BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

BACKGROUND: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them. METHODS: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis. RESULTS: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05). CONCLUSIONS PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Pleural Effusion/complications* ; Prognosis ; Retrospective Studies

Objective: To investigate the incidence and clinical characteristics of urothelial carcinoma (UC) accompanied with multiple primary carcinoma (MPC). Methods: The clinical data of 121 UC patients with MPC in Peking University Third Hospital from January 2010 to May 2018 were retrospectly analyzed. Results: UC patients with MPC accounted for 9.74% (121/1 242) of all the UC patients. The ratio of male to female patients was 2.10∶1 in the total MPC patients, but it was 1∶1 in the upper urinary tract MPC subgroup. The MPC patients were more common in elderly people, whose medium age was 68 (32-93) years old. Of all the location (131 person-time) of other tumors besides UC, the digestive system tumors occurred most frequently, accounting for 41.98% (55/131), followed by the urinary and male reproductive system tumors (20.61%, 27/131) and the female reproductive system (12.21%, 16/131). The proportion of the digestive system tumors (47.37%, 9/19) was the highest in the upper urinary tract MPC, with a total number of the other primary cancer of 19 person-time. However, the proportion of the urinary and male reproductive system tumors (37.14%, 13/35) was higher in the synchronous MPC group, with a total number of the other primary cancer of 35 person-time. Some patients had a history of radiotherapy and/or chemotherapy before UC was diagnosed. We also observed 2 cases of genetically confirmed Lynch syndrome. The median overall survival (mOS) of UC patients with MPC was 132 months, and the mOS of patients with UC as the first malignancy (including synchronous MPC and UC as the first malignancy in metachronous MPC) was 120 months. The mOS of the synchronous MPC group was 84 months, which was significantly shorter than 178 months of metachronous MPC group (χ² =14.029, P<0.001). Conclusions The incidence of UC accompanied with MPC is not low, and the most common sites of MPC are the digestive system and reproductive system. Therefore, screening for MPC in UC patients, especially those with personal or family history of tumors, as well as elderly patients, may help early diagnosis and treatment of MPC patients and improve their prognoses.

BACKGROUND: Patients with lung cancer have high risk of developing venous thromboembolism (VTE), which has been shown to have a significant impact on mortality. This study was to identify the incidence of VTE in lung cancer patients during systemic therapy and to analyze the risk factors associated with it. METHODS: We retrospectively analyzed the cases of 283 patients with lung cancer who received systemic therapy in the Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, from January 2016 to December 2018. Chi-square test and multivariate analyses were used to assess the correlation between clinical features and VTE. RESULTS: Of the patients we observed, 34 developed VTE, with an incidence of 12.01% (34/283). In patients with lower extremity varicose vein (LVV), there was an increase in the incidence of VTE (50.00% vs 9.89%, P=0.001). The incidence VTE in patients with distant metastasis was higher than that in patients without distant metastasis, and higher than that in patients with tumor-free (14.05% vs 14.00% vs 2.08%, P=0.024). The incidence of VTE in patients with active tumor was also significantly higher than that in patients without it (16.93% vs 8.18%, P=0.025). Patients with hypoalbuminemia (albumin <35 g/L) had more VTE events more than those without did (22.00% vs 9.87%, P=0.017), and patients with an elevated D-dimer level (>0.3 µg/mL) developed more VTE than those without did (17.93% vs 5.80%, P=0.006). There were no significant correlations between pathological types, blood cell count before systemic therapy including leukocyte, hemoglobin and platelet, or antiangiogenic drugs and VTE. Multivariate analysis showed that LVV, hypoalbuminemia and elevated level of D-dimer were independent risk factors of VTE. CONCLUSIONS LVV, serum albumin and D-dimer level may be potential and more effective predictors of VTE in lung cancer patients during systemic therapy. Basing on these factors, new predictive model can be built, and further study to validate its efficacy is required.

Objective To investigate the incidence and clinical characteristics of urothelial carcinoma (UC) accompanied with multiple primary carcinoma (MPC). Methods The clinical data of 121 UC patients with MPC in Peking University Third Hospital from January 2010 to May 2018 were retrospectly analyzed. Results UC patients with MPC accounted for 9.74%( 121／1 242) of all the UC patients. The ratio of male to female patients was 2.10 ∶ 1 in the total MPC patients, but it was 1 ∶ 1 in the upper urinary tract MPC subgroup. The MPC patients were more common in elderly people, whose medium age was 68 (32?93) years old. Of all the location (131 person?time) of other tumors besides UC, the digestive system tumors occurred most frequently, accounting for 41.98%( 55／131), followed by the urinary and male reproductive system tumors (20.61%, 27／131) and the female reproductive system ( 12.21%, 16／131). The proportion of the digestive system tumors (47.37%, 9／19) was the highest in the upper urinary tract MPC, with a total number of the other primary cancer of 19 person?time. However, the proportion of the urinary and male reproductive system tumors (37.14%, 13／35) was higher in the synchronous MPC group, with a total number of the other primary cancer of 35 person?time.Some patients had a history of radiotherapy and／or chemotherapy before UC was diagnosed. We also observed 2 cases of genetically confirmed Lynch syndrome. The median overall survival (mOS) of UC patients with MPC was 132 months, and the mOS of patients with UC as the first malignancy ( including synchronous MPC and UC as the first malignancy in metachronous MPC) was 120 months. The mOS of the synchronous MPC group was 84 months, which was significantly shorter than 178 months of metachronous MPC group (χ2＝14.029, P＜0.001). Conclusions The incidence of UC accompanied with MPC is not low, and the most common sites of MPC are the digestive system and reproductive system. Therefore, screening for MPC in UC patients, especially those with personal or family history of tumors, as well as elderly patients, may help early diagnosis and treatment of MPC patients and improve their prognoses.

Objective To investigate the incidence and clinical characteristics of urothelial carcinoma (UC) accompanied with multiple primary carcinoma (MPC). Methods The clinical data of 121 UC patients with MPC in Peking University Third Hospital from January 2010 to May 2018 were retrospectly analyzed. Results UC patients with MPC accounted for 9.74%( 121／1 242) of all the UC patients. The ratio of male to female patients was 2.10 ∶ 1 in the total MPC patients, but it was 1 ∶ 1 in the upper urinary tract MPC subgroup. The MPC patients were more common in elderly people, whose medium age was 68 (32?93) years old. Of all the location (131 person?time) of other tumors besides UC, the digestive system tumors occurred most frequently, accounting for 41.98%( 55／131), followed by the urinary and male reproductive system tumors (20.61%, 27／131) and the female reproductive system ( 12.21%, 16／131). The proportion of the digestive system tumors (47.37%, 9／19) was the highest in the upper urinary tract MPC, with a total number of the other primary cancer of 19 person?time. However, the proportion of the urinary and male reproductive system tumors (37.14%, 13／35) was higher in the synchronous MPC group, with a total number of the other primary cancer of 35 person?time.Some patients had a history of radiotherapy and／or chemotherapy before UC was diagnosed. We also observed 2 cases of genetically confirmed Lynch syndrome. The median overall survival (mOS) of UC patients with MPC was 132 months, and the mOS of patients with UC as the first malignancy ( including synchronous MPC and UC as the first malignancy in metachronous MPC) was 120 months. The mOS of the synchronous MPC group was 84 months, which was significantly shorter than 178 months of metachronous MPC group (χ2＝14.029, P＜0.001). Conclusions The incidence of UC accompanied with MPC is not low, and the most common sites of MPC are the digestive system and reproductive system. Therefore, screening for MPC in UC patients, especially those with personal or family history of tumors, as well as elderly patients, may help early diagnosis and treatment of MPC patients and improve their prognoses.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), indexes of systemic inflammation, have been associated with worse survival for many types of cancer. The aim of this study is to investigate the impact of NLR and PLR on overall survival (OS) and to explore the value of changes in the NLR and PLR with treatment as a response indicator in non-small cell lung cancer (NSCLC). METHODS: A total of 68 NSCLC patients in Peking University Third Hospital were eligible for retrospective analysis between April 2008 and April 2015. The pretreatment and posttreatment NLR and PLR in all patients were calculated based on complete blood counts. Potential prognostic factors such as age, gender, performance status, histology, stage, response to chemotherapy, NLR and PLR were analyzed. NLR and PLR were assessed at baseline and during chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR, NLR and clinical features with OS. RESULTS: Among the 68 cases, the values of the posttreatment NLR after two cycles of chemotherapy (NLR2) and the pretreatment NLR (NLR0) were (2.69±2.06) and (3.94±2.12), respectively. NLR2 was significantly lower than NLR0 (P=0.000). There was no difference between the pretreatment PLR (PLR0) and the posttreatment PLR after two cycles of chemotherapy (PLR2) (P<0.05). NLR2 significantly correlated with the response of first line treatment with two or four cycles of chemotherapy. The proportion of high NLR2 in the patients with progression disease was 100.0%, significantly higher than the proportion of high NLR2 in the patients with partial response or stable disease. NLR0, PLR0 and NLR2 were significantly correlated with the OS (P<0.05), but not with age, performance status, histology, stage, status and regimens of treatment (P>0.05). According to univariate analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response of 2 and 4 cycles of first line chemotherapy, status and regimens of second line treatment (P<0.05), but not with stage, status of third line or beyond treatment and radiotherapy (P>0.05). The multivariate analysis showed that NLR0 (P=0.004), the response with 4 cycles of first line chemotherapy (P=0.022) and status of second line treatment (P=0.007) were independent prognostic indicators in the 68 patients. CONCLUSIONS The study showed that NLR0 was well connected with outcomes and NLR2 was well connected with the response to first line chemotherapy in patients with advanced non-small cell lung cancer. Therefore, NLR may be a biomarker for predicting the outcomes and response of first line chemotherapy and a potential target for management of non-small cell lung cancer.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; radiotherapy ; Disease-Free Survival ; Female ; Humans ; Leukocyte Count ; Lung Neoplasms ; blood ; drug therapy ; pathology ; radiotherapy ; Lymphocytes ; cytology ; drug effects ; Male ; Middle Aged ; Neutrophils ; cytology ; drug effects ; Retrospective Studies ; Treatment Outcome

BACKGROUND: There are significantly interindividual variations of the expression level of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or Kelch-like ECH-associated protein 1 (Keap1) in our previous studies. It has been proven that Nrf2 or Keap1 is related to resistance of chemotherapeutic drugs and/or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, the expression of Nrf2 and Keap1 in lung adenocarcinoma patients with different "driver gene" is not clear. The aim of this study is to investigate the protein expression level of Nrf2 and Keap1 in lung adenocarcinoma and to elucidate the correlation between Nrf2 or Keap1 expression and the status of EGFR gene mutation and to determine the effects of Nrf2 and Keap1 on the patients. METHODS: Immunohistochemical analysis of Nrf2 and Keap1 in tumor specimens was performed in a total of 104 lung adenocarcinoma patients with the status of EGFR gene mutations or EGFR wide-type. RESULTS: The Nrf2 positive rate was 71.2% and Keap1 high expression rate was 34.6% in 104 patients. The Nrf2 positive rate significantly correlated with gender, stage and status of EGFR gene mutation (P<0.05), but not with age, smoking, differentiation and subtype of lung adenocarcinoma (P>0.05). The high expression of Keap1 was not significantly correlated with gender, age, smoking, differentiation, subtype of lung adenocarcinoma and status of EGFR gene mutation (P>0.05). The progression -free survival (PFS) and overall survival (OS) of the patients treated by EGFR-TKIs were significantly correlated with the expression level of Nrf2, but not with Keap1. The PFS and OS of the patients with Nrf2 high expression were significantly shorter than the patients with low/negative expression (P<0.05). Furthermore, Nrf2 high expression was the independent predictive factor for EGFR-TKIs induced PFS and OS (P<0.05). CONCLUSIONS The Nrf2 positive rate significantly correlated with the status of EGFR gene mutation in lung adenocarcinoma. The Nrf2 high expression significantly correlated with PFS and OS of EGFR-TKIs. Therefore, Nrf2 may be a biomarker for predicting response of EGFR-TKIs and a potential target for overcoming resistance of EGFR-TKIs.
Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Kelch-Like ECH-Associated Protein 1 ; genetics ; metabolism ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Mutation ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Neoplasm Staging ; Protein Kinase Inhibitors ; therapeutic use ; Young Adult

Background and objectiveIt is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG.MethodsThe Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were fol-lowed and their survival status were analyzed.Results There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93%vs 88%; 83%vs 81%,P=0.034) respectively. The survival rate was signiifcantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003). Among patients with advanced stage thymoma (stage III, IVa, IVb), the constitu-ent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were signiifcantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classiifcation, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were signiifcant factors, and multivariate analysis showed WHO Classiifcation, Masaoka stage, and resectability were strong independent prognostic indicators.ConclusionAlthough MG is not an independent prognostic factor, the sur-vival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.