Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. Preoperative chemoradiotherapy for esophageal or junctional cancer. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. Effects of neoadjuvant radiochemotherapy on pathological staging and prognosis for locally advanced esophageal squamous cell carcinoma. Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. Extended Transthoracic Resection Compared With Limited Transhiatal Resection for Adenocarcinoma of the Mid/Distal Esophagus: Five-Year Survival of a Randomized Clinical Trial [A prospective study of combined chemoradiotherapy followed by surgery in the treatment of esophageal carcinoma].
PURPOSE OEO2 is a r and omized , controlled trial of preoperative chemotherapy in patients undergoing radical surgery for esophageal cancer . R and om assignment was to surgery alone ( S ) or to two cycles of combination cisplatin and fluorouracil before surgery ( CS ) . Initial results reported in 2002 demonstrated an advantage for both disease-free and overall survival in the CS group . The analysis has now been up date d after a median follow-up of 6 years . PATIENTS AND METHODS OEO2 recruited 802 patients , 400 on CS and 402 on S. The nature of the first recurrence event and cause of death are detailed . Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test . Survival by extent of resection is presented . RESULTS There were 655 deaths , 335 for S and 320 for CS . The survival benefit has been maintained with a hazard ratio ( HR ) of 0.84 ( 95 % CI , 0.72 to 0.98 ; P = .03 ) which in absolute terms is a 5-year survival of 23.0 % for CS compared with 17.1 % for S. The treatment effect is consistent in both adenocarcinoma and squamous cell carcinoma . The first disease-free survival event was macroscopic residual disease from incomplete resection ( R2 ) or no resection in 26.4 % of the S group versus 14.3 % of the CS P < .001 . Three-year survival by type of resection was R0 42.4 % , R1 was 18.0 % , and R2 was 8.6 % . CONCLUSION Long-term follow-up confirms that preoperative chemotherapy improves survival in operable esophageal cancer and should be considered as a st and ard of care BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery  , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) BACKGROUND We conducted a prospect i ve r and omized controlled trial comparing surgery alone ( S ) with concurrent chemoradiotherapy followed by surgery ( CRT-S ) for resectable esophageal squamous cell carcinoma ( SCC ) based on our previous report . PATIENTS AND METHODS One hundred and one patients with stage II/III esophageal SCC were r and omized to receive either S ( 50 patients ) or CRT-S ( 51 patients ) . The chemoradiotherapy ( CRT ) consisted of cisplatin 60 mg/m(2 ) intravenously ( i.v . ) on day 1 , 5-fluorouracil ( 5-FU ) 1000 mg/m(2 ) i.v . on days 2 - 5 , cisplatin 60 mg/m(2 ) i.v . on day 22 combined with radiation therapy ( 45.6 Gy , 1.2 Gy b.i.d . on days 1 - 28 ) . Surgery was performed 3 - 4 weeks after radiotherapy was completed . For patients with disease that was stable or responsive to CRT , three additional cycles of chemotherapy ( cisplatin 60 mg/m(2 ) i.v . on day 1 , 5-FU 1000 mg/m(2 ) on days 2 - 5 every 4 weeks ) were given after surgical resection . RESULTS The median age was 62 years . The toxicity of CRT was acceptable and did not affect the post-operative morbidity and the duration of hospital stay . Clinical response was 86 % including 21 % of complete response ( CR ) rate . Pathological CR was achieved in 43 % [ 95 % confidence interval ( CI ) 27 - 59 ] of the patients who underwent surgery after CRT . At a median follow-up of 25 months , median overall survival ( OS ) was 27.3 months in S and 28.2 months in CRT-S ( P = 0.69 ) . Event-free survival ( EFS ) at 2 years was 51 % in S and 49 % in CRT-S ( P = 0.93 ) . This trial , which was statistically powered to detect a relatively large difference in 2-year survival rate from 30 % to 50 % with 80 % power , was discontinued at interim analysis because of the unexpectedly high drop-out rate for esophagectomy ( 31 % ) and result ant excessive locoregional failure rate in CRT-S arm ( 22 % versus 12 % , P = 0.31 ) , though it was not statistically significant . CONCLUSION Although preoperative CRT induced high clinical and pathological response , there was no statistically significant benefit in OS and EFS AIM To investigate the role of perioperative chemoradiotherapy ( CRT ) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma ( ESCC ) . METHODS Using preoperative computed tomography (CT)-based staging criteria , 238 patients with ESCC ( stage II-III ) were enrolled in this prospect i ve study between January 1997 and June 2004 . With informed consent , patients were r and omized into 3 groups : preoperative CRT ( 80 cases ) , postoperative CRT ( 78 cases ) and surgery alone ( S ) ( 80 cases ) . The 1- , 3- , 5- and 10-year survival were followed up . Progression-free survival ( PFS ) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause . The secondary endpoint was overall survival ( OS ) determined as the time ( in months ) between the date of therapy and the date of death . Other objectives were surgical and adjuvant therapy complications . RESULTS With median follow-up of 45 mo for all the enrolled patients , significant differences in the 1- , 3- , 5- , 10-year OS ( 91.3 % , 63.5 % , 43.5 % , 24.5 % vs 91 % , 62.8 % , 42.3 % , 24.4 % vs 87.5 % , 51.3 % , 33.8 % , 12.5 % , P = 0.0176 ) and PFS ( 89.3 % , 61.3 % , 37.5 % , 18.1 % vs 89.1 % , 61.1 % , 37.2 % , 17.8 % vs 84.5 % , 49.3 % , 25.9 % , 6.2 % , P = 0.0151 ) were detected among the 3 arms . There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm ( P > 0.05 ) . For the patients who had radical resection , significant differences in median PFS ( 48 mo vs 61 mo vs 39.5 mo , P = 0.0331 ) and median OS ( 56.5 mo vs 72 mo vs 41.5 mo , P = 0.0153 ) were detected among the 3 arms , but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm ( P > 0.05 ) . The local recurrence rates in the preoperative CRT , postoperative CRT group and S group were 11.3 % , 14.1 % and 35 % , respectively ( P < 0.05 ) . No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups ( P > 0.05 ) . Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate , and could be quickly alleviated by adequate therapy . CONCLUSION Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC PURPOSE The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery , although primary radiation therapy with concurrent chemotherapy produces similar results . As both have curative potential , there has been great interest in the use of trimodality therapy . To this end , we compared survival , response , and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer . PATIENTS AND METHODS Four hundred seventy-five eligible patients were planned for enrollment . Patients were r and omly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2 ) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy ( 50.4 Gy total : 1.8 Gy/fraction over 5.6 weeks ) followed by esophagectomy with node dissection . RESULTS Fifty-six patients were enrolled between October 1997 and March 2000 , when the trial was closed due to poor accrual . Thirty patients were r and omly assigned to trimodality therapy and 26 were assigned to surgery alone . Patient and tumor characteristics were similar between groups . Treatment was generally well tolerated . Median follow-up was 6 years . An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy ( exact stratified log-rank , P = .002 ) . Five-year survival was 39 % ( 95 % CI , 21 % to 57 % ) v 16 % ( 95 % CI , 5 % to 33 % ) in favor of trimodality therapy . CONCLUSION The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer , and support trimodality therapy as a st and ard of care for patients with this disease The role of neoadjuvant therapy in the treatment of locally advanced esophageal carcinoma still remains controversial . The aim of this study was to evaluate the effects of neoadjuvant radiochemotherapy on pathological staging and prognosis in the patients with locally advanced esophageal squamous cell carcinoma . Between January 1991 and December 2000 , 473 patients with advanced esophageal carcinoma diagnosed by endoscopic biopsy underwent surgical resection in our center . With informed consent , they were r and omized into four groups : neoadjuvant chemotherapy , neoadjuvant radiotherapy , neoadjuvant radiochemotherapy , and surgery alone ( control group ) . The preoperative computed tomography staging criteria were the following : Stage I , the tumor limited to the esophageal lumen or the thickness of the esophageal wall varied between 3 - 5 mm ; Stage II , the thickness exceeds 5 mm but no invasion to the mediastinum or distant metastasis ; Stage III , the tumor invades adjacent mediastinal structure ; and Stage IV , there is distant metastasis . The tumor resection rate , pathological stage , treatment-related complication , and survival among groups were compared . The radical resection rate for the patients in radiotherapy and radiochemotherapy groups was increased in comparison with the control group ( P < 0.05 ) . Their pathological stage after esophagectomy was regressed significantly than that of the control group ( 50.85 % , 55.08 % vs. 0 % , P < 0.05 ) . The adjuvant chemotherapy group did show significant improvement on resection rate and pathological staging compared with the control group . The treatment-related complication in the three neoadjuvant groups had no significant difference from that of the control group ( P > 0.05 ) . The 3-year survival rate of radiotherapy and radiochemotherapy groups were significantly higher than that of the control group ( 69.49 % , 73.73 % vs. 53.38 % , P < 0.05 ) . The 5-year survival rate of radiochemotherapy group was higher than that of the radiotherapy group although did not show a statistical difference ( P > 0.05 ) . Rational application of neoadjuvant radiochemotherapy seems to provide a modest benefit in radical resection and survival in patients with locally advanced esophageal carcinoma The purpose of the present study was to compare the clinical results between preoperative chemoradiotherapy followed by surgery ( CRT group ) and surgery alone ( Surgery group ) by a r and omized controlled study . Twenty-two patients were assigned to the CRT group and 23 to the Surgery group . A total radiation dose of 40 Gy was applied and in the same period , intravenous chemotherapy was performed using cisplatin ( 7 mg over 2 h ) and 5-fluorouracil ( 5-FU ; 350 mg over 24 h ) . Surgical treatment was performed in 20 patients in the CRT group except for two patients with bone metastasis after CRT . According to histological effects of primary tumors , the number of patient with Grade s 1 , 2 and 3 was 11 , 7 and 3 , respectively . Frequency of lymphatic and venous invasion was significantly lower in the CRT group than in the Surgery group . The 5-year survival rate was 57 % in the CRT group and 41 % in the Surgery group ( P = 0.58 ) . According to the histological effect in the CRT group , 5-year survival was 30 % for Grade 1 , 83 % for Grade 2 and 100 % for Grade 3 ( P = 0.0069 ) . This r and omized trial did not demonstrate a statistically significant survival difference between the CRT group and the Surgery group PURPOSE A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin , fluorouracil , and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution . We design ed a r and omized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone . MATERIAL S AND METHODS One hundred patients with esophageal carcinoma were r and omized to receive either surgery alone ( arm I ) or preoperative chemoradiation ( arm II ) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21 , fluorouracil 300 mg/m2/d on days 1 through 21 , and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20 . Radiotherapy consisted of 1.5-Gy fractions twice daily , Monday through Friday over 21 days , to a total dose of 45 Gy . Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42 . RESULTS At median follow-up of 8.2 years , there is no significant difference in survival between the treatment arms . Median survival is 17.6 months in arm I and 16.9 months in arm II . Survival at 3 years was 16 % in arm I and 30 % in arm II ( P = .15 ) . This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years , with at least 80 % power . CONCLUSION This r and omized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference BACKGROUND Resection remains the best treatment for carcinoma of the oesophagus in terms of local control , but local recurrence and distant metastasis remain an issue after surgery . We aim ed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer . METHODS 128 patients were r and omly assigned to surgery alone and 128 patients to surgery  after 80 mg/m(2 ) cisplatin on day 1 , 800 mg/m(2 ) fluorouracil on days 1 - 4 , with concurrent radiotherapy of 35 Gy given in 15 fractions . The primary endpoint was progression-free survival . Secondary endpoints were overall survival , tumour response , toxic effects , patterns of failure , and quality of life . Analysis was done by intention to treat . FINDINGS Neither progression-free survival nor overall survival differed between groups ( hazard ratio [ HR ] 0.82 [ 95 % CI 0.61 - 1.10 ] and 0.89 [ 0.67 - 1.19 ] , respectively ) . The chemoradiotherapy- and -surgery group had more complete resections with clear margins than did the surgery-alone group ( 103 of 128 [ 80 % ] vs 76 of 128 [ 59 % ] , p=0.0002 ) , and had fewer positive lymph nodes ( 44 of 103 [ 43 % ] vs 69 of 103 [ 67 % ] , p=0.003 ) . Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours ( HR 0.47 [ 0.25 - 0.86 ] vs 1.02 [ 0.72 - 1.44 ] ) . However , the trial was underpowered to determine the real magnitude of benefit in this subgroup . INTERPRETATION Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone . However , further assessment is warranted of the role of chemoradiotherapy in patients with squamous-cell tumours PURPOSE After curative resection , the prognosis of gastroesophageal adenocarcinoma is poor . This phase III trial was design ed to evaluate the benefit in overall survival ( OS ) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma . PATIENTS AND METHODS Overall , 224 patients with resectable adenocarcinoma of the lower esophagus , gastroesophageal junction ( GEJ ) , or stomach were r and omly assigned to either  perioperative chemotherapy and surgery ( CS group ; n = 113 ) or surgery alone ( S group ; n = 111 ) . Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin ( 100 mg/m(2 ) ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 800 mg/m(2)/d ) for 5 consecutive days ( days 1 to 5 ) every 28 days and three or four postoperative cycles of the same regimen . The primary end point was OS . RESULTS Compared with the S group , the CS group had a better OS ( 5-year rate 38 % v 24 % ; hazard ratio [ HR ] for death : 0.69 ; 95 % CI , 0.50 to 0.95 ; P = .02 ) ; and a better disease-free survival ( 5-year rate : 34 % v 19 % ; HR , 0.65 ; 95 % CI , 0.48 to 0.89 ; P = .003 ) . In the multivariable analysis , the favorable prognostic factors for survival were perioperative chemotherapy ( P = .01 ) and stomach tumor localization ( P < .01 ) . Perioperative chemotherapy significantly improved the curative resection rate ( 84 % v 73 % ; P = .04 ) . Grade 3 to 4 toxicity occurred in 38 % of CS patients ( mainly neutropenia ) but postoperative morbidity was similar in the two groups . CONCLUSION In patients with resectable adenocarcinoma of the lower esophagus , GEJ , or stomach , perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate , disease-free survival , and OS Objective : To determine whether extended transthoracic esophagectomy for adenocarcinoma of the mid/distal esophagus improves long-term survival . Background : A r and omized trial was performed to compare surgical techniques . Complete 5-year survival data are now available . Methods : A total of 220 patients with adenocarcinoma of the distal esophagus ( type I ) or gastric cardia involving the distal esophagus ( type II ) were r and omly assigned to limited transhiatal esophagectomy or to extended transthoracic esophagectomy with en bloc lymphadenectomy .  Patients with peroperatively irresectable/incurable cancer were excluded from this analysis ( n = 15 ) . A total of 95 patients underwent transhiatal esophagectomy and 110 patients underwent transthoracic esophagectomy .  Results : After transhiatal and transthoracic resection , 5-year survival was 34 % and 36 % , respectively ( P = 0.71 , per protocol analysis ) . In a subgroup analysis , based on the location of the primary tumor according to the resection specimen , no overall survival benefit for either surgical approach was seen in 115 patients with a type II tumor ( P = 0.81 ) . In 90 patients with a type I tumor , a survival benefit of 14 % was seen with the transthoracic approach ( 51 % vs. 37 % , P = 0.33 ) . There was evidence that the treatment effect differed depending on the number of positive lymph nodes in the resection specimen ( test for interaction P = 0.06 ) . In patients ( n = 55 ) without positive nodes locoregional disease-free survival after transhiatal esophagectomy was comparable to that after transthoracic esophagectomy ( 86 % and 89 % , respectively ) . The same was true for patients ( n = 46 ) with more than 8 positive nodes ( 0 % in both groups ) . Patients ( n = 104 ) with 1 to 8 positive lymph nodes in the resection specimen showed a 5-year locoregional disease-free survival advantage if operated via the transthoracic route ( 23 % vs. 64 % , P = 0.02 ) . Conclusion : There is no significant overall survival benefit for either approach . However , compared with limited transhiatal resection extended transthoracic esophagectomy for type I esophageal adenocarcinoma shows an ongoing trend towards better 5-year survival . Moreover , patients with a limited number of positive lymph nodes in the resection specimen seem to benefit from an extended transthoracic esophagectomy OBJECTIVE To evaluate the effect of combined chemoradiotherapy followed by surgery for patients with esophageal carcinoma . METHODS Ninety-seven patients with stage II or III esophageal carcinoma without contraindication against operation and chemoradiotherapy , were r and omly divided into two groups : combined group ( Group A ) 48 and control group ( Group B ) 49 . Patients in group A were given neoadjuvant treatment consisted of chemotherapy with 5-fluorouracil and cisplatin for 2 cycles and radiotherapy of DT36 Gy/12 f/17 d. Three weeks later , operation was performed . Patients in group B were given operation alone .  Survival rate was calculated with Kaplan-Meier method . Chi and Log-rank test was used to assess the difference between the two groups . RESULTS The radical resectability of group A and group B were 85.4 % and 65.3 % ( P = 0.018 1 ) . The lymph node metastasis rate of the two groups were 21.7 % and 45.7 % ( P = 0.019 4 ) . The T stage of group A was significantly lowered ( P = 0.003 6 ) . The local and regional recurrence rate of two groups were 34.8 % and 58.7 % ( P = 0.023 6 ) , while there was no significant difference in operative complications between the two groups . Significant improvement in the long-term survival rate was observed in group A , especially in patients who achieved partial and complete response with high 5-year survival rate of 56.5 % . CONCLUSION Preoperative neoadjuvant chemoradiotherapy is able to reduce the tumor and tumor stage , lower the lymph node metastasis rate and local or regional recurrence rate , also it can improve radical resectability and long-term survival without increasing the operative complications
Background Many studies have demonstrated that chemoradiotherapy followed by surgery ( CRTS ) prolongs the 5-year survival rate of resectable esophageal carcinoma patients .
However , the effect of CRTS on postoperative complications , local recurrence and distant metastasis remains controversial .
We performed a systematic review of the literature and conducted a meta- analysis to assess the postoperative efficacy of CRTS compared with surgery alone ( SA ) .