Xiaohua Liang

A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer

To the Editor: The cornerstone of therapy for extensive-stage small cell lung cancer (ESCLC) has been etoposide combined with platinum (EP) over the past two decades. Irinotecan plus platinum (IP) has also been demonstrated effective, while the superiority of IP over EP as first-line therapy for E-SCLC remains controversial. In the issue of May 2010, Jiang et al.1 reported a meta-analysis which demonstrated the superiority of IP versus EP in the first-line treatment of patients with E-SCLC. We have updated the data by two new studies published after the literature search completion date of the above meta-analysis. Among them, one was a randomized phase III study2 published in March 2010 and the other was a German phase III trial3 published in January 2011. In fact, the German phase III trial3 was just the final outcome of a phase II trial4 published in 2006 which was analyzed in the metaanalysis by Jiang et al.1 Using the same method as Jiang et al.1 did for meta-analysis, we complemented it including the latest data. At last, data of seven trials were analyzed. The baseline characteristics of each trial are presented in Table 1. A total of 2027 patients with E-SCLC were available for the meta-analysis. Statistical analyses were calculated using STATA 10.1 package (StataCorp, College Station, TX).

Chemotherapy with cetuximab or chemotherapy alone for untreated advanced non-small-cell lung cancer: A systematic review and meta-analysis

PURPOSE To compare the efficacy and toxicities of chemotherapy plus cetuximab (Erbitux, E; E-chemo) with chemotherapy alone (chemo alone) in patients with previously untreated advanced non-small-cell lung cancer (NSCLC). The primary endpoint was overall survival; the secondary endpoints were progression-free survival, overall response rate, one-year survival and safety. METHODS The PubMed database, the Cochrane Library, conference proceedings, database of ongoing trials and references of published trials and reviews were screened. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival and progression-free survival, relative risks (RRs) for overall response rate and one-year survival, and odds ratios (ORs) for the different types of toxicity were pooled using STATA SE10.1 package. RESULTS Four trials involving 2018 patients with previously untreated NSCLC were ultimately analyzed. The pooled HR for overall survival (HR, 0.87; 95%CI, 0.79-0.96; p=0.004) was in favor of E-chemo, which also gave rise to a higher overall response rate (RR, 1.19; 95%CI, 1.04-1.37; p=0.013). The analysis failed to show benefit of E-chemo in progression-free survival (HR, 0.91; 95%CI, 0.83-1.00; p=0.06) and one-year survival (RR, 1.10; 95%CI, 0.98-1.26; p=0.172). E-chemo indeed caused more grade 3/4 rash and infusion reaction (OR, 43.86; 95%CI, 12.46-154.44; p=0.000; OR, 3.69; 95%CI, 1.89-7.25; p=0.000; respectively). CONCLUSION Our data showed that the addition of cetuximab to chemotherapy would improve overall survival and overall response rate. It may provide new option for clinical treatment for untreated advanced non-small-cell lung cancer. The side effects of E-chemo are predictable and manageable.

A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma.

Abstract Background. Although some randomized controlled trials had compared the anti-CD20 monoclonal antibody rituximab plus chemotherapy (R-chemo) to chemotherapy alone for B-cell non-Hodgkins lymphoma, the curative effects of R-chemo were still controversial. A systematic review and meta-analysis was performed to examine the efficacy of using R-chemo compared with the identical chemotherapy alone in the patients with B-cell non-Hodgkins lymphoma. Material and methods. Medical databases and conference proceedings were searched for randomized controlled trials which compared R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed B-cell non-Hodgkins lymphoma. Endpoints were overall survival, overall response, disease control, and adverse events. Results. Twelve eligible trials were identified, reporting outcomes of 4 996 patients. Fixed-effects analysis showed overall survival to be superior for R-chemo-treated patients (relative risks [RR], 1.09; 95%confidence interval [CI], 1.06–1.12, p <0.00001). Superiority was also observed for the patients receiving R-chemo with respect to overall response (RR, 1.17; 95%CI, 1.10–1.25, p <0.00001), complete response (RR, 1.52; 95%CI, 1.27–1.82, p <0.00001), and disease control (RR, 1.36; 95%CI, 1.26–1.46, p <0.00001). R-chemo improved overall survival, overall response and disease control in patients with diffuse large B-cell lymphoma (RR, 1.11, 95%CI: 1.06–1.16, p <0.0001; RR, 1.09, 95%CI: 1.01–1.19, p = 0.03 and RR, 2.00, 95%CI: 1.59–2.53, p< 0.00001, respectively) and follicular lymphoma (RR, 1.08, 95%CI: 1.04–1.12, p <0.0001; RR, 1.19, 95%CI: 1.07–1.33, p =0.001 and RR, 2.58, 95%CI: 1.61–4.12, p <0.0001, respectively). Meanwhile, R-chemo improved overall response in patients with mantle cell lymphoma (RR, 1.22, 95%CI: 1.07–1.40, p =0.004). Conclusion. R-chemo is superior to chemotherapy alone in patients with B-cell non-Hodgkins lymphoma, especially for diffuse large B-cell lymphoma and follicular lymphoma.

DNA repair gene X-ray repair cross complementing group 1 Arg194Trp polymorphism on the risk of lung cancer: a meta-analysis on 22 studies.

Background: DNA repair gene X-ray repair cross complementing group 1 (XRCC1) Arg194Trp polymorphism has been investigated widely on lung cancer risk. However, the results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 Arg194Trp polymorphism and lung cancer risk, we performed this meta-analysis. Methods: An electronic search of the database PubMed, Embase, and Chinese National Knowledge Infrastructure was performed. The odds ratio (OR) was pooled by STATA 10.1. Subgroup analyses by ethnicity, gender, smoking, and histologic types of lung cancer were performed. Results: Twenty-two studies including 7515 cases and 9560 controls were identified ultimately. The pooled OR for total population showed that homozygous Trp/Trp variant genotype could increase lung cancer risk compared with the homozygous wild Arg/Arg genotype (OR = 1.22, 95% confidence interval [CI] = 1.04–1.44, p = 0.01); however, heterozygote Arg/Trp variant genotype could decrease lung cancer risk (OR = 0.91, 95% CI = 0.85–0.99, p = 0.02). Subgroup analyses by ethnicity confirmed the result that homozygous Trp/Trp variant genotype increased lung cancer risk in Asians (OR = 1.19, 95% CI = 1.01–1.41, p = 0.04) but not in whites. It was interesting to find that both the heterozygote Arg/Trp and the combined Trp/Trp + Arg/Trp variant genotypes could decrease the risk of lung cancer in whites (OR = 0.83, 95% CI = 0.72–0.96, p = 0.01; OR = 0.85, 95% CI = 0.74–0.98, p = 0.03, respectively) but not in Asians. Subgroup analyses by gender, smoking, and histologic types of lung cancer did not indicate any significant difference between cases and controls, excepted for male population, which carried heterozygote Arg/Trp variant genotype that could decrease lung cancer risk (OR = 0.54, 95% CI = 0.31–0.95, p = 0.03). Conclusions: Homozygous Trp/Trp variant genotype of XRCC1 Arg194Trp polymorphism could increase lung cancer risk in total population, especially in Asians. However, the heterozygote Arg/Trp variant genotype might decrease the risk of lung cancer, especially in whites.

Gefitinib versus docetaxel in previously treated advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials

Abstract Purpose. A meta-analysis of randomized controlled trials was performed to compare the efficacy, quality of life (QOL), symptom improvement and toxicities of gefitinib with docetaxel in previously treated advanced non-small-cell lung cancer. Methods. The PubMed database, the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for overall response rate, QOL and symptom improvement, and odds ratios (ORs) for main toxicities were pooled using STATA package. Results. Four multicenter, randomized controlled trials involving 2257 patients with previously treated advanced NSCLC were ultimately analyzed. The pooled HRs showed no significant difference in OS and PFS between the two groups (HR = 1.02, 95% CI = 0.92–1.12, p = 0.70; HR = 0.97, 95% CI = 0.88–1.07, p = 0.57, respectively). Gefitinib significantly improved overall response rate (RR = 1.58, 95% CI = 1.02–2.45, p = 0.04) and QOL (RR = 1.55, 95% CI = 1.27–1.88, p = 0.00 by Functional Assessment of Cancer Therapy-Lung and RR = 1.86, 95% CI = 1.43–2.42, p = 0.00 by Trial Outcome Index, respectively). Gefitinib had fewer grade 3 or 4 neutropenia and fatigue (OR = 0.02, 95% CI = 0.01–0.03, p = 0.00; and OR = 0.47, 95% CI = 0.32–0.70, p = 0.00, respectively), but more grade 3 or 4 rash (OR = 2.87, 95% CI = 1.24–6.63, p = 0.01) than docetaxel. The grade 3 or 4 nausea, vomiting and diarrhea and symptom improvement were comparable between the two drugs. Conclusions. In conclusion, although similar OS and PFS, gefitinib showed an advantage over docetaxel in terms of objective response rate, QOL and tolerability. Therefore, gefitinib is an important and valid treatment option for previously treated advanced non-small-cell lung cancer patients.

Clinicopathologic Characteristics of Typical Medullary Breast Carcinoma: A Retrospective Study of 117 Cases

Purpose This study analyzed the clinicopathologic characteristics of typical medullary breast carcinoma (TMBC) in a cohort of Chinese patients. Methods We conducted a retrospective review of clinical data including general information, pathologic results, treatment regimens, and patient survival in cases of TMBC diagnosed between February 2004 and April 2011. Results A total of 117 patients were enrolled, with a median age of 52 years (range, 28∼92 years). Stage I and II disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal receptor negative disease (estrogen receptor negative, 68.4%; progestogen receptor negative, 86.3%) was more prevalent in this population. Human epidermal growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2 negative cases represented 16.2% and 63.2% of the cohort. The triple-negative, luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of the cases, respectively. The various TMBC subtypes showed no differences regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment regimens, and 2-year recurrence rates. However, patients with triple-negative disease were more likely to be younger, when compared to those with luminal disease (P = 0.002). At a median follow-up of 56 months (range, 2–112 months), the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%, respectively. Conclusion Early stage disease dominated the study cohort, and at two years after surgery, recurrence was extremely low. The heterogeneity of molecular subtypes was clearly shown, and no apparent differences were found among the clinicopathologic characteristics of the triple-negative, luminal, and HER-2 overexpressing subtypes.

High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases.

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P < 0.001), in both adenocarcinoma (60.5 vs. 30.6%, P = 0.003) and squamous carcinoma (37.5 vs. 0%, P = 0.04). The incidence of BMs in patients with EGFR mutations was higher than in patients with wild-type EGFR (70.3 vs. 38.1%, P = 002). NSCLC patients with BMs had a higher incidence of EGFR mutations and those with mutant EGFR had a higher frequency of BMs. EGFR mutations may promote brain metastasis growth of NSCLC.

Association between axillary lymph node status and Ki67 labeling index in triple-negative medullary breast carcinoma

OBJECTIVE Medullary breast carcinoma is a rare breast carcinoma with good prognosis. Although it has been established that axillary lymph node metastasis is a poor prognostic factor, little is known about the relationship between axillary lymph node metastasis and clinicopathological characteristics of medullary breast carcinoma patients. The aim of this study was to identify factors that predict occurrence of axillary lymph node metastasis in medullary breast carcinoma patients. METHODS We performed a retrospective study of axillary lymph node status and the relevant clinicopathological characteristics in 49 triple-negative medullary breast carcinoma patients with axillary lymph node dissection between November 2004 and July 2011. RESULTS A total of 49 patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph node metastasis that was confirmed pathologically. Axillary lymph node metastasis was not associated with age, menopausal status, primary tumor size or its location, the degree of inflammation within the tumor or mitotic count. However, we found a statistically significant association between axillary lymph node metastasis and Ki67 labeling index in primary tumors (P < 0.001). CONCLUSIONS There is a positive association between Ki67 labeling index in the primary tumor and axillary lymph node metastasis in triple-negative medullary breast carcinoma patients.

MicroRNA expression profiles of granulocytic myeloid‑derived suppressor cells from mice bearing Lewis lung carcinoma

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G-MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G-MDSCs were determined and the differential expression of microRNAs between G-MDSCs from tumor-bearing mice and tumor-free mice was examined. The number of G-MDSCs in spleens of Lewis lung carcinoma (LLC)-bearing mice was ~6-fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P<0.01) and G-MDSCs account for about 72.9% of all MDSCs. The microRNA (miRNA) profiles of the G-MDSCs from spleen of LLC-bearing mice were obtained using a microRNA microarray and compared with their counterparts from spleens of tumor-free mice. A total of 43 miRNAs with >1.3-fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA-468 (miR-486), miR-192, miR-128, miR-125a, miR-149, miR-27a, miR-125b, miR-350 and miR-328, were also analyzed by RT-qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor-induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G-MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC-induced granulocytic MDSCs and the target genes that mediate their functions.

Characterization of genetic alterations in brain metastases from non‐small cell lung cancer

Brain metastasis (BM) is the primary contributor to mortality in non‐small cell lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing studies suggest the potential for personalizing therapeutic approaches, the genetic profiles and underlying mechanisms of BM progression remain poorly understood. Here, we investigated the genetic profiles of brain metastases from NSCLC in six patients with primary tumors and corresponding BM samples via whole exome sequencing and targeted panel sequencing. We have demonstrated considerable genetic heterogeneity between primary lung cancer and corresponding brain metastases specimens. High‐frequency mutations were found in NOTCH2, NOTCH2NL, FANCD2, EGFR, and TP53. Additionally, EGFR and TP53 consistently exhibited high frequencies of mutation between primary tumors and corresponding brain metastases. The implication is that most of the genetic alterations may be acquired or lost during malignant progression, and the stable EGFR and TP53 mutational status between paired primary tumors and metastatic sites confirms that most mutations detected on analysis of the primary tumor or metastases are sufficient for clinical decision‐making, and suggest there is no need to re‐biopsy recurrent tumors or metastases for most NSCLC patients.