Meta-analysis of the efficacy of postoperative adjuvant chemotherapy for stage IB non-small cell lung cancer.

BACKGROUND: Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC). METHODS: Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival. RESULTS: A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.19-1.31, P < .00001) and disease-free survival or recurrence-free survival (OR = 1.57, 95% CI 1.3-1.9, P < .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (OR = 1.52, 95% CI 1.05-2.18, P = .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (OR = 1.5, 95% CI 0.94-2.4, P = .09) was comparable to the observation group. CONCLUSION: Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone.

Recombinant human endostatin injection (Endostar) combined with PF chemotherapy and sequential intensity-modulated radiotherapy is tolerable and improves prognosis of locally advanced nasopharyngeal carcinoma: a randomized, open, multicenter phase II clinical study.

Nasopharyngeal carcinoma (NPC) is not only a common malignant disease of the head and neck, but also presented as locoregionally advanced NPC at diagnosis with poor prognosis. The efficacy of current chemoradiotherapy is unsatisfactory; therefore, in this study, we evaluated the safety and efficacy of treating locally advanced NPC using recombinant human endostatin injection (Endostar), combined with a cisplatin plus 5-fluorouracil (PF) regimen and sequential intensity-modulated radiotherapy (IMRT), and compared it with PF plus IMRT regimen. This phase II study included 83 eligible patients with stages III-IVa NPC (8th AJCC/UICC) who were randomized 1:1 into control (n = 42) and experimental (n = 41) groups. The control group received PF chemotherapy and IMRT for locally advanced NPC; One cycle of induction chemotherapy (IC) was administered before IMRT, and three cycles of adjuvant chemotherapy (AC) were administered four weeks post-radiotherapy. The experimental group received additional Endostar therapy. All patients were followed up for at least 5 years. The primary endpoints were progression-free survival (PFS) and the objective response rate. The secondary endpoints included overall survival and treatment-related toxicities. The short-term efficacy was evaluated at the end of the fourth chemotherapy cycle. Our results showed that the complete response rate of nasopharyngeal lesions was not significantly different between the experimental and control groups (80.5 vs. 71.4%, P = 0.335); however, there were significant differences in the complete response rates of cervical metastatic lymph nodes (75.6 vs. 40.5%, P = 0.001), especially for cervical N3 lymph nodes in the experimental group (55.6 vs. 9.5%, P = 0.004). The overall median follow-up time was 69.7 months. Patients in the experimental group showed significantly prolonged PFS by about four months (hazard ratio [HR] = 0.64, 95% CI: 0.41-0.99, P = 0.045). There was no significant difference in the median overall survival (P = 0.374). Furthermore, subgroup analysis indicated that the risk of death in patients with cervical N3 lymph nodes in the experimental group was reduced by 52% (HR = 0.48, 95% CI: 0.23-0.99, P = 0.046). Moreover, the incidence of radiation-induced grades 3-4 oral mucositis was significantly lower in the experimental group (29.3% vs. 54.8%, P = 0.019), while no significant differences in other severe adverse reactions were observed between the two groups (P>0.05). Taken together, our study indicated that, in patients with locally advanced NPC, Endostar in combination with PF chemotherapy and sequential IMRT significantly improved PFS, had tolerable treatment-related toxicities, improved the prognoses of patients with cervical N3 lymph nodes, and reduced the incidence of radiation-related oral mucositis.

Prognostic and clinicopathological significance of nm23-H1 expression in non-small cell lung cancer: A meta-analysis.

BACKGROUND: The relationship between the expression of nm23-H1 and the invasion and prognosis of non-small cell lung cancer (NSCLC) is still controversial. Therefore, we conducted a meta-analysis to determine the prognostic value of nm23-H1 in patients with NSCLC. And to explore the relationship between the expression of nm23-H1 and clinicopathological features in patients with NSCLC. METHODS: Literature search in PubMed, EMBASE, Cochrane Library, CNKI, and WanFang database was performed up to June 14, 2021. Studies on the expression and clinical significance of nm23-H1 in NSCLC were included. According to the inclusion and exclusion criteria, 2 researchers independently screened the literatures, extracted the data, and evaluated the quality. Meta-analysis was performed using RevMan 5.4 software (Nordic Cochran Centre, Copenhagen, Denmark). RESULTS: Twenty-five studies met our inclusion criteria and were finally included for the analysis, involving 2198 participants. Our meta-analysis revealed that nm23-H1 expression was associated with tumor differentiation (OR = 0.54, 95% CI: 0.42-0.70, P < .00001), TNM stage (OR = 1.70, 95% CI: 1.23-2.34, P = .001), and lymph node status (OR = 0.26, 95% CI, 0.17-0.39, P < .00001), but have no associate with sex, age, pathological type, and T stages. Additionally, low nm23-H1 expression reduced the 3-year survival rate (OR = 2.74, 95% CI: 1.54-4.86, P = .0006) and 5-year survival rate (OR = 2.78, 95% CI: 1.36-5.69, P = .005). CONCLUSION: Nm23-H1 can be used as a biomarker to predict tumor invasiveness and evaluate the prognosis of patients with NSCLC.

Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study.

Objective: To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC. Methods: This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results: Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events. Conclusion: Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies. Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT04411706.

Meta-analysis of the relationship between lymphovascular invasion and prognosis of patients with stage I gastric cancer.

Lymphovascular invasion is considered to be a high-risk pathological feature after radical resection of gastric cancer, but the relationship between lymphovascular invasion and the prognosis of stage I gastric cancer is still controversial. Therefore, we used meta-analysis to systematically evaluate the relationship between lymphovascular invasion and the prognosis of stage I gastric cancer. Up to September 2, 2021, the databases of PubMed, EMBASE, Cochrane Library, CNKI, and Wanfang were searched. According to the inclusion and exclusion criteria, 2 researchers independently completed the screening of literature, extraction of data, and quality evaluation. Meta-analysis was performed using RevMan 5.4 software merged with HR and 95%CI. A total of 7508 patients with stage I gastric cancer were included in 9 studies, and the positive rate of lymphovascular invasion was 17%. Lymphovascular invasion was significantly associated with shorter overall survival (OS) (univariate: HR = 4.05, 95%CI: 1.91-8.58; multivariate: HR = 2.10, 95%CI: 1.37-3.22) and relapse-free survival (RFS) (univariate: HR = 4.79, 95%CI: 2.30-9.99; multiple: HR = 2.17, 95%CI: 1.56-3.00). This study indicates that lymphovascular invasion is an independent risk factor affecting the prognosis of patients with stage I gastric cancer, and can be used as a reference index for postoperative adjuvant therapy.

The effect of adjuvant chemoradiotherapy on survival after R0 resection for stage III-N2 nonsmall cell lung cancer: A meta-analysis.

BACKGROUND: Adjuvant chemotherapy is still the standard treatment for stage III-N2 nonsmall cell lung cancer after R0 resection, and it is still controversial whether conventional adjuvant radiotherapy is needed. We used meta-analysis to try to answer whether adjuvant postoperative chemoradiotherapy (POCRT) can bring survival benefits to patients with stage III-N2 nonsmall cell lung cancer after R0 resection. METHODS: Up to June 25, 2021, the databases of PubMed, Embase, Cochrane Library, CNKI, and Wanfang were searched, and clinical studies on POCRT for stage III-N2 nonsmall cell lung cancer were included. RevMan5.4 software was used for meta-analysis. RESULTS: A total of 8959 patients were included in 5 randomized controlled trials and 17 retrospective studies. The results of the meta-analysis showed that POCRT could improve 3 and 5 years overall survival (OS) rate (OR = 1.52, 95%CI: 1.05-2.20; OR = 1.30, 95%CI: 1.16-1.46), 3 and 5 years disease-free survival (DFS) rate (OR = 1.34, 95%CI: 1.01-1.76; OR = 1.74, 95%CI: 1.43-2.12), and 5-year locoregional recurrence-free survival (LRFS) rate (OR = 2.69, 95%CI: 1.76-4.11) in patients with stage III-N2 nonsmall cell lung cancer compared with adjuvant postoperative chemotherapy (POCT) alone. But could not improve 5-year distant metastasis-free survival (DMFS) rate (OR = 1.14, 95%CI: 0.52-2.52). The results of subgroup analysis showed that postoperative sequential chemoradiotherapy could improve the 3 and 5 years OS rate (OR = 2.06, 95%CI: 1.22-3.46; OR = 1.39, 95%CI: 1.21-1.59). Three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) can improve the 3 and 5 years OS rate (OR = 1.80, 95%CI: 1.09-2.99; OR = 1.31, 95%CI: 1.04-1.66). In addition, POCRT could improve the 3-year OS rate (OR = 1.88, 95%CI: 1.21-2.92) in patients with N2 single-station lymph node metastasis compared with POCT alone. CONCLUSION: Compared with POCT alone, adjuvant POCRT can significantly improve the overall survival rate of patients with NSCLC after R0 resection of stage III-N2, especially in patients with N2 single-station lymph node metastasis. Accurate radiotherapy techniques such as 3DCRT or IMRT are recommended, and postoperative sequential chemoradiotherapy is the best treatment mode.

Efficacy and safety of sorafenib combined with TACE in the treatment of advanced hepatocellular carcinoma: A meta-analysis.

PURPOSE: Sorafenib combined with transcatheter arterial chemoembolization (TACE) is one of the common methods in the clinical treatment of advanced hepatocellular carcinoma (HCC), but its efficacy and safety are still controversial. Therefore, we used meta-analysis to evaluate the efficacy and safety of sorafenib combined with TACE in the treatment of advanced HCC. METHODS: Up to March 14, 2021, the databases of PubMed, EMBASE, Cochrane Library, CNKI and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of sorafenib combined with TACE in the treatment of primary HCC were included. Two researchers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Revman5.4 software was used for meta-analysis. RESULTS: A total of 3076 patients were included in 23 studies, including sorafenib combined with TACE group (n=1542) and TACE group (n=1534). The results of meta-analysis showed that sorafenib combined with TACE could increase the objective response rate (ORR) (RR=1.35, 95%CI: 1.24-1.48, p<0.00001), disease control rate (DCR) (RR=1.19, 95%CI: 1.11-1.28, p<0.00001), prolong the time of disease progression (TTP) (HR=0.80, 95%CI: 0.70-0.92, p=0.001), reduce the expression level of alpha-fetoprotein (AFP) (SMD=2.01, 95%CI: 1.27-2.75, p<0.00001) and vascular endothelial growth factor (VEGF) (SMD=2.62, 95% CI: 1.35-3.90, p<0.0001) in serum. However, the overall survival (OS) was not prolonged (HR=0.86, 95%CI: 0.73-1.02, p=0.09). The incidences of fatigue, diarrhea, elevated bilirubin, skin reaction of hands and feet, rash, hypertension and oral mucosal inflammation in sorafenib combined with TACE group were higher than those in TACE group (p<0.05). CONCLUSION: Sorafenib combined with TACE has some clinical benefits compared with TACE alone, but it does not seem to prolong the OS of patients with HCC, and the incidence of adverse reactions is higher, so more high-quality RCTs are needed to further study the efficacy of the combination regimen.

Laboratory investigation of permeability property of natural gravels with different particle sizes under different laying conditions.

The seepage properties of natural gravel are one of the problems to be considered in seepage project designs. In this paper, the seepage properties of the natural gravel with particle sizes of 5, 20 and 60 mm were investigated under different laying conditions. The effect of the particle size, laying depth, bulk density and pressurized head on the seepage properties of the natural gravel was analyzed by using the combined methods of theoretical analysis with physical model test. The results showed that the seepage flow in the natural gravel was non-laminar flow in the test conditions described in this paper. Meanwhile, the relationship between particle size, laying depth, bulk density, pressurized heads and seepage property was established. The seepage discharge increased with the increase of the pressurized head and particle size, and decreased with the increasing of laying depth and bulk density. The critical laying depth and bulk density can be obtained when the seepage discharge becomes zero. The empirical formula of the seepage discharge of natural gravel with different particle sizes, laying depths, bulk densities and pressurized heads was obtained with the method of nonlinear regression, which can be expressed as: Q=5.9546d0.3713γ-0.2974L-0.1156H0.1307-5.6614. The empirical formula was experimentally validated. The maximum relative error did not exceed 6.73%, proving that the empirical formula of the seepage discharge of natural gravel was rational. The results can provide an important reference to further studying the seepage properties of macropore media, and form a theoretical basis for applying the natural gravel in the seepage projects.