Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

Importance: Both pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear. Objectives: To compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer. Materials and methods: This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The primary objective was to compare the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) between the two groups. Secondary objectives were to compare the disease control rate (DCR) and to analyze adverse events (AEs) between the two groups. Results: A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab-combined chemotherapy group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P=0.634). The DCR was 92.10% and 92.10% in the sintilimab and pembrolizumab groups, respectively (P=0.991). The median PFS was 22.2 months for patients treated with sintilimab group compared with 16.5 months for patients treated with pembrolizumab group[hazard ratio (HR) = 0.743; 95% confidence interval (CI): 0.479-1.152; P = 0.599]. Patients treated with pembrolizumab did not achieve a median OS, and patients treated with sintilimab had a median OS of 30.7 months. In the sintilimab group, the incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63), and the incidence of grade 3-4 TRAEs of 42.9% (27/63). In the pembrolizumab group, the incidence of all TRAEs was 90.1% (91/101), and the incidence of grade 3-4 TRAEs was 37.6% (38/101). Conclusion: In the clinical treatment of Chinese patients with advanced squamous lung cancer, first-line treatment with sintilimab in combination with chemotherapy provided similar efficacy to pembrolizumab in combination with chemotherapy, and the treatment-related adverse effect profiles were comparable between the two groups, including similar rates of grade 3-4 and all adverse events.

XRCC2 Polymorphisms and Environmental Factors Predict High Risk of Colorectal Cancer.

BACKGROUND This case-control study aimed to analyze the association of [i]XRCC2[/i] polymorphisms (rs3218408 and rs3218384) with colorectal cancer (CRC) risk. The interaction of [i]XRCC2[/i] polymorphisms with environmental factors was investigated as well. MATERIAL AND METHODS We enrolled 147 CRC patients and 114 healthy individuals into the study. Polymerase chain reaction (PCR)-sequencing method was performed to detect rs3218408 and rs3218384 polymorphisms. Hardy-Weinberg equilibrium (HWE) was checked in the control group. Odds ratio (OR) with 95% confidence interval (CI) represented the risk of CRC. Cross-table method was used in analyzing the interaction effects. RESULTS Compared to the control group, the frequency of smokers was much higher in the case group ([i]P[/i]<0.001). A similar result was observed in drinkers (55.8% [i]vs.[/i] 40.4%, [i]P[/i]=0.013). Dietary habits of all subjects were investigated as well, showing that CRC patients ate fewer vegetables than did healthy controls (P<0.001). In the analysis of polymorphisms, rs3218408 appeared to be an independent risk factor of CRC (GG: OR=2.048, 95%CI=1.032-4.061; G allele: OR=1.445, 95%CI=1.019-2.049). There were 68 (76.4%) C allele carriers (rs3218384) among smokers, which was higher than the number of G allele carriers ([i]P[/i]<0.001). A similar outcome was observed for alcohol drinkers ([i]P[/i]=0.048), which suggests a relationship of rs3218384 with smoking and drinking. Further analysis indicated that interaction of rs3218384 with smoking increased the risk of CRC (GG and smoking: OR=3.250, 95%CI=1.235-8.556; GC+CC and smoking: OR=2.167, 95%CI=1.175-3.996). CONCLUSIONS We found that rs3218408 was related with increased risk of CRC, and the interaction of rs3218384 with smoking increased the risk of CRC.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

Association between CTLA-4 rs231775 polymorphism and risk of colorectal cancer: a meta analysis.

OBJECTIVE: Many previous studies that examined the association between CTLA-4 rs231775 polymorphism and CRC risk have produced inconsistent results. In this study, a meta-analysis was performed to systematically summarize the possible association. METHODS: We identified relevant studies using PubMed, Embase, and China National Knowledge Infrastructure literature databases. Eligible studies were selected using specific criteria. Data were extracted independently by two authors. The pooled OR with 95% CI was estimated by applying the fixed-effects model to examine the association of interest. RESULTS: Eight studies were identified for the meta-analysis. In overall analysis, we observed an significantly increased CRC risk attributed to the AG genotype as compared to the AA genotype (OR: 1.17, 95% CI: 1.02-1.35 for AG vs AA). Stratified analysis according to ethnicity also showed a significant association in Caucasians under the AG vs AA model (OR: 1.22, 95% CI: 1.03-1.46). No significant heterogeneity or publication bias was tested in our meta-analysis. CONCLUSION: In conclusion, the meta-analysis suggests that rs231775 in the CTLA-4 gene may be a risk factor for CRC, especially in Caucasians.

Association between interleukin-8 -251A/T polymorphism and risk of lung cancer: a meta-analysis.

This study is to evaluate the association between IL-8 -251A/T polymorphism and lung cancer risk in diverse populations. We performed a meta-analysis of six case-control studies that included 3,265 lung-cancer cases and 3,607 case-free controls. Overall, results showed that the IL-8 -251A/T polymorphism was not associated with a significantly increased risk of lung cancer in all genetic models. However, stratified by ethnicity, a significantly increased risk was found among Asians. In conclusion, IL-8 -251A/T polymorphism is associated with lung cancer susceptibility in Asians and the -251 A allele may increase risk of lung cancer in Asians.

Breast carcinoma with choriocarcinomatous features: a case report and review of the literature.

BACKGROUND: Breast carcinoma with choriocarcinomatous features (BCCF) is a rare variant of breast cancer, characterized by high expression of human chorionic gonadotropin (HCG) in cancer cells such as multinucleated syncytiotrophoblast-like giant cells. The first case of BCCF was reported in 1981 by Saigo and Rosen. Only one case of BCCF was reported to show no component of breast ductal carcinoma, and only partially cancer cells, such as multinucleated syncytiotrophoblast-like giant cells, expressed HCG in all previous BCCF cases. Here, we report the first BCCF case without any component of breast ductal carcinoma in which HCG was found to express in all cancer cells. CASE PRESENTATION: A 32-year-old female patient presented with a small lump in her left breast 3 years prior. The mass was clinically suspected to be breast infiltrating ductal carcinoma based on breast excisional biopsy and magnetic resonance imaging findings. Due to rupture and bleeding of the left kidney, the left kidney excisional biopsy was performed. After a retrospective analysis of the initial excised breast cancer and breast cancer metastatic to the kidney, the cancer cells were positive for HCG by immunohistochemistry, and multinucleated or mononucleated giant cells resembled syncytiotrophoblastic and cytotrophoblastic cells which could be seen in a background of poor differentiated breast carcinoma and extensive necrosis and hemorrhage in the lesion. Thus, a final diagnosis of BCCF and BCCF metastatic to the kidney was made. After combination of surgical resection (the affected left breast and left kidney wereremoved) and consecutive chemotherapy consisting of docetaxel, epirubicin, cisplatin, lobaplatin, and capecitabine, the patient achieved favorable therapeutic efficacy (the HCG level returned to normal values, the metastatic lesions in the lungs disappeared, and the survival was 37 months). Capecitabine was very efficient and highly recommended due to its superior efficacy in reducing the HCG level and eliminating the metastatic lesions in the lungs. CONCLUSIONS: This is the first report of a rare case of BCCF without any component of breast ductal carcinoma, featured by high expression of HCG in all cancer cells. Combination of surgery and chemotherapy (especially capecitabine) achieved a favorable therapeutic efficacy.

Evaluation of the immune factors in the tumor environment before and after the treatment of cetuximab combined with chemotherapy.

BACKGROUND: The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy. METHODS: Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-ß1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman's correlation analysis. RESULTS: There was no significant difference between the expression of TGF-ß1 before and after the treatment (P >0.05). The change of TGF-ß1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-ß1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-ß1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019). CONCLUSIONS: These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy.

Detection of circulating tumour cells in gastric and hepatocellular carcinoma: a systematic review.

OBJECTIVE: This systematic review was conducted to summarize the use of circulating tumour cell (CTC) detection as a prognostic indicator in gastric cancer and hepatocellular carcinoma (HCC). METHODS: Databases (MEDLINE®, EMBASE®, SCOPUS, Web of Science, Conference Proceedings Citation Index-Science, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov) were searched to identify studies that reported the detection of CTCs in patients with gastric cancer or HCC. RESULTS: Fifteen studies in patients with gastric cancer and 10 studies in patients with HCC, with a total of 793 and 577 patients, respectively, met the specific inclusion criteria for further analysis. Heterogeneity and potential bias among the studies prevented any statistical analysis. CONCLUSION: Several methodological techniques have allowed the detection of CTCs in patients with gastric cancer or HCC, but the studies identified in this report generally reported on small cohorts and there was heterogeneity and potential bias in the studies. This highlights the need for large systematic multicentre clinical trials to confirm the potential prognostic benefit of detecting CTCs in patients with cancer.