Retrospective Comparison of CAPOX and FOLFOX Dose Intensity,Toxicity, and Clinical Outcomes in the Treatment of Metastatic Colon Cancer

Purpose

The treatment of metastatic colon cancer (mCC) utilizes either combination therapies or sequential monotherapy followed by combination therapy in subsequent lines of treatment. Patients often receive therapy consisting of oxaliplatin with intravenous 5-fluoruacil (5-FU) (FOLFOX) or oral capecitabine (CAPOX). A retrospective analysis was performed comparing median dose intensity (MDI), overall survival (OS), progression-free survival (PFS), and toxicity profiles of these two regimens in mCC.

Methods

One hundred twenty-two mCC patients (pts) received either FOLFOX6 (n?=?46) or CAPOX (n?=?76). Age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status at diagnosis were balanced between groups. MDI was compared by calculating a percent of target dose achieved in the average cycle for each patient and taking the median of this value.

Results

Oxaliplatin MDI trended towards being lower in those treated with CAPOX compared to FOLFOX (87.5 vs 93 %, p?=?0.0874), and capecitabine (CA) MDI was significantly lower than 5-FU (82.0 vs 100 %, p?<?0.0001). There was a trend to more dose-limiting toxicities (DLTs) in pts treated with CAPOX (68.42 vs 54.35 %, p?=?0.1268), and grade?≥?2 toxicities were more frequent in CAPOX-treated pts (38.16 vs 15.22 % of patients, p?=?0.0079). Survival analysis demonstrated trends towards improved median OS (9.86 vs 7.46 months, p?=?0.1183) and median PFS (4.34 vs 3.33 months, p?=?0.1674) with CAPOX. In multivariate analysis, CAPOX was associated with improved OS (p?=?0.0156, hazard ratio (HR) 0.559) and disease-free survival (DFS) (p?=?0.0094, HR 0.549).

Conclusions

Patients treated with CAPOX received lower doses of oxaliplatin and fluoropyrimidine compared to FOLFOX and had toxicities of higher grade but did not have worsened clinical outcomes.     

Body Mass Index and Body Surface Area and Their Associations with Outcomes in Stage II and III Colon Cancer

Background

Our study aims were to measure the associations between body mass index (BMI) and body surface area (BSA) with outcomes for stage II and III colon cancer and to evaluate if the effect of obesity is modified by disease stage and receipt of adjuvant therapy.

Methods

Using a prospective cohort of stage II and III colon cancer patients who were referred between 2001 and 2005, we compared 3-year relapse-free survival (3-year RFS), 5-year cancer-specific survival (5-year CSS), and 5-year overall survival (5-year OS) rates among different BMI and BSA categories. Cox proportional-hazards models were constructed to explore the relationships between different body compositions and outcomes while adjusting for confounders.

Results

Postoperative height and weight were used to classify 913 patients as normal weight (n?=?424, BMI <25 kg/m²), overweight (n?=?319, BMI 25–30 kg/m²), and obese (n?=?170, BMI >30 kg/m²). Using Mosteller formula, 684 subjects had normal BSA (≤2.0 m²) and 229 had high BSA (>2.0 m²). Obese subjects experienced similar 3-year RFS (61.9 vs. 66.5 vs. 63.6 %, p?=?0.51), 5-year CSS (65.6 vs. 72.4 vs. 68.0 %, p?=?0.22), and 5-year OS (60.8 vs. 64.0 vs. 62.2 %, p?=?0.69) when compared to overweight subjects and those with normal BMIs, respectively. Likewise, individuals with high BSA had similar outcomes as those with normal BSA (66.2 vs. 63.6 %, p?=?0.64 for 3-year RFS, 70.3 vs. 68.6 %, p?=?0.62 for 5-year CSS, and 64.5 vs. 61.9 %, p?=?0.48 for 5-year OS). In Cox models, advanced age, male gender, stage III disease, and poor performance status correlated with inferior RFS, CSS, and OS, but BMI and BSA did not.

Conclusions

Obesity as measured by either BMI or BSA was not associated with differences in outcomes in stage II and III colon cancer.     

Preoperative Platelet Count Associates with Survival and Distant Metastasis in Surgically Resected Colorectal Cancer Patients

Objective

Platelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.

Design

Using a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.

Results

Patients with clinically high platelet count (≥400?×?10⁹/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR]?=?1.66, 95 % confidence interval [CI] 1.34–2.05, P?=?2.6?×?10^?6, P _{log rank}?=?1.1?×?10^?11) and recurrence (HR?=?1.90, 1.24–2.93, P?=?0.003, P _{log rank}?=?0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR?=?2.81, 1.67–4.74, P?=?1.1?×?10^?4, P _{log rank}?=?2.6?×?10^?6) but not locoregional recurrence (HR?=?0.59, 95 % CI 0.21–1.68, P?=?0.325, P _{log rank}?=?0.152). The findings were internally validated through bootstrap resampling (P?<?0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P?<?0.0001) and in patients with metastatic recurrence than locoregional (P?=?0.004) or nonrecurrent patients (P?<?0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.

Conclusion

Our data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.     

Analysis of unexplained carcinoembryonic antigen elevation after curative treatment of locally advanced rectal cancer

Background

To analyze the causes and patterns of unexplained carcinoembryonic antigen (CEA) elevation after curative treatment in locally advanced rectal cancer patients.

Methods

Among the 1309 locally advanced rectal cancer patients treated with curative resection and radiotherapy between January 2001 and June 2011, 325 patients who postoperatively developed abnormal CEA elevation were reviewed. The unexplained CEA elevation was defined as a CEA level higher than 5 ng/mL with no evidence of cancer recurrence at the time of elevation.

Results

Of the 325 patients, 143 (44%) had unexplained CEA elevations. The causes were categorized as delayed recurrence (n?=?29, 20%), non-colorectal malignancy (n?=?10, 7%), and non-malignancy-related conditions (n?=?104, 73%). Shorter intervals between treatment and the first CEA elevation, and a higher peak CEA level, were observed in the delayed recurrence group compared with the non-colorectal malignancy or non-malignancy-related group (intervals of 6.8 vs. 44.9 vs. 23.2 months, respectively, p?=?0.002; and peak CEA levels of 9.9 vs. 7.1 vs. 6.2 ng/mL, respectively, p?=?0.034). In patients who showed delayed recurrence, the interval between the first CEA elevation and diagnosis of recurrence was a median of 13.0 months (range 3.8–60.6 months). Smoking was the most common cause for non-malignancy-related conditions. The patterns of unexplained CEA elevations were defined as sporadic (n?=?78, 55%), stationary (n?=?37, 26%), and increasing (n?=?28, 20%). The patterns were significantly different depending on the cause (p?<?0.001).

Conclusions

Analysis of the patterns of unexplained CEA elevations is a reasonable approach to predict the cause of the cancer.

     

Clinical and Prognostic Significance of Coagulation Assays in Gastric Cancer

Purpose

Activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually, worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests in gastric cancer (GC) patients.

Materials and Methods

A total of 44 consecutive patients with a pathologically confirmed diagnosis of GC were enrolled into the study. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were evaluated. Control group comprised 50 age- and sex-matched individuals without history of malignancy and coagulation disorder.

Results

Median age at diagnosis was 55 years, range 19–80 years; most had men (n?=?32, 73 %) and metastatic disease (n?=?31, 70 %). The level of blood coagulation tests showed a statistically significant difference between the patient and the control groups (P?<?0.001 for all, but p?=?0.07 for PT). DD levels were significantly associated with elevated PLT and LDH levels (p?=?0.009 and p?=?0.01, respectively). Patients with metastatic disease had higher levels of F (p?=?0.001) and INR (p?=?0.027) levels. Elevated DD levels tended to be a poor prognostic factor on outcome (p?=?0.06).

Conclusion

Change in almost all coagulation tests are found in GC patients and only DD level seems to be of prognostic value.     

Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36–77 years); where males consistituted of majority of the group (88.8 %). All of patients had cirrhotic history. Fourty-six percent (n?=?25) of patients had Child-Pugh Score A, 30 % (n?=?16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p?<?0.001). Male patients had higher serum HGF levels compared with female patients (p?=?0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p?=?0.05). Poor performance status (p?<?0.001), viral etiology of cirrhosis (p?=?0.03), larger tumor size (p?=?0.01), lower serum hemogloblin levels (p?=?0.03), and not be treated for HCC (p?=?0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p?=?0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.     

Impact of Preoperative and Postoperative FOLFOX Chemotherapies in Patients with Resectable Colorectal Liver Metastasis

Purpose

Whether the survival benefit of perioperative FOLFOX in patients with liver metastases of colorectal cancer (LMCRC) is provided by preoperative chemotherapy (CT), postoperative CT, or both remains unclear. This study aimed to evaluate, in patients with resectable LMCRC, the survival impact of preoperative and postoperative separately.

Methods

Between 2000 and 2010, the 179 patients (126 men, age 61?±?11 years) with initially resectable LMCRC, who underwent liver resection (LR) and were offered pre- and/or postoperative FOLFOX were included. Twenty-four (13 %) patients did not receive CT, 27(15 %) patients received only preoperative CT, 71 (40 %) patients received only postoperative CT, and 57 (32 %) patients received both pre- and postoperative CT.

Results

Operative morbidity and mortality rates were 19 and 0.6 %, respectively. At 1, 3, and 5 years, OS and DFS rates were 97, 66, 46 and 60, 32, and 24 %, respectively. Postoperative FOLFOX was an independent predictor of increased OS (HR?=?0.55 [95 % CI, 0.35–0.87] p?=?0.01) and DFS (HR?=?0.54 [0.36–0.82] p?=?0.0017), whereas the synchronous onset of the metastasis and the presence of radiographically occult liver metastases were independent predictors of poorer OS. Alternatively, preoperative FOLFOX had no significant influence on OS (HR?=?0.96 [0.57–1.60] p?=?0.83) or DFS (HR?=?1.05 [0.66–1.66] p?=?0.87).

Conclusions

The survival benefit of FOLFOX in patients with resectable LMCRC may be provided by postoperative rather than preoperative administration.     

Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma

The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36–77 years; where majority of group were male (n?=?48, 88.8 %). All patients had cirrhotic history. Forty-six percent (n?=?25) of patients had Child-Pugh score A, 30 % (n?=?16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p?=?0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p?=?0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p?=?0.03, 0.03, and 0.05, respectively). Poor performance status (p?<?0.001), viral etiology of cirrhosis (p?=?0.03), larger tumor size (p?=?0.01), lower serum hemoglobin levels (p?=?0.03), and not be treated for HCC (p?=?0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p?=?0.53 and 0.42, respectively).     

Defining a prognostic score based on O6-methylguanine-DNA methyltransferase cut-off methylation level determined by pyrosequencing in patients with glioblastoma multiforme

We investigated the outcomes of gamma knife radiosurgery (GKRS) for elderly patients (≥?65 years) with brain metastases, and identified survival-associated factors. We retrospectively analyzed data from 115 patients treated with GKRS for 1–15 brain metastases. The median patient age was 72 years; most primary tumors were pulmonary (n?=?83). The mean lesion volume was 2.1?±?4.8 mL. A mean dose of 19.3 Gy was delivered to the mean 63.9% isodose line. The median overall survival (OS) was 5.3 months (95% confidence interval [CI] 3.5–7.1). During follow-up (median, 5.1 months), 91 patients died of primary cancer progression while 1 died of unknown causes. The 6- and 12-month local control rates were 94.9 and 88.1%, respectively. On multivariate analysis, female sex (p?=?0.005, hazard ratio [HR] 0.533, 95% CI 0.343–0.827) and a controlled primary tumor (p?<?0.001, HR 0.328, 95% CI 0.180–0.596) were significantly favorable prognostic factors. Of non-small cell lung cancer patients with EGFR mutations, 76.5% were women (p?=?0.005). The median OS of EGFR-mutant and EGFR-wildtype patients were 19.1 and 4.7 months, respectively (p?=?0.080). Brain metastases?<?3 mL showed better local control rates after GKRS (p?=?0.005). GKRS produces favorable outcomes in women with brain metastases who are ≥?65 years and have controlled primary tumors. Such patients are therefore suitable candidates for GKRS.     

Analysis of PTEN,BRAF and PI3K status for determination of benefit from cetuximab therapy in metastatic colorectal cancer patients refractory to chemotherapy with wild-type KRAS

We investigated predictive values of BRAF, PI3K and PTEN in cetuximab responses in KRAS wild-type (+) chemotherapy refractory, metastatic colorectal cancer (CRC) patients. Primary tumour tissues of 41 KRAS wild-type mCRC patients receiving cetuximab-based chemotherapy were investigated for PI3K, PTEN, KRAS and BRAF mutations. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan–Meier method and the Cox proportional hazards model was used. PTEN and PI3K expressions were 63 and 42 %, respectively. BRAF mutation was observed as 9.8 % among patients. Tumours with BRAF mutation had statistically lower response rates (RR) for cetuximab-based treatment than tumours with BRAF wild type (0 vs. 58 %, p?=?0.02). PTEN expressing tumours had statistically higher RR for cetuximab-based treatment than tumours with PTEN loss (42 vs. 12 %, p?=?0.04). PI3K expression had worse significant effect on cetuximab RR than PI3K non-expressed tumours (15 vs. 44 %, p?=?0.023). Median PFS was significantly longer in patients with PTEN expression (14 months) than in patients with PTEN loss (5 months) (HR, 0.4; p?=?0.028). Median PFS was significantly longer in patients with PI3K non-expression (15.2 months) than in patients with PI3K expression (4.1 months) (HR, 0.31; p?=?0.001). Significant difference in PFS and OS between patients with BRAF mutated and BRAF wild-type tumours was not detected. However, patients with PTEN expression had significantly longer OS (15.1 months) than patients with PTEN loss tumour (9.9 months) (HR, 0.34; p?=?0.008). Patients without PI3K expression had significantly longer OS (18.2 months) than patients with PI3K expression (10.1 months) (HR, 0.27; p?=?0.001). Multivariate analyses revealed that PTEN expression (HR, 0.48; p?=?0.02) and absence of PI3K expression (HR, 0.2; p?=?0.001) were independent prognostic factors for increased PFS. Similarly, PTEN overexpression (HR, 0.62; p?=?0.03) and absence of PI3K expression (HR, 0.27; p?=?0.005) were independent prognostic factors for increased OS. In PTEN loss, PI3K expression may be used as biomarkers to further select KRAS wild-type patients undergoing anti-epidermal growth factor receptor treatment.     

Quantitative assessment of the association between XRCC3 C18607T polymorphism and glioma risk

XRCC3 has an important function in the DNA double-strand break, and XRCC3 C18607T polymorphism is a common polymorphism at exon 7 of the XRCC3 gene. Published data on the association between XRCC3 C18607T polymorphism and glioma risk were inconclusive. Electronic databases of PubMed, and Embase were searched for studies assessing the association between XRCC3 C18607T polymorphism and glioma risk. Pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated to estimate the association. Ten studies with five studies from Caucasians and five studies from Asians were included, including 9,369 subjects. Meta-analysis of total included studies showed that XRCC3 C18607T polymorphism was associated with increased risk of glioma (T vs. C: OR?=?1.14, 95 % CI 1.02–1.28, P?=?0.02; TT vs. CC: OR?=?1.37, 95 % CI 1.03–1.83, P?=?0.03; TT vs. CC/CT: OR?=?1.31, 95 % CI 1.00–1.71, P?=?0.05; TT/CT vs. CC: OR?=?1.12, 95 % CI 1.02–1.22, P?=?0.02). Meta-analysis of the five studies from Asians showed that XRCC3 C18607T polymorphism was associated with increased risk of glioma (T vs. C: OR?=?1.22, 95% CI 1.09–1.36, P?<?0.01; TT vs. CC: OR?=?1.89, 95 % CI 1.38–2.57, P?<?0.01; TT vs. CC/CT: OR?=?1.78, 95 % CI 1.31–2.40, P?<?0.01; TT/CT vs. CC: OR?=?1.19, 95 % CI 1.04–1.36, P?=?0.01). Meta-analysis of the five studies from Caucasians didn’t find the association. In conclusion, the finding from the meta-analysis provides strong evidence for the association between XRCC3 C18607T polymorphism and glioma risk.     

Pathological and prognostic significance of hypoxia-inducible factor 1α expression in epithelial ovarian cancer: a meta-analysis

Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis. However, the association between HIF-1α and clinicopathological characteristics of epithelial ovarian cancers is controversial. We searched articles on the association between HIF-1α expression and clinicopathological variables of epithelial ovarian cancer in Cochrane Library, Pubmed, Web of Knowledge and China National Knowledge Infrastructure (CNKI) from inception to February 2014. Twenty-five studies were included in the final review. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in benign tissue (cancer vs. benign, odds ratio (OR) = 9.73 (95 % confidence interval (CI), 4.90, 19.32); P?P?P?=?0.04). The expression of HIF-1α in stages III–IV or lymph node metastasis was significantly higher than that in stages I–II or that without lymph node metastasis, respectively (OR?=?3.01 (95 % CI, 1.92–4.74); P?P?=?0.0004). HIF-1α was associated with histological grade of cancer (grades 3 vs. 1, OR?=?4.52 (95 % CI, 2.79–7.31); P?P?=?0.003; grades 3 vs. 1, OR?=?2.43 (95 % CI), 1.65–3.59; P?P?P?=?0.94; OR?=?1.06 (95 % CI, 0.73–1.55); P?=?0.75). In conclusion, HIF-1α is related to the malignant degree, FIGO stage, histological grade, lymph node metastasis and 5-year survival rate of epithelial ovarian cancer. It may play an important role in clinical treatment and prognostic evaluation.     

No evidence of correlation between p53 codon 72 G > C gene polymorphism and cancer risk in Indian population: a meta-analysis

p53 is a tumor suppressor gene, which is activated in response to several forms of cellular stress and exerts multiple antiproliferative functions, making it the most frequent target for genetic alteration in cancer. Various studies have evaluated the association between p53 codon 72 G?>?C (rs1042522) polymorphism and risk of cancer. However, results from the published studies remained inconclusive. The aim of this study is to investigate the precise association between this variant and a risk of cancer in a large-scale meta-analysis. We searched the PubMed (MEDLINE) and Google Scholar web databases for studies regarding the association of p53 codon 72 G?>?C polymorphism and risk of cancer in the Indian population. Pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated by using random effect model to assess the association. Twenty studies with 3,258 cancer cases and 4,260 healthy controls were included. Overall, no significant association was detected for C allele carrier (C vs. G: OR?=?1.135, 95 % CI?=?0.930 to 1.386, p?=?0.211) and homozygous (CC vs. GG: OR?=?1.200, 95 % CI?=?0.810 to 1.779, p?=?0.364), heterozygous (CG vs. GG: OR?=?1.204, 95 % CI?=?0.921 to 1.575, p?=?0.175), dominant (CC?+?CG vs. GG: OR?=?1.231, 95 % CI?=?0.932 to 1.625, p?=?0.144), and recessive (CC vs. GG?+?GC: OR?=?1.078, 95 % CI?=?0.792 to 1.468, p?=?0.632) genetic models, respectively. No significant publication bias was observed by using Begg’s funnel plot and Egger’s test. Present meta-analysis indicated that the p53 codon 72 G?>?C polymorphism was not associated with cancer risk. This suggests that this polymorphism may not be an independent risk factor for cancer in the Indian population.     

The role of bevacizumab in the treatment of glioblastoma

To investigate local control and radiation-induced brain necrosis in patients with melanoma brain metastases who received complete resection plus fractionated stereotactic radiosurgery (fSRS, 3?×?9 Gy) or fSRS alone. Factors associated with the clinical outcomes and the development of brain necrosis have been assessed. One hundred and twenty consecutive patients with 137 melanoma brain metastases who received surgery plus fSRS (S?+?fSRS) or fSRS alone were analyzed. All lesions evaluated in the study were treated with a dose of 27 Gy given in 3 fractions over three consecutive days. Cumulative incidence analysis was used to compare local failure (LF), distant brain failure (DBF), and radiation-induced brain necrosis (RN) between groups from the time of SRS. At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: S?+?fSRS, 14 months and 85%; fSRS, 12 months and 85% (p?=?0.2). Median DBF did not differ significantly by group, being 14 months for both groups. Nine patients who received S?+?fSRS and 20 patients treated with fSRS recurred locally (p?=?0.03). Six-month and 1-year LF rates were 5 and 12% in S?+?fSRS group and 17 and 28% in fSRS group (p?=?0.02). RN occurred in 21 patients (S?+?fSRS, n?=?14; fSRS, n?=?7; p?=?0.1). The cumulative 1-year incidence of RN was 13% after S?+?fSRS and 8% after fSRS (p?=?0.15). In conclusion, postoperative SRS (3?×?9 Gy) to the resection cavity is an effective treatment modality for melanoma brain metastases associated with better local control as compared with fSRS alone.     

Clinical and prognostic significance of Yes-associated protein in colorectal cancer

The Hippo signaling pathway is a critical regulator of organ size control during development, and its deregulation is associated with cancers. Acting downstream of this pathway, Yes-associated protein (YAP) was implicated in tumorigenesis. The present study aimed to explore the expression patterns and clinical significance of YAP in human colorectal cancer (CRC). In addition, we investigated the relationship between YAP expression and Wnt/β-catenin pathway activation in CRC. A total of 139 cases of CRC tissues were investigated by immunohistochemistry for the expression of YAP, cyclin D1, and β-catenin. The association between YAP expression and clinicopathologic features was analyzed. Our results showed that YAP was overexpressed in 52.5 % (73/139) cases of CRC and predominantly presented in the nucleus. There was an excellent correlation between YAP expression and pTNM stage (p?=?0.0024). YAP expression in CRC was significantly correlated with nodal status (p?=?0.0034), tumor status (p?=?0.0382), and cyclin D1 overexpression (p?<?0.0001). Importantly, YAP expression was associated with short overall survival (p?<?0.001). Furthermore, patients with YAP-positive and nuclear β-catenin-positive profiles had worse overall survival. Univariate and multivariate analyses revealed that YAP expression was an independent prognostic indicator of CRC (p?=?0.0207). Our results indicated that YAP overexpression contributed to the tumorigenesis and played a pivotal role in the progression in CRC, and the interaction of YAP and Wnt/β-catenin pathways needs further exploration.     

Serum levels of TUBB3 correlate with clinical outcome in Chinese patients with advanced gastric cancer receiving first-line paclitaxel plus capecitabine

The overexpression of ??-tubulin III (TUBB3) in tumor tissues was reversely related with the efficacy of paclitaxel and clinical outcome in different cancers. In this study, we aimed to investigate the association between serum levels of TUBB3 and clinical outcome in advanced gastric cancer patients receiving first-line paclitaxel plus capecitabine. One hundred and twenty-eight advanced gastric cancer patients receiving first-line paclitaxel plus capecitabine in Peking University Cancer Hospital from December 2006 to October 2010 were enrolled in the study. Serum samples from 32 healthy individuals were used as controls. TUBB3 expression level in advanced gastric cancer was significantly higher than that in healthy control group (31.6?±?17.8?ng/mL vs. 16.9?±?3.8?ng/mL, p?<?0.001). For all patients, the clinical benefit rate (CBR), median progression-free survival (PFS), and overall survival (OS) were 55.6?%, 179 and 306?days, respectively. The CBR, median PFS, and OS in patients with low (n?=?27) and high levels (n?=?101) of TUBB3 were 95.8?%/45.1?% (low vs. high, p?<?0.001), 190?days/166?days (p?=?0.064), and 360?days/297?days (p?=?0.023), respectively. Cox multivariate regression analysis demonstrated that the serum levels of TUBB3 were an independent prognostic factor for advanced gastric cancer patients (HR?=?1.950; 95?% CI, 1.242?C3.062; p?=?0.004). This study indicated that low levels of TUBB3 in serum could predict better response and survival for advanced gastric cancer patients receiving paclitaxel plus capecitabine, which could be used to select patients who would benefit from this regimen.     

The APE1 Asp148Glu polymorphism and colorectal cancer susceptibility: a meta-analysis

Background

Published data regarding the association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship.

Materials and methods

We systematically searched PubMed, Embase, and Web of Science with a time limit of August 19, 2013. Summary odds ratios (ORs) with 95 % CIs were used to assess the strength of association between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility using random-effects model.

Results

A total of eight case–control studies including 2,597 cases and 3,063 controls were included for analysis. Overall, no significant associations were found between the APE1 Asp148Glu polymorphism and colorectal cancer susceptibility for GG vs TT (OR?=?1.00, 95 % CI?=?0.73–1.36, p?=?0.00 for heterogeneity), TG vs TT (OR?=?1.17, 95 % CI?=?0.88–1.55, p?=?0.00 for heterogeneity), the dominant model GG + TG vs TT (OR?=?1.21, 95 % CI?=?0.91–1.60, p?=?0.00 for heterogeneity) nor the recessive model GG vs TG + TT(OR?=?0.95, 95 % CI?=?0.75–1.20, p?=?0.02 for heterogeneity). In subgroup analysis, no significant associations were found in the Asian or Caucasian populations.

Conclusion

This meta-analysis suggested that the APE1 Asp148Glu polymorphism was not associated with colorectal cancer susceptibility among Asians or Caucasians.     

Prognostic factors for desmoid tumor: a surgical series of 233 patients at a single institution

Desmoid tumors are rare soft tissue tumors with limited data on their management and prognosis. We sought to determine the rates of recurrence after surgery for desmoid tumors and analyze factors predictive of recurrence-free survival (RFS). From February 1976 to October 2011, 233 consecutive patients with desmoid tumors who underwent macroscopically complete resection were included in this study. Clinicopathologic and treatment characteristics were evaluated to determine predictors of recurrence. Patterns of presentation included primary (n?=?156, 67.0 %) and locally recurrent (n?=?77, 33.0 %) disease initially treated elsewhere. Most patients had a R0 resection (n?=?169, 72.5 %). In addition to surgery, 43 (18.5 %) patients received radiotherapy and 10 (4.3 %) patients received systemic therapy. Median follow-up was 54 months; recurrence disease was observed in 62 (26.6 %) patients. The estimated 5- and 10-year RFS was 74.2 % (95 % confidence interval (CI), 68.3–80.1) and 70.7 % (95 % CI, 64.2–77.2), respectively. Factors associated with worse RFS were tumor size larger than 5 cm (hazard ratio (HR)?=?3.757; 95 % CI, 1.945–7.259; p?p?=?0.006), and R1 resection status (HR?=?1.901; 95 % CI, 1.140–3.171; p?=?0.014). Patients were grouped according to the number of unfavorable prognostic factors; the 10-year RFS rates of patients with zero, one, two, and three prognostic factors were 100, 86.9, 48.5, and 34.4 %, respectively (p?相似文献   

Genetic polymorphism of DNA methyltransferase 3B 149 C>T and risk of colorectal cancer: a meta-analysis

Numerous studies have investigated the risk of colorectal cancer (CRC) associated with the polymorphism of DNA methyltransferase 3B (DNMT3B) 149 C>T, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of CRC. A comprehensive search was conducted to identify all case–control studies of the ?149C>T polymorphism of DNMT3B and CRC risk. A total of seven eligible studies, including 2,666 cases and 4,022 controls, relating the DNMT3B polymorphism of ?149C>T to the risk of CRC were identified. It suggested no significant associations between ?149C>T polymorphism of DNMT3B gene and the risk of developing CRC in the recessive, dominant, and co-dominant models (for CC versus TT: OR?=?0.90, 95 % CI?=?0.90–1.25, P _{heterogeneity}?=?0.37; for recessive model: OR?=?0.54, 95 % CI?=?0.28–1.04, P _{heterogeneity}?=?0.00001; for dominant model: OR?=?1.07, 95% CI?=?0.93–1.23, P _{heterogeneity}?=?0.83; and for C allele versus T allele: OR?=?0.70, 95 % CI?=?0.43–1.13, P _{heterogeneity}?=?0.00001). In the subgroup analysis, there is no significant associations were also found in European populations (for CC versus TT: OR?=?1.09, 95 % CI?=?0.92–1.30, P _{heterogeneity}?=?0.88; for recessive model: OR?=?1.00, 95 % CI?=?0.88–1.13, P _{heterogeneity}?=?0.14; for dominant model: OR?=?1.50, 95 % CI?=?0.89–2.54, P _{heterogeneity}?=?0.00001; and for C allele versus T allele: OR?=?0.70, 95 % CI?=?0.38–1.28, P _{heterogeneity}?=?0.00001). In conclusion, no significant association was found between the ?149C>T polymorphisms in DNMT3B and CRC susceptibility.     

Dose–response relationships between physical activity, social participation, and health-related quality of life in colorectal cancer survivors

Purpose

The purpose of this study was to examine the relationships between physical activity (PA), social participation, and health-related quality of life (HQOL) in older, long-term colorectal cancer survivors.

Methods

Male and female colorectal cancer survivors (n?=?1,768), aged ≥65 and ≥5 years post-diagnosis, completed surveys on their current PA, social participation, HQOL, health history, and relevant covariates. Analysis of covariance was used to evaluate the cross-sectional relationship between PA and social participation with the SF-36 subscales, as well as the physical component summary score (PCS) and mental health component summary score (MCS).

Results

The final analytic sample (n?=?832) was 81.5?±?5.8 years and 8.2?±?1.7 years post-diagnosis (mean ± SD). Meeting the current recommendation of 150 min/week of PA was associated with higher PCS (p?<?0.001) but not MCS (p?=?0.30). Engaging in any social participation, vs. none, was associated with MCS (p?=?0.003), but not PCS (p?=?0.13). There was a dose–response relationship between moderate–vigorous-intensity PA and PCS (p _trend<0.001). Light-intensity PA was not associated with either summary score after adjustment for moderate–vigorous PA (p?>?0.05), but in survivors performing no higher-intensity PA, it was associated with both (p?<?0.01, p?=?0.02, respectively). Participants reporting greater amounts of both planned exercise and non-exercise PA had significantly higher PCS (p _trend<0.01, p _trend?<?0.01, respectively). Individuals participating in greater weekly hours of social participation had higher PCS and MCS (p _trend<0.05) than those participating in less.

Conclusions

Among older, long-term colorectal cancer survivors, PA is related to their physical health, while social participation is predominantly related to their mental health.

Implications for Cancer Survivors

Older colorectal cancer survivors who participate socially and are engaged in PA, even non-exercise and light-intensity activities, have higher levels of physical and mental health.