Yao Liang

Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer

Aims To evaluate the clinical significance of multiple serum tumor markers (TMs) in the diagnosis of gastric cancer (GC) and establish an accurate discriminant equation to identify the presence of GC. Results The serum levels of CEA, CA19-9 and CA72-4 were higher in the GC group than in the control group (P < 0.005). The sensitivity of CEA, CA19-9 and CA72-4 in the diagnosis of GC was 20.1–27.6% individually and increased to 48.2% when they were considered in combination. By using the optimal cut-off value, the sensitivity of CEA, CA19-9 and CA72-4 for the diagnosis of GC was improved but remained unsatisfactory. In addition, we developed the equation Y = −2.185 − 0.015 X1 + 0.180 X2 + 1.226 X3 + 1.505 X4 + 2.749 X5 (X1 = Age, X2 = Sex, X3 =CEA, X4 = CA19-9 and X5 = CA72-4) to predict the presence of GC. This has better accuracy and diagnostic efficiency compared to the combination of TMs. Methods Serum carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9)and cancer antigen 72-4 (CA72-4) levels were measured in a total of 2288 patients with GC and 1869 healthy volunteers or patients with benign gastric diseases. We established a diagnostic equation using a portion of the data (training set), and validate its accuracy using the other portion of the data (testing set). Conclusions The diagnostic equation increases the accuracy rate for the diagnosis of GC and will be helpful in the clinic.

PD-L1 expression is associated with FOXP3+ regulatory T-Cell infiltration of soft tissue sarcoma and poor patient prognosis

Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010. PD-L1 and FOXP3 expression was evaluated by immunohistochemistry. Correlation between their expressions and associations with clinicopathological features were studied. Results: Among 163 STS samples, 19 (11.7%) exhibited PD-L1 positivity, and 41 (25.2%) cases expressed high FOXP3+ Treg infiltration. Significant correlation between PD-L1 expression and FOXP3+Treg infiltration in STS was identified (r=0.450, p<0.001). In univariate analysis, PD-L1 expression was significantly associated with high tumor grade and the age of patients, while the presence of FOXP3+ in tumor infiltrating Tregs was significantly associated with the age of patients, high tumor stage, higher tumor grade and tumor depth. Multivariate analysis revealed PD-L1 and FOXP3 as independent prognostic indicators significantly associated with OS and DFS. Conclusions: Our study revealed that PD-L1 and FOXP3+Tregs may work synergistically in promoting immune evasion of the tumors in soft tissue sarcoma. A combined strategy to block PD-L1/PD-1 with simultaneous depletion of Tregs may show promise in enhancing the therapeutic efficacy of these patients.

Chemoradiotherapy for Synchronous Multiple Primary Cancers with Esophageal Squamous Cell Carcinoma: a Case-control Study.

Objective: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CRT) in multiple primary cancers (MPC) of the upper digestive tract in esophageal squamous cell carcinoma (ESCC). Methods: In a screening of 1193 consecutive patients diagnosed with ESCC and received radiotherapy, 53 patients presenting synchronous MPC in the upper digestive tract were retrospectively investigated. 53 consecutive patients with esophageal non-multiple primary cancer (NPC), matched by stage, age and sex, served as control. All of the patients received concurrent CRT. The median radiation dose was 60 Gy. Chemotherapy regimens were based on platinum and/or 5-fluorouracil. Clinical outcomes and treatment toxicities were compared. Results: Clinic-pathologic characteristics were well balanced between groups. MPC mostly located in esophagus (43, 81.8%), followed by hypopharynx (8, 15.1%) and stomach (2, 3.8%). In MPC and NPC patients, 94.3% and 96.2% completed the intended treatment. The immediate response rate was 73.6% vs 75.5%, with complete response rate of 11.3% vs 24.5% and partial response rate of 62.3% vs 51.0%. Two-year overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were 52.2% vs 68.9% (p=0.026), 32.9% vs 54.0% (p=0.032), 60.8% vs 87.8% (p=0.002) and 64.0% vs 70.8% (p=0.22), respectively. Acute grade 3-4 toxicities were observed in 64.2% vs 54.7%, significantly higher in radiation esophagitis (49.1% vs 28.3%, p<0.001), and mucositis (11.3% vs 00p=0.027). Conclusions: Compared with matched NPC, ESCC accompanied with synchronous MPC was related to significantly impaired survival, elevated risk of locoregional disease progression and higher incidence of severe esophagitis and mucositis, following concurrent chemoradiotherapy. Future study on reasons for decreased efficacy of chemoradiotherapy will help to optimize treatment. Advanced radiation techniques may play a role in protecting normal tissues and reduce acute toxicities.

Combined use of the neutrophil-lymphocyte and platelet-lymphocyte ratios as a prognostic predictor in patients with operable soft tissue sarcoma

Background: Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with poor prognosis in soft tissue sarcoma (STS). The aim of the present study is to determine whether the combination of NLR and PLR (CNP) can better predict patient survival after resection for STS. Methods: We included 310 STS patients in this retrospective study. Preoperative CNP was calculated as follows: patients with both elevated NLR (>2.51) and PLR (>191.1) were given a score of 2; patients showing an increase in one or neither were allocated a score of 1 or 0, respectively. Results: Cut-off values of 2.51 and 191.1 were defined as elevated NLR and PLR, respectively. Elevated CNP was significantly associated with older age (P=0.034), larger tumor size (P=0.025), deeper tumor location (P=0.044), higher tumor grade (P=0.028), a more advanced stage according to the American Joint Committee on Cancer (AJCC) (P=0.005), shorter overall survival (OS) (P=0.000) and shorter disease-free survival (DFS) (P=0.000). Multivariate analysis indicated CNP but not NLR or PLR to be an independent prognostic factor for OS and DFS (P=0.000 and P=0.001, respectively). Conclusions: Preoperative CNP is associated with tumor progression and can be considered an independent marker of postoperative survival in patients with STS.

Treatment-related adverse effects with pazopanib, sorafenib and sunitinib in patients with advanced soft tissue sarcoma: a pooled analysis

Objective Research efforts have investigated therapies targeting tyrosine kinase signaling pathways. We performed a pooled analysis to determine the frequency of severe adverse effects in patients with soft tissue sarcoma treated with pazopanib, sorafenib and sunitinib. Materials and methods We performed a comprehensive search of PubMed, Web of Science, Ovid, the Cochrane Library and Embase databases from the drugs’ inception to May 2017 to identify clinical trials. All-grade and severe adverse events (AEs; grade≥3) were analyzed. Results A total of 10 trials published between 2009 and 2016, including 843 patients, were eligible for analysis. We included 424 patients (three studies) who received pazopanib 800 mg daily, 353 patients (five studies) who received sorafenib 400 mg twice daily and 66 patients (two studies) who received sunitinib 37.5 mg daily. The incidence of AEs is different among the three VEGFR-tyrosine kinase inhibitors (TKIs). Pazopanib showed higher incidence of all-grade nausea, diarrhea and hypertension compared with sorafenib and sunitinib. However, patients in the sorafenib group experienced a significantly higher frequency of all-grade rash (26.1%), hand–foot syndrome (33.4%) and mucositis (38.5%). The difference was highly significant for sorafenib vs. pazopanib in the incidence of all-grade rash (odds ratio [OR] 1.649, 95% CI 1.086–2.505, P=0.023), hand–foot syndrome (OR 3.096, 95% CI 1.271–7.544, P=0.009) and mucositis (OR 4.562, 95% CI 2.132–9.609, P<0.001). Moreover, the frequency of grade ≥3 mucositis was significantly higher in the sunitinib group compared with the pazopanib or sorafenib group (7.6% vs. 1.3%, OR 6.448, 95% CI 1.499–27.731, P=0.013). Conclusion Statistically significant differences in certain common adverse effects, such as all-grade and severe AEs, were detected among pazopanib, sorafenib and sunitinib in the current study. Early and prompt management is critically needed to avoid unnecessary dose reductions and treatment-related discontinuations.

Prognostic value of the C-reactive protein/Albumin Ratio (CAR) in patients with operable soft tissue sarcoma

Background The preoperative C-reactive protein/Albumin ratio (CAR) is valuable for predicting the prognosis of patients with various types of cancers. The aim of the present study is to investigate the prognostic value of the preoperative CAR and compare it with other systemic inflammatory response markers in patients with soft tissue sarcoma (STS). Methods This retrospective study included 206 patients with STS. The optimal cutoff value of the CAR was determined by receiver operating characteristic (ROC) analysis. The impact of the CAR and other clinicopathological features on overall survival (OS) and disease-free survival (DFS) was evaluated using univariate and multivariate Cox regression analyses. Kaplan-Meier survival analyses were used to compare groups classified by the CAR. Additionally, the area under the receiver operating characteristic curve (AUC) was used to compare the predictive ability of the CAR, high-sensitivity modified Glasgow prognostic score (Hs-mGPS), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). Results The optimal cut-off value of the CAR was 0.1035 according to the ROC analysis. An increased CAR (≥0.1035) was significantly associated with older age, larger tumor size, deep tumor location, higher tumor grade and more advanced American Joint Committee on Cancer (AJCC) stage (all P<0.05). Patients with an elevated CAR (≥0.1035) exhibited a shorter median survival time and lower 5-year OS rate than those with a CAR<0.1035 (68.2 vs 115.8 months, P = 0.000; 44.6% vs 80.9%, P = 0.000, respectively). The results of a multivariate analysis indicated that the CAR (Hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.47-4.14, P = 0.001) was an independent prognostic factor for OS along with tumor grade (P<0.05). Additionally, the CAR exhibited a greater AUC value (0.662) than the NLR and PLR, but the value was equal to the Hs-mGPS. Conclusions The preoperative CAR is an independent prognostic factor predicting prognosis in STS and exhibits superior prognostic ability compared to the established inflammation-based prognostic indices.

A comprehensive analysis comparing the eighth AJCC gastric cancer pathological classification to the seventh, sixth, and fifth editions

To perform a comprehensive analysis comparing the prognostic and discriminative ability of the eighth AJCC gastric cancer (GC) pathological classification to that of the seventh, sixth and fifth editions, and secondly to assess their long‐term significance. Patients who had undergone R0 gastrectomy were identified and restaged accordingly. To evaluate and confirm any difference in prognostic ability between the competing editions, the Akaike information criterion (AIC) and Bayesian information criterion (BIC) were computed and compared since both have different analytic strengths. The area under the curve (AUC) with 95% CI based on the time‐dependent receiver‐operating characteristics analyses were also calculated to assess any change in prognostic rankings from the first to tenth postoperative year. The rankings calculated by both statistical methods showed similar results, in which the seventh edition was identified as possessing the best prognostic ability. Additionally, these ranks were found to remain consistent over the ten postoperative years, but demonstrated no clinical significance as their respective 95% CIs calculated by the AIC, BIC, and AUC were found to overlap. However, the more detailed staging classifications of the eighth edition was shown to display the best prognostic demarcation for stratifying patients with higher‐staged disease. This study thereby identified the eighth AJCC GC edition to possess similar long‐term prognostic ability as to its previous three editions but contrastingly demonstrated the best distinctive ability for stratifying overall survival and can thus be considered as being clinically more reliable.