Liang Dai

Survival after neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: A meta-analysis

The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone.

Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo

Background We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism. Methods Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo. Results Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341–0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350–0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably. Conclusions HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.

Cross-Platform Comparison of Four Leading Technologies for Detecting EGFR Mutations in Circulating Tumor DNA from Non-Small Cell Lung Carcinoma Patient Plasma

Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison. Fifteen EGFR mutations across twenty NSCLC patients were identified. Firefly NGS, cobas-ARMS and ddPCR all displayed superior sensitivity while ADx-ARMS was better suited for the qualitative detection of EGFR mutations with allele frequency higher than 1% in plasma and tissue samples. We observed high coincidence between the plasma and tissue EGFR mutational profiles for three driver mutations (L858R, exon 19 deletion and G719X) that are known targets of first generation EGFR-TKI therapies among patients who relapsed. Discrepancies between tissue and plasma EGFR mutational profiles were mainly attributable to spatial and temporal tumor heterogeneity, mutation inhibition due to therapy response and drug resistance (T790M). This study illustrates the challenges associated with selection of a technology platform for EGFR ctDNA analysis in the context of treatment evaluation and drug resistance detection.

The equivalent efficacy of multiple operations for multiple primary lung cancer and a single operation for single primary lung cancer.

BACKGROUND The incidence of synchronous and metachronous multiple primary lung cancers (MPLCs) has been increasing recently. The new multidisciplinary classification of lung adenocarcinoma and TNM Classification of Lung Cancer (7(th) edition, 2009), have improved the understanding of MPLC. Most researchers recommend that surgical therapy should be actively pursued if the patients physical condition and lung function permit it and if a complete cure can be achieved. However, few studies have reported the long-term efficacy of surgical treatment for MPLC, which we explored in this study. METHODS A total of 1,290 Lung cancer patients from a prospectively maintained database, treated by a single surgeon group between January 2000 and July 2013, at Beijing Cancer Hospital, Peking University, were reviewed. We retrospectively analyzed the clinical data of 31 patients diagnosed with MPLC out of 1290 lung cancer patients, focusing on long-term survival. RESULTS MPLC patients accounted for 2.4% (31/1,290) of the patient cohort: 27 had synchronous MPLC (87.1%) and 4 had metachronous MPLC (12.9%). The 1-, 3- and 5-year postoperative survival rates were 100%, 75.8% and 75.8%. On stratification according to TNM stage, the 1-, 3- and 5-year of patients with stage I cancer (20 patients) were 100%, 77.2% and 77.2%, not statistically significant with those for the entire cohort (1,290 patients; 95.4%, 80.5% and 66.2%, P=0.455). CONCLUSIONS When the patients physical condition and tumor-related factors permit it, surgery should be the first choice of treatment for MPLC; it is associated with an equivalent efficacy to that of surgery for single primary lung cancer.

Expression of p63 and CK5/6 in early-stage lung squamous cell carcinoma is not only an early diagnostic indicator but also correlates with a good prognosis

Non‐small cell lung cancer (NSCLC) accounts for 80% of lung cancers, and lung squamous cell carcinoma (SQCC) is one of the main types. Advances in the treatment of lung SQCC are lacking when compared to lung adenocarcinoma. The main treatment for early‐stage SQCC is surgery. However, factors affecting the efficacy of surgical treatments for early‐stage lung SQCC remain unclear. In this study, we examined the significance of commonly used lung SQCC diagnostic markers p63, p40, and cytokeratin (CK)5/6 in prognosis.

Efficacy of repeated surgery is superior to that of non-surgery for recurrent/second primary lung cancer after initial operation for primary lung cancer: Efficacy of repeated surgery for LC

The current study aimed to determine the oncological efficacy and surgical safety of multiple pulmonary resections (MPRs) after prior curative surgery for local regional recurrent or second primary lung cancers.

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy: HOXA13 and ESCC chemoresistance

Chemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance.

The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma

Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. The endogenous DNA damage response confers chemoresistance to these agents by repairing DNA damage. The initiation and transduction of the DNA damage response (DDR) signaling pathway, which is dependent on the activation of ATM (ataxia-telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), is essential for DNA damage repair, the maintenance of genomic stability and cell survival. Therefore, ATM or ATR inhibition is considered as a promising strategy for sensitizing cancer cells to chemotherapy. This study is aimed to explore the effect of ATR inhibitor on sensitizing ESCC (esophageal squamous cell carcinoma) cells to cisplatin, and whether ATM deficiency could impact the sensitization. We found that 21.5% of ESCC cases had ATM deficiency and that patients with ATR activation after neoadjuvant chemotherapy had worse chemotherapy response and poorer overall survival than that without ATR activation (32 mons vs. >140mons). Then, it was shown that VE-822 inhibited ATR-CHK1 pathway activation, leading to the accumulation of cisplatin-modified DNA. And it inhibited cell proliferation, induced cell cycle arrest in G1 phase and enhanced cell apoptosis. Moreover, VE-822 significantly sensitized ESCC cells to cisplatin, and these two drugs had synergistic effects, especially in ATM-deficient cells, in vitro and in vivo. Our results suggest that ATR inhibition combining with cisplatin is a new strategy for managing patients with ESCC, especially those with ATM-deficiency. However, this is an idea that requires further validation.

Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients Treated with Surgery

BACKGROUND AND OBJECTIVE It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC) patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors. METHODS All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2) and preoperative N2 (IIIa3/a4). Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis. RESULTS The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001), 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020). Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001) and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032) were independent prognostic factors for stage N2-IIIa lung cancer patients. CONCLUSIONS The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with high selective stage N2-IIIa NSCLC to obtain a comparatively satisfying long-term survival.
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Neuroendocrine Differentiation is not a Malignant Index of Non-small Cell Lung Cancer

BACKGROUND A debate has been ongoing whether non-small cell lung cancer(NSCLC) with neuroendocrine(NE) differentiation likely indicates malignant behavior, poor prognosis, and sensitivity to chemotherapy. In response to this issue, we retrospectively investigated NE differentiation in NSCLC patients who underwent anatomical pulmonary surgery. METHODS A total of 274 patients who met the inclusion criteria through January 2000 to December 2008 were enrolled in this study because they had the detailed material and enough paraffin tumor samples for tissue microarray. The recommended antibody panel consisted of CgA, Syn, NCAM, Leu-7, PGP9.5, and MAP-2. We also counted Ki-67 in the tissues to present the nuclear proliferation index. The Kaplan-Meier estimator and the Cox proportional hazard model multivariate analysis were applied to observe the relationship between NE differentiation and postoperative survival of the patients. RESULTS The Cox analysis of different NE score combinations on the prognosis of NSCLC after surgical treatment did not reach statistical significance (score 1, score 2, and score≥3 vs score 0, P=0.527; score 0 vs score ≥1, P=0.791; score<2 vs score≥2, P=0.163; score<3 vs score≥3, P=0.293). The Kaplan-Meier estimator did not give significant difference in the survival of NE score combinations in each pTNM layer. In the perioperative chemotherapy group, we also did not find a positive correlation for the survival analysis of NE score combinations (score 1, score 2, and score≥3 vs score 0, P=0.692; score 0 vs score≥1, P=0.922; score<2 vs score ≥2, P=0.264; score<3 vs score≥3, P=0.484). CONCLUSIONS The NE differentiation of NSCLC reflects some structure and functional characteristics of NELT, although it cannot be used as an independent factor of biological behavior and survival for NSCLC patients who underwent surgery in our group.