Efficacy and toxicity of nedaplatin and 5-FU with radiation treatment for advanced esophageal carcinomas

BACKGROUND: Nedaplatin, a new analog of cisplatin, has been developed and marketed in recent years in Japan. In this study, we evaluated the efficacy and toxicity of a regimen of nedaplatin and 5-FU with radiation in patients with advanced esophageal carcinomas. MATERIALS AND METHODS: Between June 1999 and December 2002, 42 patients with advanced and unresectable thoracic esophageal squamous cell carcinomas (SCCs) were enrolled into this study. Twenty-five of these 42 patients were considered to have inoperable tumors due to distant organ metastasis, distant lymph node metastasis, severe organ dysfunction and rejection of surgery by the patients. The remaining 17 patients received neoadjuvant treatment followed by surgery. The clinical responses of the primary tumors were evaluated. RESULTS: Response and toxicity could be assessed in 22 of the 25 patients with unresectable esophageal SCCs. Two of these 22 achieved a complete response (CR), 15 had a partial response (PR) and 5 showed no change (NC). The overall response rate (CR + PR) was 77%. The one- and 2-year survival rates were 30.7% and 10.2%, respectively, with a median survival time (MST) of 10.1 months. Of the 17 patients who received neoadjuvant treatment, 14 underwent subsequent surgery. Preoperatively, 2 of these 17 patients achieved a CR, 10 had a PR and 5 showed NC. The overall response rate for all 39 patients was 74%. The pathological complete response (pCR) rate of the 14 patients who underwent surgery was 28.6%. Their one- and 2-year survival rates were 48.2% and 12.1%, respectively, with an MST of 12.2 months. Toxicity was evaluated in the 39 patients whose responses were assessed. Toxicity higher than grade 3 occurred in 8 out of 39 (20.5%) patients, and 6 (15.4%), 3 (7.7%) and one (2.6%) had grade 3 leukopenia, thrombocytopenia and anemia, respectively. CONCLUSION: In conclusion, this study indicates that combination chemoradiotherapy with nedaplatin and 5-FU is safe and efficacious for patients with advanced esophageal carcinomas. We recommend further evaluation of this treatment regimen in such patients.     

Impact on survival of surgery after concomitant chemoradiotherapy for locally advanced cancers of the esophagus

BACKGROUND: To evaluate the results of chemoradiotherapy with or without surgery in locally-advanced esophageal carcinomas (T3 and/or nodal involvement). METHODS: One hundred twelve patients with locally-advanced carcinoma of the esophagus without histologically proven invasion of the tracheobronchial tree or distant visceral metastases were treated with concomitant chemoradiotherapy followed by re-evaluation; surgery was performed or chemoradiotherapy continued, based on tumor regression and the patient's general status. Chemoradiotherapy consisted of concomitant 5-fluorouracil (5FU)(1 g/m(2) day 1-3), cisplatinum (50 mg/m(2) day 1 and 2), and external beam irradiation up to a dose of 40 or 43.2 Gy. After a 4-week rest period, radical esophagectomy or a new cycle of chemoradiotherapy (up to a total dose of 65 Gy) was performed. RESULTS: A complete clinical response was obtained in 25.7% of the patients and a partial response in 45.9%. Fifty patients underwent surgery, but only 38 patients had an esophagectomy. Post-esophagectomy mortality was 5.3%. A complete histologic response rate of 23.7% was obtained. Two- and 5-year survival rates were, respectively, 41.5% and 28.6% for the whole population. According to multivariate analysis, prognostic factors for survival were Karnofsky index, esophagectomy, and response to chemoradiotherapy. Five-year survival for patients who experienced a partial response to radiation and chemotherapy was 49.1% for those who had surgery and 23.5% for those treated without surgery (p = 0.003). There was no obvious benefit for the small number of patients treated surgically after complete response to radiation and chemotherapy. Toxicity, essentially hematologic, was moderate. CONCLUSION: For locally-advanced esophageal carcinomas, esophagectomy, after concomitant chemoradiotherapy, could improve the survival rate, especially for patients who responded partially to the latter.     

局部晚期食管鳞状细胞癌术后放疗和化疗的前瞻性研究

目的 评价局部晚期食管鳞状细胞癌(FSCC)手术后放射治疗和化疗的疗效.方法 将1997年1月至2004年6月间入院的158例ESCC(Ⅱ-Ⅲ期)患者随机分为术后放化疗组(78例)和单纯手术组(80例).后经微调和排查,实际术后放化疗组为74例,单纯手术组为77例.对比两组患者的并发症发生率、局部复发率和远处转移率、生存率及无进展生存率.结果 患者平均随访45个月,术后放化疗组的并发症发生率与单纯手术组比较,差异无统计学意义(P>0.05).术后放化疗组局部复发和远处转移率低于单纯手术组(P<0.05).术后放化疗组的中位生存时间(53.5个月)与单纯手术组(37个月)比较,差异有统计学意义(P<0.05),两组的1年生存率比较,差异无统计学意义(P>0.05),但3、5和10年生存率比较,术后放化疗组优于单纯手术组(P<0.05).术后放化疗组的中位无进展生存期(46个月)与单纯手术组(34个月)比较,差异有统计学意义(P<0.05),两组1年无进展生存率比较,差异无统计学意义(P>0.05),但3、5和10年无进展生存率比较,术后放化疗组优于单纯手术组(P<0.05).结论 术后合理应用放化疗可有效提高局部晚期ESCC患者的无进展生存时间及长期生存率.     

新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效比较

目的探讨新辅助放化疗联合手术治疗局部晚期食管癌较单纯手术治疗能否改善总生存率。方法Ⅱa～Ⅲ期食管癌患者60例,随机分成新辅助放化疗联合手术组及单纯手术治疗组,每组30例。化疗使用PF方案,DDP 75 mg/（m2.d）,d1,5-FU 500 mg/（m2.d）,d1-5持续滴注,第1次化疗与第1次放疗同时实施,每3周1个疗程,放疗期间共2个疗程。放化疗结束后2-4周行食管癌根治术。放疗剂量PTV靶区给予每次2.0 Gy,5次/周,总剂量50 Gy。结果给予新辅助放化疗联合手术组患者必要的对症支持治疗,患者均能够完成同期放化疗。新辅助放化疗联合手术组并发症多于单纯手术组,但两组比较差异无统计学意义。1、2、3年生存率新辅助放化疗联合手术组分别为83.3%、65.3%、42.8%,单纯手术组分别为80.0%、41.6%、25.0%（χ2=3.992,P=0.046）。结论新辅助放化疗联合手术治疗可以改善局部晚期食管癌的总生存率,且不明显增加术后并发症,值得临床推广应用。     

Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves the survival of clinical stage II/III esophageal squamous cell carcinoma patients

The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed to improve survival through locoregional control, leading to prevention of micrometastasis. We investigated whether or not neoadjuvant CRT led to survival benefits in TNM stage?II/III esophageal cancer patients. We retrospectively reviewed 62 patients with stage II or III esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant CRT. All patients received esophagectomy 4-7 weeks after CRT consisting of 40?Gy irradiation and chemotherapy (5-FU, 500?mg/m2/day, days 1-5 and cisplatin, 10-20?mg/body, days 1-5). Clinical response and survival rates were analyzed using Kaplan-Meier methods, with p<0.05 considered as significant. The clinical effect rate of CRT for both primary tumors and metastatic nodes was 82.3%. Operative and hospital mortality rates were 1.65 and 6.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.6 and 49.2%, respectively. A significant difference was noted between stages?II and III for both OS and DFS. The 5-year OS rates were 64.2% for stage II, 33.1% for stage III (T4 and non-T4) and 46.9% for stage III (non-T4 only) patients. The depth of tumor invasion (T3 vs. T4), resectability (R0 vs. R1, R2), lymph node metastasis (positive vs. negative), and the effect of CRT were proven to be independent prognostic factors for univariate analysis, with resectability and the effect of CRT for multivariate analysis. These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant CRT appears to be a promising option for these patients.     

局部晚期食管鳞癌新辅助放化疗联合手术治疗的临床疗效分析

目的 探讨新辅助放化疗联合手术治疗局部晚期食管鳞癌的临床疗效,并分析临床完全缓解率(cCR)与病理完全缓解率(pCR)的关系。方法 回顾性选取2001—2013年局部晚期胸段食管鳞癌患者 158例,全组均采用术前同期放化疗联合手术方式,化疗采用以铂类为基础化疗方案,放疗剂量为40 Gy,2.0 Gy/次,5 次/周。Kaplan-Meier法计算OS和DFS,Logrank法检验并单因素预后分析,Cox模型多因素预后分析。结果 全组患者的pCR率为41.1%。新辅助放化疗后 44例cCR患者中 32例(73%)达pCR,114例非cCR患者中 33例(28.9%)达pCR (P=0.000)。cCR预测pCR的敏感性、特异性分别为49.2%、87.1%,阳性、阴性预测值分别为72.7%、71.1%。3年总样本数为 53例。全组 3年OS、DFS分别为53.9%、48.6%,cCR的显著高于非cCR的(P=0.012、P=0.026),pCR的显著高于非pCR的(P=0.000、0.000)。多因素分析显示放化疗后病理反应和化疗方案是影响OS的因素。最常见≥3级急性不良反应为白细胞减少(34.2%)。结论 新辅助放化疗联合手术治疗局部晚期食管鳞癌可获得较高pCR率且不良反应可耐受,放化疗后cCR率与pCR率、OS密切相关。     

Endoscopic response predicts for survival and organ preservation after primary chemoradiotherapy for esophageal cancer

PURPOSE: To determine the role of endoscopic surveillance in predicting organ preservation and survival after primary chemoradiotherapy (CRT) for esophageal cancer. MATERIALS AND METHODS: Fifty-six consecutive patients with nonmetastatic esophageal cancer were treated with primary CRT between May 1993 and April 1999 with curative intent and subsequent surveillance with endoscopy and CT scans. Patients with residual disease on endoscopy and/or CT 6 weeks after CRT were considered for immediate esophagectomy. The remaining patients continued endoscopic surveillance and were considered for esophagectomy only when local relapse was detected. Five-year survival was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to identify significant factors associated with disease-specific survival. RESULTS: With a median follow-up of 62 months, the 5-year overall and disease-specific survival was 30% (95% confidence interval [CI]: 17%-43%) and 37% (95% CI: 22%-50%), respectively. Fourteen of 24 (58%) patients who survived more than 2 years did not require an esophagectomy. On univariate analysis, favorable prognostic factors for disease-specific survival were female gender (p = 0.026), CT-defined N(0) status (p = 0.027), and negative endoscopy at 6 weeks after CRT (p < 0.0001). On multivariate analysis, N(0) status and negative endoscopy after CRT remained significant (p = 0.03 and p < 0.0001, respectively) for disease-specific survival. On multivariate analysis for overall survival, female gender and negative endoscopy were significant (p = 0.35 and p < 0.001, respectively). The hazard ratios for disease-specific survival with positive nodal status and positive endoscopy were 2.44 (95% CI: 1.14-5.3) and 5.18 (95% CI: 2.3-11.6), respectively. CONCLUSIONS: Endoscopic response after primary CRT for esophageal cancer was the most significant predictive factor for overall and disease-specific survival. Regular endoscopic surveillance after CRT achieved survival rates comparable to other strategies and successfully preserved the esophagus in the majority of patients who survived more than 2 years.     

Chemoradiotherapy using platinum analogs/5-FU for advanced esophageal cancer

We evaluated the efficacy of concurrent chemoradiotherapy (CRT) using cisplatin/nedaplatin and 5-FU for advanced esophageal cancer. Thirteen patients with locally advanced esophageal cancer (T4 cases) and 3 with recurrence of esophageal cancer were treated with radiotherapy (40-70 Gy) and 5-FU combined with cisplatin/nedaplatin concurrently. T4 patients who obtained down-staging by CRT also underwent esophagectomy. A complete response was obtained in one case, partial response in 8 cases, and no change in 7 cases. The overall response rate was 56.3%. A pathological complete response was obtained in one case in which curative resection was performed after CRT. Bone marrow suppression was observed in 68.8% and grade 3 and 4 bone marrow suppression was observed in 43.8%. Concurrent CRT using cisplatin/nedaplatin and 5-FU for advanced esophageal cancer has a high response rate and patients obtaining down-staging by CRT as a neoadjuvant therapy have a chance for long survival after curative resection in locally advanced cases.     

同步放化疗治疗局部晚期子宫颈鳞癌的临床研究

 目的 探讨同步放化疗治疗局部晚期子宫颈鳞癌的疗效及不良反应。方法 2001年至2002年收治121例60岁以下初治局部晚期子宫颈鳞癌患者，随机行同步放化疗（同步组）与单纯放疗（单放组）。所有患者均进行全盆野外照射4次／周， 2.0 Gy／次，量达30 Gy后，改为四野照射，放疗结束时B点剂量50 Gy；腔内治疗1次／周，A点剂量5 ~ 7 Gy／次，放疗结束时腔内治疗提供A点剂量40 ~ 45 Gy；同步组于腔内治疗前一天静脉滴注顺铂40 mg，1次／周，白细胞＜3.5×109／L时停止化疗。结果 同步组与单放组有效率分别为98.4 %、100 %，1、2、3年生存率分别为97.8 %和96.2 %、88.4 %和84.4 %、71.3 %和68.4 %，盆腔复发及远处转移率分别为21.0 %和16.9 %、11.3 %和15.3 %，差异均无统计学意义；恶心、呕吐以同步组程度略重、发生率高，差异有统计学意义。结论 同步放化疗较单纯放疗治疗60岁以下局部晚期子宫颈鳞癌，1、2、3年生存率未见显著提高，但生存质量有所改善，复发转移率未见改善，恶心、呕吐程度及发生率增高。     

Chemoradiotherapy for T3 and T4 squamous cell carcinoma of the esophagus using low-dose FP and radiation: a preliminary report

We conducted this study to evaluate the clinical significance of preoperative concurrent chemoradiotherapy (CRT) followed by esophagectomy in the management of T3 and T4 esophageal cancer. Thirty patients with squamous cell carcinoma of the esophagus received CRT followed by surgery. Preoperative CRT consisted of 5-fluorouracil (500 mg/m(2) by 24 h infusion for 5 days), cisplatin (15 mg/m(2) on days 1-5), and concurrent radiotherapy (a total dose of 40 Gy delivered in daily fractions of 2 Gy, 5 times per week). Esophagectomy was planned for 4-6 weeks after treatment and restaging. All 30 patients completed preoperative CRT. A clinical response (PR+CR) of the primary tumor was obtained in 82.8%, and a response of metastatic nodes was seen in 23.1%. Radical resection was possible in 17 of 29 operated patients (58.6%). The postoperative mortality rate was 6.9%, and the hospital mortality rate was 10.3%. Ten out of 29 operated patients (34.5%) had no residual cancer in the resected esophagus, corresponding to pathological CR. The 1-year survival rate was 80.6%, the 2-year survival rate was 62.7%, and the 3-year survival rate was 53.8%. The clinical response group and the R0 or R1 group showed better survival than other patients. Preoperative CRT should be given to patients with squamous cell carcinoma, while esophagectomy remains the standard therapy for responders and has a tolerable mortality.     

The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma

BACKGROUND: Tumor viability assessed by pathologic analysis of resected specimens in patients with preoperatively treated esophageal adenocarcinoma (EAC) is a prognostic indicator. The feasibility of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) and surgery for patients with locoregionally advanced EAC has been demonstrated. In this study, the authors evaluated the efficacy of CCRT compared with traditional concurrent chemoradiotherapy (CRT). METHODS: The authors retrospectively reviewed 247 consecutive patients with EAC who presented for planned surgery after treatment with either CCRT or CRT from January 1997 through August 2003. Patient demographics, comorbidities, and tumor characteristics were analyzed. Pathologic tumor response, overall survival, and disease-free survival were assessed according to treatment. RESULTS: One hundred seventeen patients received CCRT, and 130 patients received CRT before planned surgical resection. CCRT resulted in a 64% tumor response rate compared with a 51% tumor response rate in the CRT group (odds ratio, 1.73; P = .035). In the CCRT group, the median overall survival was 55 months, and the 3-year overall survival rate was 59%; in the CRT group, the median overall survival was 25 months, and the 3-year overall survival rate was 41% (hazard ratio [HR], 0.69; P = .041). In the CCRT group, the median disease-free survival was 43 months, and the 3-year disease-free survival rate was 54%; in the CRT group, the median disease-free survival was 18 months, and the 3-year disease-free survival rate was 36% (HR, 0.72; P = .047). Subset analysis of patients with clinical Stage III/IVA disease showed a median overall survival of 51 months with a 3-year overall survival rate of 58% in the CCRT group and a median overall survival of 20 months with a 3-year overall survival rate of 28% in the CRT group (HR, 0.57; P = .019). CONCLUSIONS: In patients with EAC, CCRT improved tumor response significantly compared with traditional CRT alone. Overall survival and disease-free survival were increased in patients who received CCRT, especially in the subset of patients who had more advanced disease.     

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival.

PURPOSE: Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS: All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION: Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.     

Treatment outcome and recursive partitioning analysis-based prognostic factors in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy

PURPOSE: To analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree. RESULTS: At a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002). CONCLUSION: Although preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated.     

Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial

BackgroundThe aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy.Patients and methodsBetween July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities.ResultsForty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P = 0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P = 0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P = 0.068), particularly for patients suffering from node-positive disease (P = 0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival.ConclusionsDefinitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.     

Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma

PURPOSE: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer. PATIENTS AND METHODS: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. RESULTS: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. CONCLUSION: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.     

局部中晚期食管癌术前新辅助放化疗联合食管癌根治术的临床研究

目的 评价局部晚期食管癌患者对术前neoCRT并手术的耐受性,术前新辅助放化疗疗效以及对肿瘤切除率、术后并发症发生率、围术期死亡率的影响。 方法 2011—2015年间共收治达入组条件胸段食管癌患者 74例。术前同期放化疗方案:长春瑞滨 25 mg/m²第1、8、22、29天,顺铂 25 mg/m²第 1—4、22~25天,同期常规分割放疗2.0 Gy/d,总量40 Gy。放化疗结束后 4~8周行食管癌根治术(neoCRT+手术),拒绝手术患者行根治性放化疗(DCRT),术前放化疗后拒绝进一步治疗患者予随访(neoCRT)。 结果 44例完成术前neoCRT+手术均为R₀切除,pCR达43%;17例拒绝手术改成DCRT;13例neoCRT。neoCRT+手术、DCRT、neoCRT患者 2年OS率分别为79%、75%、17%,DFS率分别为75%、55%、17%。neoCRT与neoCRT+手术OS率不同(P=0.000),与DCRT也不同(P=0.001),neoCRT+手术组与DCRT相近(P=0.415)。neoCRT与neoCRT+手术DFS率不同(P=0.000),与DCRT也不同(P=0.002),neoCRT+手术与DCRT相近(P=0.416)。全组术前放化疗临床有效率87%,术前放化疗 56例患者出现≥3级骨髓抑制(76%),术后肺部感染、吻合口瘘、吻合口狭窄发生率及围术期死亡率分别占21%、12%、7%、2%。 结论 术前放化疗联合手术治疗局部中晚期食管癌能取得较高的临床有效率和pCR率,明显降低食管癌的分期,有望提高生存率,但放化疗不良反应、围术期并发症需重视。     

Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients

PURPOSE: To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group. RESULTS: Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis. CONCLUSIONS: Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.     

Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer

PURPOSE: To evaluate the local control rates, survival rates, and patterns of failure for esophageal cancer patients receiving preoperative concurrent chemotherapy and hyperfractionated radiotherapy followed by esophagectomy. METHODS AND MATERIALS: From May 1993 through January 1997, 94 patients with resectable esophageal cancers received continuous hyperfractionated radiation (4,800 cGy/40 fx/4 weeks), with concurrent FP chemotherapy (5-FU 1 g/m(2)/day, days 2-6, 30-34, CDDP 60 mg/m(2)/day, days 1, 29) followed by esophagectomy 3-4 weeks later. If there was evidence of disease progression on preoperative re-evaluation work-up, or if the patient refused surgery, definitive chemoradiotherapy was delivered. Minimum follow-up time was 2 years. RESULTS; All patients successfully completed preoperative treatment and were then followed until death. Fifty-three patients received surgical resection, and another 30 were treated with definitive chemoradiotherapy. Eleven patients did not receive further treatment. Among 91 patients who received clinical reevaluation, we observed 35 having clinical complete response (CR) (38.5%). Pathologic CR rate was 49% (26 patients). Overall survival rate was 59.8% at 2 years and 40.3% at 5 years. Median survival time was 32 months. In 83 patients who were treated with surgery or definitive chemoradiotherapy, the esophagectomy group showed significantly higher survival, disease-free survival, and local disease-free survival rates than those in the definitive chemoradiation group. CONCLUSION: Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates compared to the definitive chemoradiation group.     

新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效比较

目的 比较新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效。方法 ⅡA~Ⅲ期食管癌患者80例,随机分为新辅助放化疗联合手术组及单纯手术治疗局部晚期食管癌组,每组40例。PF方案化疗,DDP （顺铂）75 mg/ (m²·d),d1,5-Fu（氟尿嘧啶） 500 mg/ (m² ·d),d1~5持续滴注,第1次化疗与第1次放疗同一天实施,每3周为1疗程,放疗期间共用2疗程。放化疗结束后4周行食管癌根治术。放疗组PTV靶区给予每次2.0 Gy,5次/周,总剂量40 Gy。生存分析采用Kaplan-Meier 法,组间比较行Log rank 检验。结果 新辅助放化疗联合手术组并发症多于单纯手术组,但是两组之间差异无统计学意义。1、2、3年生存率新辅助放化组联合手术分别为87.5％、71.5％、53.7％,单放手术组的分别为85％、46.4％、34.8%,P=0.023。结论 新辅助放化疗联合手术治疗可以改善局部晚期食管癌的总生存率,且不明显增加术后并发症。     

改良Ivor-Lewis手术或Sweet手术联合放化疗治疗胸段食管鳞癌的疗效分析

目的 回顾性分析改良Ivor Lewis手术或Sweet手术后辅助放化疗治疗胸段食管鳞癌的疗效及影响预后的危险因素。方法 914例胸段食管鳞癌患者按不同术式分为改良Ivor-Lewis手术组（n=424例）和Sweet手术组（n=490）;其中Ⅱ期及以上患者按术后有无联合放化疗分为单纯手术组（n=297）与术后辅助放化疗组（n=446）。采用Kaplan-Meier法计算总生存（OS）,Log-rank检验比较不同手术方式及术后是否联合放化疗患者的生存差异,Cox比例风险模型分析影响预后的危险因素。结果 改良Ivor-Lewis术组与Sweet术组患者的1、3、5年生存率分别为86.3％、63.7％、44.5％和90.2％、64.9％、45.0％。单纯手术组与术后辅助放化疗组的中位OS分别为36.1个月和46.1个月（P=0.004）。改良Ivor Lewis术组单纯手术者和术后辅助放化疗者的中位OS分别为34.6个月和46.8个月,差异有统计学意义（P=0.038）。Sweet术组单纯手术者和术后辅助放化疗者的中位OS分别为37.0个月和 45.1个月,差异有统计学意义（P=0.036）。2种术式无论是单纯手术亚组之间或术后联合放化疗亚组之间的中位OS比较,差异均无统计学意义（P＞0.05）。改良Ivor-Lewis术Ⅱ期患者术后接受放化疗的中位OS较单纯手术者并未明显获益（P＞0.05）,在Sweet术Ⅱ期患者中也得到相似结果（P＞0.05）;Ⅲ期及以上患者术后接受辅助放化疗,其中位OS相较单纯手术者获得改善（P＜0.05）。Cox比例风险模型分析显示,年龄、组织学分化程度、切端、癌栓、浸润深度、阳性淋巴结数、UICC 分期、是否接受术后辅助放化疗均为影响预后的独立因素,而手术方式的选择与预后无关（P＞0.05）。结论改良Ivor-Lewis术和Sweet术均可选择作为胸段食管鳞癌的手术方式,应根据患者的实际情况综合分析并制定个体化治疗方案。对于Ⅲ期及以上患者,术后辅助放化疗能够有效改善预后。