进展期胃癌新辅助化疗的研究进展

目的总结进展期胃癌新辅助化疗的研究进展。方法采用文献复习的方法,对有关进展期胃癌新辅助化疗研究进展的文献进行综述。结果进展期胃癌的新辅助化疗可显著提高R0切除率,提高远期生存率,降低死亡风险。对于无远处转移的局部进展期胃癌的新辅助化疗时间一般为6~9周,然后根据疗效评价结果决定是否进行手术治疗;进一步深入的临床研究及化疗敏感程度检测方法的改进有助于新辅助化疗标准的统一。结论进展期胃癌新辅助化疗的疗效已比较明确,但其在适应证、化疗方案、用药时限、疗效评价指标等方面尚无明确的统一标准,仍需要多中心、大型的临床试验进行深入的研究。     

分子靶向药物在胃肠道肿瘤综合治疗中的应用

分子靶向药物在晚期胃肠道肿瘤治疗中,被证实可提高患者的客观缓解率并延长总生存期.因此,其在局部进展期胃肠道肿瘤综合治疗中的价值被逐渐重视.曲妥珠单抗用于HER-2基因阳性的局部进展期胃癌新辅助化疗中的临床研究正在进行中,结果值得期待.大量研究证明,西妥昔单抗联合化疗对于KRAS基因野生型潜在可切除的结直肠癌肝转移患者,能提高手术切除率并延长总生存期;而贝伐珠单抗在KRAS基因突变型结直肠癌肝转移术前转化治疗中的作用正在评估中.对于可切除的结直肠癌肝转移,虽现有的证据显示,分子靶向药物在新辅助治疗中未能带来长期生存益处,但最终结论仍存议甚多.对于局部进展期直肠癌患者,新辅助化疗中的西妥昔单抗在二期临床研究中未能显示治疗获益,贝伐珠单抗的作用同样需要在三期临床研究后进一步证实.与晚期肿瘤单一治疗模式不同,在肿瘤综合治疗中,需要系统评估分子靶向药物与细胞毒药物、手术以及放疗之间可能的相互影响及协同作用,制定出科学并适用于临床实践的综合治疗模式.     

Neoadjuvant Chemotherapy of Breast Cancer: Tumor Markers as Predictors of Pathologic Response,Recurrence, and Survival

Abstract: This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR?) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR? patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR? patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR? and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.     

The essentials of locoregional control in the treatment of gastric cancer.

Gastric cancer is the fourth most frequent cancer in the world. For curative treatment and local control of gastric cancer, surgery is essential. The extent of the lymph node dissection is still under debate. Only one available trial showed significantly increased overall survival, whereas in all other randomised trials no significant difference could be found. As surgery alone often is not sufficient in the curative treatment in gastric cancer, different (neo)adjuvant treatment strategies have extensively been studied. The recently published MAGIC trial showed downstaging, downsizing and an improved overall survival for patients treated with perioperative chemotherapy, compared to surgery alone (difference 13%, p = 0.009). The INT 0116 trial on the other hand, demonstrated the benefit of postoperative chemoradiotherapy compared to surgery alone for patients with a curative resection of gastric cancer. However, the quality of resections in this trial was poor, illustrating the importance of standardisation by quality control. This could be done by the Maruyama index, which quantifies the likelihood of unresected disease. In the Netherlands, the CRITICS trial has recently been launched, which will be a quality controlled trial comparing postoperative chemoradiotherapy and chemotherapy on survival and/or locoregional control in patients who receive neoadjuvant chemotherapy followed by a D1+ gastric resection.     

Does Graded Histologic Response After Neoadjuvant Chemotherapy Predict Survival for Completely Resected Gastric Cancer?

Background After publication of the MAGIC trial results, preoperative chemotherapy is increasingly used to treat advanced gastric cancer before resection. Tools for measuring response must be assessed. Methods We identified all patients with gastric cancer treated with neoadjuvant chemotherapy and R0 resection between 1991 and 2005 from a prospective database. Patients receiving preoperative radiation were excluded. Histologic response to treatment was graded from 0% to 100% by a single pathologist. Kaplan-Meier survival analysis was performed to identify the relationship between response and outcome and to identify factors predictive of disease-specific survival (DSS). Multivariate analysis was performed to identify independent predictors. Results A total of 168 patients underwent R0 resection after receiving neoadjuvant chemotherapy. Thirty-three percent of tumors were at the gastroesophageal junction. Cisplatin-based therapy was used for 68% of patients. Twenty-two percent of patients had a >50% pathologic response to treatment. Median follow-up after resection for all patients was 25 months. Median DSS for all patients was 33 months. Three-year DSS improved from 44% to 69% with at least a 50% histologic response (P = .01). Factors associated with decreased DSS included positive nodes at resection, pT3 tumor or greater, high grade, perineural or vascular invasion, and <50% response. Multivariate analysis identified nodal status and perineural or vascular invasion as independent predictors of survival. Conclusions Posttreatment nodal status and perineural or vascular invasion at resection, but not graded histologic response, independently predict DSS after neoadjuvant chemotherapy and surgical resection of gastric cancer.     

Long-term survival of resectable subset after induction chemotherapy in patients with locally advanced head and neck cancer

BACKGROUND: Although meta-analysis showed that survival improved with concurrent chemoradiation in locally advanced head and neck cancer, neoadjuvant chemotherapy is still unique, because it renders curative surgery feasible for marginally resectable head and neck cancer patients. METHODS: We reviewed patients with locally advanced head and neck cancer, who had been treated with neoadjuvant chemotherapy between June 1984 and February 2001 at the Seoul National University Hospital. RESULTS: A total of 167 patients were included. After 2 to 3 chemotherapy cycles, either surgery (38 patients) or radiation (104 patients) was conducted. Those who received surgery exhibited better survival than those who received radiation [median survival: not reached vs 33.6 months (95% CI: 22.6-44.7), p = .006]. The 5-year and 10-year survival rates of surgery group were 63.2% and 59.8%. CONCLUSION: The potential benefit of neoadjuvant chemotherapy with surgery in patients with locally advanced head and neck cancers merits further evaluation in future clinical trials.     

Prediction of Response and Prognosis by a Score Including Only Pretherapeutic Parameters in 410 Neoadjuvant Treated Gastric Cancer Patients

Background

Response to neoadjuvant chemotherapy is an independent prognostic factor in locally advanced gastric cancer. However, no prospectively tested pretherapeutic parameters predicting response and/or survival in gastric cancer are available in clinical routine.

Methods

We evaluated the prognostic significance of various clinical pathologic parameters in 410 patients who were treated with neoadjuvant chemotherapy followed by gastrectomy. Clinical and histopathologic response evaluation was performed by using standardized criteria. A prognostic score was created on the basis of the variables identified in the multivariate analysis.

Results

Three pretherapeutic parameters were identified as positive predictive factors for response and prognosis: tumor localization in the middle third of the stomach (P?=?0.001), well-differentiated tumors (P?=?0.001), and intestinal tumor type according to Laurén classification (P?=?0.03). A prognostic index was constructed, dividing the patients into three risk groups: low (n?=?73), intermediate (n?=?274), and high (n?=?63). The three groups had significantly different clinical (P?=?0.007) and histopathologic response rates (P?=?0.001) and survival times, with a median survival time that was not reached in the low-risk group, 39.2?months in the intermediate-risk group, and 20.5?months in the high-risk group. The corresponding 5-year survival rates were 65.3, 41.2, and 21.2% (P?Conclusions A simple scoring system based on three clinicopathologic parameters accurately predicts response and prognosis in neoadjuvant treated gastric cancer. This system provides additional useful information that could be applied to select gastric cancer patients pretherapeutically for different treatment approaches. Prospective testing of the score in an independent patient cohort is warranted.     

Clinical Correlation of Endoscopic Ultrasonography with Pathologic Stage and Outcome in Patients Undergoing Curative Resection for Gastric Cancer

Background Endoscopic ultrasonography (EUS) is considered valuable for preoperative staging of gastric cancer and defining patient eligibility for enrollment in neoadjuvant protocols. The aim of this study was to correlate EUS staging with pathologic evaluation and outcome in patients undergoing curative R0 resection for gastric cancer. Methods All patients who underwent preoperative clinical assessment of T/N stage with EUS and subsequent R0 resection for gastric adenocarcinoma between 1993 and 2003 were identified from a prospective database. Patients who received neoadjuvant chemotherapy were excluded. Clinical staging results from preoperative EUS were compared with postoperative pathologic staging results and correlated with clinical outcome. Results Two hundred twenty-five patients with gastric cancer underwent EUS followed by R0 resection, without preoperative chemotherapy. The accuracy of the individual EUS T stage was 57% (127 of 223) and was 50% for N stage (110 of 218). Although EUS was less able to predict outcome according to individual T stage, patients with lesions ≤T2 on EUS had a significantly better outcome than patients with lesions ≥T3. Preoperative assessment of risk was not predicted by EUS N stage alone. Patients identified as high risk on EUS and those with a combination of serosal invasion and nodal disease had both the highest concordance with pathology and a significantly worse outcome (P = .02). Conclusions The concordance between EUS and pathologic results was lower than expected for individual T and N stages. Patients with lesions ≤T2 had a significantly better prognosis than patients with more advanced lesions. Individual EUS N stage has limited value in preoperative risk assessment. Combined assessment of serosal invasion and nodal positivity on EUS identifies 77% of patients at risk for death from gastric cancer after curative resection.     

Complete 5-year follow-up of a prospective phase II trial of preoperative chemoradiotherapy for esophageal cancer

BACKGROUND: Conclusive evidence supporting the routine use of multimodality therapy in esophageal cancer is lacking. However, since long-term survival after esophagectomy alone is unusual, clinical trials designed to identify effective therapeutic regimens are essential. We report here the 5-year results of a phase II induction chemoradiotherapy trial. METHODS: From August 1991 to January 1995, 44 patients with esophageal or gastroesophageal junction carcinoma were treated with a combination of 5-fluorouracil, cisplatin, and interferon-alpha with concurrent external beam radiotherapy. RESULTS: Forty-one (93%) patients completed chemoradiotherapy, with most toxic events recorded as grade I or II. Curative resection (all gross tumor removed) was achieved in 36 of 37 surgical explorations, with 10 tumors demonstrating complete pathologic response and 23 showing partial pathologic response. Median follow-up for survivors was 75 months (range, 60-100 months). Five-year survival for all patients was 32%, with a median survival of 28 months. Five-year disease-free survival in patients with curative resection was 36% (median, 26 months) and overall survival was 39% (median, 34 months). Five-year survival for patients with curative resection whose disease responded to chemoradiotherapy was 42% (median overall survival, 36 months). Local-regional recurrence alone occurred in 3 patients, distant failure alone in 12 patients, and combined local-regional and distant failure in 2 patients. A Cox proportional hazards model identified both pathologic tumor and nodal stage as independent predictors of disease-free survival. Fourteen patients (32%) were 5-year survivors; 1 of these patients later experienced disease recurrence and died. CONCLUSIONS: Preoperative chemoradiotherapy can result in a long-term and durable disease-free state. Only large, multi-institutional phase III trials can determine whether combined modality therapy is superior to resection alone.     

Two commonly used neoadjuvant chemoradiotherapy regimens for locally advanced stage III non-small cell lung carcinoma: long-term results and associations with pathologic response

BACKGROUND: We performed this study to determine the outcomes (pathologic response, survival, local-regional control, and toxicity) in patients treated with neoadjuvant chemoradiotherapy and planned operation for stage IIIA non-small cell lung carcinoma. METHODS: Patients treated from 1993 to 2000 with neoadjuvant chemoradiotherapy and a predetermined plan for subsequent surgical resection for stage III non-small cell lung carcinoma were analyzed. All patients underwent pretreatment evaluation at the university's Multidisciplinary Lung Cancer Center. Most patients (87%) had complete mediastinoscopy staging, and all were believed to be poor candidates for up-front operation because of bulky extent of disease. The radiotherapy program used conventional, 2-dimensionally planned treatment to 45 to 54 Gy in 1.8- to 2-Gy fraction size. Concurrent chemotherapy consisted of etoposide/cisplatin or carboplatin/paclitaxel. Study end points included resectability, pathologic response, local-regional control, survival, and toxicity. An exploratory comparison between pathologic response and long-term survival was performed. An exploratory comparison between older chemotherapy (etoposide/cisplatin) and third-generation chemotherapy (carboplatin/paclitaxel) was also performed. RESULTS: Of 53 patients, 45 (85%) were deemed surgical candidates after induction therapy. Twenty-two (42% of the initial cohort) patients had a major pathologic response to stage 0, I, or II disease. The 5-year actuarial survival was 31%. Major pathologic response was associated with improved survival (48% vs 24%; P =.027). The overall rate of early death potentially related to therapy in this series was 9%; this mostly occurred in patients who underwent right pneumonectomy. There was no difference in efficacy or mortality between etoposide/cisplatin and radiotherapy versus carboplatin/paclitaxel and radiotherapy, although the latter regimen was associated with less grade 3 or higher acute toxicity necessitating interruption or hospitalization during neoadjuvant treatment (P =.02). In-field local control was achieved in 83% of all patients (90% of the patients who underwent resection). Brain metastases as the first site of treatment failure occurred in 23% of all patients. CONCLUSIONS: Neoadjuvant concurrent chemoradiation delivers high resectability, major pathologic response rate, and excellent local-regional control, with encouraging long-term survival considering the patient population studied. Major pathologic response correlates with long-term survival. Neoadjuvant carboplatin/paclitaxel and radiotherapy is an appropriate framework on which to add new therapies.     

局部进展期胃癌术前化疗的疗效分析

目的 探讨局部进展期胃癌术前化疗的疗效及安全性,以及影响术前化疗胃癌患者复发死亡的因素.方法 回顾性分析2007年7月至2011年6月间复旦大学附属中山医院肿瘤内科收治的49例局部进展期胃癌患者的临床资料.采用Cox比例风险模型来分析新辅助化疗患者复发死亡的危险因素.结果 其中48例患者化疗后在术前接受了影像学评估,术前化疗的有效率和疾病控制率分别为33.3％(16/48)和93.8％(45/48);另有1例因在化疗期间胃穿孔行急诊手术而未接受影像学评估.治疗后89.8％(44/49)的患者获得根治手术,其中90.9％的患者(40/44)接受了D2淋巴结清扫术.术后淋巴结转阴率为30.6％(15/49);术后病理有反应32例,其中2例获得完全病理缓解.术前化疗期间血液学毒性反应主要为白细胞下降,非血液学毒性反应主要为恶心呕吐,以1～2级为主.49例患者平均住院时间为11.6 d,其中2例(4.1％)分别因术后胰漏和胰周渗液而延长了住院时间.49例患者均接受了术后随访,中位随访时间为21.6个月,中位无复发生存期为29.6个月(95％CI:24.0～35.2),中位总生存期为34.6个月(95％CI:29.8～39.4).多因素预后分析显示,影像学疗效(P.=0.038,RR=0.168,95％CI:0.031～0.904)和病理反应(P=0.007,RR=0.203,95％CI:0.064～0.642)是影响本组患者术后复发死亡的独立因素.结论 术前化疗对于局部进展期胃癌具有较高的疾病控制率和R0切除率;影像学疗效和病理反应是影响局部进展期胃癌术前化疗患者最重要的预后指标.     

Multidisciplinary approach to esophageal and gastric cancer

Despite marked advances in surgical therapy for patients with esophageal, esophagogastric, and gastric cancers, the overall prognosis of these patients has not markedly improved during the past decades. Multidisciplinary approaches using adjuvant postoperative and neoadjuvant preoperative therapeutic principles have received increasing attention with regard to the management of these patients. A series of randomized, prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in esophageal, esophagogastric junction, or gastric cancer. The available data on the role of neoadjuvant preoperative therapy are not yet conclusive. Although neoadjuvant therapy may reduce the tumor mass in many patients, several randomized, controlled trials have shown that, compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, that is, potentially resectable, tumors. In contrast, in patients with locally advanced tumors, that is, patients in whom complete tumor removal with primary surgery seems unlikely, neoadjuvant therapy increases the likelihood of complete tumor resection on subsequent surgery, but only patients with objective histopathologic response to preoperative therapy seem to benefit from this approach. Consequently, in the future, improvements in the overall survival of patients with esophageal, esophagogastric junction, or gastric cancer most likely will be achieved only by tailored therapeutic strategies that are based on the individual tumor location, tumor stage, and consideration of established prognostic factors. A clear classification of the underlying tumor entity, a profound knowledge of the prognostic factors applicable, a thorough preoperative staging, and identification of parameters that allow for the prediction of response to preoperative therapy will become essential for the selection of the optimal therapeutic modality for individual patients.     

Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer

PurposeBecause the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC).MethodsA total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05.ResultsOf 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43–2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87–3.26) and overall survival (HR:1.88, 95% CI:1.02–3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models.ConclusionsOur analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.     

Extended Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer Demonstrates Promising Postoperative Outcomes and Survival

Background

The optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined. Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head.

Methods

Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospectively maintained registry. Included patients were initiated on a 24-week course of neoadjuvant chemotherapy. Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent. Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed.

Results

Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy. Thirty-nine (61 %) met resection criteria and underwent operative exploration with curative intent, and 31 (48 %) were resected. Of the resected patients, 18 (58 %) had positive lymph nodes, 15 (48 %) required en-bloc venous resection, 27 (87 %) had a R0 resection, and 3 (10 %) had a complete pathologic response. There were no postoperative deaths at 90 days, 16 % of patients had a severe complication, and the 30-day readmission rate was 10 %. The median overall survival of all 64 patients was 23.6 months, whereas that of unresectable patients was 15.4 months. Twenty-five of the resected patients (81 %) are still alive at a median follow-up of 21.6 months.

Conclusions

Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma, selects a subset of patients for curative surgery with low perioperative morbidity, and is associated with favorable survival.     

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目的研究蒽环类联合紫杉类方案对三阴型乳腺癌进行新辅助化疗的疗效,应用动态增强磁共振成像(MRI)及组织病理学进行疗效评价。方法选择2008年1月至2011年12月北京大学第一医院乳腺疾病中心初始实施蒽环类联合紫杉类新辅助化疗并完成手术的三阴型乳腺癌病人为研究对象。疗效评价包括动态增强MRI临床评价及组织病理学评价。定义MRI评价包括临床完全缓解、临床部分缓解为临床评价有效,计算临床有效率;定义病理分级G3~G5为病理评价有效,计算病理有效率。结果共诊治1190例新发乳腺癌,其中三阴型乳腺癌129例(占10.8%),41例符合入组标准,新辅助治疗临床评价有效率为65.85%(27/41),病理评价有效率为85.37%(35/41),其中病理完全缓解率(pCR)为36.59%(15/41),新辅助治疗MRI评价与病理评价符合率为77.1%。结论蒽环类联合紫衫类方案是治疗三阴型乳腺癌的有效方法。动态增强MRI能准确评价三阴型乳腺癌新辅助化疗疗效,并与病理评价相符合。     

Complete Response to Neoadjuvant Chemoradiation for Rectal Cancer Does Not Influence Survival

Background: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation.Methods: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses.Results: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases.Conclusions: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Neoadjuvant chemotherapy as a treatment strategy for multiple bilobar liver metastases from colorectal carcinoma

Hepatic resection remains the only potentially curative therapy for patients with colorectal liver metastases. Because most have multiple bilobar liver metastases, surgical resection is possible in only 25-58% of patients with colorectal liver metastases. Currently, attention is focused on the potential for neoadjuvant chemotherapy to render formerly unresectable patients resectable. The availability of more efficacious chemotherapy agents and an inventive approach to delivery schedules have resulted in an increase in the number of candidates for hepatic resection after neoadjuvant chemotherapy. Although tumor response varies with regimen and/or route of chemotherapy for colorectal liver metastases, with 16-63% tumor response rates, hepatic resection for responders after neoadjuvant chemotherapy gives survival benefits, with 20-48% 5-year survival rates after surgery. Provided that neoadjuvant chemotherapy controls multiple bilobar liver metastases well, aggressive hepatic resection should be considered for patients with those lesions. As a treatment strategy for multiple bilobar liver metastases, neoadjuvant chemotherapy is a useful to increase resection rates and may contribute to the improvement of prognosis in patients with such lesions.     

Multimodal treatment of gastric cancer

Gastric cancer is the second leading cause of death from malignant disease worldwide.Although complete surgical resection remains the only curative modality for early stage gastric cancer,surgery alone only provides long-term survival in 20%of patients with advancedstage disease.To improve current results,it is necessary to consider multimodality treatment,including chemotherapy,radiotherapy and surgery.Recent clinical trials have shown survival benefit of combining different neoadjuvant or adjuvant protocols compared with surgery with curative intent.Furthermore,the implementation of chemotherapy with novel targeted agents could play an important role in the multimodal management of advanced gastric cancer.In this paper,we focus on a multidisciplinary approach in the treatment of gastric cancer and discuss future strategies to improve the outcome for these patients.     

进展期胃癌患者FOLFOX4与XELOX新辅助化疗的临床观察

目的：观察FOLFOX4和XELOX新辅助化疗方案对局部进展期胃癌的近期治疗效果以及毒副反应。方法：将2006年7月至2007年8月70例进展期胃癌患者随机分为3组,FOLFOX4新辅助化疗组25例,XELOX组20例,单纯手术组25例。新辅助化疗组行术前化疗2个疗程,化疗结束后4周进行胃癌根治术;单纯手术组行胃癌标准根治术（D2或D2＋）。结果：FOLFOX4组总有效率为52.0%,XELOX组总有效率为55.0%（P〉0.05）。FOLFOX4组恶心、呕吐、白细胞减少和口腔黏膜炎等毒副反应发生率高,而XELOX组以上毒副反应发生率低,仅表现为轻度的手足综合征。新辅助组患者根治性手术切除率为88.9%,单纯手术组为72.0%（P〈0.05）。结论：作为胃癌的新辅助化疗方案XELOX组与FOLFOX4组相似,进展期胃癌患者在新辅助化疗后,再进行手术治疗,可以提高手术根治率和切除率,但XELOX方案毒副作用较轻,化疗时间短,对机体损伤小,易于接受。     

Additive Chemotherapie bei Lebermalignomen zur Verbesserung der Operabilität

Complete tumor resection is the only curative option for patients with colorectal liver metastases. Hepatic resection is frequently not possible for technical reasons: because of large tumors, multiple or bilateral metastases, or tumors that are too close to vessels. In these cases chemotherapy might downstage the tumor volume and facilitate secondary curative resection in patients initially not eligible for curative surgery. Treatment with fluorouracil (5-Fu) alone has resulted in disappointing response rates of about 10-20% in patients with colorectal liver metastases, which make these protocols useless in the neoadjuvant setting. Because regional chemotherapy into the hepatic arteria results in significantly higher response rates (40-50%), some studies have documented some success in secondary curative surgery after regional chemotherapy of initially unresectable colorectal liver metastases. However, regional chemotherapy is invasive and therefore not standard therapy for every patient with colorectal liver metastases. Recently new exciting treatment options have become available for colorectal cancer. Combinations of chemotherapy consisting of irinotecan and 5-Fu/FA or oxaliplatin and 5-Fu/FA result in response rates of 50% and can be considered a new standard first-line chemotherapy for patients with metastatic colorectal cancer. Recently, two encouraging retrospective studies have been published with chronomodulated chemotherapy of oxaliplatin and 5-Fu/FA in the setting of neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases. With this multidisciplinary approach, antitumor activity of chemotherapy appears to be translated into a long-term survival benefit and some patients with initially unresectable colorectal liver metastases can potentially be cured. As a consequence, on the premises of close cooperation between surgeons and internists, more patients with metastatic colorectal cancer will be cured in the future.