ABSTRACT
Objective:To investigate the real-world efficacy of osimertinib and icotinib in metastatic non-small cell lung carcinoma (NSCLC) patients.Methods:A retrospective analysis was performed on clinical data of 151 newly-diagnosed patients with epidermal growth factor receptor (EGFR) -positive advanced NSCLC in Renmin Hospital of Wuhan University from March 2018 to May 2022. The patients were divided into osimertinib group ( n=53) and icotinib group ( n=98) according to treatment method. The objective response rate (ORR) , disease control rate (DCR) , progression-free survival (PFS) and overall survival (OS) were compared between the two groups. The factors influencing prognosis were analyzed by using Cox regression models. Subgroup analysis was performed according to metastatic site and EGFR mutation type. Results:ORR was 56.6% (30/53) and 59.2% (58/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.09, P=0.759) . DCR was 83.0% (44/53) and 91.8% (90/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=2.68, P=0.102) . The median PFS was 11.7 months and 11.8 months for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.06, P=0.802) . The median OS was not reached for patients in both the osimertinib group and icotinib group, with no statistically significant difference ( χ2<0.01, P=0.969) . The results of multivariate analysis showed that adrenal metastases ( HR=1.89, 95% CI: 1.04-3.41, P=0.036) was an independent prognostic factor for PFS. Gender ( HR=2.22, 95% CI: 1.08-4.58, P=0.031) and adrenal metastases ( HR=4.87, 95% CI: 1.76-13.46, P=0.002) were independent prognostic factors for OS. The results of the subgroup analysis showed that in patients with pleural metastases (median PFS: 11.7 months vs. 9.3 months, median OS: not reached vs. not reached) , adrenal metastases (median PFS: 8.7 months vs. 5.6 months, median OS: 20.0 months vs. 15.3 months) , 19DEL mutations (median PFS: 14.5 months vs. 13.3 months, median OS: not reached vs. 40.7 months) , the osimertinib group tended to have better survival outcomes. Conversely, in patients with contralateral lung metastases (median PFS: 8.3 months vs. 11.2 months, median OS: not reached vs. 40.7 months) , bone metastases (median PFS: 11.7 months vs. 11.8 months, median OS: not reached vs. 34.5 months) , liver metastases (median PFS: 8.7 months vs. 9.1 months, median OS: not reached vs. 23.8 months) , brain metastases (median PFS: 11.7 months vs. 15.3 months, median OS: 22.4 months vs. 35.3 months) and 21L858R mutations (median PFS: 9.5 months vs. 10.0 months, median OS: 22.4 months vs. not reached) , the icotinib group tended to have better survival outcomes, but with no statistically significant differences (all P>0.05) . Conclusion:Both osimertinib and icotinib have good therapeutic efficacy in patients with EGFR-positive advanced NSCLC, thus can be used as first-line treatment options.
ABSTRACT
In recent decades, immune checkpoint inhibitors (ICIs) have ushered in a new era in oncology treatment. Despite the remarkable efficacy of ICIs, there are still many patients who do not benefit from immunotherapy alone. Combination therapy is currently the main research direction in China and abroad. Metformin can enhance the number and function of T cells, affect macrophage polarization, promote natural killer cell activation and regulate immune checkpoint expression. A large number of preclinical and clinical studies are exploring the efficacy and safety of ICIs in combination with metformin in different tumors.
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Objective:To investigate the safety and efficacy of chemoradiotherapy compared with chemotherapy after R0 excision in pN + esophageal squamous cell carcinoma (ESCC) patients. Methods:A retrospective analysis was performed on the pathological data of 99 pN + ESCC patients who underwent radical esophagectomy with R0 resection in Renmin Hospital of Wuhan University from January 2017 to December 2020. According to postoperative adjuvant treatment methods, the patients were divided into chemo-radiotherapy group ( n=41) and chemotherapy group ( n=58). The main outcome measures were disease-free survival (DFS), overall survival (OS) and the incidences of treatment-related adverse events. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors. Results:The median DFS and OS of 99 patients were 20.0 months and 28.0 months respectively. The 1- and 3-year DFS rates were 60.8% and 34.5% respectively. The 1- and 3-year OS rates were 83.5% and 40.2% respectively. The median DFS was 39.0 months in the chemoradiotherapy group and 10.0 months in the chemotherapy group, and the 1- and 3-year DFS rates were 79.4% vs. 48.3% and 57.3% vs. 24.5% respectively, with a statistically significant difference ( χ2=12.27, P<0.001). The median OS in the chemoradiotherapy group was not reached, and 21.0 months in the chemotherapy group, and the 1- and 3-year OS rates of the chemoradiotherapy group and chemotherapy group were 92.1% vs. 75.9% and 60.8% vs. 27.3%, with a statistically significant difference ( χ2=11.12, P=0.001). Univariate analysis showed that pN stage ( HR=0.58, 95% CI: 0.34-0.97, P=0.038), nerve invasion ( HR=1.88, 95% CI: 1.11-3.20, P=0.020) and adjuvant therapy ( HR=0.37, 95% CI: 0.21-0.67, P<0.001) were independent influencing factors of DFS in pN + ESCC patients. Adjuvant therapy ( HR=0.33, 95% CI: 0.17-0.66, P=0.001) was an independent factor influencing OS in pN + ESCC patients. Multivariate analysis showed that pN stage ( HR=0.54, 95% CI: 0.30-0.97, P=0.038) and adjuvant therapy ( HR=0.38, 95% CI: 0.21-0.69, P=0.001) were independent prognostic factors of DFS. Adjuvant therapy ( HR=0.34, 95% CI: 0.17-0.69, P=0.003) was an independent prognostic factor for OS. During adjuvant therapy, there were statistically significant differences in the incidences of leukopenia [65.85% (27/41) vs. 31.03% (18/58), χ2=11.75, P=0.001], thrombocytopenia [29.27% (12/41) vs. 10.34% (6/58), χ2=5.78, P=0.016], radioactive esophagitis [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001], and radioactive pneumonia [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001] between the two groups. Conclusion:Compared with chemotherapy, chemoradiotherapy can significantly improve DFS and OS of pN + ESCC patients with R0 resection after radical surgery, and the adverse reactions can be tolerated. pN stage and adjuvant therapy are independent prognostic factors for DFS, and adjuvant therapy is an independent prognostic factor for OS.
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Cervical cancer is the second most common cancer in women worldwide. It is clear that persistent infection of high-risk human papillomaviruses (HR-HPVs) is the main cause for this disease. Among the several HPV types associated with carcinoma, HPV-16 is the most prevalent type and present in about 50% of tumor specimens. The major capsid protein (L1) of HPV can self-assemble into virus-like particles (VLPs) with immunogenicity similar to infectious virions. Neutralizing epitopes are the structural basis of the current prophylactic HPV vaccines. The efficacy of HPV vaccines is critically dependent upon the integrity of type-specific neutralizing epitopes. Recently, considerable headway has been made in studying the epitopes of HPV16 based on neutralizing antibodies. Notably, more and more HPV16 variants have appeared along with increasing immune pressure. To study the phenotypic variations in HPV16 L1 protein, 1 204 naturally occurring sequences were analyzed and a phylogenetic tree was then constructed including four clades. Moreover, after compared the aforementioned sequences with the 114K reference sequence, eight "hot mutation sites" , six "specialized mutation sites" and 20 "epitope-related mutation sites" were found. Generally, sera raised against VLPs can neutralize the corresponding HPV types, but not other types. However, it is not known whether intragenotypic variants of human papillomavirus type 16 (HPV-16) can be neutralized by sera vaccinated with a single variant VLPs. It is, therefore, imperative to understand the neutralizing epitopes and intragenotypic variants of HPV-16 for the production of prophylactic vaccines with high potency and broad coverage.
ABSTRACT
Objective@#To validate a pseudovirus-based neutralization assay for the detection of antibodies against human papillomavirus (HPV) in human serum samples.@*Methods@#The specificity, accuracy, precision, range of linearity, limit of detection and robustness of the neutralization assay were evaluated using HPV-negative serum samples, vaccinated serum samples with quadri-valent vaccine, and international standards for detecting antibodies against HPV16 and HPV18.@*Results@#Based on the data of the HPV-naïve samples, the criteria of positivity was determined as follows: the 50% inhibitory dose (ID50) of the tested sample was not less than 40 and 2-fold not less than that for bovine papillomavirus. The neutralization assay showed good accuracy with a recovery rate of 87%-122% and excellent reproducibility with intra- and inter-assay variation of 5%-27% and 10%-26% respectively. The HPV16 and HPV18 international standards were used to define the limit of quantification, which was 1.28 IU/ml for HPV16 and 0.96 IU/ml for HPV18. Acceptable ranges of variation for the key parameters of this assay were defined, which showed the good robustness of the pseudovirus-based neutralization assay.@*Conclusion@#The pseudovirus-based neutralization assay for the detection of HPV antibodies showed good specificity, accuracy, sensitivity, and robustness, suggesting that it could be used to evaluate the immunogenicity of HPV vaccines.