Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

Essential role of TRPC6 in the proliferation of gastric cancer and its mechanism / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer.</p><p><b>METHODS</b>The expression of TRPC6 protein was assessed in gastric cancer tissues and normal tissues adjacent to the cancer from 30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell growth, cell cycle of a human gastric cancer cell line AGS cells, tumor progression and development of xenografted human gastric cancer in a mouse model was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier analysis. All statistical tests were two-sided.</p><p><b>RESULTS</b>The TRPC6 protein in the tumor tissues and para-tumor tissues was (21.60 ± 8.32)% versus (7.14 ± 2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96 hours, the growth inhibition rates of gastric cancer cells were (36.90 ± 1.13)%, (44.06 ± 2.17)%, (52.12 ± 2.76)% and (50.89 ± 1.97)%, respectively. The clone formation rates of control group and DNC6 group were (14.70 ± 3.00)% versus (43.80 ± 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48 hours, the G(2)/M phase arrest was (20.34 ± 1.98)%, (24.31 ± 2.37)%, (27.70 ± 2.36)%, (35.10 ± 3.0)% in the DNC6 group and (18.40 ± 2.01)%, (18.0% ± 1.72)%, (17.50 ± 1.74)%, (16.80 ± 1.71)% in the control group, respectively. Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the mouse models with xenografted human tumors (P < 0.05).</p><p><b>CONCLUSION</b>In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.</p>

Evaluation of preoperative radiotherapy or chemoradiotherapy in sphincter preservation for locally advanced middle-low rectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of preoperative radiotherapy or chemoradiotherapy on the sphincter preservation and local tumor control as well as survival for the patient with locally advanced middle-low rectal cancer.</p><p><b>METHODS</b>121 locally advanced middle-low rectal cancer patients were treated with preoperative radiotherapy or chemoradiotherapy followed by surgery after rest of 4 to 6 weeks. 103 of these patients who underwent radical surgery were finally included in this study. The irradiation regimen was: 40 Gy/4 - 5 weeks, whereas 57 of these 103 patients received concurrent chemotherapy of 5-Fu or Xeloda. Sphincter-preserving surgery was performed in 59 patients and abdominoperineal resection in 44 patients. The survival was estimated by Kaplan-Meier model, and the differences between groups were compared using Log rank test. Multivariate analysis was performed by Cox's model.</p><p><b>RESULTS</b>Ten patients (9.7%) achieved a complete pathological response (pCR) to preoperative radiotherapy or chemoradiotherapy. The sphincter preservation rate was 57.3%. The 3-year overall survival (OS) and disease free survival (DFS) was 66.3% and 59.5%, respectively. Univariate analysis showed that pCR and postoperative pTNM stage were prognostic factors affecting survival, whereas, only pTNM stage was an independent prognostic factor (P = 0.003) by multivariate analysis.</p><p><b>CONCLUSION</b>Neoadjuvant preoperative radiotherapy and chemoradiotherapy is effective in local tumor control and improving survival for locally advanced middle-low rectal cancer, which can raise the rate of sphincter-preserving surgery, and achieve comparable result to abdominoperineal resection.</p>

Clinical observation of breast-conserving operation combined with radiotherapy for 43 patients with breast cancer / 上海第二医科大学学报

Objective To investigate the efficacy,side effects and cosmetic effects of breast-conserving operation combined with radiotherapy for patients with breast cancer. Methods Forty-three patients with early stage of breast cancer(n=30 for stage I and n=13 for stage II) were performed extended resection plus axillary lymph node dissection or quadrant resection plus axillary lymph node dissection.After operation,tangential field irradiation was conducted with 50 Gy of X ray,tumor bed was irradiated with additional 10 Gy of electron beam,and supraclavicular field irradiation was also administered with 30 Gy of X ray and 22 Gy of electron beam. Results There was no recurrence during the follow up for 14 to 50 months.The acute side effects of radiotherapy included breast complaints(n=10,grade Ⅰ,23.26%),skin erythema and hyperpigmentation(n=19,grade Ⅰ,44.19%),moist desquamation(n=5,grade Ⅱ,11.63%) and radiation esophagitis(n=4,grade Ⅰ,9.30%),while one patient experienced radiation esophagitis one month after radiotherapy.No such complications as skin fibrosis and necrosis,angiotelectasis,breast and upper extremity edema occurred.The short-term cosmetic effects were satisfactory to 93.02% of all the patients. Conclusion For early stage of breast cancer(stage I and stage Ⅱ),breast-conserving operation combined with radiotherapy may yield satisfactory survival rate and short-term cosmetic effects,as well as low incidences of side effects.