Prospective randomized trial of combined oncological therapy for gastric carcinoma A prospective, randomized trial of pre-operative and intraoperative radiotherapy versus surgery alone in resectable gastric cancer. A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma Preoperative versus postoperative chemoradiotherapy for rectal cancer. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Preoperative or postoperative therapy for resectable oesophageal cancer: an updated practice guideline. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up Intensity-modulated radiotherapy combined with chemotherapy for the treatment of gastric cancer patients after standard D1/D2 surgery Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: Intergroup trial CALGB 80101. Phase 3 trial of postoperative chemotherapy alone versus chemoradiation therapy in stage III-IV gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. [Adjuvant intraoperative radiotherapy of stomach carcinoma]. Concentrated preoperative radiotherapy for resectable gastric cancer: 20-years follow-up of a randomized trial. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study.
One hundred forty‐two patients with all stages of gastric carcinoma were prospect ively stratified into two divisions according to T.N.M. stage following , but irrespective of the type of surgical procedure . Division I ( T 1‐3 , N 1‐2 , M O ) was r and omized into a control group , and a treatment group who received 2000 rad in 8 fractions over 10 days with intravenous 5 Fluorouracil ( 5 F.U. ) at a dose of 500 mg daily × 4 days preirradiation and then 12.5 mg/kg daily for 5 days every 28 days for six courses . Division II ( T4 or M1 ) was r and omized into three groups ; a control group , a group who received radiotherapy and 5 F.U. in the same schedule as division one and a group who received Thiotepa 45 mg intravenously daily for three days and then every 28 days for 6 months . Four and one‐half years after commencement of the trial 86 % of the patients had died . There was no difference in survival rate between the treatment and control groups , ( p > 0.5 ) in Division I or II . Survival appeared to correlate with the T.N.M. stage of disease and not therapy . Blind assessment of the quality of life showed no difference between the treatment groups and the controls . In the dose schedules used , this form of oncological therapy had no efect on survival or quality of life in patients with gastric carcinoma . Cancer 44:385‐391 , 1979 INTRODUCTION Worldwide , gastric cancer remains one of the most common malignancies . Discouraging survival rates after surgical treatment promote the study of adjuvant therapy . A prospect ively , r and omized , controlled clinical trial was performed in order to determine whether pre-operative and intraoperative radiotherapy improves treatment results of gastrectomy for stomach carcinoma . METHODS From 1993 to 1998 , 112 patients were r and omized and underwent exploratory laparotomy ; among them 78 satisfied protocol requirements and entered in the trial . Patients in the experimental group were treated with pre-operative radiotherapy ( 20 Gy/5 days ) , gastrectomy and intraoperative radiotherapy ( 20 Gy using 8 - 12 electrons ) . Patients in the control group underwent surgery alone . RESULTS Incidence and distribution of post-operative complications were similar in both groups except significantly higher incidence of pancreatitis after surgical treatment . No late radiation-related morbidity was registered . There was no significant difference in survival between the two treatment groups ( Chi(2)=1.026 , df=1 , P=0 . 311 ) as well as in N0 ( Chi(2)=0.0029 , df=1 , P=0.956 ) and T1 - 2 subgroups ( Chi(2)=0.1928 , df=1 , P=0.660 ) . In contrast , combined treatment had marked survival advantage in more advanced stages : in the case of lymph-node involvement ( Chi(2)=4.19 , df=1 , P=0.04 ) and extragastric tumour extension ( Chi(2)=4.118 , df=1 , P=0.042 ) . CONCLUSION The proposed intensive treatment programme is feasible , shows good acute and late tolerance and has the potential to improve survival in patients with locally advanced gastric cancer BACKGROUND AND PURPOSE The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established . In this study , we compared postoperative intensity-modulated radiotherapy plus chemotherapy ( IMRT-C ) with chemotherapy-only in this patient population . MATERIAL S AND METHODS We r and omly assigned patients with D2 lymph node dissection in gastric cancer to  IMRT-C or chemotherapy-only groups . The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20 mg of leucovorin per square meter of body-surface area per day for 5 days , followed by 45 Gy of IMRT for 5 weeks , with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy . Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT . Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group . RESULTS The median overall survival ( OS ) in the chemotherapy-only group was 48 months , as compared with 58 months in the IMRT-C group ; the hazard ratio for death was 1.24 ( 95 % confidence interval , 0.94 - 1.65 ; P=0.122 ) . IMRT-C was associated with increases in the median duration of recurrence-free survival ( RFS ) ( 36 months vs. 50 months ) , the hazard ratio for recurrence was 1.35 ( 95 % confidence interval , 1.03 - 1.78 ; P=0.029 ) . COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors . Rates of all grade adverse events were similar in the two treatment groups . CONCLUSIONS IMRT-C improved RFS , but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer . Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation  as effective surgical adjuvant therapy  for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded This controlled trial compared the survival of 90 patients with locally advanced gastric carcinoma treated with either chemotherapy alone ( 5‐FU and methyl‐CCNU ) or external radiotherapy of 5000 rad combined with the same chemotherapy .  The minimum period of followup is 4 years . During the initial 12 months , combined modality therapy was associated with an increased number of early deaths attributable to progression of tumor within the radiation field , or nutritional and hematologic complications . During the second to fourth years of followup , patients treated with combined radiation therapy have shown a significantly lower death rate compared to those treated with chemotherapy alone , with eight of 45 patients alive and disease‐free . Patients who received only chemotherapy , in contrast , have demonstrated a continued probability for tumor relapse and death , with three of 45 patients alive at 4 years . Palliative resection of the primary tumor was associated with an improved survival , independent of the form of postoperative therapy employed . It is possible that the superior late survival achieved with combined modality therapy in this program can be further improved with measures to decrease the toxicity of upper abdominal irradiation , and with the use of more effective forms of chemotherapy BACKGROUND Postoperative chemoradiotherapy is the recommended st and ard therapy for patients with locally advanced rectal cancer . In recent years , encouraging results with preoperative radiotherapy have been reported . We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either  preoperative or postoperative chemoradiotherapy . The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day , five days per week , and fluorouracil , given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy . Surgery was performed six weeks after the completion of chemoradiotherapy . One month after surgery , four five-day cycles of fluorouracil ( 500 mg per square meter per day ) were given . Chemoradiotherapy was identical in the postoperative-treatment group , except for the delivery of a boost of 540 cGy . The primary end point was overall survival . RESULTS Four hundred twenty-one patients were r and omly assigned to receive preoperative chemoradiotherapy  and 402 patients to receive postoperative chemoradiotherapy . The overall five-year survival rates were 76 percent and 74 percent , respectively ( P=0.80 ) . The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group ( P=0.006 ) . Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group , as compared with 40 percent of the patients in the postoperative-treatment group ( P=0.001 ) ; the corresponding rates of long-term toxic effects were 14 percent and 24 percent , respectively ( P=0.01 ) . CONCLUSIONS Preoperative chemoradiotherapy , as compared with postoperative chemoradiotherapy , improved local control and was associated with reduced toxicity but did not improve overall survival PURPOSE In the West , curative ( R0 ) resection is achieved in approximately 50 % of patients with localized gastric carcinoma , and more than 60 % die of cancer following an R0 resection . A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate , pathologic complete response ( pathCR ) rate , safety , and survival in patients with resectable gastric carcinoma . PATIENTS AND METHODS Operable patients with localized gastric adenocarcinoma were eligible . Staging also included a laparoscopy and endoscopic ultrasonography ( EUS ) . Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil , leucovorin , and cisplatin , followed by 45 Gy of radiation plus concurrent fluorouracil . Patients were then staged and surgery was attempted . RESULTS Thirty-four patients were registered at three institutions . One ineligible patient was excluded . Most patients had a promixal cancer and EUST3N1 design ation . Twenty-eight ( 85 % ) of 33 patients underwent surgery . The R0 resection rate was 70 % and pathCR rate was 30 % . A pathologic partial response ( < 10 % residual carcinoma in the primary ) occurred in eight patients ( 24 % ) . EUS T plus N and postsurgery T plus N correlation showed significant downstaging ( P = < .01 ) . The median survival time for 33 patients was 33.7 months . Patients achieving a pathCR or pathPR had a significantly longer median survival time ( 63.9 months ) than those achieving less than pathPR ( 12.6 months ; P = .03 ) . There were two treatment-related deaths . CONCLUSION Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy result ed in substantial pathologic response that result ed in durable survival time . This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy PURPOSE An attempt was made to define the role of radiotherapy before operation for AGC . METHODS AND MATERIAL S From January 1978 to May 1989 , a prospect i ve r and omized trial on preoperative radiotherapy ( R+S ) vs. surgery alone ( S ) for AGC was carried out in 370 patients . Patients were r and omized into a combined group ( R+S , 171 patients ) or a surgery alone group ( S , 199 patients ) by the envelope method . 8-MV photon or telecobalt was used for the preoperative radiation therapy , using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia , lower segment of the esophagus , fundus , lesser curvature , and hepatogastric ligament . Surgery was performed after 2 to 4 weeks rest . RESULTS The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10 % and 19.75 % , 20.26 % and 13.30 % , respectively . The survival curves of these two groups diverged right from the beginning after the operation over the ninth year . Statistics by Kaplan-Meier log rank test proves that the difference is significant ( chi2 = 6.74 , p = 0.0094 ) . The immediate results were : resection rate 89.5 % and 79.4 % ( p < 0.01 ) ; pathologic stage after resection T2 12.9 % and 4.5 % ( p < 0.01 ) , T4 40.3 % and 51.3 % ( p < 0.05 ) , lymph node metastasis rates 64.3 % and 84.9 % ( p < 0.001 ) ; operative mortality rates 0.6 % and 2.5 % ; intrathoracic leak rates 1.8 % and 4.0 % , respectively . The causes of failure were : local uncontrol and recurrence 38.6 % vs. 51.7 % ( p < 0.025 ) , regional lymph node metastasis 38.6 % vs. 54.6 % ( p < 0.005 ) , distant metastasis 24.3 % vs. 24.7 % . CONCLUSION Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia PURPOSE Preoperative therapy for localized gastric cancer has considerable appeal . We hypothesized that , in a cooperative group setting , preoperative chemoradiotherapy would induce a 20 % pathologic complete response ( pathCR ) rate . Combined-modality therapy quality , survival , and safety were secondary end points . PATIENTS AND METHODS Patients with localized gastric adenocarcinoma were eligible . A negative laparoscopic evaluation was required . Patients received two cycles of induction fluorouracil , leucovorin , and cisplatin followed by concurrent radiation and chemotherapy ( infusional fluorouracil and weekly paclitaxel ) . Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed . Quality of therapy was assessed with other end points . RESULTS Twenty institutions participated . Forty-nine patients were entered and 43 were assessable ( 12 % stage IB ; 37 % stage II ; and 52 % stage III ) . The pathCR and R0 resection rates were 26 % and 77 % , respectively . At 1 year , more patients with pathCR ( 82 % ) are living than those with less than pathCR ( 69 % ) . Grade 4 toxicity occurred in 21 % of patients .  Chemotherapy , radiotherapy , and surgery per protocol ( including acceptable variations ) occurred in 98 % , 44 % , and 63 % of patients , respectively . A D2 dissection was performed in 50 % of patients . Of 18 major radiotherapy variations , 17 were due to the lack of inclusion of the L3 - 4 vertebral interphase as prespecified . CONCLUSION For localized gastric cancer , preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20 % in a cooperative group setting . The quality of surgery improved ( 50 % with D2 dissection ) possibly because surgery was part of this trial . With some refinements , this preoperative chemoradiotherapy strategy is poised for a r and omized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer PURPOSE Surgical resection of gastric cancer has produced suboptimal survival despite multiple r and omized trials that used postoperative chemotherapy or more aggressive surgical procedures . We performed a r and omized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure ( LRF ) following surgery . We originally reported results with 4-year median follow-up . This up date , with a more than 10-year median follow-up , presents data on failure patterns and second malignancies and explores selected subset analyses . PATIENTS AND METHODS In all , 559 patients with primaries ≥ T3 and /or node-positive gastric cancer were r and omly assigned to observation versus radiochemotherapy after R0 resection . Fluorouracil and leucovorin were administered before , during , and after radiotherapy . Radiotherapy was given to all LRF sites to a dose of 45 Gy . RESULTS Overall survival ( OS ) and relapse-free survival ( RFS ) data demonstrate continued strong benefit from postoperative radiochemotherapy . The hazard ratio ( HR ) for OS is 1.32 ( 95 % CI , 1.10 to 1.60 ; P = .0046 ) . The HR for RFS is 1.51 ( 95 % CI , 1.25 to 1.83 ; P < .001 ) . Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse . Second malignancies were observed in 21 patients with radiotherapy versus eight with observation ( P = .21 ) . Subset analyses show robust treatment benefit in most subsets , with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect . CONCLUSION Intergroup 0116 ( INT-0116 ) demonstrates strong persistent benefit from adjuvant radiochemotherapy . Toxicities , including second malignancies , appear acceptable , given the magnitude of RFS and OS improvement . LRF reduction may account for the majority of overall relapse reduction . Adjuvant radiochemotherapy remains a rational st and ard therapy for curatively resected gastric cancer with primaries T3 or greater and /or positive nodes BACKGROUND Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases . We investigated the effect of surgery plus postoperative ( adjuvant ) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction . METHODS A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were r and omly assigned to surgery plus postoperative chemoradiotherapy or surgery alone . The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day , plus 20 mg of leucovorin per square meter per day , for five days , followed by 4500 cGy of radiation at 180 cGy per day , given five days per week for five weeks , with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy . One month after the completion of radiotherapy , two five-day cycles of fluorouracil ( 425 mg per square meter per day ) plus leucovorin ( 20 mg per square meter per day ) were given one month apart . RESULTS The median overall survival in the surgery-only group was 27 months , as compared with 36 months in the chemoradiotherapy group ; the hazard ratio for death was 1.35 ( 95 percent confidence interval , 1.09 to 1.66 ; P=0.005 ) . The hazard ratio for relapse was 1.52 ( 95 percent confidence interval , 1.23 to 1.86 ; P<0.001 ) . Three patients ( 1 percent ) died from toxic effects of the chemoradiotherapy ; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group , and grade 4 toxic effects occurred in 32 percent . CONCLUSIONS Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection PURPOSE The INT0116 study has established postoperative chemoradiotherapy as the st and ard of care for completely resected gastric adenocarcinoma . However , the optimal chemoradiation regimen remains to be defined . We conducted a prospect i ve , multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery . METHODS AND MATERIAL S Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible .  Adjuvant therapy consisted of one cycle of epirubicin , cisplatin , and 5-FU ( ECF ) , followed by radiotherapy with concurrent infusional 5-FU , and then two additional cycles of ECF . Radiotherapy was delivered using precisely defined , multiple-field , three-dimensional conformal techniques . RESULTS A total of 54 assessable patients were enrolled from 19 institutions . The proportion of patients commencing Cycles 1 , 2 , and 3 of ECF chemotherapy were 100 % , 81 % , and 67 % respectively . In all , 94 % of patients who received radiotherapy completed treatment as planned . Grade 3/4 neutropenia occurred in 66 % of patients with 7.4 % developing febrile neutropenia . Most neutropenic episodes ( 83 % ) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF . Grade 3/4 gastrointestinal toxicity occurred in 28 % of patients . In all , 35 % of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment . At median follow-up of 36 months , the 3-year overall survival rate was estimated at 61.6 % . CONCLUSIONS This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting . A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored , r and omized Phase III trial AIMS Oesophageal cancer is an aggressive disease and the optimal therapy for patients with resectable tumours remains unclear . A systematic review and companion practice guideline were published in 2004 ; however , new evidence has become available since the publication of the original report . An up date of the literature search and a revision of the recommendations were undertaken to incorporate the new data . The following research question was addressed : should patients with resectable oesophageal cancer receive preoperative or postoperative therapy together with surgery ? The outcomes of interest were survival , adverse effects and quality of life . MATERIAL S AND METHODS The literature search of the original systematic review was up date d to April 2007 . MEDLINE , EMBASE , Cochrane Library and abstract s from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were search ed for reports of r and omised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy . After the completion of the draft systematic review and practice guideline , the report was distributed through a mailed survey to 133 health care providers in Ontario for review and feedback . RESULTS The up date d literature search yielded eight new r and omised controlled trial reports and seven new meta- analysis reports for consideration , together with the evidence review ed in the original review publication . Of the 31 practitioners who responded to the mailed survey , 80 % agreed with the draft recommendations as stated , 83 % agreed that the report should be approved as a practice guideline and 86 % indicated that they would probably use the guideline in their own practice . CONCLUSIONS Preoperative cisplatin-based chemotherapy plus radiotherapy is recommended as the preferred modality for the management of surgically resectable patients with oesophageal cancer .  Preoperative cisplatin-based chemotherapy alone is an alternative choice for the management of these patients PURPOSE The extent of lymph node dissection appropriate for gastric cancer is still under debate . We have conducted a r and omized trial to compare the results of a limited ( D1 ) and extended ( D2 ) lymph node dissection in terms of morbidity , mortality , long-term survival and cumulative risk of relapse . We have review ed the results of our trial after follow-up of more than 10 years . PATIENTS AND METHODS Between August 1989 and June 1993 , 1,078 patients with gastric adenocarcinoma were r and omly assigned to undergo a D1 or D2 lymph node dissection . Data were collected prospect ively , and patients were followed for more than 10 years . RESULTS A total of 711 patients ( 380 in the D1 group and 331 in the D2 group ) were treated with curative intent . Morbidity ( 25 % v 43 % ; P < .001 ) and mortality ( 4 % v 10 % ; P = .004 ) were significantly higher in the D2 dissection group . After 11 years there is no overall difference in survival ( 30 % v 35 % ; P = .53 ) . Of all subgroups analyzed , only patients with N2 disease may benefit of a D2 dissection . The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections , splenectomy , pancreatectomy , and age older than 70 years . CONCLUSION Overall , extended lymph node dissection as defined in this study generated no long-term survival benefit . The associated higher postoperative mortality offsets its long-term effect in survival . For patients with N2 disease an extended lymph node dissection may offer cure , but it remains difficult to identify patients who have N2 disease .  Morbidity and mortality are greatly influenced by the extent of lymph node dissection , pancreatectomy , splenectomy and age . Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided BACKGROUND External-beam radiotherapy ( delivered either preoperatively or postoperatively ) is frequently used in local management of sarcomas in the soft tissue of limbs , but the two approaches differ substantially in their potential toxic effects . We aim ed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults . METHODS After stratification by tumour size ( < or = 10 cm or > 10 cm ) , we r and omly allocated 94 patients to preoperative radiotherapy ( 50 Gy in 25 fractions ) and 96 to postoperative radiotherapy  ( 66 Gy in 33 fractions ) . The primary endpoint was rate of wound complications within 120 days of surgery . Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes . FINDINGS Median follow-up was 3.3 years ( range 0.27 - 5.6 ) . Four patients , all in the preoperative group , did not undergo protocol surgery and were not evaluable for the primary outcome . Of those patients who were eligible and evaluable , wound complications were recorded in 31 ( 35 % ) of 88 in the preoperative group and 16 ( 17 % ) of 94 in the postoperative group ( difference 18 % [ 95 % CI 5 - 30 ] , p=0.01 ) . Tumour size and anatomical site were also significant risk factors in multivariate analysis . Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment ( p=0.0481 ) . INTERPRETATION Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy , the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy , and the size and anatomical site of the tumour The overall survival in patients with gastric cancer is low , even among those undergoing resection . It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer . Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial . 436 patients entered a prospect i ve , r and omised , controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin , doxorubicin , and fluorouracil  after gastrectomy for adenocarcinoma . After at least 5 years , there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer . Following stratified r and omisation , 145 patients were allocated to  surgery alone  , 153 to receive adjuvant radiotherapy , and 138 to adjuvant combination chemotherapy . The overall 2-year and 5-year survival were 33 % ( 95 % confidence interval 31 - 35 % ) and 17 % ( 13 - 21 % ) . No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone . The 5-year survival for surgery alone was 20 % , for surgery plus radiotherapy 12 % , and for surgery plus chemotherapy 19 % . Surgery , therefore , remains the st and ard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials Background The purpose of the current study is to evaluate the efficacy and complications of concurrent chemoradiotherapy ( CCRT ) for the treatment of gastric cancer patients after D1/D2 surgery . Methods Sixty-eight untreated gastric cancer patients ( T3/T4 and /or N+ ) were enrolled . After surgery , they were r and omized into two groups : the CCRT group and the single chemotherapy group . Radiotherapy patients were treated according to the Intergroup 0116 guidelines . The chemotherapy consisted of continuously administered 5-fluorouracil ( 5-FU ) and tetrahydrofolic acid ( LV ) . The CCRT began 28 days after the first cycle of chemotherapy , and chemotherapy was given within the first four and last three days during the CCRT period , at a radiation dosage of 45 Gy/25 f , i.e. , 1.8 Gy 5 times per week . Two cycles of the same chemotherapy were administrated 1 month after the radiotherapy . Five cycles of 5-FU and LV were applied to CG . Results One- , two- , and three-year survival rates were 85.9 , 73.4 , and 67.7 % , respectively , in the CCRT group and 68.0 , 50.0 , and 44.1 % , in the single chemotherapy group ( P < 0.05 ) . The corresponding disease-free survival rates were 73.5 , 64.7 , and 55.8 % in the CCRT group and 61.8 , 38.2 , and 29.4 % in the single chemotherapy group ( P < 0.05 ) . The major side effects were gastrointestinal reactions and neutrocytopenia . In both the CCRT and single chemotherapy groups , the incidence of these side effects was 73.5 % ( 25/34 ) and 44.1 % ( 15/34 ) ( P < 0.05 ) for Grade I and Grade II anorexia , 82.35 % ( 28/34 ) and 73.5 % ( 25/34 ) ( P > 0.05 ) for nausea and vomiting , and 70.6 % ( 24/34 ) and 44.1 % ( 15/34 ) ( P < 0.05 ) for neutrocytopenia , respectively . The other indices showed no significant differences . Conclusions Our findings indicate that CCRT can increase the one- , two- , and three-year total survival rates , as well as the disease-free survival rates of gastric cancer patients ( T3/T4 and /or N+ ) who have been initially treated with surgery . The major adverse reactions were Grade I and Grade II nausea and vomiting , as well as myelosuppression . CCRT is well tolerated 4003 Background : Following curative resection of gastric or GEJ adenocarcinoma , INT-0116 demonstrated superior survival for pts who received postoperative bolus 5-FU and leucovorin ( LV ) before and after concomitant 5-FU and RT compared to surgery alone . We assessed whether a postoperative chemoRT regimen that replaces 5-FU/LV with a potentially more active systemic therapy ( ECF ) improves overall survival ( OS ) . METHODS Patients with resected gastric or GEJ adenocarcinoma were r and omly assigned to either : Arm A : 1 cycle of 5-FU 425 mg/m2/day plus LV20 mg/m2/day for 5 days/month , followed by 45 Gy ( 1.8 Gy/day ) and concurrent 5-FU ( 200 mg/m2/day CI throughout RT ) , followed by 2 cyclesof 5-FU/LV ; or Arm B : 1 cycle of ECF ( E 50 mg/m2 day 1 , C 60 mg/m2 day 1 , and 5-FU 200 mg/m2/day CI days 1 - 21 ) followed by 45 Gy ( 1.8 Gy/day ) and concurrent 5-FU ( 200 mg/m2/day CI throughout RT ) , followed by 2 cycles of reduced dose of ECF ( E 40 mg/m2 day 1 , C 50 mg/m2 day 1 , and 5-FU 200 mg/m2/day CI days 1 - 21 ) . RESULTS Between 4/03 and 5/09 , 546 pts were enrolled . There were no significant differences between arms with regard to age , sex , race , performance status , T or N stage or extent of lymphadenectomy . Treatment related deaths occurred in 8 ( 3 % ) pts on Arm A ( 5-FU/LV ) and 1 ( < 1 % ) pt on Arm B ( ECF ) . Grade 4 toxicity : 40 % , Arm A v 26 % , Arm B ( p<0.001 ) . Major toxicities ( ≥ gr . 3 ) included : neutropenia ( 53 v 48 % ) , diarrhea ( 15 v 7 % ) , and mucositis ( 15 v 7 % ) for Arms A and B , respectively . With 242  deaths reported , median OS was 37 months in Arm A and 38 months in Arm B ( HR , 1.03 ; 95 % CI , 0.80 - 1.34 ; p=0.80 ) . 3yr-OS was 50 % in Arm A and 52 % in Arm B. Median disease-free survival ( DFS ) was 30 months in Arm A and 28 months in Arm B ( HR , 1.00 ; 95 % CI , 0.79 - 1.27 ; p=0.99 ) . 3yr-DFS was 46 % in Arm A and 47 % in Arm B. CONCLUSIONS Following curative resection of gastric or GEJ adenocarcinoma , postoperative chemoRT using ECF before and after 5-FU/RT does not improve survival when compared to bolus 5-FU/LV before and after 5-FU/RT PURPOSE To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0 ) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection . METHODS AND MATERIAL S The chemotherapy arm received 5 cycles of fluorouracil and leucovorin ( FL ) , and the chemoradiation therapy arm received 1 cycle of FL , then radiation therapy of 45 Gy concurrently with 2 cycles of FL , followed by 2 cycles of FL . Intent-to-treat analysis and per- protocol analyses were performed . RESULTS Between May 6 , 2002 and June 29 , 2006 , a total of 90 patients were enrolled . Forty-four were r and omly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm . Treatment was completed as planned by 93.2 % of patients in the chemotherapy arm and 87.0 % in the chemoradiation therapy arm . Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival ( LRRFS ) but not disease-free survival . In subgroup analysis for stage III , chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy ( 93.2 % vs 66.8 % , P=.014 ; 73.5 % vs 54.6 % , P=.056 , respectively ) . CONCLUSIONS Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma , we carried out a r and omized trial comparing surgery and surgery+adjuvant IORT . The study included 115 patients within a 74-month period , 51 of them received a single application of 28 Gy to the celiac axis . Patients were comparable with regard to age , sex , tumor stage and operative morbidity . The difference in mean survival time  ( IORT : 26.9 months vs. non-IORT , 30.8 months ) and tumor-related death in the long-term course ( mean follow-up period 29.2 months ) with 29.4 % ( 15/51 ) in the IORT-treated patients vs. 31.2 % ( 20/64 ) in non-irradiated patients did not reach significance BACKGROUND AND OBJECTIVES The role of radiation therapy in resectable gastric cancer is question able . To study the value of concentrated preoperative radiotherapy , a r and omized clinical trial had been carried out . METHODS From 1974 to 1978 , 152 patients were r and omized and underwent exploratory laparotomy ; in 50 patients curative surgery was not possible , while 102 patients satisfied protocol requirements and entered in the trial . Patients in the experimental group were treated with preoperative radiotherapy ( 20 Gy/5 days ) and subtotal or total gastrectomy . Patients in the control group underwent surgery alone . RESULTS Study showed acceptable tolerance of radiotherapy regime with no increase of postoperative mortality and morbidity . There was no significant difference in survival between the two treatment groups ( chi 2 = 0.349 , df = 1 , P = 0.555 ) . Subset analysis also failed to demonstrate significant survival advantages of the combined treatment ; however , some positive trends were seen in patients with locally advanced gastric cancer . CONCLUSIONS Concentrated preoperative radiotherapy in the dose of 20 Gy is safe and feasible , but seems to be insufficient to improve survival in gastric cancer patients . However , the results are promising in selected subgroups of patients , which encourages future trials with adjuvant radiation therapy Abstract A prospect i ve , controlled double-blind study involving a substantial number of patients suggests that 5-fluorouracil ( 5-F.U. ) significantly augments the effectiveness of radiation therapy  for locally unresectable carcinoma of the stomach , pancreas , and large bowel . It is also possible that rarely this therapy may be curative . This approach should not be advocated as routine treatment since the vast majority of these patients still die of their cancer ; and , if the present results are not spurious , the method offers only a few extra months of life . These results should , however , serve as stimulus and foundation for continued study of augmented radiation therapy  in the treatment of advanced gastrointestinal cancer In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients , a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated . In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment , 293 patients were r and omized into three respective treatment groups : surgery alone , surgery preceded by preoperative radiation ; and surgery followed by preoperative radiation and hyperthermia . Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3- or 5-year survival in gastric cancer patients in comparison with surgery alone . Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1 % ( from 35.5 + /- 4.9 % to 57.6 + /- 6.3 % , P < 0.05 ) and 5-year survival of 21.3 % ( from 30.1 + /- 4.7 to 51.4 + /- 6.6 % , P < 0.05 ) . In unresectable gastric cancer patients , radiation therapy and radiation therapy with hyperthermia both increase mean survival . In conclusion ; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone . Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed PURPOSE The ARTIST ( Adjuvant Chemoradiation Therapy in Stomach Cancer ) trial was the first study to our knowledge to investigate the role of postoperative chemoradiotherapy therapy in patients with curatively resected gastric cancer with D2 lymph node dissection . This trial was design ed to compare postoperative treatment with capecitabine plus cisplatin ( XP ) versus XP plus radiotherapy with capecitabine ( XP/XRT/XP ) . PATIENTS AND METHODS The XP arm received six cycles of XP ( capecitabine 2,000 mg/m2 per day on days 1 to 14 and cisplatin 60 mg/m2 on day 1 , repeated every 3 weeks ) chemotherapy . The XP/XRT/XP arm received two cycles of XP followed by 45-Gy XRT ( capecitabine 1,650 mg/m2 per day for 5 weeks ) and two cycles of XP . RESULTS Of 458 patients , 228 were r and omly assigned to the XP arm and 230 to the XP/XRT/XP arm . Treatment was completed as planned by 75.4 % of patients ( 172 of 228 ) in the XP arm and 81.7 % ( 188 of 230 ) in the XP/XRT/XP arm . Overall , the addition of XRT to XP chemotherapy did not significantly prolong disease-free survival ( DFS ; P = .0862 ) . However , in the subgroup of patients with pathologic lymph node metastasis at the time of surgery ( n = 396 ) , patients r and omly assigned to the XP/XRT/XP arm experienced superior DFS when compared with those who received XP alone ( P = .0365 ) , and the statistical significance was retained at multivariate analysis ( estimated hazard ratio , 0.6865 ; 95 % CI , 0.4735 to 0.9952 ; P = .0471 ) . CONCLUSION The addition of XRT to XP chemotherapy did not significantly reduce recurrence after curative resection and D2 lymph node dissection in gastric cancer . A subsequent trial ( ARTIST-II ) in patients with lymph node-positive gastric cancer is planned PURPOSE The Avastin in Gastric Cancer ( AVAGAST ) trial was a multinational , r and omized , placebo-controlled trial design ed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer . PATIENTS AND METHODS Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily for 14 days every 3 weeks . Fluorouracil was permitted in patients unable to take oral medications . Cisplatin was given for six cycles ; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity . The primary end point was overall survival ( OS ) . Log-rank test was used to test the OS difference . RESULTS In all , 774 patients were enrolled ; 387 were assigned to each treatment group ( intention-to-treat population ) , and 517 deaths were observed . Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin ( hazard ratio 0.87 ; 95 % CI , 0.73 to 1.03 ; P = .1002 ) . Both median progression-free survival ( 6.7 v 5.3 months ; hazard ratio , 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .0037 ) and overall response rate ( 46.0 % v 37.4 % ; P = .0315 ) were significantly improved with bevacizumab versus placebo . Preplanned subgroup analyses revealed regional differences in efficacy outcomes . The most common grade 3 to 5 adverse events were neutropenia ( 35 % , bevacizumab plus fluoropyrimidine-cisplatin ; 37 % , placebo plus fluoropyrimidine-cisplatin ) , anemia ( 10 % v 14 % ) , and decreased appetite ( 8 % v 11 % ) . No new bevacizumab-related safety signals were identified . CONCLUSION Although AVAGAST did not reach its primary objective , adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer
BACKGROUND Worldwide , almost one million new cases of stomach cancer were diagnosed in 2012 , making it the fifth most common cancer , and the third leading cause of cancer deaths .
The current tumor node metastasis ( TNM ) staging system represents a consensus between the East and the West , and will serve as a strong foundation upon which to build future evidence .
In this review article , we first discuss the definition and optimal surgery for locally advanced gastric cancer , followed by the general principles when considering a pre vs. postoperative radiotherapy ( RT ) strategy .
We then provide a synthesis of the existing r and omized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer .
CONCLUSIONS AND FUTURE DIRECTIONS Technical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer , and surgical st and ards to ensure the delivery of high quality surgery , have matured in recent years .