Development and validation of a nomogram for predicting overall survival of gastric cancer patients after D2R0 resection.

OBJECTIVE: The aim of the study was to find factors associated with overall survival (OS) and establish a nomogram predicting OS of patients with gastric cancer (GC) after D2R0 resection. METHODS: Demographic and clinicopathologic factors of patients with GC underwent D2R0 surgical resection were retrospectively collected from medical records, telephone interview or outpatient follow-up. To find factors significantly associated with OS, univariate and multivariate analyses were conducted. The concordance index (C-index) was used to measure the accuracy of the nomogram. Discrimination and calibration of the nomogram were tested using the patients in the validation set. RESULTS: Overall, patients with 890 GC underwent D2R0 surgical resection were included. Based on the results of univariate analysis and multivariate analysis, T stage, number of metastatic local lymph nodes, lymph node positive rate, adjuvant chemotherapy and diameter of tumour were used to construct a nomogram predicting OS of patients with GC after surgical resection. In the validation cohort, the C-index was 0.73 and the nomogram performed well in predicting OS. CONCLUSION: The nomogram was able to accurately predict OS of patients with GC underwent curative surgery and performed well in internal validation, which would also be useful for the decision-making of doctors.

[Effects of shRNA on Cisplatin-resistant Non-small Cell Lung Cancer Cell A549 via Silencing CCAT2].

OBJECTIVE: To investigate the effects of short hairpin RNA (shRNA) on the proliferation, invasion, apoptosis and tumor formation of non-small cell lung cancer cisplatin-resistant cell line (A549/DDP) via silencing of colon cancer associated transcript 2 ( CCAT2). METHODS: TA549/DDP cells were transfected with shRNA- CCAT2 (sh- CCAT2) or shRNA-negative control (shRNA-NC), and untransfected A549/DDP cells were used as the control group. CCAT2 mRNA expression in three groups of A549/DDP cells was detected by quantitative real-time PCR (qRT-PCR). The proliferation of three groups of A549/DDP cells treated with different mass concentrations of DDP (0-8 mg/L) was detected by MTT. According to the proliferation experiment results, 2 mg/L was selected as DDP concentration for subsequent experiments. The effects of 2 mg/L DDP treatment on the proliferation, apoptosis, and invasion ability of each group of cells (with untreated A549/DDP cells as the control group) were tested by clone formation experiments, flow cytometry analysis and Transwell experiments. The expression levels of cell proliferation marker proteins (Ki67, PCNA), apoptosis marker proteins (Caspase-3, Caspase-9) and invasion marker proteins (VEGF, MMP-14) were detected by Western blot. Nude mice were injected subcutaneously with A549/DDP cells, A549/DDP cells transfected with shRNA-NC or A549/DDP cells transfected with sh- CCAT2. DDP was intraperitoneally injected at the concentration of 2 mg per kilogram of mice body weight totally for 7 times with an interval of 3 d. A control group was injected subcutaneously with A549/DDP cells, and an equal volume of normal saline instead of DDP was injected intraperitoneally. The tumor volume was detected every 5 d for a total of 30 d. Mice were sacrificed and tumor tissues were taken out 30 d later. CCAT2 mRNA expression level in tumor tissues was detected by RT-PCR, and tumor cell apoptosis was detected by TUNEL staining. RESULTS: Compared with the control group and the shRNA-NC transfection group, the expression level of CCAT2 mRNA was decreased in sh- CCAT2 transfected A549/DDP cells ( P<0.01). The decrease degree of cell proliferation was more pronounced after treating with 2 to 8 mg/L of DDP ( P<0.01). Compared with the control group, in the three groups that treated with DDP, the formation of clones and the expression of proliferation marker proteins Ki67 and PCNA were reduce ( P<0.01), while the rate of apoptosis and the expression of apoptosis marker proteins Caspase-3 and Caspase-9 were increased ( P<0.01). Also, the number of invasion cell and the expression of invasion marker proteins VEGF and MMP-14 were reduced in the three groups that treated with DDP ( P<0.01). Among the three groups of DDP-treated cells, the changes in sh- CCAT2 transfected cells was the most obvious ( P<0.01). Compared with the control group, the tumor volume of the three DDP treatment groups was smaller and the differences were statistically significant at 30 d ( P<0.01). The expression of CCAT2 mRNA was decreased in tumor tissues ( P<0.01), while apoptosis increased ( P<0.01). Among the three DDP treatment groups, the A549/DDP cell group transfected with sh- CCAT2 showed the most notable changes ( P<0.01). CONCLUSION: sh- CCAT2 can inhibit the proliferation of A549/DDP cells, induce apoptosis and reduce the cell invasion ability, thereby inhibiting the growth of A549/DDP cells.

Cost-effectiveness analysis of colon cancer treatments from MOSIAC and No. 16968 trials.

AIM: To compare XELOX and FOLFOX4 as colon cancer adjuvant chemotherapy based on MOSAIC and No. 16968 trails from Chinese cost-effectiveness perspective. METHODS: A decision-analytic Markov model was developed to compare the FOLFOX4 and XELOX regimens based MOSAIC and No. 16968 trial. Five states were included in our Markov model: well (state 1), minor toxicity (state 2), major toxicity (state 3), quitting adjuvant chemotherapy (state 4), and death due to adjuvant chemotherapy (state 5). Transitions among the 5 states were assumed to be Markovian. Costs were calculated from the perspective of the Chinese health-care payer. The utility data were taken from published studies. Sensitivity analyses were used to explore the impact of uncertainty factors in this cost-effectiveness analysis. RESULTS: Total direct costs of FOLFOX4 and XELOX per patient were $19884.96 ± 4280.30 and $18113.25 ± 3122.20, respectively. The total fees related to adverse events per patient during the entire treatment were $204.75 ± 16.80 for the XELOX group, and $873.72 ± 27.60 for the FOLFOX4 group, and the costs for travel and absenteeism per patient were $18495.00 for the XELOX group and $21,352.68 for the FOLFOX4 group. The base-case analysis showed that FOLFOX4 was estimated to produce an additional 0.06 in quality adjusted life years (QALYs) at an additional cost of $3950.47 when compared to the XELOX regimen over the model time horizon. The cost per QALY gained was $8047.30 in the XELOX group, which was $900.98 less than in the FOLFOX4 group ($8948.28). The one way sensitivity analysis demonstrated that the utility for the well state and minor toxicity state greatly influenced the incremental cost-effectiveness ratio of FOLFOX4. CONCLUSION: In term of cost-comparison, XELOX is expected to dominate FOLFOX4 regimes; Therefore, XELOX provides a more cost-effective adjuvant chemotherapy for colon cancer patients in China.

Safety and efficacy of radiation and chemoradiation in patients over 70 years old with inoperable esophageal squamous cell carcinoma.

The aim of the present study was to perform a retrospective analysis to investigate the outcome and toxicity of radiation (RT) and chemoradiation (CRT) in elderly, inoperable patients >70 years old. Between 2003 and 2012, 1,024 patients with squamous cell carcinoma (SCC) of the esophagus were treated at the Department of Thoracic Cancer, West China Hospital (Chengdu, China). Of these patients, 37 were >70 years old and had not undergone surgery, and were selected for analysis. Of these 37 patients, CRT had been administered to 20 (54%). Actuarial survival rates were determined by the Kaplan-Meier method. The one-year survival rate in the CRT group (n=20) was 85%, while 35% of patients in the RT group (n=17) survived for more than one year. The overall and progression-free survival in the CRT group versus the RT group were 17 months [95% confidence interval (CI), 11.861-22.139] versus eight months (95% CI, 6.674-9.326) (P=0.013) and 14 months (95% CI, 9.617-18.383) versus five months (95% CI, 2.311-7.689) (P=0.01), respectively. Patients irradiated with a dose of >50 Gy exhibited an improved survival rate compared with patients who received a dose of ≤50 Gy (18 vs. 14 months; P=0.049). Furthermore, patients with an Eastern Cooperative Oncology Group (ECOG) score of ≤1 had an improved prognosis compared with those with an ECOG score of 2 (14 vs. seven months; P=0.006). The two regimens were well-tolerated and there were no therapy-associated mortalities. The current retrospective study indicated that patients of >70 years old with inoperable esophageal SCC and a good ECOG score exhibit comparably better safety levels with CRT and improved survival rates compared with RT alone.