Meta-analysis Of Overall Survival Research Articles

A meta-analysis of overall survival and response in metastatic adrenocortical carcinoma: A review of 23 prospective trials of 880 patients.

4 Background: Metastatic adrenocortical carcinoma (mACC) is a rare, aggressive tumour of the adrenal gland, with historically poor survival and limited established treatment modalities. The aim of this study was to systematically search for and analyse all prospective trials for mACC to establish benchmark response and survival outcomes. The study was registered on PROSPERO CRD42023430557. Methods: A systematic review and meta-analysis of five databases was performed between June 2023- July 2023. Key outcomes extracted included patient demographics, overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was calculated using a random effects model and inverse variance methods. Time-to-event outcomes including PFS and OS, were extracted digitally from available Kaplan- Meier curves using the IPDfromKM tool and individual patient data (IPD) was generated as per Guyot et al. The PFS and OS data from individual studies were then pooled using a multivariate extension of the DerSimonian–Laird method to generate summary survival curves. Results: The final 23 trials (5 Phase 1b, 16 Phase II and 3 Phase 3) encompassed 880 patients were retrieved. Pooled ORR was 9.0% overall (2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy). Median OS was 9.9 months (7.4 months for targeted therapy, 11.2 months for chemotherapy and 10.6 months for immunotherapy). Median PFS was 2.6 months (2.7 months for targeted therapy, 3.0 months for chemotherapy and 2.1 months for immunotherapy). Kaplan-Meier curves for OS were available for 10 treatment lines (n = 605), with a pooled median OS of 9.9 months (95% CI 7.7-11.9) and 12-month OS of 41.6% (95CI 33.1-51.2). Median OS was 7.4 months for patients receiving targeted therapy (95% CI 4.7–12.0), 11.2 months for patients receiving chemotherapy (95% CI 6.9–14.7) and 10.6 months for patients receiving immunotherapy (95% CI 4.4–13.2]. 12-month OS was 30.4% (95% CI 15.9-58.3) for patients receiving targeted therapy, 45.4% (95% CI 33.7-61.2) for patients receiving chemotherapy and 45.3% (95% CI 36.2-56.6) for patients receiving immunotherapy. Conclusions: This study found that current treatments strategies confer limited survival and response benefit in mACC and highlight the need for research into the pathogenesis and novel strategies in the disease. Immunotherapy and chemotherapy demonstrate modest benefits for patients and future trials should attempt to surpass the survival benchmarks set in this study.

207 Does Adjuvant Radiotherapy Lead to Increased Survival in Patients with Adenoid Cystic Carcinoma of the Breast? a Systematic Review and Meta-Analysis

Abstract Aim Adenoid cystic carcinoma (ACC) of the breast accounts for approximately 0.1% of all breast tumours (Zhang et al, 2021). The aim of this systematic review and meta-analysis was to determine whether adjuvant radiotherapy provides an additional benefit when compared to surgery alone in terms of overall survival in patients with ACC. Method A total of 3,330 records were identified and screened following database, conference proceedings, and currently registered studies search. Data from 5 case series was extracted. A random-effects meta-analysis of overall survival (OS) at 1, 2, 3-, 4-, 5- and 10-years post-intervention was performed. Results Adjuvant radiotherapy and surgery alone led to similar OS at all points post-intervention. For instance, 5-year survival following use of adjuvant radiotherapy was 92.8% (95% CI: 90.5%-94.7%), compared to 88.7% (95% CI: 81.9%-94.2%) with surgery alone. The confidence intervals overlap, which was the case for all points post-intervention. Conclusions Similar OS for both adjuvant radiotherapy and surgery alone (and overlapping confidence intervals), suggest the former may not provide an additional benefit in terms of OS in patients with ACC. Considering the negative side effects of radiotherapy, it could be argued that surgery alone should be used for the treatment ACC. However, this conclusion is hindered by the low number of studies included in this meta-analysis and their low level of evidence. This could be attributed to the low incidence of ACC. Further data should be collected to more reliably determine their optimal treatment.

Preoperative C-reactive protein-to-albumin ratio as a prognostic factor in biliary tract cancer: A systematic review and meta-analysis.

The preoperative C-reactive protein-to-albumin ratio is a novel inflammation-based prognostic marker in various cancers. However, its prognostic role in biliary tract cancer is unknown. We conducted a systematic review and meta-analysis to evaluate the prognostic value of preoperative C-reactive protein-to-albumin ratio in biliary tract cancer. A systematic search of the literature for studies evaluating the prognostic value of C-reactive protein-to-albumin ratio in patients undergoing surgery for biliary tract cancer was conducted, and a random effects meta-analysis of overall survival and recurrence-free survival was performed. Nine studies with 1292 participants were included. The preoperative C-reactive protein-to-albumin ratio negatively correlated with overall survival (hazard ratio, 2.44 [95% confidence interval: 1.98-2.90]; P < .001) and recurrence-free survival (hazard ratio, 2.73 [95% confidence interval: 2.01-3.70]; P < .001). Subgroup analysis showed that an elevated preoperative C-reactive protein-to-albumin ratio predicted poor overall survival, regardless of the cutoff value, sample size, histological type, and treatment. An elevated preoperative C-reactive protein-to-albumin ratio is significantly associated with poor prognosis in patients undergoing surgery for biliary tract cancer. The C-reactive protein-to-albumin ratio may be an independent prognostic biomarker for overall survival and recurrence-free survival in patients undergoing surgery for biliary tract cancer.

Meta-analysis of overall survival and postoperative neurologic deficits after resection or biopsy of butterfly glioblastoma.

Butterfly glioblastoma (bGBM) is a grade 4 glioma with a poor prognosis. Surgical treatment of these cancers has been reviewed in the literature with some recent studies supporting resection as a safe and effective treatment instead of biopsy and adjuvant therapy. This meta-analysis was designed to determine whether there are significant differences in overall survival (OS) and postoperative neurologic deficits (motor, speech, and cranial nerve) following intervention in patients who underwent tumor resection as part of their treatment, compared to patients who underwent biopsy without surgical resection. A literature search was conducted using PubMed (National Library of Medicine) and Embase (Elsevier) to identify articles from each database's earliest records to May 25, 2021, that directly compared the outcomes of biopsy and resection in bGBM patients and met predetermined inclusion criteria. A meta-analysis was conducted to compare the effects of the two management strategies on OS and postoperative neurologic deficits. Six articles met our study inclusion criteria. OS was found to be significantly longer for the resection group at 6months (odds ratio [OR] 2.94, 95% confidence interval [CI] 1.23-7.05) and 12months (OR 3.75, 95% CI 1.10-12.76) than for the biopsy group. No statistically significant differences were found in OS at 18 and 24months. Resection was associated with an increased rate of postoperative neurologic deficit (OR 2.05, 95% CI 1.02-4.09). Resection offers greater OS up to 1year postintervention than biopsy alone; however, this comes at the cost of higher rates of postoperative neurologic deficits.

Does breast-conserving surgery with radiotherapy in BRCA-mutation carriers significantly increase ipsilateral breast tumor recurrence? A systematic review and meta-analysis.

Breast-conserving surgery (BCS) is often preferred for localized, small breast cancers, but its safety and efficacy in BRCA-mutation carriers is still controversial. This meta-analysis aimed to determine whether there was any significant difference in the incidence of ipsilateral breast tumor recurrence (IBTR) between BRCA-mutation carriers who underwent BCS and controls with sporadic breast cancer. A PubMed search was conducted through March 2020 to identify studies examining the risk of IBTR after BCS in BRCA-mutation carriers versus controls. The Cochrane risk-of-bias tool was used to assess the risk of bias. The pooled risk ratio (RR) was calculated using the random-effects model. Thirteen studies involving 701 BRCA-mutation carriers and 4788 controls in total were eventually analyzed. In the meta-analysis, IBTR after BCS was significantly higher in BRCA-mutation carriers (RR: 1.589; 95% confidence interval (CI) 1.247-2.024; P < 0.001). Subgroup analysis of the follow-up time found that the RR for IBTR increased as the observation period lengthened (median follow-up: ≧ 7years [RR: 1.505; 95% CI 1.184-1.913] and ≧ 10years [RR: 1.601; 95% CI 1.201-2.132], respectively). However, a qualitative meta-analysis of overall survival in three cohort studies found no evidence to suggest a deterioration in overall survival in patients with BCS. The present study demonstrated that BRCA-mutation carriers with BCS have a higher risk of IBTR, which tended to persist for a long period and become more apparent with longer observation.

Survival Outcomes of De Novo vs Inverted Papilloma–Associated Sinonasal Squamous Cell Carcinoma

Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Fertility sparing surgery vs radical surgery for epithelial ovarian cancer: a meta-analysis of overall survival and disease-free survival

BackgroundThe aim of this systematic review and meta-analysis was to compare overall survival and disease-free survival after fertility sparing surgery (FSS) vs radical surgery in stage 1 epithelial ovarian cancer (EOC).MethodsA systematic literature search of PubMed, BioMed Central, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar was carried out. Databases were searched for English language studies from inception to 1st November 2019. Adjusted hazard ratios (HR) were extracted and pooled for a meta-analysis. Meta-regression was performed for baseline patient characteristics.ResultsEight observational studies compared 2223 patients undergoing FSS with 5809 patients undergoing radical surgery. Overall survival was reported from all eight studies. The pooled HR was non-significant (HR, 1.03; 95%CI, 0.80–1.31; p = 0.84) denoting no difference in overall survival between FSS and radical surgery. Data on disease-free survival was available from five studies. Our analysis indicated no difference in disease-free survival between EOC patients undergoing FSS or radical surgery (HR, 1.07; 95%CI, 0.73–1.58; p = 0.72). On meta-regression, there was no a statistically significant effect of cancer stage, grade and histology on the pooled HR.ConclusionOn the basis of currently available observational studies there seems to be no difference in overall survival and disease-free survival with either surgical techniques for stage 1 EOC patients. Disease stage, tumor grade and histology does not appear to influence outcomes. Further homogenous studies shall improve the quality of evidence on this debatable subject.

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis.

ObjectiveTo assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC).MethodsWe searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events.ResultsFor advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70–0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85–1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68–0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49–1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99–1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63–0.86).ConclusionsMeta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.

Survival advantage of laparoscopic versus open resection for colorectal liver metastases: A patient-level meta-analysis of propensity-score-matched studies

Background: Propensity-score matched (PSM) studies currently constitute the highest level of evidence in addressing the long-term oncologic efficacy of laparoscopic versus open resection for colorectal liver metastases (CLM). However, individual PSM studies are limited by the reporting of overall survival in ways not amenable to traditional methods of meta-analysis, as well as violation of the proportional hazards assumption. We performed an individual participant data (IPD) meta-analysis of overall survival based on PSM studies which compared laparoscopic versus open hepatectomy for patients with CLM. Materials and Methods: We searched EMBASE, Scopus and Medline for propensity-score matched studies without language restriction from inception to Dec 6, 2018. Overall survival information of individual participants were reconstructed from published Kaplan-Meier curves with the aid of a computer vision program. Survival models (taking into account random-effects, time-varying effects, and non-proportional hazards) were fitted to compare overall survival of patients who underwent laparoscopic versus open surgery. Results: Individual patient data from 10 propensity-score-matched studies involving 2,539 participants were reconstructed. Laparoscopic resection was associated with lower mortality over the entire duration of follow-up (stratified HR=0.831, 95% CI: 0.719-0.960, P=0.0120). There was evidence of time-varying effects (P=0.0212), and HRs were found to increase in magnitude over time: HR=0.991 [P=0.9320], HR=0.868 [P=0.0482], HR=0.804 [P=0.0026], HR=0.729 [P=0.0007], and HR=0.638 [P=0.0011] at 1, 2, 3, 5, and 10 years respectively. At 10- and 15-year follow-up, the restricted mean survival time (RMST) were 9.6 months and 32.3 months longer in the laparoscopic arm, corresponding to a 13.4% and 40.8% gain in RMST respectively (allP<0.0001). Conclusions: All analyses indicated a consistent survival benefit in favor of laparoscopic over open resection for CLM in the long-term. Mechanisms for the delayed divergence in survival curves, which emerges only after 2 years post-resection, warrant further research.

Prognostic Significance of the Lymphocyte-to-Monocyte Ratio in Bladder Cancer Undergoing Radical Cystectomy: A Meta-Analysis of 5638 Individuals.

Introduction A growing number of studies have explored the association between the pretreatment lymphocyte-to-monocyte ratio (LMR) and survival outcomes in various cancers. However, its prognostic significance on bladder cancer remains inconsistent. The aim of this meta-analysis was to evaluate the prognostic value of pretreatment LMR in bladder cancer. Methods The MEDLINE, EMBASE, Cochrane Library, and CNKI databases were comprehensively searched for relevant studies. A meta-analysis of overall survival (OS), recurrence-free survival (RFS), or cancer-specific survival (CSS) clinicopathological features was conducted. Results Nine studies containing 5,638 cancer patients were analyzed in this meta-analysis. Patients with high LMR tended to have favourable OS (HR: 0.63, 95% CI: 0.50-0.80, P < 0.001), RFS (HR: 0.59, 95% CI: 0.38-0.91, P = 0.017), and CSS (HR: 0.76, 95% CI: 0.70-0.83, P < 0.001). Moreover, low LMR was highly correlated with age (≥60), differentiation (low), T stage (III-IV), lymph node metastasis (yes), and concomitant Cis (yes). Conclusion Pretreatment LMR might be a useful predictor of survival outcomes in patients with bladder cancer.

Open Versus Endoscopic Approach for Sinonasal Melanoma: A Systematic Review and Meta-analysis.

Open resection (OR) of sinonasal mucosal melanoma (SNM) traditionally has been the gold standard for treatment. However, endoscopic resection (ER) has recently become a surgical alternative. The aim of this study was to compare survival outcomes between OR and ER of SNM. A literature search encompassing PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Google Scholar was performed. Two reviewers independently screened for original studies comparing survival outcomes between OR and ER for SNM. Data were systematically collected on study design, patient demographics, outcomes, and level of evidence. Quality assessment was performed using the Newcastle-Ottawa scale (NOS). Meta-analysis of overall survival and disease-free survival was performed using random-effects models. The initial search yielded 2078 abstracts, of which 9 cohort studies were included for a total of 510 patients from 6 different countries. The average quality of all included studies using the NOS was 7.7 stars. Six out of 7 studies reported no differences in the stages of SNM between patients receiving ER versus OR. Overall survival was longer in the ER group versus OR group (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.49-0.95). There was no significant difference in disease-free survival between groups (HR: 0.59, 95% CI: 0.28-1.25). Based on the available literature, an endoscopic approach for SNM resection has survival outcomes that are similar or greater compared to an open approach.

Radiofrequency ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival.

Background and aimsSo far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA.MethodsA primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. Thirty-four studies published from 2003 to 2017 were analyzed. They included 11,216 hepatocellular carcinoma patients.ResultsThe results showed that Child–Pugh B vs Child–Pugh A (HR =2.32; 95% CI: 2.201–2.69; P<0.0001) and albumin–bilirubin score 1 vs 0 (HR =2.69; 95% CI: 2.10–3.44; P<0.0001) were predictive of poor OS. Tumor size as a continuous variable was not predictive of OS, although it was predictive of OS when we considered the size as a cutoff value (.2 cm vs <2 cm: HR =1.41; 95% CI: 1.23–1.61; P<0.0001; >3 cm vs <3 cm: HR =1.43; 95% CI: 1.17–1.74; P<0.0001) and in presence of >1 nodule (HR =1.59; 95% CI: 1.46–1.74; P<0.0001). Alpha-fetoprotein >20 ng/mL (HR =1.46; 95% CI: 1.25–1.70; P<0.0001) was the only predictive factor of poor prognosis.ConclusionOur meta-analysis highlighted that the maximum benefit of RFA in terms of OS and RFS is reached in the presence of Child–Pugh A, albumin–bilirubin score 1, single-nodule tumor sized <2 cm, and alpha-fetoprotein <20 ng/mL.

Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women

To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2315 patients aged ≤ 40 years at diagnosis. Here, we identify two SNPs associated with early-onset DFS, rs715212 (Pmeta = 3.54 × 10−5) and rs10963755 (Pmeta = 3.91 × 10−4) in ADAMTSL1. The effect of these SNPs is independent of classical prognostic factors and there is no heterogeneity between cohorts. Most importantly, the association with rs715212 is noteworthy (FPRP <0.2) and approaches genome-wide significance in multivariable analysis (Pmultivariable = 5.37 × 10−8). Expression quantitative trait analysis provides tentative evidence that rs715212 may influence AREG expression (PeQTL = 0.035), although further functional studies are needed to confirm this association and determine a mechanism.

Chemotherapy for advanced gastric cancer.

Chemotherapy for advanced gastric cancer.

Second-line Treatments for Advanced Gastric Cancer: A Network Meta-Analysis of Overall Survival Using Parametric Modelling Methods.

IntroductionAdvanced gastric cancer (AGC) is one of the most common forms of cancer and remains difficult to cure. There is currently no recommended therapy for second-line AGC in the UK despite the availability of various interventions. This paper aims to compare different interventions for treatment of second-line AGC using more complex methods to estimate relative efficacy, fitting various parametric models and to compare results to those published adopting conventional methods of synthesis.MethodsSeven studies were identified in an existing literature review evaluating seven comparators, which formed a connected network of evidence. Citations were limited to randomised controlled trials in previously-treated AGC patients. Evidence quality was assessed using the Cochrane Collaboration’s tool. Studies were assessed for the availability of Kaplan–Meier curves for overall survival. Individual patient data (IPD) were recreated using digitisation software along with a published algorithm in R. The data were analysed using multi-dimensional network meta-analysis (NMA) methods. A series of parametric models were fitted to the pseudo-IPD. Both fixed and random-effects models were fitted to explore long-term survival prospects based on extrapolation methods and estimated mean survival.ResultsRelative efficacy estimates were compared to those previously reported, which utilised conventional NMA methods. Results presented were consistent within findings from other publications and identified ramucirumab plus paclitaxel as the best treatment; however, all the treatments assessed were associated with poor survival prospects with mean survival estimates ranging from 5.0 to 12.7 months.ConclusionWhilst the approach adopted in this paper does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent cost-effectiveness modelling and may have greater impact when considering an indication where observed data is particularly immature or survival prospects are more positive, which may then lead to more informative decision-making for drug reimbursement.Electronic supplementary materialThe online version of this article (doi:10.1007/s40487-017-0048-0) contains supplementary material, which is available to authorized users.

Lenalidomide (LEN) Maintenance Following High-Dose Melphalan and Autologous Stem Cell Transplant (ASCT) in Patients (Pts) With Newly Diagnosed Multiple Myeloma (MM): A Meta-Analysis of Overall Survival (OS)

Lenalidomide (LEN) Maintenance Following High-Dose Melphalan and Autologous Stem Cell Transplant (ASCT) in Patients (Pts) With Newly Diagnosed Multiple Myeloma (MM): A Meta-Analysis of Overall Survival (OS)

Quantitative Analysis of Circulating Cell-Free DNA for Correlation with Lung Cancer Survival: A Systematic Review and Meta-Analysis.

Despite the growing interest in circulating cell-free DNA (cfDNA), no conclusive evidence exists on the value of quantitative analysis of cfDNA for the prediction of lung cancer survival. We performed a systematic review and meta-analysis of primary studies to estimate the impact of higher baseline cfDNA levels on survival outcomes of patients with lung cancer. A comprehensive search was performed using the PubMed, Web of Knowledge, and Cochrane databases up to March 2016. The methodologic quality of identified studies was assessed by the Newcastle-Ottawa scale. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, while publication bias was evaluated by funnel plot and Egger's test. Among the 17 studies identified, 16 studies (n= 1723 patients) and 5 studies (n= 640) were included in the meta-analysis of overall survival (OS) and progression-free survival (PFS), respectively. Despite the fact that the association with PFS did not reach statistical significance (hazard ratio 1.12% [95% confidence interval 0.91-1.37), the pooled analysis for OS showed evidence of an increased risk of death in patients with higher baseline cfDNA levels (hazard ratio 1.76 [95% confidence interval 1.38-2.25]; p < 0.001). Further subgroup and sensitivity analyses confirmed this relationship, although significant between-study heterogeneity was still detected in most comparisons. The Egger's test revealed no statistical evidence of publication bias in the results. Our findings support the clinical validity of quantitative analysis of cfDNA for the prediction of lung cancer survival. Nevertheless, the establishment of a robust standardized method for determination of optimal cutoff thresholds is required to define the clinical relevance of cfDNA quantification for lung cancer management.

Predictive Value of Ercc1 and Xpd Polymorphisms for Clinical Outcomes of Patients Receiving Neoadjuvant Therapy: A Prisma-Compliant Meta-Analysis.

Excision repair cross complementing 1 (ERCC1) and xeroderma pigmentosum group D (XPD) play important roles in the nucleotide excision repair (NER) pathway. The correlation between ERCC1 polymorphisms (rs11615 and rs3212986) and XPD polymorphisms (rs13181 and rs1799793) with the response rate and overall survival of cancer patients who accept neoadjuvant therapy has been extensively investigated. However, the results are inconclusive. In this study, we performed a meta-analysis to determine the strength of this correlation. A comprehensive literature search was conducted in Medline, PubMed, and Embase up to February 2015. A review of all titles and abstracts was performed by 2 of the authors to screen the articles based on the eligibility criteria. Clinical trials, observational studies, and epidemiological studies describing ERCC polymorphisms and neoadjuvant treatment were considered for review. The response rate was analyzed using pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall survival was assessed using the hazard ratio (HR) with corresponding 95% confidence intervals. In the present meta-analysis, we demonstrated that the ERCC1 rs3212986 polymorphism was significantly correlated with the response rate of esophageal cancer patients to neoadjuvant therapy (OR = .49, 95% CI = 0.31-0.76, heterogeneity P = 0.480). Furthermore, a considerable correlation was observed between ERCC1 rs11615 and the response rate of esophageal cancer patients to neoadjuvant therapy (OR = 0.228, 95% CI = 0.125-0.418, heterogeneity P = 0.291). No correlation was observed in the meta-analysis of overall survival. The individual studies included in our study differed in their patient selection and therapeutic protocols, which might lead to some bias in the results. These findings indicate that the ERCC1 rs11615 and ERCC1 rs312986 polymorphisms may be candidate pharmacogenomic factors capable of predicting the response rate of esophageal cancer patients who accept neoadjuvant therapy. Further studies are warranted.

Overall Survival, Disease-Free Survival, Local Recurrence, and Nipple-Areolar Recurrence in the Setting of Nipple-Sparing Mastectomy: A Meta-Analysis and Systematic Review.

Nipple-sparing mastectomy (NSM) is an increasingly common procedure; however, concerns exist regarding its oncological safety due to the potential for residual breast tissue to harbor occult malignancy or future cancer. A systematic literature review was performed. Studies with internal comparison arms evaluating therapeutic NSM versus skin-sparing mastectomy (SSM) and/or modified radical mastectomy (MRM) were included in a meta-analysis of overall survival (OS), disease-free survival (DFS), and local recurrence (LR). Studies lacking comparison arms were only included in the systematic review to evaluate mean OS, DFS, LR, and nipple-areolar recurrence (NAR). The search yielded 851 articles. Twenty studies with 5594 patients met selection criteria. The meta-analysis included eight studies with comparison arms. Seven studies that compared OS found a 3.4% risk difference between NSM and MRM/SSM, five studies that compared DFS found a 9.6% risk difference between NSM and MRM/SSM, and eight studies that compared LR found a 0.4% risk difference between NSM and MRM/SSM. Risk differences for all outcomes were not statistically significant. The systematic review included all 20 studies and evaluated OS, DFS, LR, and NAR. Studies with follow-up intervals of <3 years, 3-5 years, and >5 years had mean OS of 97.2, 97.9, and 86.8%; DFS of 93.1, 92.3, and 76.1%; LR of 5.4, 1.4, and 11.4%; and NAR of 2.1, 1.0, and 3.4%, respectively. This study did not detect adverse oncologic outcomes of NSM in carefully selected women with early-stage breast cancer. Use of prospective data registries, notably the Nipple-Sparing Mastectomy Registry, will add clarity to this important clinical question.

Addition of Taxane to Induction Therapy in Head and Neck Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Head and neck cancer, mostly squamous cell carcinoma, ranks sixth among the most common cancers. Despite progress in treatment in recent years, survival remains poor. Since induction chemotherapy has been associated with survival benefit, it is a reasonable treatment option. The standard protocol up to recently has been cisplatin and 5-flourouracil. The addition of taxanes to the standard induction protocol has shown superiority in terms of the overall response rate. Nevertheless, not all trials demonstrated survival benefit. We aimed to evaluate the effect of taxane added to the standard protocol of induction therapy. Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared the addition of taxane to the standard induction protocol of cisplatin and 5-flourouracil for patients with head and neck malignancy. We searched The Cochrane library, PubMed, LILACS, conference proceedings, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios (HRs) for time-to-event were determined and pooled. Results: A total of 4 trials comprising 1,441 patients were included in this meta-analysis. All patients were available for the meta-analysis of overall survival. Patients treated with the addition of taxane had statistically significant overall survival [HR = 0.82, 95% confidence interval (CI) 0.71-0.94] and progression-free survival (HR = 0.82, 95% CI 0.72-0.93). No effect was observed in larynx preservation rate (relative risk = 0.88, 95% CI 0.64-1.19). The rate of hematological adverse events was higher in the taxane group than in the control group. Conclusions: These results suggest that induction therapy with the addition of taxane is superior to induction therapy with cisplatin and 5-flourouracil in terms of overall survival and progression-free survival. The higher rate of neutropenia and neutropenic fever should be taken into consideration when making treatment decisions.