Clinical Characteristics and Prognosis of 76 Lung Adenocarcinoma Patients Harboring EGFR Mutations with Pleural Effusion at Initial Diagnosis: A Single-center Retrospective Study / 中国肺癌杂志

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.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor / 中国肺癌杂志

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.

Blood T cell diversity associated with the prognosis of advanced non-small cell lung carcinoma treated with first-line pemetrexed based chemotherapy.

BACKGROUND: The tumor microenvironment is associated with prognosis in advanced non-small cell lung carcinoma (NSCLC). The aim of this study was to explore the relationship between blood T cell diversity and survival of patients treated with pemetrexed-based chemotherapy for nonsquamous NSCLC. METHODS: This prospective clinical study enrolled 26 patients with advanced NSCLC treated with 4-6 cycles of first-line pemetrexed combined with platinum-based therapy. The complementarity-determining region 3 (CDR3) located in the T cell receptor beta chain (TCR ß chain) was captured and deeply sequenced using next-generation sequencing (NGS) technology, and the correlation between TCR changes and efficacy after chemotherapy was analyzed. RESULTS: Patients with an inferior quarter diversity index showed a significantly shorter progression-free survival (PFS) than the others (median, 5.0 months vs. 8.1 months, P = 0.014). After two cycles of chemotherapy, the TCR diversity was significantly higher than the baseline (P = 0.034). Just as with the baseline, patients with an inferior quarter diversity index at the endpoint of cycle 2 showed a shorter progression-free survival (PFS) than the others (median, 5.0 months vs. 8.4 months, P = 0.024). CONCLUSIONS: In advanced NSCLC patients treated with first-line pemetrexed combined with platinum, the low level of blood TCR diversity at baseline with an endpoint of two cycles of chemotherapy was correlated with a poor prognosis.

Retrospective Analysis of Risk Factors for Venous Thromboembolism in 283 Patients with Lung Cancer during Systemic Therapy / 中国肺癌杂志

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 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.

Impact of the Pretreatment or Posttreatment NLR and PLR on the Response of First Line Chemotherapy and the Outcomes in Patients with Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

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) (P0.05). 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 (P0.05). 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.

CT-guided 125I radioactive seed implantation for locally recurrent rectal cancer / 中华放射医学与防护杂志

Objective To evaluate the efficacy and adverse reactions of CT-guided 125I radioactive seed implantation in treatment of locally recurrent rectal cancer (LRRC).Methods Thirty patients with LRRC who refused operation or were unable to endure pelvic radiotherapy received 125I seed implantation under CT guidance.Three-dimensional treatment planning system was used to calculate the number,activity,and dose of the seeds needed.The activity of seeds ranged from 14.8 to 29.6 MBq with a median of 25.9 MBq,the seed numbers ranged from 33 to 137 with a median of 74.5,the prescription doses ranged from120-160 Gy,and the actual verification dose D90 ranged from 75.91 to 159.32 Gy with a median of 119.77 Gy.Dosimetric verification by CT scanning was conducted immediately after the treatment.Follow-up was conducted for 15.2 months(4.2-35.0 months).Results The follow-up rate was 93.3％.The pain relief rate was 95.2％.The overall response rate was 50.0％,including a complete response rate of 13.3％ and a partial response rate of 36.7％.The 1-and 2-year local control rates were 30.0％ and 8.0％ respectively.The median local control survival time was 7.8 month.The 1-and 2-year survival rates were 66.5％ and 32.9％ respectively.The median overall survival time was 21.5 months.Complications,mainly adverse effects of skin and urinary system (frequent urination,urgent urination,and dysuria) occurred in 6 patients with a rate of 20.0％.Conclusions Minimally invasive and with satisfying efficacy and tolerable complications,CT-guided 125I radioactive seed implantation is a favorable option for treatment of LRRC,especially for the patients who have undergone previous pelvic radiation.