First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.

[The impact to operation safety of preoperative renal artery embolization for management of diameter≥10 cm renal cell carcinoma].

Objective: To study the impact to operation safety of preoperative renal artery embolization for management of ≥10 cm renal cell carcinoma. Methods: The clinical data of 239 cases with ≥10 cm renal cell carcinoma which all had underwent operation in Department of Urology, Peking University First Hospital from January 2002 to December 2014 were retrospectively analyzed. Fifty-three patients underwent preoperative renal artery embolization (therapeutic group) and 186 patients did not (control group). The effect of embolization on operative time, transfusion requirements, hospitalization, ICU stay and perioperative complications were analyzed by comparing the two groups using rank sum test and χ(2) test or Fisher exact test. Results: Comparing the therapeutic group and control group, there was significant difference in tumor location (on the left or right). The mean age, sex, mean primary tumor size, and TNM stage were similar in both groups. Comparing the therapeutic group and control group, there were more open surgeries in therapeutic group (96.2% vs. 82.3%, χ(2)=6.438, P=0.013). There were no significant differences in mean operative time (238 (525) minutes vs. 208 (583) minutes, Z=-2.182, P=0.062). The mean blood transfusion (700 (1 900) ml vs. 925 (8 800) ml, Z=-1.064, P=0.006) had significant difference. The therapeutic group had a longer mean hospitalization (21 (50) days vs. 15 (79) days, Z=-4.322, P=0.000) and higher rate of intensive care unit stay (54.7% vs. 34.4%, χ(2)=6.103, P=0.027). There was no significant difference in perioperative complications between two groups (0 vs.3.2%, P=0.408). Conclusion: Preoperative renal artery embolization in ≥10 cm renal cell carcinoma patients undergoing operation provides benefit in increasing operation safety and reducing perioperative death.

[Clinical features and prognosis of rare subtypes of renal cell carcinoma].

Objective: To investigate the clinical features and prognosis of rare subtypes of renal cell carcinoma. Methods: This retrospective study collected the data of 52 rare subtypes of renal cell carcinoma of patients who underwent surgery from January 2002 to December 2014 at Department of Urology, Peking University First Hospital. There were 12 patients with collecting duct carcinoma, 5 patients with Xp11.2 translocation renal cell carcinoma, 5 patients with mucinous tubular and spindle cell carcinoma, 30 patients with unclassified renal cell carcinoma. The study group included 25 male and 27 female patients, with mean age of 52 years. The mean tumour size was (6.5±3.9) cm (range: 1.5 to 21.0 cm). The basic clinical features, gross appearance, Fuhrman nuclear grade, TNM staging and prognosis of rare subtypes of RCC were studied. The OS curves were obtained for rare subtypes of renal cell carcinoma using the Kaplan-Meier method and compared using a Log-rank test. Results: The rate of lymph node and distant metastasis were 34.6% (18/52) and 17.3% (9/52). Malignancies were screened and detected by color Doppler ultrasonography or CT scan, however, no case was diagnosed before operation or aspiration, all cases were confirmed by the pathological examination. The average period of postoperative follow-up process was 65 months, and the mean survival time was (34±23) months. Conclusion: The clinical features of rare subtypes of renal cell carcinoma are similar to those of clear cell renal cell carcinoma, while the imaging changes will be helpful for diagnosis before operation.

Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of non-small cell lung cancer.

The associations between single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) and cancer risk and disease outcome have been extensively analyzed. We investigated the association between age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of non-small cell lung cancer (NSCLC) patients. The D-loop region of mtDNA from NSCLC patients was amplified and sequenced. The age-at-onset curve of NSCLC patients was calculated using the Kaplan-Meier method at each SNP site and values were compared using the log-rank test. The SNP sites of nucleotides 200G/A and 16362T/C were identified to determine their association with age-at-onset of NSCLC using the log-rank test. The nucleotide 207G/A was identified for its association with age-at-onset at a borderline significance level (P = 0.060). We found that genetic polymorphisms in the D-loop were predictive markers for age-at-onset in NSCLC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can be used to identify NSCLC patient subgroups at high risk of early onset.

[Associations between adverse childhood experiences and adulthood substance use among lesbians].

Objective: To investigate the associations between adverse childhood experiences (ACE) and substance use behaviors among lesbians to provide a scientific basis for high-risk population identification and formulation of targeted intervention measures. Methods: Lesbians who participated in routine AIDS voluntary counseling, testing services, activities, and peer recommendations were recruited from July to December 2018, with the help of LesPark in Beijing. Convenient sampling method was used. Demographic characteristics, ACE, and substance use behaviors of subjects were investigated using an online platform powered by www.wjx.cn. Subsequently, the associations between ACE and adulthood substance use behaviors were evaluated using the logistic regression model. The SPSS 22.0 was used for statistical analysis. Results: A total of 294 lesbians were recruited in the study, 81.3% (239/294) of them were lesbians, and 18.7% (55/294) were bisexuals. Besides, 55.8% (164/294) of subjects reported they had had ACE, with proportions of lesbians experiencing abuse, neglect, and family dysfunction as 33.3% (98/294), 24.5% (72/294), and 32.7% (96/294), respectively. 55.1% (162/294) of the lesbians reported they had smoked in the past 30 days, 11.2% (33/294) reported having drug-use behavior in the past three months, and 22.8% (67/294) claimed drinking alcohol weekly. Multivariate logistic regression analysis showed that lesbians with ACE were at high risks to smoke (OR=1.87, 95%CI: 1.13-3.08), drink (OR=2.13, 95%CI: 1.18-3.84), and use drugs (OR=3.33, 95%CI: 1.29-8.61) in adulthood. Moreover, lesbians with childhood family dysfunction were at higher risk of smoking cigarettes (OR=2.60, 95%CI: 1.46-4.62) and drinking alcohol (OR=2.65, 95%CI: 1.44-4.87). At the same time, those with abuse experience were at higher risk of drug use (OR=3.17, 95%CI: 1.26-7.96). Conclusions: Substance use behaviors, including cigarette smoking, drinking alcohol, and drugs use, were common among lesbians. Positive associations were found between ACE and adulthood substance use behaviors.

Investigation on genetic traits and selection of interspecific somatic hybrid progenies in tobacco.

The interspecific somatic hybrid plants were produced in 1980 by protoplast fusions between N. tabacum and N. rustica, and N. tabacum and N. glauca. The results of this study on the genetic traits and selection of the hybrid progenies for seven years showed that the performances of the somatic hybrids (SH) were typical intermediate forms of the two species involved in each somatic hybridization, and that segregation began in SH3 and (SH)BC2 generations (the SH1 backcrossed to N. tabacum twice). However, stable lines and male sterile lines from SH1 until the present, were also obtained. The fertilities of the hybrid progenies were generally poor. The characteristics of the recurrent parent were accumulated, and the chromosome numbers of the hybrid plants were gradually decreased as the number of backcrossing generations increased. Some new types of tobacco with certain commercial values have been selected for used in the present study. The conclusion reached, based on our results, is that the somatic hybridization technology has now been successfully utilized to create unique breeding lines of tobacco, and represents a powerful, new tool for crop improvement.