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1.

Purpose

To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients.

Patients and Methods

Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence.

Results

HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47-10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55-24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42-20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02-22.48; P = .002).

Conclusion

PI3K-AKT-mTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation.  相似文献   

2.

Purpose

To perform a retrospective analysis of the prognostic relevance of clinicopathologic parameters in a well-documented cohort of patients treated with all-trans-retinoic acid (ATRA)-based induction regimens in order to discover which indicators can predict a high risk of early death (ED) and patient survival.

Patients and Methods

We analyzed data of 288 newly diagnosed adult acute promyelocytic leukemia patients in Hangzhou, China. The median follow-up time was 32 months (range, 6-78 months).

Results

The 3-year disease-free and overall survival rates were 90.83% and 91.69%, respectively. In the multivariable analysis, older age (≥ 60 years) was the only independent risk factor for ED (hazard ratio [HR] = 15.057; P = .004). High white blood cell count was not a risk factor for ED (P = .055), but it was for relapse (HR = 2.7; P = .009). FLT3 mutation (HR = 3.9; 95% confidence interval, 1.4 to 10; P = .007) and older age (≥ 60 years) (HR = 5.3; 95% confidence interval, 2.4 to 11; P < .001) were prognostic factors for poorer disease-free and overall survival. Interestingly, CD15 negativity (HR = 0.23; P = .049) was a prognostic factor for relapse. The ED rate was 5.9% (17/288 patients).

Conclusion

The perceived impact of the identification of these high-risk factors should be described in order to decide whether any modifications to treatment strategy should be entertained.  相似文献   

3.

Objective

To determine long-term survival of visceral pleural invasion (VPI) and parenchymal invasion (PAI) (angiolymphatic and/or vascular) on survival of NSCLCs less than 30 mm in maximum diameter.

Methods

Kaplan-Meier survivals for NSCLCs, with and without VPI and/or PAI, were determined for a prospective cohort of screening participants stratified by pathologic tumor size (≤10 mm, 11–20 mm, and 21–30 mm) and nodule consistency. Log-rank test statistics were calculated.

Results

The frequency of PAI versus VPI was significantly lower in patients with subsolid nodules than in those with solid nodules (4.9% versus 27.7% [p < 0.0001]), and correspondingly, Kaplan-Meier lung cancer survival was significantly higher among patients with subsolid nodules (99.1% versus 91.3% [p = 0.0009]). Multivariable Cox regression found that only tumor diameter (adjusted hazard ratio [HR] =1.07, 95% confidence interval [CI]: 1.01–1.14, p = 0.02) and PAI (adjusted HR = 3.15, 95% CI: 1.25–7.90, p = 0.01) remained significant, whereas VPI was not significant (p = 0.15). When clinical and computed tomography findings were included with the pathologic findings, Cox regression showed that the risk of dying of lung cancer increased 10-fold (HR = 10.06, 95% CI: 1.35–75.30) for NSCLCs in patients with solid nodules and more than twofold (by a factor of 2.27) in patients with moderate to severe emphysema (HR = 2.27, 95% CI: 1.01–5.11), as well as with increasing tumor diameter (HR = 1.06, 95% CI: 1.01–1.13), whereas PAI was no longer significant (p = 0.19).

Conclusions

Nodule consistency on computed tomography was a more significant prognostic indicator than either PAI or VPI. We propose that patients with NSCLC with VPI and a maximum tumor diameter of 30 mm or less not be upstaged to T2 without further large, multicenter studies of NSCLCs, stratified by the new T status and that classification be considered separately for patients with subsolid or solid nodules.  相似文献   

4.

Background

The role of histology subtype on the prognosis of T1-2 breast cancer patients receiving breast-conserving surgery (BCS) is not clear.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Program was used to compare overall survival, second primary cancer-free survival (CFS), and local recurrence risk (LR) for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), both receiving BCS.

Results

The study enrolled 196,688 patients with T1-2 disease receiving BCS, including 12,906 with ILC and 183,782 with IDC. Patients with IDC showed higher unadjusted annual rates of BCS than ILC. Five- and 10-year estimated survival rates were, respectively, 92.06% and 86.14% in ILC, compared to 90.50% and 85.26% in IDC (P = .12). In multivariable Cox regression, ILC patients showed advantage over IDC in overall survival (hazard ratio [HR] = 0.93, P = .001), whereas no significant differences in CFS (HR = 1.03, P = .33) and LR (HR = 1.17, P = .06) were found, which were consistent with results from matched cohort. In subgroup analyses, patients with grade III ILC had poorer CFS (HR = 1.23, P = .009) and higher LR (HR = 1.59, P = .01) than IDC.

Conclusion

Histologic type is of prognostic importance in T1-2 patients receiving BCS, and surgeons should be cautious in performing BCS for individuals with grade III ILC.  相似文献   

5.

Background

The prognostic value of tumor sidedness in metastatic colorectal cancer (CRC) has been established, but its impact on nonmetastatic disease remains unclear. Our study aimed to explore the prognostic effect of tumor sidedness by subgroup survival analyses, according to histology and tumor grade in stage I-IV CRCs.

Methods

A retrospective population-based study was conducted based on Surveillance, Epidemiology and End Results (SEER) data. Population data in the SEER 9 registry (1975-2014) were used to determine survival trends of CRCs, and associated population data in the SEER 18 registry (2000 to 2014) were used to assess the prognostic impact of tumor sidedness on CRCs.

Results

The 5-year cause-specific survival for all subgroups of CRCs improved from 1975 to 2014. Of 238,826 patients, 44.2% had right-sided cancer. Patients with right-sided cancer were more likely to be older, to be women, to have disease of mucinous or signet-ring cell histology, to have more poorly differentiated tumors, and to be diagnosed with a more advanced disease stage. Multivariate Cox regression showed stage I-II right-sided cancers had better cause-specific survival than the left-sided cancers (left colon: hazard ratio [HR] = 1.091, 95% confidence interval [CI], 1.052-1.132; rectum: HR = 1.363; 95% CI, 1.304-1.425; P < .001), while stage III and IV right-sided cancers had worse cause-specific survival. In subgroup analyses by histology and tumor grade within stage III CRCs, right-sided poorly differentiated mucinous adenocarcinoma showed significantly better survival (left colon: HR = 1.352; 95% CI, 1.145-1.596; rectum: HR = 1.125; 95% CI, 0.916-1.381; P = .002).

Conclusion

The relationship between sidedness and prognosis in CRCs depends on stage and histopathologic characteristics, especially for stage III disease.  相似文献   

6.
7.

Background

Breast cancer (BC) is one of the most prevalent and reported cancers among Saudi women. Detection of BC in the early invasive stage (stages I, II) has an advantage in treating patients over detection in the late invasive stage (stages III, IV). Tumor markers are used to aid in diagnosis, treatment monitoring, and recurrence detection of malignant tumors. 8-hydroxy-2’-deoxyguanosine (8-OHdG) is a marker of nucleic damage owing to oxidative stress.

Patients and Methods

We studied the blood levels of 8-OHdG in 50 women with benign breast tumors, 50 women with BC, and 50 healthy women as a control group.

Results

The concentrations of 8-OHdG were significantly increased in the BC group (55.2 ng/dL) compared with the benign tumor group (30.2 ng/dL) and with the healthy control group (9.08 ng/dL). The same pattern was observed with other diagnostic markers, including carcinoembryonic antigen and cancer antigen 15-3. Significant positive correlations between 8-OHdG and both carcinoembryonic antigen (r = 0.63; P < .001) and cancer antigen 15-3 (r = 0.51; P < .001) were noticed. The levels of 8-OHdG were significantly higher in stage I (81 ng/dL) compared with stage II (51 ng/dL; P < .05), stage III (38 ng/dL; P < .01), and stage IV (19 ng/dL; P < .001). In addition, serum 8-OHdG had a high diagnostic performance in BC (area under the curve, 0.86; sensitivity = 82%; specificity = 80% at cutoff value 21.4 ng/mL). 8-OHdG is associated with BC risk according to logistic regression analysis.

Conclusion

We concluded that the significant increase of serum levels of 8-OHdG in patients with BC can be used as a potential noninvasive biomarker for early detection of BC. However, large sample sizes from different stages and types of BC should be included in any future study to confirm the present findings before translating the findings into routine clinical application.  相似文献   

8.

Introduction

Mosaic loss of chromosome Y (mLOY) is the most commonly detectable mosaic chromosomal event in cancers; however, its underlying relationship with tumorigenesis is still unclear.

Methods

We conducted a mendelian randomization study to systematically investigate the effect of mLOY on lung cancer based on a published genome-wide association study and inferred the causal relationship between mLOY and lung cancer. Kaplan-Meier and Cox regression analyses were used to evaluate the effect of mLOY on lung cancer prognosis.

Results

We discovered that genetically defined mLOY was a protective factor against lung cancer development in nonsmokers but not in smokers (lifelong nonsmokers: OR = 0.80, 95% confidence interval [CI]: 0.69–0.93, p = 4.03×10–3; smokers: OR = 0.96, 95% CI: 0.89–1.04, p =2.90 × 10–1, pHeterogeneity = 3.83 × 10–2). A U-shaped curve between the copy number level of chromosome Y and lung cancer risk was fitted (p for linearity Wald = 8.81 × 10–10) to support the idea that heavy mLOY caused by acquired damaging environmental factors may have effects on lung cancer that are different from those of genetically defined mLOY, whereas genetically predicted mLOY was linearly associated with a decreased lung cancer risk (p for linearity Wald = 0.15). In addition, increased genetically defined mLOY was also significantly associated with a better outcome of lung cancer (HR = 0.86, 95% CI: 0.75–0.98, p = 2.03 × 10–2).

Conclusions

In summary, we propose a "two-sides" model: “natural” mLOY reduces the risk and ensures a better prognosis of lung cancer, although the effect can be abolished by an aberrant loss of chromosome Y caused by environmental risk factors. Our results reveal a complex relationship between mLOY and lung cancer and provide important implications for the prevention of lung cancer.  相似文献   

9.

Background

Women have been shown to experience longer overall survival after colorectal cancer (CRC) diagnosis than men even after adjusting for disease stage and management. However, the etiology of this observation is not well understood, and the impact of non-CRC health conditions on survival has not been described. We aimed to evaluate the prognostic role of sex on CRC-specific outcomes.

Patients and Methods

All patients who underwent primary resection of stage I to III CRC from 2001 to 2005, and who were referred to cancer centers in a large, representative Canadian province were reviewed. Baseline patient characteristics, including common comorbidities, were compared between men and women. Multivariable analysis was used to evaluate the associations between sex and survival outcomes.

Results

We identified 1837 patients. Median age was 69 (interquartile range 60-76) years, and there were 867 women (47%) and 970 men (53%). Men were more likely to report ischemic heart disease, diabetes, dyslipidemia, and obesity (all P < .001). On multivariable analysis, men had worse overall and recurrence-free survival compared to women (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.15-1.64; and HR = 1.40, 95% CI, 1.18-1.67, respectively). However, CRC-specific outcomes, including CRC-specific survival and time to recurrence, did not differ significantly between men and women (HR = 1.15, 95% CI, 0.91-1.45; and HR = 1.12, 95% CI, 0.90-1.40, respectively).

Conclusion

Women diagnosed with early stage CRC lived longer and had better general health than men. When noncancer causes of death were excluded, however, the trajectory of CRC appeared similar irrespective of sex. Early identification and better management of comorbidities may narrow the survival gap between men and women.  相似文献   

10.
11.

Introduction

The role of prophylactic cranial irradiation (PCI) is controversial in patients with extensive stage small cell lung cancer. The aim of this study was to determine the impact of PCI in these patients.

Methods

We performed a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Central Register. The primary outcome was overall survival (OS).

Results

We identified five studies comprising 984 patients, of whom 448 received PCI and 536 did not receive PCI. In pooled estimates, PCI did not statistically improve OS compared with controls (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.60–1.11; I2 = 77%; p = 0.19). However, the PCI group had a significant advantage in 1-year survival compared to the no-PCI group (37.1% versus 27.1%; risk ratio = 0.87; 95% CI: 0.80–0.95; I2 = 47%; p = 0.002), and the pooled estimates indicated that progression-free survival and the risk of brain metastasis were associated with significant benefit in the PCI group (HR = 0.83; 95% CI: 0.70–0.98; I2 = 22%; p = 0.03; and HR = 0.34; 95% CI: 0.23–0.50; I2 = 0%; p < 0.001, respectively).

Conclusions

Our findings suggest that PCI in patients with extensive stage small cell lung cancer may lead to a significant benefit in 1-year survival, progression-free survival, and the risk of brain metastasis, despite the lack of a significant advantage in OS.  相似文献   

12.

Introduction

This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.

Methods

In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days–on, 4 days–off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.

Results

A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2–5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6–5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820–1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9–11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7–11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776–1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).

Conclusions

Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated.  相似文献   

13.

Introduction

Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail.

Methods

Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS.

Results

Of the 110 patients with ALK-positive NSCLC who were identified, 105 received crizotinib as their initial ALK inhibitor. With a median follow-up time of 47 months, the median OS time from diagnosis of stage IV disease was 81 months (6.8 years). Brain metastases at diagnosis of stage IV disease (hazard ratio = 1.01, p = 0.971) and year of stage IV presentation (p = 0.887) did not influence OS. More organs with tumor at diagnosis of stage IV disease was associated with worse OS (HR = 1.49 for each additional organ with disease, including the CNS [p = 0.002]). Each additional month of pemetrexed-based therapy was associated with a 7% relative decrease in risk of death.

Conclusion

Patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes.  相似文献   

14.

Purpose

To determine a subset of women who could undergo ovary-sparing radical cystectomy (OSRC) for bladder cancer without compromising oncologic safety.

Patients and Methods

A retrospective review was performed of 164 consecutive women who underwent cystectomy at a single tertiary-care center from 1997 to 2018. Clinicopathologic and preoperative radiographic data were reviewed. Univariable and multivariable logistic regression models adjusting for pathologic stage, lymphovascular invasion (LVI), and carcinomain-situ were performed to evaluate the risk of ovarian and reproductive organ (RO) involvement.

Results

A total of 123 women with a median age of 71 years underwent radical cystectomy (RC) with removal of ROs for primary bladder cancer. Nineteen women (15%) had RO involvement by bladder cancer, and 5 of them (4%) were specifically found to have ovarian involvement. Patients with ovarian involvement of bladder cancer had more locally advanced disease (P = .01), LVI (P = .003) and positive margins (P = .003). On multivariable logistic regression, ≥ pT3 (odds ratio = 10.2; 95% confidence interval, 2.0-51.6; P = .005) and LVI (odds ratio = 3.9; 95% confidence interval, 1.1-14.2; P = .037) were associated with increased risk of RO involvement. Among 15 patients excluded for having a nonbladder primary malignancy, a third had RO involvement, and 2 (13%) had ovarian metastases. No women in our cohort had a primary ovarian malignancy detected at the time of RC.

Conclusion

Women with ovarian involvement by malignancy at the time of RC either had locally advanced disease with LVI or a non-bladder primary malignancy. The risk of incompletely resecting the primary malignancy would be rare if OSRC was performed on women with organ-confined (≤T2) urothelial carcinoma.  相似文献   

15.

Background

For oligometastatic lung adenocarcinoma patients with sensitive epidermal growth factor receptor (EGFR) mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in oligometastatic lung adenocarcinoma patients.

Patients and Methods

We conducted a retrospective study to assess the effects of LCT on progression-free survival (PFS) and overall survival (OS). Patients with advanced-stage oligometastatic lung adenocarcinoma harboring sensitive mutation of epidermal growth factor receptor (EGFR) who received EGFR–tyrosine kinase inhibitor (TKI) or EGFR-TKI plus LCT were admitted to Shanghai Chest Hospital from January 2010 to December 2016. The PFS and OS of the 2 groups were accordingly analyzed.

Results

A total of 231 patients (143 patients who received LCT plus EGFR-TKI [combination group] and 88 patients who only received EGFR-TKI only [monotherapy group]) were included in this study. Median PFS was significantly longer in the combination group (15 months; 95% confidence interval [CI], 13.611-16.389) than in the monotherapy group (10 months; 95% CI, 8.936-11.064; hazard ratio = 0.610; 95% CI, 0.461, 0.807; P = .000). The median OS in the combination group was 34 months (95% CI, 27.889, 40.111) versus 21 months (95% CI, 18.445, 23.555) in the monotherapy group (hazard ratio = 0.593; 95% CI, 0.430-0.817; P = .001).

Conclusion

LCT combined with TKIs therapy was a feasible method that significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with EGFR mutations, and it thus might be considered as an important medical treatment during clinical management.  相似文献   

16.
17.

Objectives

The paper aimed to compare the efficacy of log odds (LODDS) compared to a classification based on the distribution of involved lymph nodes (pN) and lymph node ratio (LNR).

Methods

Material was collected retrospectively from an online survey-based database of the Polish Lung Cancer Group and included a group of 17,369 patients who received radical surgical treatment (R0) due to lung cancer.

Results

In the whole group the median survival for N0, N1 and N2 was 76.1, 41.7 and 24.2 months, respectively. The median survival for individual LODDS categories (?6,-4], (?4,-3], (?3,-2], (?2,-1], (?1,0], (0,1] and (1,2] was 76.5, 76.3, 71.7, 45.4, 25.0, 19.1 and 17.7 months, respectively. The median survival for LNR in individual categories (0), (0,0.25], (0.25,05], (0.5075] and (0.75,1.0] was 75.6, 40.3, 24.1, 18.8 and 16.4 months, respectively. A multi-variant analysis demonstrated that each LODDS category is an independent prognostic factor: (?4,-3] (HR = 0.982; 95% CI 0.867–1.112; P = 0.775), (?3,-2] (HR = 1.114; 95% CI 0.984–1.262; P = 0.089), (?2,-1] (HR = 1.241; 95% CI 1.080–1.425; P = 0.002), (?1,0] (HR = 1.617; 95% CI 1.385–1.887; P < 0.0001), (0,1] (HR = 1.918; 95% CI 1.579–2.329; P < 0.0001) and (1,2] (HR = 2.016; 95% CI 1.579–2.573; P < 0.0001).

Conclusions

Based on LODDS it is possible to discriminate patients with regard to lung cancer stage more effectively compared to pN and LNR classification, and it is also a better classification system.  相似文献   

18.

Introduction

The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the acylphosphatase 2 gene and the SNP-SNP interactions on breast cancer (BC) risk in Chinese Han women.

Patients and Methods

A logistic regression model was used to examine the association between SNPs and BC risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP interaction.

Results

Logistic regression analysis showed that BC risk was significantly higher in carriers with the rs1682111-A allele than those with the TT genotype (TA + AA vs. TT; adjusted OR, 1.47; 95% CI, 1.21-1.92). In addition, we also found that BC risk was significantly higher in carriers with the rs10439478-C allele than those with the AA genotype (AC + CC vs. AA); adjusted OR, 1.67; 95% CI, 1.29-2.11. We found a significant 2-locus model (P = .0010) involving rs1682111 and rs10439478; the cross-validation consistency of this model was 10 of 10, and the testing accuracy was 60.11%. Participants with the TA or AA of rs1682111 and the AC or CC of rs10439478 genotype have the highest BC risk, compared with subjects with the TT of rs1682111 and the AA of rs10439478 genotype (OR, 2.52; 95% CI, 1.67-3.44), after covariate adjustment for gender, age, age at menarche, number of children, and body mass index.

Conclusions

Minor allele of rs1682111 and rs10439478 and its interaction were associated with increased BC risk.  相似文献   

19.

Introduction

The murine double minute 4 (MDM4) protein is a negative regulator of p53, and its upregulation has been observed in many tumor types. Previous literature suggested that genetic variations in the MDM4 gene are associated with risk of different cancers. The objective of the present study was to examine the effect of 3 common genetic variants of MDM4, rs4245739 A>C, rs11801299 G>A, and rs1380576 C>G, on the risk of breast cancer (BC) in a southeast Iranian population sample.

Patients and Methods

A total of 265 BC patients and 221 healthy women were included in this case-control study. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification refractory mutation system-PCR methods for detection of MDM4 polymorphisms.

Results

Our findings showed that rs1380576 C>G was associated with a reduced risk of BC using co-dominant (GC vs. CC: odds ratio [OR], 0.54; 95% confidence interval [CI], 0.34-0.84; P = .006; and GG vs. CC: OR, 0.49; 95% CI, 0.26-0.94; P = .044), dominant (CG+GG vs. CC: OR, 0.54; 95% CI, 0.35-0.82; P = .004), and allele models (G vs. C: OR, 0.74; 95% CI, 0.57-0.96; P = .025). However, our study failed to show any relationship between rs4245739 A>C and rs11801299 G>A variants and BC risk (P > .05). We also found no significant association between MDM4 variants and clinical characteristics of BC patients (P > .05).

Conclusion

Our findings proposed that the MDM4 rs1380576 C>G polymorphism was a protective factor for BC risk in our population. Additional studies with larger sample sizes and diverse ethnicities are required to confirm our findings.  相似文献   

20.

Introduction

Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42?1.91). Herein, we present an updated analysis.

Methods

A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025).

Results

As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%?42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33?0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti?programmed death 1/anti?programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32?0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events.

Conclusions

The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.  相似文献   

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