival Benefit from Adding Cetuximab or Panitumumab to Oxaliplatin-Based Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer in KRAS Wild Type Patients: A Meta-Analysis

Background

The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MAbs) remains controversial in colorectal cancer (CRC). The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC) through meta-analysis.

Methods

Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab) in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. Hazard ratios (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals.

Results

This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn’t result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95) or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13). The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75) or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36). Patients who received combined therapy didn’t have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]). Toxicities slightly increased in anti-EGFR drugs group.

Conclusions

The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in survival benefit and response rate. More RCTs are warranted to evaluate the combination of chemotherapy and targeted therapy.     

The Role of BRCA Status on the Prognosis of Patients with Epithelial Ovarian Cancer: A Systematic Review of the Literature with a Meta-Analysis

Objective

The role of BRCA dysfunction on the prognosis of patients with epithelial ovarian cancer (EOCs) remains controversial. This systematic review tried to assess the role of BRCA dysfunction, including BRCA1/2 germline, somatic mutations, low BRCA1 protein/mRNA expression or BRCA1 promoter methylation, as prognostic factor in EOCs.

Methods

Studies were selected for analysis if they provided an independent assessment of BRCA status and prognosis in EOC. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a modified quality scale.

Results

Of 35 evaluable studies, 23 identified BRCA dysfucntion status as a favourable prognostic factor. No significant differences were detected in the global score of quality assessment. The aggregated hazard ratio (HR) of overall survival (OS) of 34 evaluable studies suggested that BRCA dysfunction status had a favourable impact on OS (HR = 0.69, 95% CI 0.61–0.79), and when these studies were categorised into BRCA1/2 mutation and low protein/mRNA expression of BRCA1 subgroups, all of them demonstrated positive results (HR = 0.67, 95% CI: 0.57–0.78; HR = 0.62, 95% CI: 0.51–0.75; and HR = 0.51, 95% CI: 0.33–0.78, respectively), except for the subgroup of BRCA1 promoter methylation (HR = 1.59, 95% CI: 0.72–3.50). The meta-analysis of progression-free survival (PFS), which included 18 evaluable studies, demonstrated that BRCA dysfunction status was associated with a longer PFS in EOC (HR = 0.69, 95% CI: 0.63–0.76).

Conclusions

Patients with BRCA dysfunction status tend to have a better outcome, but further prospective clinical studies comparing the different BRCA statuses in EOC is urgently needed to specifically define the most effective treatment for the separate patient groups.     

Immediate Postmastectomy Breast Reconstruction Showed Limited Advantage in Patient Survival after Stratifying by Family Income

Background

Postmastectomy breast reconstruction is widely used in breast cancer patients for its aesthetic effect. Although several studies have casted suspicion upon the oncological safety of immediate breast reconstruction after mastectomy, the potential impact of different reconstruction methods on patient survival remains unclear.

Patients and Methods

We identified 35,126 female patients diagnosed with breast cancer from January 1, 1998 to December 31, 2002 in the Surveillance, Epidemiology, and End Results database. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients who underwent mastectomy with or without immediate breast reconstruction (autologous reconstruction or implant reconstruction) using Cox proportional hazard regression models.

Results

In multivariate analysis unadjusted for family income, patients undergoing immediate postmastectomy reconstruction exhibited improved BCSS [pooled reconstruction (any types of reconstruction): hazard ratio (HR)  =  0.87, 95% confidence interval (CI) 0.80–0.95, P = 0.001] and OS (pooled reconstruction: HR = 0.70, 95% CI 0.65–0.75, P<0.001) compared to patients who underwent mastectomy alone. However, after stratifying by family income, patients receiving reconstruction showed limited advantage in BCSS and OS compared with those undergoing mastectomy alone. When comparing between the two reconstruction methods, no significant differences were observed in either BCSS (implant versus autologous reconstruction: HR = 1.11, 95%CI 0.90–1.35, P = 0.330) or OS (implant versus autologous reconstruction: HR = 1.07, 95% 0.90–1.28, P = 0.424).

Conclusions

Compared to mastectomy alone, immediate postmastectomy reconstruction had limited advantage in survival after adjusting for confounding factor of family income. Our findings, if validated in other large databases, may help to illustrate the actual effect of immediate postmastectomy reconstruction on patient survival.     

Treatment Outcome of Radiotherapy Alone versus Radiochemotherapy in IE/IIE Extranodal Nasal-Type Natural Killer/T Cell Lymphoma: A Meta-Analysis

Background

Previous studies have revealed conflicting findings concerning the efficacy of radiotherapy (RT) and radiochemotherapy (RCT) in IE/IIE extranodal nasal-type natural killer/T cell lymphoma (ENKTL). In this study, we conducted a comprehensive meta-analysis to address this issue.

Methods

We systematically searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EmBase, BISOS, Clinical Trials and some Chinese databases for relevant studies, and 2 prospective and 15 retrospective studies involving a total of 1595 patients met our inclusion criteria.

Results

The meta-analysis showed no significant differences in complete remission (CR) [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.42–1.72, p = 0.65], 5-year overall survival (OS) [hazard ratio (HR) 1.11, 95% CI 0.85–1.45, p = 0.43] and 5-year progression free survival (PFS) (HR 1.07, 95% CI 0.75–1.53, p = 0.70) in patients who received RT versus RCT. Furthermore, the addition of CT decreased neither systemic failure (SL) (OR 0.75, 95% CI 0.47–1.21, p = 0.24) nor locoregional failure (LF) (OR 1.17, 95% CI 0.68–2.01, p = 0. 57).

Conclusions

RCT did not have an obvious advantage over RT for treating IE/IIE ENKTL.     

Monocarboxylate Transporters 1–4 in NSCLC: MCT1 Is an Independent Prognostic Marker for Survival

Introduction

Monocarboxylate transporters (MCTs) 1–4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.

Methods

Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I–IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.

Results

In univariate analyses; ↓MCT1 (P = 0.021) and ↑MCT4 (P = 0.027) expression in cancer cells, and ↑MCT1 (P = 0.003), ↓MCT2 (P = 0.006), ↓MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3–2.8, P = 0.001), ↓MCT2 (HR: 2.4, CI 95%: 1.5–3.9, P<0.001), ↓MCT3 (HR: 1.9, CI 95%: 1.1–3.5, P = 0.031) and ↑MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1–2.7, P = 0.016) were significant independent poor prognostic markers for DSS.

Conclusions

We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.     

PIK3CA Gene Mutations and Overexpression: Implications for Prognostic Biomarker and Therapeutic Target in Chinese Esophageal Squamous Cell Carcinoma

Aims

To evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese esophageal squamous cell carcinoma (ESCC) patients, and their correlation with clinicopathological characteristics and clinical outcomes.

Methods

Direct sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in 406 Chinese ESCC patients. PIK3CA expression was evaluated using immunohistochemistry analysis. The associations of PIK3CA gene mutations and PIK3CA expression with clinicopathological characteristics and clinical outcome were examined.

Results

Thirty somatic point mutations (30/406, 7.4%) were identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA mutations were not correlated with clinicopathological characteristics or clinical outcomes. However in the ESCC patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival (multivariate hazard ratio (HR) = 10.493, 95% CI: 2.432–45.267, P = 0.002). Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in cancer tissue (P<0.001). PIK3CA overexpression was independently associated with higher risk of local recurrence (multivariate HR  = 1.435, 95% CI: 1.040–1.979, P = 0.028). In female ESCC patients, PIK3CA overexpression was independently correlated with worse overall survival (multivariate HR  = 2.341, 95% CI: 1.073–5.108, P = 0.033).

Conclusions

Our results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.     

Prognostic Significance of Neutrophil Lymphocyte Ratio in Patients with Gastric Cancer: A Meta-Analysis

Background

Several studies have shown that neutrophil lymphocyte ratio (NLR) may be associated with the prognosis of gastric cancer (GC), but the results are controversial.

Methods

This study was performed to evaluate the prognostic implications of neutrophil lymphocyte ratio of GC in all available studies. We surveyed 2 medical databases, PubMed and EMBASE, to identifyall relevant studies. Data were collected from studies comparing overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) in patients with GC.

Results

Ten studies (n = 2,952) evaluated the role of NLR as a predictor of outcome were involved for this meta-analysis (10 for OS, 3 for DFS, and 2 for PFS). Overall and disease-free survival were significantly better in patients with low NLR value and the pooled HRs was significant at 1.83 ([95% CI], 1.62–2.07) and 1.58 ([95% CI], 1.12–2.21), respectively. For progression-free survival, the pooled hazard ratio of NLR was significant at 1.54 ([95% CI], 1.22–1.95). No evidence of significant heterogeneity or publication bias for OS and DFS was seen in any of the included studies.

Conclusion

This meta-analysis indicated that elevated NLR may be associated with a worse prognosis for patients with GC.     

Interferon-Based Therapy Decreases Risks of Hepatocellular Carcinoma and Complications of Cirrhosis in Chronic Hepatitis C Patients

Background

Interferon-based therapy (IBT) has been the standard of care for hepatitis C virus (HCV) infection. However, conflicting results exist regarding the effects of IBT on risk of developing hepatocellular carcinoma (HCC) and cirrhosis-associated complications, and most included highly selected patients.

Methods

This 8-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 (>23.7 million). Patients with newly detected HCV infections (n = 11,264) were classified based on treatment and clinical outcomes. IBTs were defined as regimens that included interferon- alfa, pegylated interferon- alfa -2a, or pegylated interferon- alfa -2b for at least 3 months. The Cox proportional hazards models were used to estimate the hazard ratio (HR) and associated confidence interval (CI) of HCC and cirrhosis-associated complications for IBT.

Results

The 8-year incidence rate for HCC was 3.9% among patients who received IBT and 5.6% among those who did not. The HCC-free survival rate was significantly higher among patients receiving IBT during the 8-year period than their counterpart (adjusted HR, 0.50; 95% CI, 0.31–0.81; P = .004). Similarly, the event-free survival rates for esophageal variceal bleeding (adjusted HR, 0.45; 95% CI, 0.22–0.91; P = .026), hepatic encephalopathy (adjusted HR, 0.38; 95% CI, 0.21–0.69; P = .001), ascites (adjusted HR, 0.28; 95% CI, 0.14–0.57; P<.001), and cirrhosis (adjusted HR, 0.63; 95% CI, 0.44–0.91; P = .013) were significantly higher among patients who received IBT than those who did not, after adjustment for associated factors.

Conclusion

Treatment with interferon may reduce the 8-year risk of HCC and cirrhosis-associated complications in patients with chronic HCV infection.