Aiwen Wu

A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy

A preclinical trial identified 4 of 20 (20%) gastric cancer (GC) patient-derived xenografts responded to cetuximab. Genome-wide profiling and additional investigations revealed that high EGFR mRNA expression and immunohistochemistry score (3+) are associated with tumor growth inhibition. Furthermore, EGFR amplification were observed in 2/4 (50%) responders with average copy number 5.8 and >15 respectively. Our data suggest that a GC subtype with EGFR amplification and overexpression benefit from cetuximab treatment.

Post-operative imatinib in patients with intermediate or high risk gastrointestinal stromal tumor.

AIMS This study aims to determine whether adjuvant treatment with imatinib improves recurrence-free survival (RFS) in Chinese patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST) compared with those not receiving adjuvant therapy. We also sought a correlation between c-KIT mutations and RFS. METHODS Patients who had undergone complete tumor resection with intermediate or high risk of recurrence were enrolled in a single-center, non-randomized, prospective study. Patients either received adjuvant imatinib therapy (400 mg once-daily) for 3 years or did not. Mutation analyses of c-KIT were performed on available archival tumor samples. RESULTS 105 patients were enrolled: 56 in the treatment group and 49 in the control group. Median follow-up was 45(43.1-46.9) months. RFS at 1, 2 and 3 years were higher in the treatment group than in the control group (100% vs. 90% at 1 year; 96% vs. 57% at 2 years; 89% versus 48% at 3 years, P < 0.001, HR = 0.188). Subgroup analyses showed that adjuvant therapy significantly decreased the risk of recurrence in patients whether at high risk or at intermediate risk compared with control patients (3-year RFS: 95% vs. 72%, in intermediate risk; 85% versus 31% in high risk; P < 0.001). In addition, imatinib adjuvant treatment decreased the risk of death (P = 0.025, [corrected] HR = 0.254). CONCLUSIONS Adjuvant imatinib can improve 1-, 2- and 3-year RFS rates in patients at intermediate or high risk of recurrence after complete tumor resection. CLINICAL TRIALS REGISTRATION NUMBER ChiCTR-TCC-00000582.

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial.

PURPOSE We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique. MATERIALS AND METHODS Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS). RESULTS Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively. CONCLUSIONS The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.

Differences in Gastric Cancer Survival Between the U.S. and China

Previous comparisons of gastric cancer between the West and the East have focused predominantly on Japan and Korea, where early gastric cancer is prevalent, and have not included the Chinese experience, which accounts for approximately half the worlds gastric cancer.

Prognostic value of metastatic lymph node ratio as an additional tool to the TNM stage system in gastric cancer

BACKGROUND Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system. METHODS This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival. RESULTS Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival (p < 0.001). CONCLUSIONS rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.

Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer.

Although the role of peri‐operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established.

Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer

BackgroundThis study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy.MethodsWe completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy.ResultsThere were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups.ConclusionThe FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.

Neoadjuvant chemoradiation therapy for resectable esophago-gastric adenocarcinoma: a meta-analysis of randomized clinical trials

BackgroundThe efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor.MethodsWe systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR).ResultsSeven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63–0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant.ConclusionPatients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.

Apoptosis index correlates with chemotherapy efficacy and predicts the survival of patients with gastric cancer

The objectives of this study are to investigate the apoptotic changes in gastric adenocarcinoma following neoadjuvant chemotherapy and to illuminate its correlation with response. One 67 gastric cancer patients with cT2-4 or TanyN1-3M0 between January 2006 and December 2007 were included. All patients had previous gastrectomy and D2 lymphadenectomy with curative intent performed. A total of 12 cycles of preoperative mFOLFOX7 chemotherapy was recommended for all patients, and 83 patients received only adjuvant chemotherapy. Resected specimens were subjected to in situ TUNEL assay and scanned with Applied Imaging Ariol SL-50. Apoptosis index (AI) was significantly higher in the patient received preoperative chemotherapy (CS group) than in the patient did not (S group). In the CS group, AI was found to have a strong positive correlation with the pathological response (rho = 0.403, P = 0.0002). A ROC curve presented a score of 49.4 as the AI cutoff value for response, dividing the CS group into two subgroups with significantly different prognoses (P = 0.003) and further allowing identification of 8 patients with significantly better prognosis out of 48 patients evaluated as grades 1a–b according to a pathological response evaluation (P = 0.022). In conclusion, AI is correlated with efficacy of preoperative chemotherapy and prognosis of gastric cancer patients following neoadjuvant chemotherapy. An AI cutoff value for response may be used as a complementary approach to current pathological response evaluations to help identify potential responders.

Controlling angiogenesis in gastric cancer: A systematic review of anti-angiogenic trials

PURPOSE Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of anti-angiogenic agents in gastric cancer. DESIGN A systematic search of PubMed, Embase and conference databases is performed to identify clinical trials with specific anti-angiogenic agents in gastric cancer treatment RESULTS The risk of disease progression (37-52%) and death (19-22%) with ramucirumab as second-line treatment decreases in phase III trials in advanced gastric cancer. No significant improvement in overall survival (OS) with the addition of bevacizumab to chemotherapy is shown. Bevacizumab or ramucirumab combined with traditional chemotherapy is associated with higher adverse event rate compared to chemotherapy alone. Except for apatinib, phase II trials of other tyrosine kinase inhibitors (TKIs) may improve overall response rate, but there are no significant improvements in OS and progression-free survival (PFS) when combined with chemotherapy. CONCLUSION Phase III trials in advanced gastric cancer have demonstrated improved outcome with ramucirumab as second-line treatment. Most of the other studies on anti-angiogenic agents in gastric cancer have reported improvement in response rate but not in OS compared to chemotherapy alone. Future research is expected in optimizing the anti-angiogenic therapy combined with traditional treatment.