Aiqin Gu

The Value of Autofluorescence Bronchoscopy Combined with White Light Bronchoscopy Compared with White Light Alone in the Diagnosis of Intraepithelial Neoplasia and Invasive Lung Cancer: A Meta-Analysis

Objective: To compare the accuracy of autofluorescence bronchoscopy (AFB) combined with white light bronchoscopy (WLB) versus WLB alone in the diagnosis of lung cancer. Methods: The Ovid, PubMed, and Google Scholar databases from January 1990 to October 2010 were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for sensitivity and specificity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer were pooled by Review Manager. Results: Twenty-one studies involving 3266 patients were ultimately analyzed. The pool relative sensitivity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer was 2.04 (95% confidence interval [CI] 1.72–2.42) and 1.15 (95% CI 1.05–1.26), respectively. The pool relative specificity on a per-lesion basis of AFB + WLB versus WLB alone was 0.65 (95% CI 0.59–0.73). Conclusions: Although the specificity of AFB + WLB is lower than WLB alone, AFB + WLB seems to significantly improve the sensitivity to detect intraepithelial neoplasia. However, this advantage over WLB alone seems much less in detecting invasive lung cancer.

Association of XPD Polymorphisms with Severe Toxicity in Non-Small Cell Lung Cancer Patients in a Chinese Population

Purpose: Platinum agents cause DNA cross-linking and adducts. Xeroderma pigmentosum group D (XPD) plays a key role in the nucleotide excision repair pathway of DNA repair. Genetic polymorphisms of XPD may affect the capacity to remove the deleterious DNA lesions in normal tissues and lead to greater treatment-related toxicity. This study aimed to investigate the association of three polymorphisms of XPD at codons 156, 312, and 711, with the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients. Experimental Design: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to genotype the three polymorphisms in 209 stage III and IV non–small cell lung cancer patients treated with platinum-based chemotherapy. Results: The variant homozygotes of XPD p.Arg156Arg (rs238406) polymorphism were associated with a significantly increased risk of grade 3 or 4 hematologic toxicity (adjusted odds ratios, 3.24; 95% confidence interval, 1.35-7.78; P for trend = 0.009), and, more specifically, severe leukopenia toxicity (P for trend = 0.005). No statistically significant association was found for the three polymorphisms and grade 3 or 4 gastrointestinal toxicity. Consistent with these results of single-locus analysis, both the haplotype and the diplotype analyses revealed a protective effect of the haplotype “CG” (in the order of p.Arg156Arg-p.Asp312Asn) on the risk of grade 3 or 4 hematologic toxicity. Conclusions: This investigation, for the first time, provides suggestive evidence of an effect of XPD p.Arg156Arg polymorphism on severe toxicity variability among platinum-treated non–small cell lung cancer patients.

Hsa-miR-196a2 functional SNP is associated with severe toxicity after platinum-based chemotherapy of advanced nonsmall cell lung cancer patients in a Chinese population.

Rs11614913 is a polymorphism in hsa‐miR‐196a2 reported to alter mature microRNA expression and function. This single‐nucleotide polymorphism (SNP) was reported to be associated with susceptibility and prognosis of lung cancer.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

OBJECTIVE To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). METHODS A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. RESULTS A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. CONCLUSIONS The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

NAD(P)H: Quinone oxidoreductase 1 (NQO1) C609T polymorphism and lung cancer risk: A meta-analysis.

No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. We conducted a computer retrieval of PubMed and Embase databases prior to May 2013. References of retrieved articles were also screened. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. According to the inclusion criteria, 25 articles (32 studies) were finally included. There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African Americans, or Hispanics. In Caucasians, a significant association was found in allele comparison model (T vs. C) (P = 0.04, OR = 1.09, 95% CI 1.00–1.19, Pheterogeneity = 0.24, fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model (TT + CT vs. CC) (P = 0.05, OR = 1.20, 95% CI 1.00–1.43, Pheterogeneity = 0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P = 0.03, OR = 1.21, 95% CI 1.01–1.44, Pheterogeneity = 0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P = 0.03, OR = 1.68, 95%CI 1.05–2.68, Pheterogeneity = 0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P = 0.02, OR = 2.79, 95% CI 1.14–6.85, Pheterogeneity = 0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Our study suggested that NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians. This polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.

Role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma: Experience of a single institution in China.

Objectives:  To evaluate diagnostic yield and the safety of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) for mediastinal/hilar lymph nodes and intrapulmonary masses.

Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non‐small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression‐free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)‐positive, advanced lung adenocarcinoma who received first‐line crizotinib therapy with that of patients who received first‐line standard chemotherapy, and also the PFS benefit of first‐line versus second‐line crizotinib treatment. Data on 80 patients with ALK‐positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first‐line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second‐line therapy after progressive disease (PD) occurred on first‐line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5–20.0 months) in patients who received first‐line crizotinib as compared with 5.4 months (95% CI: 4.4–6.5 months) in patients who received first‐line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11–0.36; P < 0.001). In patients who received second‐line crizotinib therapy, the median PFS was 9.9 months (95% CI: 6.4–13.4 months). The difference between first‐line and second‐line crizotinib treatment was not statistically significant (adjusted hazard ratio for progression, 0.56; 95% CI: 0.29–1.11; P = 0.092). Thus, there was a significant PFS benefit of first‐line crizotinib versus first‐line standard chemotherapy in Chinese patients with ALK‐positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second‐line therapy after PD had occurred on first‐line chemotherapy.

Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2)EGFRMutation‐Positive Non‐Small Cell Lung Cancer: A Prospective, Single‐Arm, Phase II Study

Abstract Lessons Learned. The findings of this prospective, single‐arm, phase II study showed that neoadjuvant erlotinib was well tolerated and might improve the radical resection rate in patients with stage IIIA‐N2 epidermal growth factor receptor mutation‐positive non‐small cell lung cancer (NSCLC). Erlotinib shows promise as a neoadjuvant therapy option in this patient population. Next‐generation sequencing may be useful for predicting outcomes with preoperative tyrosine kinase inhibitors (TKIs) in patients with NSCLC. Large‐scale randomized controlled trials investigating the role of TKIs in perioperative therapy, combining neoadjuvant and adjuvant treatments to enhance personalized therapy for patients in this precision medicine era, are warranted. Background. Information on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy in non‐small cell lung cancer (NSCLC) is scarce. We evaluated whether neoadjuvant erlotinib improves operability and survival in patients with stage IIIA‐N2 EGFR mutation‐positive NSCLC. Methods. We conducted a prospective, single‐arm, phase II study. Patients received erlotinib 150 mg per day for 56 days in the neoadjuvant period. The primary endpoint was the radical resection rate. Results. Nineteen patients were included in the final analysis. After erlotinib treatment, 14 patients underwent surgery. The radical resection rate was 68.4% (13/19) with a 21.1% (4/19) rate of pathological downstaging. The objective response rate was 42.1%; 89.5% (17/19) of patients achieved disease control, with a 10.3‐month median disease‐free survival among patients who underwent surgery. Among all 19 patients who received neoadjuvant therapy, median progression‐free survival (PFS) and overall survival were 11.2 and 51.6 months, respectively. Adverse events (AEs) occurred in 36.8% (7/19) of patients, with the most common AE being rash (26.3%); 15.8% experienced grade 3/4 AEs. Quality of life (QoL) improvements were observed after treatment with erlotinib for almost all QoL assessments. Effects of TP53 mutation on prognosis were evaluated in eight patients with adequate tissue samples. Next‐generation sequencing revealed that most patients had a TP53 gene mutation (7/8) in addition to an EGFR mutation. No TP53 mutation, or very low abundance, was associated with longer PFS (36 and 38 months, respectively), whereas high abundance was associated with short PFS (8 months). Conclusion. Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next‐generation sequencing may predict outcomes with preoperative TKIs.

Dynamics of EGFR mutations in plasma recapitulates the clinical response to EGFR-TKIs in NSCLC patients

Objectives Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. Patients and methods Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study. EGFR mutations including L858R, exon 19 deletion (19-del) and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples. Results We observed a significant reduction in plasma EGFR mutation abundance during the first two-month of TKI treatment. Acquiring of secondary T790M gatekeeper mutation or completed “loss” of EGFR mutations represented two major categories of resistance profiles. Moreover, we demonstrated that levels of plasma EGFR mutations highly correlated with changes of tumor diameter as determined by radiographic imaging, or development of new lesions. In a subset of patients, we further showed that reappearance of EGFR mutations could be detected in plasma up to 5 months ahead of progressive disease (PD), suggesting an early detection of drug resistance. Conclusions Our findings suggest that genomic analysis using plasma cfDNA may offer an effective approach to monitor clinical response and emergence of resistance.

Use of SuperARMS EGFR Mutation Detection Kit to Detect EGFR in Plasma Cell-free DNA of Patients With Lung Adenocarcinoma

Micro‐Abstract We assessed the performance of SuperARMS for the detection of EGFR mutations using plasma cell‐free DNA in 180 patients with advanced lung adenocarcinoma in the present study. SuperARMS and ARMS‐based methods have shown highly concordant results. SuperARMS can identify more mutation sites than ARMS. SuperARMS is a promising method for the clinical detection of EGFR mutations, especially for patients with insufficient biopsy samples. Background The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly selective and sensitive and able to detect 41 of the most common somatic mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR). It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8% to 99.2% normal DNA. The present study assessed the performance of SuperARMS in detecting EGFR mutations in cell‐free DNA (cfDNA) samples derived from plasma in patients with advanced lung adenocarcinoma. Materials and Methods A total of 180 patients with advanced clinical stage lung adenocarcinoma were retrospectively registered. The concordance between the EGFR mutations detected by SuperARMS and ARMS (AmoyDx EGFR 29 Mutations Detection Kit) was analyzed. Results Of the 180 samples, 57 (31.7%) were positive for EGFR mutations using SuperARMS, with 38 (21.1%) positive using ARMS. For the entire cohort, the positive, negative, and overall concordance rates were 97.3% (95% confidence interval [CI], 86.2%‐99.5%), 85.3% (95% CI, 78.6%‐90.2%), and 87.8% (95% CI, 82.2%‐91.8%), respectively. The kappa value was 0.69 (95% CI, 0.57‐0.81). For the 61 treatment‐naive patients and 119 previously treated patients, the kappa values were 0.59 (95% CI, 0.37‐0.79) and 0.74 (95% CI, 0.60‐0.87), respectively. SuperARMS identified 9 samples harboring the T790M mutation; of these, only 1 (11.1%) was detected using ARMS. Conclusion SuperARMS is a promising plasma‐based assay for EGFR mutations, including T790M. It might be useful in advanced‐stage lung adenocarcinoma patients whose tissue biopsy samples are insufficient for a traditional diagnostic EGFR assay or for patients with a poor performance status.