Prognostic Significance of Epidermal Growth Factor Receptor Expression in Colon Cancer Patients Undergoing Curative Surgery

Background To investigate the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for prediction of cancer behavior and clinical outcomes in colon cancer patients undergoing potentially curative surgery. Methods EGFR determination using a commercially available immunohistochemistry kit was performed in tissues from 149 colon cancer patients receiving primary surgical treatment and in 25 normal colon mucosa specimens from noncancer patients. EGFR positivity was correlated in univariate and multivariate analyses with disease recurrence and survival. In addition, p27, p53, and vascular endothelial growth factor expression were assessed by immunohistochemistry in 104 patients and correlated with EGFR tumor expression and clinical outcome. Results EGFR expression was detected in approximately one third of colon cancer patients (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was correlated with disease recurrence and worse survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, Dukes’ staging, p27, and EGFR expression were the only independent covariates. In particular, in Dukes’ A and B patients the 5-year survival probability was 96% for EGFR-negative and high p27 expression cases and was 30.7% for EGFR-positive and low p27 expression cases. Conclusions EGFR expression was an independent prognostic indicator of disease recurrence and poor survival in colon cancer patients undergoing curative surgery. In the context of novel therapeutic options such as molecularly targeted therapies, these findings suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR-positive colon cancer patients.     

Stage-Specific Effect of Adjuvant Therapy Following Gastric Cancer Resection: a Population-based Analysis of 4,041 Patients

Background Adjuvant chemoradiotherapy improved survival in patients with resected gastric adenocarcinoma in the Southwest Oncology Group/Intergroup 0116 trial. Our objective was to examine the impact of adjuvant treatment on overall survival (OS) in the general population. Methods Patients 18–85 years old who had undergone resection of non-metastatic gastric adenocarcinoma between May 2000 and December 2003, were identified from the Surveillance Epidemiology and End Results (SEER) database. Patients who had received pre-operative irradiation, had unknown stage or radiation status, or had a survival of 3 months or less from the date of diagnosis were excluded. Survival of those who received post-operative irradiation was compared with those who did not; Kaplan-Meier methods and Cox proportional hazards models were used. Results Of 4,041 patients, there was improved survival for those receiving adjuvant irradiation for stages III and IVM0, with a median OS of 31 versus 24 months (P = 0.005) and 20 versus 15 months (P < 0.001), respectively, and a trend for improved survival in univariate analysis of stage II (P = 0.0535). In final adjusted analysis, adjuvant irradiation significantly improved OS in stages III (HR: 0.71, P = 0.0007) and IVM0 (HR: 0.66, P < 0.0001). Adjusted analysis using a propensity score suggested that the benefit of adjuvant irradiation was similar in stage-II and -III patients. However, there was no statistical improvement in survival for stage-Ib and -II patients who had received adjuvant irradiation. Conclusions In this population-based analysis, adjuvant radiotherapy for stage-III and IVM0 gastric cancer significantly improved OS. Analysis of stage-Ib and -II patients is limited by small numbers, but there may not be the same benefit.     

Prognostic Significance of Circumferential Resection Margin Following Total Mesorectal Excision and Adjuvant Chemoradiotherapy in Patients with Rectal Cancer

Background This study was designed to evaluate the prognostic value of circumferential resection margin (CRM) in rectal cancer patients who underwent curative resection with adjuvant chemoradiotherapy (CRT). Methods We studied 504 patients who underwent total mesorectal excision with adjuvant CRT for rectal cancer between 1997 and 2001. The patients were divided into two groups: a negative CRM group (CRM > 1 mm) and a positive CRM group (CRM ≤ 1 mm). The survival rates, local recurrence rates, and systemic recurrence rates were compared between groups. Results The negative CRM group had 460 patients and the positive CRM group had 44 patients. The 5-year local and systemic recurrence rates were 11.3 and 25.3%, respectively, in the negative CRM group and 35.2 and 60.8% in the positive CRM group, respectively. The cancer-specific 5-year survival rates for the two groups were 72.5 and 26.9% (P < .001), respectively. CRM was found to be an independent prognostic factor by multivariate analyses which were adjusted for known outcome predictors (P < .001). Conclusion Oncological outcome for patients in the positive CRM group is less favorable than for those in the negative CRM group. Adjuvant CRT is not a definite treatment modality that can be used to compensate for a positive CRM following TME and adjuvant CRT in patients with TNM stage II or III rectal cancer.     

Multimodality Management of Esophageal Cancer

Esophageal cancer is a morbid disease with a grim prognosis. The outcomes of treatment even in non-metastatic disease undergoing potentially curative surgery are poor with 5-year survival ranging from 20 to 35 %. Several multimodality treatment options have been investigated in well-conducted randomised trials and meta-analyses evaluating both neoadjuvant and adjuvant therapies. However, there is still lack of uniform practice in the management of operable esophageal cancer. We review the current evidence for multimodality treatment of esophageal cancer, critically analysing the evidence supporting the use of each strategy, the pros and cons of each approach and discuss our approach in management. Neoadjuvant chemotherapy or chemoradiotherapy are currently the standard of care in localised esophageal cancer.     

多学科协作诊治模式下运行结直肠癌综合治疗的临床对照研究

目的探讨四川大学华西医院结直肠外科多学科协作（MDT）诊治模式的运行效果。方法回顾性分析从2006年12月至2007年5月，在四川大学华西医院结直肠外科住院治疗的大肠癌患者的病历资料，比较MDT组与非MDT组的疗效。结果MDT组围手术期住院时间及外科住院时间少于非MDT组（P〈0．05），但住院总时间上2组间差异无统计学意义（P〉0．05）。在手术治疗结果上，MDT组肿瘤手术切除率高于非MDT组（P〈0．05）。从术后早期并发症的发生情况分析，MDT组术后早期肠梗阻发生率低于非MDT组（P〈0．05），但吻合口漏和吻合口出血发生率2组间差异无统计学意义（P〉0．05）。经过5～10个月的随访，MDT组的患者术后肿瘤复发率低于非MDT组（P〈0．05），而术后吻合口狭窄和肠梗阻的发生率，2组间差异无统计学意义（P〉0．05）。结论结直肠肿瘤MDT模式针对大肠癌采用综合治疗方案，不仅有利于治疗方案的合理时间分配，而且提高了治疗效果。但对于MDT模式的影响因素尚缺乏系统性研究，同时还需将MDT模式中手术治疗的多模式环节进一步完善，以推出更为细化的围手术期MDT模式。     

Adjuvant Systemic Therapy of Breast Cancer

The first procedure in primary breast cancer is usually the surgical excision of the tumor. However, a medical therapy is necessary in almost all patients to treat the systemic component of the disease. Which medical approach is recommended depends on the biology of the tumor itself. Endocrine-responsive tumors must be treated by an endocrine therapy according to their menopausal status. In HER2/neu-overexpressing tumors, the monoclonal antibody trastuzumab is part of the standard treatment in combination with chemotherapy. Hormone receptor-negative and non-HER2/neu-overexpressing tumors as well as endocrine-responsive tumors with a high proliferation index or additional risk factors must be treated with chemotherapy as well. This review article gives further information about the available agents and schedules.     

Prognostic Factors in 2230 Korean Colorectal Cancer Patients: Analysis of Consecutively Operated Cases

To define the prognostic factors in Korean colorectal cancer patients, univariate and multivariate analysis were performed on data from 2230 consecutive patients who underwent resection for colorectal cancer at the Seoul National University Hospital. The prognostic variables used for the analysis included patient's age, gender, bowel obstruction, bleeding, symptom duration, preoperative leukocyte count, preoperative serum carcinoembryonic antigen (CEA) level, Dukes' stage, tumor location, tumor size, depth of bowel wall invasion, number of lymph node metastases, histologic differentiation, and gross morphology of tumor. The overall 5-year survival rate was 62%. In the univariate analysis, all the factors except sex, symptom duration, and tumor size were associated with prognosis. Among the factors significant in the univariate analysis, Dukes' stage (p < 0.001), number of lymph node metastasis (p < 0.001), CEA level (p < 0.001), tumor location (p= 0.003), gross morphology of tumor (p= 0.017), and depth of bowel wall invasion (p= 0.031) were significant in the multivariate analysis. Several differences in prognostic factors between colon cancer and rectal cancer were observed. In the multivariate analysis, gross tumor morphology was significant only for colon cancer, and histologic differentiation was significant only for rectal cancer. Lymph node metastasis was an independent prognostic variable for both colon and rectal cancer, but its significance was more prominent for rectal cancer. Although Dukes' stage is the most reliable prognostic predictor, this study shows that other factors (preoperative CEA level, gross morphology of tumor, location of tumor, nodal status) also provide important information for the outcome of the patient.     

Re-Challenging Taxanes in Recurrent Breast Cancer in Patients Treated with (Neo-)Adjuvant Taxane-Based Therapy

SUMMARY: Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxane-naive populations cannot reliably be used as references. Patients and Methods: The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval (<1 year: 34.8%; 1-2 years: 42.9%; >2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of >2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.     

Prognostic Factors for Survival in Patients With Locally Recurrent Extremity Soft Tissue Sarcomas

Background Factors prognostic for survival in patients with locally recurrent extremity soft tissue sarcomas (STS) are poorly defined, thus making it difficult to identify high-risk patients who may benefit from adjuvant therapy.Methods A total of 1421 patients underwent surgical treatment for primary extremity STS at a single institution between 1982 and 2002. Of these, 179 (13%) patients underwent complete surgical resection of an isolated local recurrence and were the subjects of this study. Clinicopathologic factors from both the primary tumor and the local recurrence were analyzed.Results The median interval to initial local recurrence was 16 months: 65% developed a local recurrence by 2 years and 90% by 4 years. Only four patients who presented with a low-grade primary tumor progressed to a high-grade local recurrence. Independent prognostic factors for disease-specific survival after local recurrence were a high histological grade (hazard ratio, 5.1; P = .0004), a large local recurrence tumor size (hazard ratio, 1.5; P = .0001), and a short local recurrence–free interval (hazard ratio, 1.6; P = .0001). Patients who developed a local recurrence >5 cm in 16 months (n = 44; 0 low grade) had a 4-year disease-specific survival of 18%, compared with 81% for patients who developed a local recurrence 5 cm in >16 months (n = 46; 11 low grade).Conclusions Histological grade, local recurrence size, and local recurrence–free interval are independently predictive of survival in patients with locally recurrent extremity STS. A large local recurrence that develops in a short interval indicates a biologically aggressive tumor with a high tumor-specific mortality. Patients who develop such recurrences are ideal subjects for systemic neoadjuvant therapy trials.     

A Decision Analysis Model Identifies the Interval of Efficacy for Transarterial Chemoembolization (TACE) in Cirrhotic Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Introduction For liver transplant candidates with hepatocellular carcinoma (HCC), the ability of neoadjuvant transarterial chemoembolization (TACE) to improve outcomes remains unproven. The objective of our study was to determine if there was a specific time interval where neoadjuvant TACE would decrease the number of HCC patients removed from the pretransplant waitlist. Materials and Methods A decision model was developed to simulate a randomized trial of neoadjuvant treatment with TACE vs. no TACE in 600 virtual patients with HCC and cirrhosis. Transition probabilities for TACE morbidity (1 ± 1%), TACE response rates (30 ± 20%), and disease progression (7 ± 7% per month) were assigned by systematic review of the literature (18 reports). Sensitivity analyses were performed to determine time thresholds where TACE would decrease the number of delisted patients. Results TACE treatment had statistical benefit at waitlist time breakpoints of 4 and 9 months (P < 0.05). When waitlist times were less than 4 months, waitlist attrition was similar (20% vs. 34%, P = 0.08). When waitlist times exceed 9 months, waitlist dropout rates re-equilibrated (33% vs. 46%, P = 0.06). Review of the current literature determined that only those studies reporting on patients with waitlist times between 4 and 9 months found a benefit to neoadjuvant TACE. Conclusions This analysis indicates that the benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9 months from first TACE. These data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency. Presented at the 7th World Congress of the International Hepato Pancreato Biliary Association Meeting, September 6, 2006, Edinburgh, Scotland.     

Prognostic Evaluation of Breast Cancer Patients with Evident Bone Marrow Metastasis

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty‐four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6–70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(?) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I–II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor‐positive, high‐grade, advanced‐stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor‐positive, multicentric, grade III, advanced‐stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single‐agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.     

胰腺癌术后免疫治疗抗感染作用机制的探讨

目的：了解免疫治疗剂胸腺肽－α1在腺胰癌术后抗感染中的作用机制。方法：选择60例胰腺癌根治术病人，分为用药组和对照组。用药组病人在手术后使用胸腺肽－α1，对照组不予使用。观察临床疗效、内毒素和细胞因子（IL－2、IL－6、IL－10和TNF－α）水平的变化，以及T淋巴细胞亚群CD3^ 、CD4^ 、CD8^ 和NK细胞百分率的变化。结果：胰腺癌手术组病人使用胸腺肽α－1后肿瘤坏死因子（TNF）－α水平明显下降，白介素（IL）－2、IL－10水平明显升高；手术后1周用药组的CD3^ 、CD4^ 百分率较手术前升高，且明显高于对照组。用药组术后1周临床有效率达100％，高于对照组（80％）。结论：胸腺肽－α1在胰腺癌术后可提高免疫力的功能，有利于病人恢复。