Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: A randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second scandinavian trial in esophageal cancer A prospective study of combined therapy 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. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus Feasibility study of neoadjuvant chemoradiotherapy with cisplatin plus 5-fluorouracil and elective nodal irradiation for stage II/III esophageal squamous cell carcinoma. Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. 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. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. 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. [A multi-centered randomized controlled study of neo-adjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of esophagus: an interim analysis]. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. [A prospective study of combined chemoradiotherapy followed by surgery in the treatment of esophageal carcinoma].
In a prospect i ve multicenter study , 186 patients with squamous cell esophageal carcinoma , who after evaluation were considered suitable for surgery , were r and omized to 4 treatment groups : Group 1 , surgery alone ; Group 2 , pre-operative chemotherapy ( cisplatin and bleomycin ) and surgery ; Group 3 , pre-operative irradiation ( 35 Gy ) and surgery ; Group 4 , pre-operative chemotherapy , radiotherapy , and surgery .  Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy . Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival .  Female patients had a significantly better survival than males . The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival , whereas the chemotherapy regime used did not influence survival . RésuméDans une étude prospect i ve , multicentrique , 186 patients ayant un cancer épidermoïde de l'oesophage ont été r and omisée dans quatre groupes : le groupe 1 a eu la chirurgie seule ; le groupe 2 , une chimiothérapie préopératoire ( cis-platine et bléomycine ) ; le groupe 3 , une radiothérapie préopératoire suivie de chirurgie ; et le groupe 4 , une chimiothérapie et une radiothérapie préopératoires suivies de chirurgie . La survie à trois ans a été supérieure chez l'ensemble des patients ayant reçu la radiothérapie préopératoire par rapport à ceux qui n'en ont pas eu . Aucune différence de survie n'a pu être mise en évidence dans les groupes ayant eu ou pas de chimiothérapie . La survie des femmes a été significativement supérieure à celle des hommes . Ces résultats indiquent que la radiothérapie préopératoire apporte un plus en ce qui concerne la survie à moyen terme , alors que la chimiothérapie n'influence pas la survie . ResumenEn un estudio prospect ivo multicéntrico sobre 186 pacientes con carcinoma escamocelular del esófago c and idatos para cirugía , se constituyeron cuatro grupos para r and omización : Grupo 1 , cirugía solamente ; Grupo 2 , quimioterapia preoperatoria ( cisplatino y bleomicina ) y cirugía ; Grupo 3 , irradiación preoperatoria ( 35 Gy ) y cirugía ; Grupo 4 , quimioterapia preoperatoria , radioterapia y cirugía . La comparación entre el grupo que recibió quimioterapia y el que no la recibió no demostró diferencia significativa en cuanto a supervivencia . Las pacientes femeninas exhibieron una mejor supervivencia que los pacientes masculinos . Los result ados indican que la irradiación preoperatoria tuvo un efecto benéfico sobre la sobrevida a término medio , en tanto que la quimioterapia , en el regimen utilizado , no tuvo influencia sobre la supervivencia Between January 1986 and December 1992 , sixty-nine patients with squamous esophageal cancer were r and omized to one or the other of two treatment groups . Group 1 ( 35 patients ) were scheduled to receive chemotherapy ( cisplatinum and 5-fluorouracil ) and radiation , followed by resection , while group 2 ( 34 patients ) received resection alone . Of the 35 patients entering combined treatment , 26 completed the protocol and 9 received only chemoradiation . A complete response to preoperative therapy was shown by 7 patients , and a partial response by the other 7 patients . Survival rates at one year and five years were slightly better among patients receiving combined treatment than among those undergoing surgery alone , but overall survival did not differ statistically between the two groups . Nor were operative mortality and complications statistical different between the two groups 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 Background . Despite well‐established surgical approaches , the prognosis for patients with squamous cell carcinoma of the esophagus remains dismal . To assess the benefit of adjuvant chemotherapy and radiation therapy ( CRT ) , a r and omized trial with and without sequential preoperative CRT was undertaken ; CRT combined 20 Gy and two courses of 5‐FU and cisplatin 130 Background : Based on the JCOG 9907 trial results , neoadjuvant chemotherapy with cisplatin ( CDDP ) plus 5-fluorouracil ( 5-FU ) is considered a st and ard treatment for stage II/III esophageal squamous cell carcinoma ( ESCC ) in Japan . However , patient survival remains unsatisfactory . We conducted a feasibility study of neoadjuvant chemoradiotherapy ( NeoCRT ) with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC . METHODS Eligibility criteria included clinical stage II/III ( UICC 6th , non-T4 ) ESCC , PS 0 - 1 , and age 20 - 75 years .  Chemotherapy consisted of 2 courses of 5-FU infusion ( 1000 mg/m2 , days 1 - 4 ) and a 2-h CDDP infusion ( 75 mg/m2 , day 1 ) , with a 4-week interval . Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor , metastatic lymph nodes and regional lymph nodes . After completion of CRT , transthoracic esophagectomy with extensive lymphadenectomy ( > D2 ) was performed . The primary endpoint was the completion rate of NeoCRT and R0 resection . RESULTS From July 2010 to June 2011 , 33 patients were enrolled , including 2 ineligibles . In 31 eligible patients , the median age was 63 years ( range , 40 - 73 ) ; male/female : 28/3 ; PS0/1 : 19/12 ; cStage IIA/IIB/III : 2/10/19 . During CRT , the most common grade 3 or 4 toxicities were leukopenia ( 65 % ) , neutropenia ( 65 % ) , anemia ( 13 % ) , thrombocytopenia ( 13 % ) , febrile neutropenia ( 13 % ) , anorexia ( 16 % ) , esophagitis ( 16 % ) , and hyponatremia ( 16 % ) . In total , 31 patients ( 100 % ) underwent CRT and 25 ( 81 % ) underwent surgery ; 1 patient ( 3 % ) did not undergo surgery due to disease progression , and the other 5 patients ( 16 % ) are scheduled for surgery . Among patients who underwent surgery , there was 1 treatment-related death , and the incidence of operative morbidity was similar to that in previous studies . According to RECIST , the overall response rate was 63 % after CRT completion . Pathological complete response was achieved in 11 patients ( 44 % ) who underwent esophagectomy . CONCLUSIONS NeoCRT was well tolerated and appears to be highly promising . The r and omized controlled trial compared with neoadjuvant chemotherapy is needed and will be started 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 BACKGROUND We conducted a multicenter , r and omized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus . METHODS The preoperative combined therapy consisted of two one-week courses ; each involved radiotherapy , in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each , and 80 mg of cisplatin per square meter of body-surface area , administered 0 to 2 days before the first day of radiotherapy . The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes , to be performed immediately after r and omization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy . RESULTS A total of 297 patients entered the study ; 11 were found to be ineligible , and 4 were lost to follow-up . Of the remaining 282 , 139 were assigned to surgery alone and 143 to combined therapy . After a median follow-up of 55.2 months , no significant difference in overall survival was observed ; the median survival was 18.6 months for both groups . As compared with the group treated with surgery alone , the group treated preoperatively had longer disease-free survival ( P=0.003 ) , a longer interval free of local disease ( P=0.01 ) , a lower rate of cancer-related deaths ( P=0.002 ) , and a higher frequency of curative resection ( P=0.017 ) . However , there were more postoperative deaths ( P=0.012 ) in the group treated preoperatively with chemoradiotherapy . Three prognostic factors were found to influence survival in a multivariate analysis : the disease stage , based on computed tomography ; the location of the tumor ; and whether the surgical resection was curative . CONCLUSIONS In patients with squamous-cell esophageal cancer , preoperative chemoradiotherapy did not improve overall survival , but it did prolong disease-free survival and survival free of local disease 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 BACKGROUND Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma . We conducted a prospect i ve , r and omized trial comparing surgery alone with combined chemotherapy , radiotherapy , and surgery . METHODS Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 ( fluorouracil , 15 mg per kilogram of body weight daily for five days , and cisplatin , 75 mg per square meter of body-surface area on day 7 ) and a course of radiotherapy ( 40 Gy , administered in 15 fractions over a three-week period , beginning concurrently with the first course of chemotherapy ) , followed by surgery . The patients assigned to surgery had no preoperative therapy . RESULTS Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery  , 10 and 1 , respectively , were withdrawn for protocol violations . At the time of surgery , 23 of 55 patients ( 42 percent ) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases , as compared with 45 of the 55 patients ( 82 percent ) who underwent surgery alone ( P<0.001 ) . Thirteen of the 52 patients ( 25 percent ) who underwent surgery after multimodal therapy had complete responses as determined pathologically . The median survival of patients assigned to multimodal therapy was 16 months , as compared with 11 months for those assigned to surgery alone ( P=0.01 ) . At one , two , and three years , 52 , 37 , and 32 percent , respectively , of patients assigned to multimodal therapy were alive , as compared with 44 , 26 , and 6 percent of those assigned to surgery , with the survival advantage favoring multimodal therapy reaching significance at three years ( P=0.01 ) . CONCLUSIONS Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus 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 OBJECTIVE To evaluate the safety and validity of neo-adjuvant chemoradiotherapy followed by surgery for locally advanced esophageal carcinoma . METHODS Patients with IIB , III staged squamous cell carcinoma of thoracic esophagus were r and omly allocated to either preoperative chemoradiotherapy followed by surgery ( arm A ) or surgery alone ( arm B ) . In arm A , chemotherapy and radiotherapy were performed concurrently . Patients received two cycles of vinorelbine and cisplatin . Vinorelbine at 25 mg/m(2 ) per day was administered as a bolus infusion at d1 , d8 , d22 and d29 . Cisplatin at 75 mg/m(2 ) was administered by an intravenous infusion at d1 and d22 ( or 25 mg/m(2 ) days 1 - 4 and 22 - 25 ) . A total radiotherapeutic dose of 40 Gy was delivered in 20 daily fractions of 2.0 Gy each ( 5 d/wk for 4 weeks ) . Three-incisioned esophagectomy was performed at Weeks 4 - 6 after chemoradiotherapy . Primary outcome was overall survival time . An interim analysis was performed in June 2011 . RESULTS From July 2007 to June 2011 , 123 eligible patients were r and omly assigned at 7 cooperative cancer centers ( 54 cases in arm A vs 69 cases in arm B ) . In arm A , the clinical response rate of chemoradiotherapy was 90.7 % . All patients finished the preoperative chemoradiotherapy . Forty-nine cases continued to receive esophagectomy . The pathological complete response rate was 29.6 % . The rate of R0 resection in arm A was significant higher than that in arm B(96.0 % vs 85.5 % , P = 0.015 ) . The most common grade 3/4 toxicity of chemoradiotherapy was leukopenia occurring in 33 cases ( 61.1 % ) . Vomiting and esophagitis were usually of Grade 1/2 . No patient died or ab and oned surgery because of chemoradiation toxicity . Between arms A and B , operative duration , blood loss , duration of chest tube drainage and length of postsurgical hospital stay were similar . The incidences of postoperative heart failure ( 2.0 % vs 1.4 % , P = 1.000 ) , anastomotic leakage ( 8.2 % vs 11.6 % , P = 0.759 ) and hoarseness ( 6.1 % vs 4.3 % , P = 0.691 ) were not significantly different . The incidence of pulmonary infection in arm A was slightly higher than that in arm B ( 8.2 % vs 1.4 % , P = 0.094 ) . No perioperative deaths occurred in either group . There were no significant differences in overall survivals at 1 , 2 years between arms A and B ( 85.6%/75.5 % vs 79.1%/66.1 % , P = 0.207 ) . The disease-free survivals at 1 , 2 years in arm A were slightly higher than in arm B ( 86.6%/83.2 % vs 70.9%/61.8 % , P = 0.075 ) . CONCLUSION Neo-adjuvant chemoradiation followed by surgery may achieve a high clinical response rate and pathologic complete tumor regression rate . It significantly increases the R0 resection rate and down stage the esophageal cancer patients . But its ultimate efficacy awaits further follow-up studies 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 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 The effectiveness of chemoradiotherapy followed by surgery ( CRTS ) in patients with resectable esophageal carcinoma remains controversial .
We performed a systematic review of the literature with meta- analysis .