Prognostic value of preoperative serum tumor markers in gastric cancer

AIM:To evaluate the prognostic value of preoperative carcinoembryonic antigen(CEA), carbohydrate antigen(CA)19-9, and CA50 in patients undergoing D2 resection.METHODS:We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9,and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses.RESULTS:The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age(P < 0.001), sex(P = 0.022), tumor size(P = 0.007) and depth of invasion(P = 0.018); CA19-9 with tumor size(P = 0.042)and lymph node metastasis(P < 0.001); and CA50 onlywith lymph node metastasis(P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy(P = 0.027).CONCLUSION:Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy.

Paclitaxel based vs oxaliplatin based regimens for advanced gastric cancer

AIM:To compare the efficacy and safety of paclitaxel combined with fluorouracil plus cisplatin(PCF),and oxaliplatin combined with fluorouracil plus leucovorin(FOLFOX-4) regimens for advanced gastric cancer(AGC).METHODS:Ninety-four patients with AGC were randomly assigned to receive paclitaxel(50 mg/m2 iv) on days 1,8 and 15,cisplatin(20 mg/m2 iv) and ? uorouracil(750 mg/m2 iv) on days 1-5,or oxaliplatin(85 mg/m2 iv) and leucovorin(200 mg/m2 iv) on day 1,followed by bolus fluorouracil(400 mg/m2 iv) and fluorouracil(600 mg/m2 iv) on days 1 and 2.The primary end point was the 1-year survival time.RESULTS:The overall response rate(ORR) of the pa-tients was 48.0% and 45.5% to PCF and FOLFOX-4,respectively.The disease control rate(DCR) of PCF and FOLFOX-4 was 82.0% and 81.8%,respectively.The median survival times(MSTs) of the patients were 10.8 and 9.9 mo,respectively,after treatment with PCF and FOLFOX-4.The 1-year survival rate of the patients was 36.0% and 34.1%,respectively,after treatment with PCF and FOLFOX-4.No significant difference was observed in ORR,DCR,MST or 1-year survival rate between the two groups.The most common adverse events were anemia,nausea and vomiting,and grade 3/4 alopecia in PCF treatment group,and anemia,grade 1/2 neurotoxic effect and grade 3/4 neutropenia in FOLFOX-4 treatment group.CONCLUSION:Patients with AGC have a similar response rate to PCF and FOLFOX-4 regimens with a similar survival rate.The PCF and FOLFOX-4 regimens are efficacious and tolerable as a promising therapy for AGC.

Expert consensus on maintenance treatment for metastatic colorectal cancer in China

The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.

Combination chemotherapy with paclitaxel,cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma:a multicenter prospective study

Objective： To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU （PCF） as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction （EGJ） adenocarcinoma in China. Methods： The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/（mLd） intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results： Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy （group A） and 34 received the regimen as the second-line therapy （group B） with the median age of 59 years old and Karnofsky performance status （KPS） score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival （mOS） was 12.0 months （95% CI： 7.9-16.2 months） in group A and 7.3 months （95% CI： 4.3-10.3 months） in group B, respectively. The median progression-free survival （mPFS） was 5.7 months （95% CI： 4.1-7.2 months） and 5.0 months （95% CI： 3.1-6.9 months）, respectively. The response rate （CR^PR） was 40% （16/40; 95% CI： 24.9-56.7%） in group A and 22.6% （7/31; 95% CI： 9.6-41.1%） in group B. Major grade 3 or 4 adverse events include neutropenia （41.3 %）, febrile neutropenia （9.3 %）, nausea/anorexia （10.7%）, and vomiting （5.3 %）. There was no treatment-related death. Conclusions： The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.

HOX transcript antisense intergenic RNA represses E-cadherin expression by binding to EZH2 in gastric cancer

AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA(HOTAIR) in gastric cancer(GC) migration and invasion.METHODS Quantitative real-time polymerase chain reaction(qp CR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve(AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qp CR,western blot and immunohistochemistry were used to evaluate the m RNA and protein expression of E-cadherin. RNAbinding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin.RESULTS The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues(p < 0.001). Its over-expression was correlated with tumor-node-metastasis(TNM) stage(p = 0.024),tumor invasion(p = 0.018),lymph node metastasis(p = 0.023),and poor prognosis(p < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival(p = 0.033),together with TNM stage(p = 0.002) and lymph node metastasis(p = 0.002). The AUCROC was up to 0.709(95%CI: 0.623-0.785,p < 0.001). Knockdown of HOTAIR by si RNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines,and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.

Temozolomide for treatment of brain metastases: A review of 21 clinical trials

Brain metastases from solid tumours are associated with poor prognosis despite aggressive treatment. Temozolomide can be used for the treatment of glioblastoma multiforme as well as melanoma. It has also been shown to have activity in patients with brain metastases from various malignancies, since it can cross the blood-brain barrier. To better understand the efficacy of temozolomide in the treatment of brain metastases, we carried out a review of 21 published clinical trials to determine whether temozolomide would benefit patients with brain metastases from solid tumours. Information regarding complete response, partial response, stable disease, objective response and objective response rate were collected to assess clinical outcomes. A modest therapeutic effect was observed when temozolomide was used as a single agent, however, the combination of temozolomide with whole-brain radiotherapy and/or other anticancer drugs exhibited encouraging activity. Thus, future high quality studies are warranted to confirm our findings.

Prognostic value of perioperative leukocyte count in resectable gastric cancer

AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.

Plasma Vitamin D Levels And Vitamin D Receptor Polymorphisms Are Associated with Survival of Non-small Cell Lung Cancer

Objective：Vitamin D and its receptor（VDR） involve in multiple cellular processes and play an important role in the initiation and progression of malignancy.Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms（SNPs） in VDR may be of prognostic significance in non-small cell lung cancer（NSCLC）.Methods：We examined plasma 25-hydroxyvitamin D [25（OH）D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay（ELISA） and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.Results：Patients with higher plasma 25（OH）D levels had worse survival than patients with lower ones（P for trend = 0.048）.The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival（adjusted HR = 1.61,95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51,95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG）.A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased（P for trend = 0.003）.There were no significant associations between VDR polymorphisms and plasma 25（OH）D levels.Conclusion：Our findings indicate that plasma 25（OH）D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.

A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis:sensitive to chemical and biological therapy

Mycosis fungoides is a common cutaneous T-cell lymphoma,which is usually characterized by chronic,indolence progression,with absence of typical symptoms in early stage,metastasis to lymph nodes,bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma.It can result in secondary skin infection which is a frequent cause of death. At present,no curative therapy existed.Therapeutic purpose is to induce remission,reduce tumor burden and protect immune function of patients.A case of patient with advanced severe mycosis fungoides receiving CHOP plus interferon a -2a was reported here,with disease-free survival of 7 months and overall survival of over 17.0 months,and current status as well as developments of mycosis fungoides were briefly introduced.

Co-mutations in tumor immune microenvironment and immunotherapy

Tumor microenvironment mainly includes fibroblasts,macrophages,endothelial cells,and immune cells.The heterogeneity of tumor immune microenvironment(TIME)affects the response of different patients to immunotherapy.Cancer immunotherapy using immune checkpoint inhibitiors(ICIs),which can be achieved by antibodies blocking the programmed cell death 1(PD-1)/programmed death ligand-1(PD-L1)or the cytotoxic T lymphocyte-associated protein 4(CTLA-4)pathway alone or in combination,prompts a new paradigm shift in oncology.However,the response rates to the ICIs in cancer patients are relatively low and the results of the reported biomarkers for predicting the treatment efficacy are conflicting.Therefore,novel and reliable biomarkers are urgently needed to monitor tumor-specific immune responses,avoid immune-related adverse events,and improve clinical efficacy.

Combination therapies with mitogen-activated protein kinase kinase inhibitors and immune checkpoint inhibitors in non-small cell lung cancer

In the past few decades,tremendous advances have been made in terms of advaneed non-small cell lung cancer(NSCLC).The identification of oncogenic drivers and the development of targeted therapies led to the development of"pre&sion"medicine.On the other hand,more attention has been paid to cancer immune escape and a new class of immunomodulatory agents has been developed.It is very attractive to explore the combination strategies of the two approaches,which may also be meaningful from the perspective of immunology.