Chemotherapy for cholangiocarcinoma: An update. Neoadjuvant chemotherapy versus surgery alone for locally advanced gastric cancer: a retrospective comparative study. Preoperative versus postoperative docetaxel-cisplatin-fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial. Neoadjuvant chemotherapy for non-small cell lung cancer. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2 Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial Impact of Hospital Volume on Recurrence and Survival After Surgery for Gastric Cancer Adjuvant Chemoradiotherapy With Epirubicin, Cisplatin, and Fluorouracil Compared With Adjuvant Chemoradiotherapy With Fluorouracil and Leucovorin After Curative Resection of Gastric Cancer: Results From CALGB 80101 (Alliance). Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study) Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis A phase III randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil and mitomycin C versus 5-fluorouracil alone in curatively resected gastric cancer. Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS) Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach. Comparing Efficacy of Preoperative neo-Adjuvant Chemotherapy and Surgery versus Surgery Alone in Patients with Resectable Gastroesophageal Cancer Is There a Role for Palliative Gastrectomy in Patients with Stage IV Gastric Cancer? Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer: Mature Results of the Phase 2 PBM-PFU Protocol Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Neoadjuvant chemotherapy: not the best option in estrogen receptor-positive, HER2-negative, invasive classical lobular carcinoma of the breast? Concentrated preoperative radiotherapy for resectable gastric cancer: 20-years follow-up of a randomized trial. Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study. Adjuvant treatments following curative resection for gastric cancer A Phase 2 Trial of Neoadjuvant Temozolomide Followed by Hypofractionated Accelerated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Patients With Glioblastoma. Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: a subset analysis of the Head and Neck Contracts Program. The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial. 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Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment: Results of a Randomized Trial Comparing Modulation of 5-FU + Levamisole With Folinic Acid or With Interferon-α [A randomized controlled trial of surgical adjuvant therapy with mitomycin C, 5-fluorouracil and OK-432 in patients with gastric cancer]. [Cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (II). Cooperative study group on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer supported by the Ministry of Health and Welfare ( A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy: The “SMART” Approach for Resectable Malignant Pleural Mesothelioma An evaluation of the effectiveness of extended lymph node dissection in patients with gastric cancer: a retrospective study of 1403 cases at a single institution. Adjuvant chemoradiotherapy in patients with stage III or IV radically resected gastric cancer: a pilot study. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. Treatment of Pancreatic Cancer: Challenge of the Facts
Cholangiocarcinomas ( bile duct cancers ) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic , perihilar and extrahepatic bile ducts . Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management . First of all , it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients . Overall , cholangiocarcinomas have a very poor prognosis . The 5-year survival rate is 5%-10 % . In cases with a potentially curative surgery , 5-year survival rates of 25%-30 % are reported . Therefore , it is necessary to increase the cure rate from surgery , exploring the survival benefit of any adjuvant strategy . It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas . There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined . The most relevant studies in the adjuvant setting are one from Japan , the well known ESPAC-3 and BILCAP from the United Kingdom and a meta- analysis . We show the results of these trials . According to medical oncology guidelines , postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins , as well as for those with a complete resection but node-positive disease . Clinical trials are ongoing . The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients : ( 1 ) patients who have had surgery but with macroscopic residual disease ; ( 2 ) patients with locally recurrent disease after potentially curative treatment ; and ( 3 ) patients with locally unresectable disease at presentation . In these patients , surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local tumor effects . Nowadays , no neoadjuvant therapy can be considered a st and ard approach for the treatment of patients with cholangiocarcinoma . There are promising results and r and omized trials are needed in patients with a metastatic cholangiocarcinoma . In systemic therapy , no single drug or combination has consistently increased median survival beyond the expected 8 - 12 mo . It is always recommended that patients enrol in clinical trials . Clinical trials have shown that the more st and ard chemotherapy for a first line regimen of gemcitabine plus cisplatin ( or oxaliplatin as a potentially better tolerated agent ) is superior to gemcitabine alone . Leucovorin-modulated 5-fluorouracil , capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status . After progression in patients with an adequate performance status , active regimens that could be considered include gemcitabine plus capecitabine , or erlotinib plus bevacizumab , for second line treatment BACKGROUND / AIMS Preoperative chemotherapy is considered an effective treatment option for patients with gastric cancer . We retrospectively evaluated neoadjuvant chemotherapy with oxaliplatin , leucovorin and 5-flurouracil ( OLF ) in patients with locally advanced gastric cancer to determine its feasibility , as well as impact on the curative resection rate and patients ' survival . METHODOLOGY A total of 87 patients with locally advanced gastric cancer that underwent preoperative chemotherapy combined with surgery or surgery alone were r and omly matched according to the clinical TNM stage . The clinical responses to chemotherapy were assessed . The curative rate , postoperative complications and patients ' survival between both groups were compared . RESULTS The two groups were well matched . Complete or partial response was observed in 51.7 % ( 15/29 ) of patients in the OLF group , and three ( 10.3 % ) of them had complete pathologic response . The curative resection rates were 89.7 % in the OLF group and 77.6 % in the surgery alone group . The postoperative complications were equal for both groups . The mean survival is 20.6 months in the OLF group vs. 19.9 months in the surgery alone group ( p=0.02 ) . CONCLUSIONS Neoadjuvant chemotherapy using OLF combination is active in gastric cancer and the toxicity level is acceptable . This treatment improves the curative resection rate and patients ' survival in locally advanced gastric cancer BACKGROUND Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses . Perioperative chemotherapy in locally advanced resectable gastric cancer ( RGC ) has been reported improving survival by two large r and omized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined . We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospect i ve r and omized phase III trial , of which we present the 10-year follow-up data . PATIENTS AND METHODS Patients with cT3 - 4 anyN M0 or anyT cN1 - 3 M0 gastric carcinoma , staged with endoscopic ultrasound , computed tomography , bone scan , and laparoscopy , were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2 ) day 1 , cisplatin 75 mg/m(2 ) day 1 , and fluorouracil 300 mg/m(2)/day over days 1 - 14 , either before ( arm A ) or after ( arm B ) gastrectomy . Event-free survival was the primary end point , whereas secondary end points included overall survival , toxicity , down-staging , pathological response , quality of life , and feasibility of adjuvant chemotherapy . RESULTS This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual . Of the 70 enrolled patients , 69 were r and omized , 34 to arm A and 35 to arm B. No difference in EFS ( 2.5 years in both arms ) or OS ( 4.3 versus 3.7 years , in arms A and B , respectively ) was found . A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy . A 12 % pathological complete response was observed in arm A. CONCLUSION Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC . The early stopping could mask the real effectiveness of neoadjuvant treatment . However , the complete pathological tumour responses , feasibility , and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting Even with aggressive surgical treatment , relapse rates remain high for patients with resectable non-small cell lung cancer ( NSCLC ) . In an effort to improve survival in these patients , numerous clinical trials have evaluated neoadjuvant and adjuvant chemotherapy . Three large , r and omized clinical trials and two meta-analyses have demonstrated a survival benefit for adjuvant cisplatin-based chemotherapy compared to surgery alone . Adjuvant chemotherapy has become the st and ard of care for patients with resected NSCLC . A neoadjuvant approach offers several potential advantages over adjuvant therapy , including earlier treatment of micrometastatic disease , improved compliance and pathologic confirmation of efficacy . R and omized trials have shown neoadjuvant therapy to be feasible and safe and some studies have yielded promising efficacy . The applicability of these results has been limited due to patient heterogeneity , imprecise staging and lack of st and ardization with respect to inclusion of radiation therapy . With novel agents , improved staging , better supportive care and relevant molecular markers , a neoadjuvant strategy is promising for future clinical trials in NSCLC BACKGROUND D2 gastrectomy is recommended in US and European guidelines , and is preferred in east Asia , for patients with resectable gastric cancer .  Adjuvant chemotherapy improves patient outcomes after surgery , but the benefits after a D2 resection have not been extensively investigated in large-scale trials . We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer . METHODS The capecitabine and oxaliplatin adjuvant study in stomach cancer ( CLASSIC ) study was an open-label , parallel-group , phase 3 , r and omised controlled trial undertaken in 37 centres in South Korea , China , and Taiwan . Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were r and omly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine ( 1000 mg/m(2 ) twice daily on days 1 to 14 of each cycle ) plus intravenous oxaliplatin ( 130 mg/m(2 ) on day 1 of each cycle ) for 6 months or surgery only . Block r and omisation was done by a central interactive computerised system , stratified by country and disease stage . Patients , and investigators giving interventions , assessing outcomes , and analysing data were not masked . The primary endpoint was 3 year disease-free survival , analysed by intention to treat . This study reports a prespecified interim efficacy analysis , after which the trial was stopped after a recommendation by the data monitoring committee . The trial is registered at Clinical Trials.gov ( NCT00411229 ) . FINDINGS 1035 patients were r and omised ( 520 to receive chemotherapy and surgery , 515 surgery only ) . Median follow-up was 34·2 months ( 25·4 - 41·7 ) in the chemotherapy and surgery group and 34·3 months ( 25·6 - 41·9 ) in the surgery only group . 3 year disease-free survival was 74 % ( 95 % CI 69 - 79 ) in the chemotherapy and surgery group and 59 % ( 53 - 64 ) in the surgery only group ( hazard ratio 0·56 , 95 % CI 0·44 - 0·72 ; p<0·0001 ) . Grade 3 or 4 adverse events were reported in 279 of 496 patients ( 56 % ) in the chemotherapy and surgery group and in 30 of 478 patients ( 6 % ) in the surgery only group . The most common adverse events in the intervention group were nausea ( n=326 ) , neutropenia ( n=300 ) , and decreased appetite ( n=294 ) . INTERPRETATION Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer . FUNDING F Hoffmann-La Roche and Sanofi-Aventis PURPOSE To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients ( excluding patients who were T1N0 ) , we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated . PATIENTS AND METHODS From January 1993 to December 1994 , 252 patients were enrolled into the study and allocated r and omly to adjuvant chemotherapy or surgery alone . The chemotherapy comprised intravenous mitomycin 1.33 mg/m2 , fluorouracil ( FU ) 166.7 mg/m2 , and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery , and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2 . The primary end point was relapse-free survival . Overall survival and the site of recurrence were secondary end points . RESULTS Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection . There were no treatment-related deaths and few serious adverse events . There was no significant difference in relapse-free and overall survival between the arms ( 5-year relapse-free survival 88.8 % chemotherapy v 83.7 % surgery alone ; P = .14 and 5-year survival 91.2 % chemotherapy v 86.1 % surgery alone ; P = .13 , respectively ) . Nine patients ( 7.1 % ) in the chemotherapy arm and 17 patients ( 13.8 % ) in the surgery-alone arm had cancer recurrence . CONCLUSION There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection , and there was no statistical difference between the two arms relating to the types of cancer recurrence . We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice BACKGROUND Despite aggressive local therapy , patients with locally advanced bladder cancer have a significant risk of distant metastases . This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin ( GC ) in improving the outcome of this group of patients over radical cystectomy alone .  PATIENTS AND METHODS A total of 114 patients with newly diagnosed bladder cancer ( T3 - 4 , N0 - 2 , M0 ) were r and omized to radical cystectomy alone  or initial 3 cycles of GC , then managed according to response . Patients who achieved complete response completed 6 cycles of GC followed by local radiation therapy ( RT ) only . If tumors were downstaged to T1 , complete transurethral resection was done , followed by 3 cycles of GC and then RT . Patients with partial response underwent radical cystectomy followed by 3 cycles of GC . Patients with stable disease or disease progression underwent radical cystectomy . RESULTS The overall response rate to GC was 55.1 % , and complete response was achieved in 28.6 % . The 3-year overall survival ( OS ) was 51.9 % versus 51.2 % in the chemotherapy and surgery arms , respectively ( P = .399 ) . The 3-year disease-free survival was 31.8 % in the chemotherapy arm and 45.1 % in the surgery arm ( P = .06 ) . Bladder preservation was achieved in 22.5 % of patients in the neoadjuvant arm . OS was 78 % in responding patients and 100 % in patients with complete response . CONCLUSION Neoadjuvant GC did not improve survival in locally advanced bladder cancer over radical cystectomy alone . However , bladder preservation was feasible , and OS in responding patients was impressive . Therefore , predictive models to select patients are needed . This is the largest prospect i ve study of squamous cell carcinoma and transitional cell carcinoma using neoadjuvant GC Purpose To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer , a multicenter phase III clinical trial was conducted in Japan . Patients and methods From January 1993 to March 1998 , 268 patients were r and omized to adjuvant chemotherapy ( 135 patients ) or surgery alone ( 133 patients ) . All patients underwent gastrectomy with D2 or greater lymph node dissection . The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure , postoperative intravenous cisplatin ( day 14 ) and 5-fluorouracil ( day 14–16 ) , and daily oral FU ( UFT ) starting 4 weeks after surgery for 12 months . The primary endpoint was overall survival . Relapse-free survival and site of recurrence were secondary endpoints . Results Fifty-two patients ( 38.5 % ) in the adjuvant chemotherapy arm completed the chemotherapy regimen . There were 4 ( 1.49 % ) treatment-related deaths , 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm ( 2 did not receive chemotherapy ) . Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm . There was no significant difference in 5-year overall survival ( 62.0 % adjuvant chemotherapy vs. 60.9 % surgery-alone , P = 0.482 ) and 5-year relapse-free survival rates ( 57.5 % adjuvant chemotherapy vs. 55.6 % surgery-alone ; P = 0.512 ) . Conclusion There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection PURPOSE European Organisation for Research and Treatment of Cancer ( EORTC ) trial 22921 compared adjuvant fluorouracil-based chemotherapy ( CT ) to no adjuvant treatment in a 2 x 2 factorial trial with r and omization for preoperative (chemo)radiotherapy in patients with resectable T3 - 4 rectal cancer . The results showed no significant impact of adjuvant CT on progression-free or overall survival , although a difference seemed to emerge at approximately , respectively , 2 and 5 years after the start of preoperative treatment . We further explored the data with the aim of refining our underst and ing of the long-term results . PATIENTS AND METHODS Data of 785 of the 1,011 r and omly assigned patients who whose disease was M0 at curative surgery were used . Using meta-analytic methods , we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery ( disease-free survival [ DFS ] ) and survival in patient subgroups . RESULTS Although there was no statistically significant impact of adjuvant CT on DFS for the whole group ( P > .5 ) , the treatment effect differed significantly between the ypT0 - 2 and the ypT3 - 4 patients ( heterogeneity P = .009 ) : only the ypT0 - 2 patients seemed to benefit from adjuvant CT ( P = .011 ) . The same pattern was observed for overall survival . CONCLUSION Exploratory analyses suggest that only good-prognosis patients ( ypT0 - 2 ) benefit from adjuvant CT . This could explain why , in the whole group , the progression-free and overall survival diverged only after the poor-prognosis patients ( ypT3 - 4 ) had experienced treatment failure . Patients in whom no downstaging was achieved did not benefit . This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT BACKGROUND To study the survival benefit of adjuvant chemotherapy in gastric cancer , seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer . METHODS 579 patients were enrolled in the study , stratified by disease stage ( T1 , n=188 ; T2 , n=323 ) , and allocated r and omly adjuvant chemotherapy or no further treatment .  285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible . Six cases were excluded because they did not fulfill the entry criteria . The treatment group had intravenous mitomycin ( 1.4 mg/m2 ) and fluorouracil ( 166.7 mg/m2 ) twice weekly for 3 weeks after surgery , and oral UFT ( uracil plus tegafur , 300 mg daily ) for 18 months . Analyses were by intention to treat . FINDINGS No serious toxic effects were observed in the treatment group . At median follow-up of 72 months , 59 patients in the control group and 47 in the treatment group had died . There was no significant difference in survival between the groups ( 5-year survival 82.9 % control vs 85.8 % treated ; hazard ratio 0.738 [ 95 % CI 0.498 - 1.093 ] ) . 5-year survival of patients with T1 ( mucosal or submucosal ) cancer in the control and treatment groups was 94.9 % versus 92.0 % , and that of patients with T2 ( muscularis propria or subserosa ) cancer was 76.9 % versus 83.0 % . However , a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response . INTERPRETATION There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer ( T1 and T2 ) after curative gastrectomy . Patients with T1 cancer can be excluded from future trials , because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy Background : Some , but not all , studies using registry data have suggested a small but significant long-term survival advantage following a curative surgical resection of gastric cancer at hospitals where the volume of such surgeries is high . However , because such data may be significantly influenced by the impact of postoperative mortality , and may be imbalanced for factors important to survival , the true nature of this relationship remains uncertain . Methods : We conducted a nested volume- outcome study in a sample of 448 surgical survivors with stage IB through IV ( M0 ) gastric and gastroesophageal junction adenocarcinoma , previously r and omized to adjuvant chemoradiation after surgery or surgery alone , to measure the effect of hospital surgical volume , as assessed by Medicare cl aims data , on overall survival and gastric cancer recurrence . Results : In this selected sample of postoperative survivors , hospital surgical volume was not predictive of overall survival ( P = 0.46 ) or disease-free survival ( P = 0.43 ) at a median follow-up of 8.9 years . However , patients who underwent either a D1 or D2 dissection at a high- or moderate-volume center experienced an adjusted hazard ratio of 0.80 ( 95 % CI , 0.53–1.20 ) for overall survival and 0.78 ( 95 % CI , 0.53–1.14 ) for disease-free survival compared with those patients resected at a low-volume hospital ; these results were not statistically significant . When a D0 resection was performed , hospital procedure volume showed no impact on survival . Conclusions : Excluding the impact of perioperative mortality by utilizing prospect ively recorded data from a large postoperative adjuvant trial , hospital procedure volume had no overall effect on long-term gastric cancer survival . The potential benefit of moderate- to high-volume centers for patients who underwent a D1 or D2 dissection requires confirmation in larger studies Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma , Intergroup Trial 0116 ( Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and gastroesophageal junction adenocarcinoma : Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil ( FU ) and leucovorin ( LV ) compared with surgery alone . CALGB 80101 ( Alliance ; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma ) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival . Patients and Methods Between April 2002 and May 2009 , 546 patients who had undergone a curative resection of stage IB through IV ( M0 ) gastric or gastroesophageal junction adenocarcinoma were r and omly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy ( FU plus LV arm ) or postoperative epirubicin , cisplatin , and infusional FU ( ECF ) before and after combined FU and radiotherapy ( ECF arm ) . Results With a median follow-up duration of 6.5 years , 5-year overall survival rates were 44 % in the FU plus LV arm and 44 % in the ECF arm ( Plogrank = .69 ; multivariable hazard ratio , 0.98 ; 95 % CI , 0.78 to 1.24 comparing ECF with FU plus LV ) . Five-year disease-free survival rates were 39 % in the FU plus LV arm and 37 % in the ECF arm ( Plogrank = .94 ; multivariable hazard ratio , 0.96 ; 95 % CI , 0.77 to 1.20 ) . In post hoc analyses , the effect of treatment seemed to be similar across all examined patient subgroups . Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma , postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with st and ard FU and LV before and after radiotherapy Background At time of diagnosis , less than 10 % of patients with pancreatic adenocarcinomas ( PDAC ) are considered to be immediately operable ( i.e. resectable ) . Considering their poor overall survival ( OS ) , only tumours without vascular invasion ( NCCN 2017 ) should be considered for resection , i.e. those for which resection with disease-free margins ( R0 ) is theoretically possible in absence of presurgery treatment . With regard to high R1 rates and undetectable locoregional and /or metastatic spreading prior to surgery explain ( at least in part ) the observed 1-year relapse and mortality rates of 50 and 25 % , respectively . Today , upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe . The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence . Indeed , only 47 to 60 % patients received any adjuvant therapy after resection compared to more than 75 % for neoadjuvant therapy . No previous prospect i ve study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC . Methods PANACHE01-PRODIGE48 is a prospect i ve multicentre controlled r and omized non comparative Phase II trial , evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy ( 4 cycles of mFOLFIRINOX or FOLFOX ) relative to the current reference treatment ( surgery and then adjuvant chemotherapy ) in patients with resectable PDAC . The main co- primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence . Discussion The “ ideal ” cancer treatment for resectable PDAC would have the following characteristics : administration to the highest possible proportion of patients , ability to identify fast-progressing patients ( i.e. poor c and i date s for surgery ) , a low rate of R1 resections ( through optimisation of local disease control ) , and an acceptable toxicity profile . The neoadjuvant approach may meet all these criteria . With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX , these two regimens are potential c and i date s for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.Trial registration Clinical Trials.gov , NCT02959879 . Trial registration date : November 9 , 2016 Abstract Background Neoadjuvant therapy-based protocol s for potentially resectable pancreatic adenocarcinoma ( PAC ) have not been directly compared with adjuvant protocol s in large prospect i ve r and omized trials . This study aim ed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model . Methods A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo- and /or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC . Base-case probabilities were derived from the published data of 21 prospect i ve phases 2 and 3 trials ( 3708 patients ) between 1997 and 2014 . The primary outcome measures determined in an intent-to-treat fashion were overall and quality -adjusted survival rates . One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes . Results The median overall survival and 2-year survival rates for the patients in the st and ard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm . Quality -adjusted survival was 18.4 and 19.8 months , respectively . Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 % , the neoadjuvant strategy is no longer the favored option . Conclusions The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer . However , the benefits in terms of overall and quality -adjusted survival are modest BACKGROUND A phase III single-center r and omized trial was performed in order to determine whether the addition of mitomycin C ( MMC ) and /or doxorubicin to 5-fluorouracil ( 5-FU ) as adjuvant chemotherapy could influence survival in patients with curatively resected gastric cancer . PATIENTS AND METHODS A total of 416 patients who had undergone curative resection for stage IB-IIIB gastric adenocarcinoma were stratified according to the stage and type of surgery , and then r and omized to receive one of the three chemotherapy regimens , 5-FU alone ( F ) or 5-FU and MMC ( FM ) or 5-FU , doxorubicin and MMC ( FAM ) within 5 weeks after surgery . RESULTS Of 416 patients registered , 395 ( 133 in F , 131 in FM and 131 in FAM ) were assessable . Median follow-up duration was 91 months . Five-year overall survival rates were 67.2 % for F , 67.0 % for FM and 66.7 % for FAM ( P = 0.97 ) . Five-year disease-free survival rates were 62.1 % for F , 63.3 % for FM and 62.5 % for FAM ( P = 0.83 ) . Hematological toxicities were more frequent in the FM and FAM groups , whereas stomatitis was more common in the F group . CONCLUSIONS Compared with adjuvant 5-FU alone , the addition of MMC and /or doxorubicin to 5-FU did not influence survival in patients with resected gastric cancer Background A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases ( cT1 - 3 N0 - 1 M0 ) . A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone . Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients . We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed . The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has , however , to be proven in a r and omized phase III trial . Methods / design The CROSS trial is a multicenter , r and omized phase III , clinical trial . The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer , with inclusion of 175 patients per arm . The objectives of the CROSS trial are to compare median survival rates and quality of life ( before , during and after treatment ) , pathological responses , progression free survival , the number of R0 resections , treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma . Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis . Paclitaxel ( 50 mg/m2 ) and Carboplatin ( Area-Under-Curve = 2 ) are administered by i.v . infusion on days 1 , 8 , 15 , 22 , and 29 . External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy , 5 fractions a week . After completion of the protocol , patients will be followed up every 3 months for the first year , every 6 months for the second year , and then at the end of each year until 5 years after treatment . Quality of life question naires will be filled out during the first year of follow-up . Discussion This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen . Trial registration IS RCT From 1975 to 1988 , 120 consecutive patients with locally advanced ( T3/T4 or N1/N2 ) adenocarcinoma of the stomach underwent attempted curative resection . Seventy patients were treated with surgery alone while 50 patients also received adjuvant therapy consisting of either chemotherapy ( 5-FU/FAM ) alone , radiation therapy alone , or chemotherapy+radiation therapy . Adjuvant therapy was tolerated relatively well with only one patient experiencing a grade 3 ( RTOG/EORTC ) toxicity , and none experiencing grade 4/5 toxicity . In patients with T3/T4 tumors , the median survival was 10 months for surgery alone as compared to 18 months for the adjuvant treatment group , and a 5-year survival of 10 % versus 24 % in the adjuvant therapy group ( p = .01 ) . In patients with lymph node positive disease , the median survival was 10 months in patients treated with surgery as compared to 15 months for those treated with adjuvant therapy , and a 5-year survival of 8 % for surgery alone versus 16 % for the adjuvant therapy group ( p = .04 ) . Patients having both T3/T4 tumor and positive lymph nodes had a median survival of 9 months with surgery versus 13 months for the adjuvant therapy group , and a 5-year survival of 4 % versus 22 % ( p = .03 ) for the adjuvant group . Seventy-four patients were evaluable for pattern of relapse . Thirty developed locoregional recurrence ; 17 of 38 ( 45 % ) in the surgery alone group and 13 of 36 ( 36 % ) in the adjuvant therapy group . The improvement in local control in the adjuvant group was totally accounted for by the group receiving both chemotherapy and radiation therapy , in which the recurrence rate was 19 % . Statistically significant improvement in the 2-year local control rate was limited to patients with negative surgical margins who received radiation , 93 % , versus those who did not , 55 % ( p = 0.03 ) . The modest improvement in survival seen in patients receiving adjuvant therapy appears to be related to improved local control . No improvement in the rate of distant failure was seen . Chemotherapeutic regimens used seem to be critical in enhancing the effects of radiation in improving local control and survival . Results may be further improved by the extended use of intraoperative radiation Background Recent research es have led to find strategies to prevent relapse and to improve survival for gastric cancer patients , including preoperative neo-adjuvant approaches . However , the efficacy of some neo-adjuvant regimens including 5-fluorouracil , cisplatin , and docetaxel have been less investigated . The present study evaluated the outcome and mid-term survival of patients with gastric cancer who undergoing this regimen . Methods In a r and omized double-blinded controlled trial performed at the Firoozgar hospital in Tehran in 2011 - 12 , 61 patients were r and omly assigned to treatment ( 32 to neo-adjuvant chemotherapy with docetaxel , cisplatin and 5-fluorouracil ( 5-FU ) before surgery and 27 to surgery alone ) . The present study tried to assess the efficacy of neoadjuvant chemotherapy regarding improvement of mid-term survival , complications , and R0 resection status . Results The two groups were matched in terms of gender , mean age , cancer location , and TNM staging . However , R0 resection in the former group was 85.7 % ; while this indicator in the isolated surgery group was significantly lower ( 61.5 % ) . Regarding WHO performance , no significant difference was observed across the two groups . Patients in  neo-adjuvant chemotherapy group were followed for mean follow-up time 10.32 months and those who categorized in isolated surgery group were followed for mean follow-up time 10.88 months . Mid-term mortality rate in the two groups was 14.3 % and 15.4 % , respectively ( p = 0.866 ) . In this regard , 3- , 6- , and 9-month survival rate in neo-adjuvant chemotherapy group was 96.4 % , 89.3 % , and 85.7 % , respectively . These survival rates in the surgery group were 92.3 % , 88.5 % , and 84.6 % , respectively . Multivariable logistic regression analysis showed that among all study variables , only R0 resection status could predict mid-term mortality .  Conclusion Neo-adjuvant chemotherapy and surgery compare to surgery alone more improve R0 resection status , but mid-term survival rate is similar in the two regiments . R0 resection status can effectively predict appropriate mid-term survival in undertreated patients Patients with metastatic gastric cancer are currently not considered operative c and i date s and are most often offered systemic therapy . Palliative resection of the primary tumor has been considered irrelevant to the outcome and has been recommended only for palliation of symptoms . We have examined the role of palliative gastrectomy and its impact on survival in patients with stage IV gastric cancer at initial diagnosis between 1990 and 2000 . A total of 105 patients with stage IV disease were identified during this period ; 81 of them ( 77.1 % ) had no resection , and 24 ( 22.9 % ) underwent palliative gastric resection .  Mean survival in those without resection who received chemotherapy ( with or without radiation ) treatment was 5.9 months ( 95 % confidence interval 4.2–7.6 ) . For those with resection and adjuvant therapy , mean survival time was 16.3 months ( 95 % confidence interval 4.3–28.8 months ) . Kaplan-Meier survival analysis showed significantly better survival in those with resection and adjuvant therapy ( log-rank test , P = 0.01 ) . Mortality and morbidity rates associated with palliative resection were 8.7 % and 33.3 % , respectively , which did not differ statistically from the 3.7 % and 25.3 % in patients who underwent curative gastrectomy during same period of time . However , the length of hospitalization ( 22 versus 16 days ) was significantly higher compared with those without stage IV disease . These data suggest that palliative resection combined with adjuvant therapy may improve survival in a selected group of patients with stage IV gastric cancer .  Palliative gastrectomy plus systemic therapy should be compared with systemic therapy alone in a r and omized trial Objective The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonr and omized , phase 2 Yale University  cisplatin , bleomycin , methotrexate , and 5-FU protocol are presented . Methods Sixty-seven patients were prospect ively accrued with a median follow-up of 5.4 years , and st and ard parameters of toxicity and efficacy were studied . Both univariate and multivariate analyses were applied . Results The 5-year disease-free survival of 78 % for the 25 patients in the adjuvant group , of which 80 % had high-risk features including positive margins , parametria , and lymph nodes and 28 % had adenocarcinomas , was comparable to recent relevant literature . Only 64 % of patients in this group received consolidation radiation therapy , which did not impact on survival . Only 12 % of patients recurred distantly . Notably , those who received 4 months or more of chemotherapy had prolonged survival ( P = 0.012 ) . In the neoadjuvant group , chemotherapy response rate among 42 patients ( with stages 1B-IIIB cancer ) was 79 % ( 50 % partial response , 29 % complete response ) , and no patient progressed . In the subgroup of 22 patients who underwent surgery after chemotherapy  , 59 % had nonsquamous histology . Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy . Ninety-five percent received postoperative radiation therapy . There was a 9 % pathologic complete response rate , with positive lymph nodes found in 27 % . Notably , those who received 3 months or less of chemotherapy had improved overall survival ( P = 0.030 ) . Survival rates of these 22 patients at 3 and 5 years were 73 % and 63 % , respectively . Although not r and omized , these survival rates were similar to those achieved with chemoradiation . Conclusions Although there are several logistical/ design features of the cisplatin , bleomycin , methotrexate , and 5-FU regimen that are not in line with the current chemotherapy era , our experience with this well-tolerated regimen can serve as a proof of principle . Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place . It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases PURPOSE The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure . PATIENTS AND METHODS All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy . Chemotherapy regimens were bolus fluorouracil ( 5-FU ) , 5-FU and leucovorin , 5-FU and levamisole , and 5-FU , leucovorin , and levamisole . Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy . RESULTS One thous and six hundred ninety-five patients were entered and fully assessable , with a median follow-up of 7.4 years . There was no difference in overall survival ( OS ) or disease-free survival ( DFS ) by drug regimen . DFS and OS decreased between years 5 and 7 ( from 54 % to 50 % and 64 % to 56 % , respectively ) , although recurrence-free rates had only a small decrease . The local recurrence rate was 14 % ( 9 % in low-risk [ T1 to N2 + ] and 18 % in high-risk patients [ T3N+ , T4N ] ) . Overall , 7-year survival rates were 70 % and 45 % for the low-risk and high-risk groups , respectively . Males had a poorer overall survival rate than females . CONCLUSION There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation . Local and distant recurrence rates are still high , especially in T3N+ and T4 patients , even with full adjuvant chemoradiation therapy OBJECTIVES Stage III non-small cell lung cancer ( NSCLC ) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable , bulky nodal disease . This review up date s the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients . METHODS Systematic search es were conducted through MEDLINE , Embase , and the Cochrane Data base for Systematic Review up to December 2011 , focusing primarily on r and omized trials , selected meta-analyses , practice guidelines , and review s. RESULTS For individuals with stage IIIA or IIIB disease , good performance scores , and minimal weight loss , treatment with combined chemoradiotherapy results in better survival than radiotherapy alone . Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported . Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation . Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy ; however , weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate . The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery . Postoperative radiotherapy  improves local control without improving survival . CONCLUSIONS Multimodality therapy is preferable in most subsets of patients with stage III lung cancer . Variability in the patients included in r and omized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios . Future trials are needed to investigate the roles of individualized chemotherapy , surgery in particular cohorts or setting s , prophylactic cranial radiation , and adaptive radiation PURPOSE To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients had MPM with clinical stage T1 - 3 , N0 - 2 , M0 disease considered to be completely resectable and a WHO performance status of 0 to 2 .  Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 , given every 28 days . Surgery had to consist of a complete extrapleural pneumonectomy , including resection of pericardium and diaphragm . Postoperative radiotherapy was to be considered for all patients . RESULTS Nineteen patients with MPM were included in this pilot study . According to the European Organization for Research and Treatment of Cancer prognostic score , two patients were in the good prognosis group , and 17 patients were in the poor prognosis group . The response rate to neoadjuvant chemotherapy was 32 % . The major toxicity was thrombocytopenia . Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality . Major surgical complications occurred in six patients , and all were treated successfully . Thirteen patients received postoperative radiotherapy . The median survival time was 23 months . Two patients remain alive and free of disease 41 and 38 months after initiation of therapy . CONCLUSION For patients with potentially operable MPM , the availability of active and well-tolerated chemotherapy regimens , the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center , and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy In 1973 , the European Institute of Oncology performed the first prospect i ve neoadjuvant chemotherapy study in locally advanced , inoperable breast cancer . The original purpose was to downstage the primary tumor in order to achieve surgical resection . This approach has subsequently increased in popularity , and in the last 10 years , r and omized controlled trials of neoadjuvant chemotherapy have been performed with a view to further downstage the primary tumor and lymph nodes in order to achieve greater rates of breast-conserving surgery and to test whether systemic therapy given earlier would confer a survival benefit . Although the net result of these trials did demonstrate a higher rate of breast conservation , no overall survival benefit was seen . However , in subgroup analysis , there was a significant survival benefit in patients in whom a complete pathologic response ( pCR ) was achieved . In the National Surgical Adjuvant Breast and Bowel Project B-18 trial of neoadjuvant chemotherapy , at 9 years median follow-up , the overall survival rate for patients achieving a pCR was 85 % compared with 73 % in those in whom residual cancer was detected on histopathologic examination . For disease-free survival , the respective rates were 75 % and 58 % . After adjustment for other prognostic factors , achievement of a pCR was associated with a 50 % reduction in deaths compared with the group as a whole . Mauri et al evaluated nine r and omized studies , with a total of 3,946 patients with breast cancer in whom neoadjuvant therapy was compared with adjuvant systemic therapy .  They found no statistically or clinical ly significant difference between neoadjuvant therapy and adjuvant therapy arms with regard to overall survival , disease progression , or distant disease recurrence . However , they observed that neoadjuvant therapy was associated with an increased risk of locoregional disease recurrence compared with adjuvant therapy , especially in trials where more patients in the neoadjuvant arm received radiation therapy without surgery . In several retrospective studies , the pCR rates in invasive ductal breast carcinoma ( no special type ) have been shown to be approximately 15 % or less , whereas the pCR rates in invasive lobular carcinoma have been shown to be 2 % or less . Katz et al review ed r and omized trials of neoadjuvant chemotherapy and noted that the pCR rate was 1.7 % in invasive lobular carcinoma and 11.6 % in invasive ductal breast carcinoma ( no special type ) . Regarding invasive lobular carcinoma , they concluded : “ the benefit from systemic chemotherapy for individuals with this form of breast disease is unclear . ” Similarly , two retrospective studies have demonstrated low rates of successful breast conservation for patients with lobular carcinoma who underwent neoadjuvant chemotherapy . In patients who received breast-conserving  surgery  after neoadjuvant therapy , Soucy et al found surgical margin involvement in 43 % of patients with lobular carcinoma compared with 16 % of patients with invasive ductal carcinoma ( no special type ) . Another study , from the M. D. And erson Cancer Center , of 284 consecutive patients diagnosed with pure invasive lobular carcinoma between 1998 and 2006 compared patients who received neoadjuvant chemotherapy with those who received primary surgery as first-line treatment and concluded that neoadjuvant chemotherapy did not increase the rates of breast conservation in this morphologic subtype . It should be noted that the above studies are retrospective , not r and omized , trials . In the three r and omized trials of neoadjuvant endocrine therapy ( P024 conducted by the Letrozole Neoadjuvant Breast Cancer Study Group , IMPACT [ Immediate Preoperative Anastrozole , Tamoxifen , or Combined with Tamoxifen ] , and PROACT [ Pre-Operative “ Arimidex ” Compared to Tamoxifen ] ) for women with estrogen receptor ( ER ) –positive disease , none of which carried out analysis of histological tumor type ( ie , lobular v ductal [ no special type ] ) , a higher rate of breast conservation was observed in women who received preoperative endocrine treatment . The lack of subgroup analysis in these three studies does not allow one to draw conclusions regarding histologic type-specific effectiveness of neoadjuvant endocrine treatment , although classical lobular carcinoma is well recognized as more often being ER positive than ductal tumors ( no special type ) . JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 28 NUMBER 22 AUGUST 1 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 PURPOSE The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit . Gemcitabine ( GEM ) has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer . We evaluated the feasibility of postoperative administration of GEM alone , followed by concurrent GEM and irradiation ( RT ) after curative resection for pancreatic adenocarcinoma . METHODS AND MATERIAL S GEM 1000 mg/m(2 ) on Days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by GEM 300 mg/m(2 ) weekly + 40 Gy in a split course . Twenty-two patients ( median age 59 years , range 39 - 74 , Performance Status 0 - 1 ) with Stage II and III curatively resected pancreatic head adenocarcinoma were included . RESULTS For GEM alone , all patients received the three planned courses , with dose reductions in 7 ( 32 % ) of 22 patients . All patients , except two , completed full chemoradiation ; one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia and the other stopped RT after 32 Gy because of early disease progression . No reduction in GEM during RT was necessary ; no toxic death was noted ; and World Health Organization Grade 3 - 4 hematologic and nonhematologic toxicities occurred in 8 ( 36 % ) and 7 ( nausea , vomiting ) ( 32 % ) of 22 patients respectively . No late toxicity developed . After a median follow-up of 15 months , 11 patients were alive , and 2 patients had died of causes unrelated to their disease or toxicity , The median disease-free survival and overall survival was 6 and 15 months , respectively . CONCLUSION This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer . Its intensification with continuous RT is currently being investigated The results of a prospect i ve r and omized trial of adjuvant treatment after curative resection for gastric cancer are reported . The study consisted of three arms : ( 1 ) surgery only ; ( 2 ) chemotherapy ( 5‐fluoro‐uracil ( FU ) and 1‐(2‐chloroethyl)‐3‐(4‐methylcyclohexil)‐1‐nitrosourea ( Me‐CCNU ) ) after surgery ; ( 3 ) chemo‐immunotherapy ( FU , Me‐CCNU and levamisole ) after surgery .  Between March 1977 and June 1981 , 235 patients were included in the study by 18 co‐operating institutions . Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity , necessitating interruption of treatment . Two of these patients died of marrow aplasia . Statistical analysis of survival showed that prognosis was influenced by the well‐known prognostic variables , invasion of the wall , nodal status and site of tumour . The different treatments in the three arms , however , did not show any impact on prognosis , even when adjustments were made for the most relevant prognostic variables . Given the lack of effect on survival and the presence of clinical ly important toxicity , FU and Me‐CCNU ± levamisole can not be recommended as adjuvant therapy for resected gastric cancer PURPOSE We performed a phase 2 trial of neoadjuvant temozolomide ( TMZ ) , followed by hypofractionated accelerated radiation therapy ( HART ) with concurrent TMZ , and adjuvant TMZ in patients with newly diagnosed glioblastoma to determine whether neoadjuvant TMZ would safely improve outcomes in this group of patients prior to subsequent cytotoxic therapy . METHODS AND MATERIAL S Adult patients with newly diagnosed glioblastoma and a Karnofsky Performance Status > 60 were eligible .  Neoadjuvant TMZ administration started 2 to 3 weeks from surgery at a daily dose of 75 mg/m2 for 2 weeks prior to delivery of HART ( 60 Gy in 20 daily fractions ) with concurrent and adjuvant TMZ . The primary endpoints were feasibility and toxicity . The secondary endpoints included overall survival ( OS ) and progression-free survival . RESULTS Fifty patients were accrued . The median follow-up period was 44.0 months for patients at risk and 22.3 months for all 50 patients . Except for 1 patient in whom infection developed and another patient with progression during HART , all patients completed protocol therapy as planned . The median OS and progression-free survival were 22.3 months ( 95 % confidence interval , 14.6 - 42.7 months ) and 13.7 months ( 95 % confidence interval , 8.0 - 33.3 months ) , respectively . The 4-year OS rates were 30.4 % for the entire cohort and 53.3 % and 14.0 % for patients with methylated ( n=21 ) and unmethylated ( n=27 ) MGMT gene promoter tumors , respectively . One patient had grade 5 pancytopenia during HART , and another patient had transient grade 4 hepatotoxicity . A second surgical procedure was performed in 13 patients : 2 had intracranial infection , 3 had recurrences , 4 had recurrences and radiation-induced damage , and 4 had only radiation-induced damage . CONCLUSIONS This novel approach of neoadjuvant TMZ is associated with an encouraging favorable long-term survival with acceptable toxicity . A future comparative trial of the efficacy of this regimen is warranted To evaluate the efficacy of adjuvant chemotherapy for patients with advanced head and neck squamous cancer , the Head and Neck Contracts Program conducted a three-arm study comparing st and ard surgery and radiation , induction chemotherapy ( cisplatin and bleomycin ) plus st and ard therapy , and induction chemotherapy plus st and ard therapy followed by maintenance cisplatin for 6 months . As previously reported , this trial of 462 patients demonstrated no significant difference in disease-free survival or survival , but a significantly lower metastatic rate in the maintenance arm . To determine whether particular subgroups may have benefited from adjuvant therapy , we evaluated results based on primary site , and tumor ( T ) and node ( N ) stage . Of the 192 patients with oral cavity cancer , those on the maintenance arm had a significantly improved 3-year disease-free survival ( 67 % ) compared with the st and ard arm ( 49 % ) or induction arm ( 44 % ) ( overall P = .05 ) . For hypopharyngeal and laryngeal cancers there was no marked overall benefit . For the 106 patients with T1 plus T2 disease , there was marginal improvement in disease-free survival for the maintenance group ( 72 % ) compared with the st and ard group ( 47 % ) or induction group ( 43 % ) ( overall P = .09 ) . There was no advantage for patients with T3 and T4 disease . There was superior disease-free survival for patients with N1 disease on the maintenance arm ( 70 % ) compared with the st and ard arm ( 42 % ) ( P = .024 ) . The same was true for disease-free survival in 109 patients with N2 disease : st and ard ( 52 % ) , induction ( 30 % ) , maintenance ( 84 % ) ( overall P less than .001 ) . There was no benefit for N3 disease . A significant survival advantage with  maintenance chemotherapy  was only seen for N2 disease ( overall P = .04 ) . Since head and neck cancer patients are a heterogeneous group , there may be particular sites and stages for which adjuvant chemotherapy would be advantageous , and subset analysis can help indicate directions for new trials Purpose : Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer . Although many of the adverse effects of castration therapy are manageable , they can have a detrimental effect on quality of life . Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ( ‘ Casodex ’ ) 150 mg adjuvant to radiotherapy in patients with T1 - 4 , M0 , any n prostate cancer . Methods : The subset of patients within the early prostate cancer ( EPC ) program who received radiotherapy with curative intent ( n = 1,370 ) were included in the analysis . These patients were r and omized to receive oral bicalutamide 150 mg once daily ( n = 699 ) or placebo ( n = 671 ) . Results : The median follow-up for patients included in this analysis was 7.2 years . In patients with locally advanced disease ( n = 305 )  , bicalutamide adjuvant to radiotherapy significantly improved : progression-free survival ( PFS ) , reducing the risk of objective progression by 44 % compared with radiotherapy alone [ hazard ratio ( HR ) 0.56 ; 95 % confidence interval ( CI ) 0.40 , 0.78 ; P < 0.001 ) . Prostate-specific antigen (PSA)–PFS , reducing the risk of PSA progression by 59 % compared with radiotherapy alone ( HR 0.41 ; 95 % CI 0.30 , 0.55 ; P < 0.001 ) . Overall survival , reducing the risk of death by 35 % compared with radiotherapy alone ( HR 0.65 ; 95 % CI 0.44 , 0.95 ; P = 0.03 ) . This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths ( 16.1 vs 24.3 % , respectively ) . There was no significant difference in PFS or overall survival in patients with localized disease ( n = 1,065 ) . Conclusions : In patients with locally advanced disease  , bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival , PFS and PSA – PFS compared with radiotherapy alone . The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy ( Bolla et al. in Lancet 360:103–108 , 2002 ; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285–1290 , 2005 ) . In addition , the clinical benefit of bicalutamide 150 mg in locally advanced patients , but not in those with localized disease , is consistent with the overall results from the EPC program ( McLeod et al. BJU Int 97:247–254 , 2006 ) . Given the quality -of-life advantages of bicalutamide relative to castration , bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer BACKGROUND In our r and omised , controlled , phase 3 trial NeOAdjuvant Herceptin ( NOAH ) trial in women with HER2-positive locally advanced or inflammatory breast cancer , neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival . We report up date d results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy . METHODS We did this multicentre , open-label , r and omised trial in women with HER2-positive locally advanced or inflammatory breast cancer . Participants were r and omly assigned ( 1:1 ) , by computer program with a minimisation technique , to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab ( concurrently with neoadjuvant chemotherapy and continued after surgery ) . A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone . Our primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered at www.controlled-trials.com , IS RCT N86043495 . FINDINGS Between June 20 , 2002 , and Dec 12 , 2005 , we enrolled 235 patients with HER2-positive disease , of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab . 99 additional patients with HER2-negative disease were included in the parallel cohort . After a median follow-up of 5.4 years ( IQR 3.1 - 6.8 ) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease . 5 year event-free survival was 58 % ( 95 % CI 48 - 66 ) in patients in the trastuzumab group and 43 % ( 34 - 52 ) in those in the chemotherapy group ; the unadjusted hazard ratio ( HR ) for event-free survival between the two r and omised HER2-positive treatment groups was 0.64 ( 95 % CI 0.44 - 0.93 ; two-sided log-rank p=0.016 ) . Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab . Of the 68 patients with a pathological complete response  ( 45 with trastuzumab and 23 with chemotherapy alone ) , the HR for event-free survival between those with and without trastuzumab was 0.29 ( 95 % CI 0.11 - 0.78 ) . During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related ( grade 2 lymphostasis and grade 2 lymphoedema , each in one patient in the trastuzumab group , and grade 2 thrombosis and grade 2 deep vein thrombosis , each in one patient in the chemotherapy-alone group ) . INTERPRETATION These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer , and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease A prospect i ve r and omized trial was performed in patients with advanced squamous cell carcinomas ( SCC ) of the oral cavity , larynx , and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following " curative " resection . Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were r and omized to receive either surgery alone ( n = 27 ) or surgery with postoperative radiation ( n = 24 ) . Five patients were excluded from the study after r and omization because of in eligibility or protocol violations . Overall recurrence rates of 55.6 % and 36.8 % were noted in the surgery and surgery with adjuvant radiotherapy arms , respectively ( p = NS ) . This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral , nonoperated neck . Thus far , no significant differences in either locoregional or overall survival have been noted between the two treatment arms . In this preliminary analysis , adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival Background The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer ( LARC ) dramatically . But a major achievement has been the development of total mesorectal excision ( TME ) as a surgical st and ard and the recognition that the surgeon is the predominant prognostic factor . The benefit of preoperative hypofractionated radiotherapy ( SCRT ; five fractions each of 5 Gy ) , initially established by the Swedish Rectal Cancer Trial , has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group . The concept of combined neoadjuvant radiochemotherapy ( conventional radiation of about 50 Gy with chemotherapy ) has not been compared over surgery alone with TME . However , the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy ( RCT ) was better than postoperative radiochemotherapy in terms of local control . Methods and design Patients with histological proven rectal cancer staged T2N+ or T3 are r and omized to receive either SCRT ( 25 Gy in five fractions of 5 Gy ) plus TME-surgery within 5 days or RCT ( 50.4 Gy in 28 fractions of 1.8 Gy , continuous infusion 5-fluorouracil ) plus TME-surgery 4–6 weeks later . All patients receive adjuvant chemotherapy ( 12 weeks continuous infusional 5-FU ) and are followed up for 5 years . TME- quality is independently documented by the surgeon and the pathologist . Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years . Secondary endpoints are overall survival , disease-free survival , complete resection rate ( R0 resection ) , rate of sphincter saving resection , acute and late toxicity ( radiation related side effects ) , and quality of life ( including long term bowel function ) . Discussion Similar long-term survival , local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies . In addition to other ongoing ( and recently published ) comparative trials we include a larger number of patients for adequate power , apply quality -controlled TME and try to avoid the adjuvant treatment bias by m and atory adjuvant chemotherapy in both groups . Further more , stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive ( sphincter saving ) surgical approach Abstract Purpose : To evaluate FAM [ 5-FU ( 5-fluorouracil ) , doxorubicin , mitomycin C ] chemotherapy as adjuvant therapy for patients with resected TNM stage I , II , or III gastric carcinoma . Patients and Methods : One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles ( 1 year ) of postoperative FAM chemotherapy with observation only . Results : The median follow-up on this study was 9.5 years . For all patients , no differences ( log-rank analysis ) in disease-free survival ( p=0.45 ) and overall survival ( p=0.57 ) between FAM therapy ( 93 cases ) and surgery ( 100 cases ) were observed . Quality of surgical resection affected survival irrespective of FAM use . Cases with curative resection , defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm , had superior survival compared to cases not meeting these requirements ( p<0.001 ) . FAM was well tolerated with 6 % ( five of 90 ) of cases demonstrating grade IV hematologic toxicity . There were two drug-related fatalities ( one cardiomyopathy , one hematolytic uremic syndrome ) . Conclusion : FAM is not effective adjuvant therapy for TNM stage I , II , and III patients with resected gastric cancer . Future adjuvant studies must emphasize prospect i ve surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period BACKGROUND Complete surgical resection of gastric cancer is potentially curative , but long-term survival is poor . METHODS Patients with histologically proven adenocarcinoma of the stomach of stages IB , II , IIIA and B , or IV ( T4N2M0 ) and treated with potentially curative surgery  were r and omly assigned to follow-up alone or to intravenous treatment with four cycles ( repeated every 21 days ) of PELF ( cisplatin [ 40 mg/m(2 ) , on days 1 and 5 ] , epirubicin [ 30 mg/m(2 ) , days 1 and 5 ] , L-leucovorin [ 100 mg/m(2 ) , days 1 - 4 ] , and 5-fluorouracil [ 300 mg/m(2 ) , days 1 - 4 ] in a hospital setting . Frequencies and severity of adverse events were determined . Overall survival ( OS ) and disease-free survival ( DFS ) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model . All statistical tests were two-sided . RESULTS From January 1995 through September 2000 , 258 patients were r and omly assigned to chemotherapy ( n = 130 ) or surgery alone ( n = 128 ) . Patient characteristics were well balanced between the two arms . Among those who received chemotherapy , grade 3 or 4 toxic effects including vomiting , mucositis , and diarrhea were experienced by 21.1 % , 8.4 % , and 11.8 % of patients , respectively . Leucopenia , anemia , and thrombocytopenia of grade 3 or 4 were experienced by 20.3 % , 3.3 % , and 4.2 % of patients , respectively . After a median follow-up of 72.8 months , 128 patients ( 49.6 % ) experienced recurrence and 139 ( 53.9 % ) deaths were observed , one toxicity-related . Relative to treatment with surgery alone , adjuvant chemotherapy did not increase disease-free survival ( hazard ratio [ HR ] of recurrence = 0.92 ; 95 % confidence interval [ CI ] = 0.66 to 1.27 ) or overall survival ( HR of death = 0.90 ; 95 % CI = 0.64 to 1.26 ) . CONCLUSIONS Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival . The estimated effect of chemotherapy ( 10 % reduction in the hazard of death or relapse ) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) protocol R-01 between November 1977 and October 1986 . Their average time on study was 64.1 months . The patients were r and omized to receive no further treatment  ( 184 patients ) , postoperative adjuvant chemotherapy with 5-fluorouracil , semustine , and vincristine ( MOF ) ( 187 patients ) , or postoperative radiation therapy ( 184 patients ) . The chemotherapy group , when compared with the group treated by surgery alone , demonstrated an overall improvement in disease-free survival ( P = .006 ) and in survival ( P = .05 ) . Employing the proportional hazards model , a global test was used to determine the presence of treatment interactions . Investigation of stratification variables employed in this study indicated that sex , and to a lesser extent age and Dukes stage , made individual contributions to the disease-free survival and the survival benefit from chemotherapy . When evaluated according to sex , the benefit for chemotherapy at 5 years , both in disease-free survival ( 29 % vs. 47 % ; P less than .001 ; relative odds , 2.00 ) and in survival ( 37 % vs. 60 % ; P = .001 ; relative odds , 1.93 ) , was restricted to males . When males were tested for age trend with the use of a logistic regression analysis , chemotherapy was found to be more advantageous in younger patients . When the group receiving post-operative radiation ( 4,600 - 4,700 rad in 26 - 27 fractions ; 5,100 - 5,300 rad maximum at the perineum ) was compared to the group treated only by surgery , there was an overall reduction in local-regional recurrence from 25 % to 16 % ( P = .06 ) . No significant benefit in overall disease-free survival ( P = .4 ) or survival ( P = .7 ) from the use of radiation has been demonstrated . The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant . In conclusion , this investigation has demonstrated a benefit from adjuvant chemotherapy ( MOF ) for the management of rectal cancer . The observed advantage was restricted to males . Postoperative radiation therapy reduced the incidence of local-regional recurrence , but it failed to affect overall disease-free survival and survival This research aim ed to investigate the efficacy of S-1 plus oxaliplatin ( SOX ) as perioperative chemotherapy for locally advanced gastric cancer . We enrolled 102 patients with preoperative clinical stage T3 - 4N × M0 gastric cancer who were then r and omly assigned to receive SOX as either perioperative chemotherapy ( group A , 50 patients ) or postoperative adjuvant chemotherapy ( group B , 52 patients ) . Short-term curative efficacy and adverse effects of perioperative chemotherapy were analyzed . The rates of R0 resection , surgical complications , combined multiple organ resection , overall survival ( OS ) , and disease-free survival ( DFS ) were compared between the groups . Results showed an overall response rate in group A of 42 % , with a disease control rate of 94 % and a tumor down-staging rate of 50 % . An R0 resection rate of 90 % was achieved in group A , which was significantly higher than that in group B ( 75 % ) . No surgical mortality was observed , and the differences in surgical complications and combined multiple organ resection rates between the groups were not significant . The postoperative pathological examination of 4 patients in group A did not show any cancer cells in the tumor bed , result ing in a histological complete remission rate of 8 % . The average OS and DFS for group A patients were 17.928 and 16.134 months , respectively , which were both longer than that of group B patients . However , the differences were not significant . In all , our results shows that in locally advanced gastric carcinoma , SOX perioperative chemotherapy is effective and results in a significantly improved R0 resection rate compared to postoperative SOX administration . Perioperative SOX does not cause additional surgical complications and has low adverse reaction rates ; moreover , it appears to prolong survival In a trial of adjuvant chemotherapy with mitomycin and 5-FU followed by oral UFT for T1 and T2 gastric cancer after curative gastrectomy , there was no significant difference in survival between the treated and control ( surgery alone ) groups ( 5-year survival rate , 82.9 % control vs 85.8 % treated ) . Although not significantly different , 5-year survival for patients with T2 cancer was slightly higher in the treated group than in the control group ( 76.9 % control vs 83.0 % treated ) . This finding suggests that T2 cancer should remain the target of further trials of adjuvant chemotherapy Abstract Locally advanced gastric cancer ( LAGC ) is best treated with surgical resection . Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer . This study aim ed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU ( DOF ) regimen and bevacizumab in LAGC patients . Eighty LAGC patients were r and omized to receive DOF alone ( n = 40 ) or DOF plus bevacizumab ( n = 40 ) as neoadjuvant therapy  before surgery . The lesions were evaluated at baseline and during treatment . Circulating tumor cells ( CTCs ) were counted using the FISH test . Patients were followed up for 3 years to analyze the disease-free survival ( DFS ) and overall survival ( OS ) . The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group ( 65 % vs 42.5 % , P = 0.0436 ) . The addition of bevacizumab  significantly increased the surgical resection rate and the R0 resection rate ( P < 0.05 ) . The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group ( P = 0.0335 ) . Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group ( 15.2 months vs 12.3 months , P = 0.013 ) , the 2 groups did not differ significantly in OS ( 17.6 ± 1.8 months vs 16.4 ± 1.9 months , P = 0.776 . Cox proportional model analysis showed that number of metastatic lymph nodes , CTC reduction , R0 resection , and neoadjuvant therapy are independent prognostic factors for patients with LAGC . Neoadjuvant of DOF regimen plus bevacizumab  can improve the R0 resection rate and DFS in LAGC . These beneficial effects might be associated with the reduction in CTC counts BACKGROUND To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma ( LAPC ) . METHODS Patients with histologically confirmed LAPC were given 3 - 6 cycles of fixed-dose rate gemcitabine/capecitabine every 3 weeks . At the end of chemotherapy , patients were restaged and underwent surgery if the disease was not classified as unresectable . Our institutional criteria were used to classify respectability , which was recategorized on the basis of National Comprehensive Cancer Network ( NCCN ) criteria retroactively . The primary end point was rate of microscopic curative resection . RESULTS Forty-three eligible patients ( 18 with borderline resectable disease and 25 with unresectable disease on the basis of NCCN criteria ) were enrolled . The radiologic response rate was 18.6 % . Grade three or worse adverse events were mainly h and -foot syndrome ( 11 % ) , and there were no grade four adverse events . Surgery was performed in 17 patients ( 39.5 % ) ; pathologic curative resection ( R0 ) was achieved in 14 patients ( 32.5 % ) among total 43 patients , and 82.3 % ( 14/17 ) among the 17 resected patients . With 43-month follow-up , the median overall was 16.6 months with a median progression-free survival of 10.0 months . Median overall survival was 23.1 months in patients who underwent surgery and 13.2 months in patients who could not complete the surgery ( P = .017 ) . CONCLUSION A subset of patients with borderline or unresectable pancreatic cancer could be performed curative tumor resection after neoadjuvant chemotherapy . Some patients might be benefit on survival from neoadjuvant chemotherapy after surgical resection Background : The benefit of adjuvant therapy in curatively resected lymph node-positive colon cancer was established using 5-fluorouracil ( 5-FU ) and levamisole ( LEV ) for 12 months . 5-FU cytotoxicity can be modulated by folinic acid ( FA ) or interferon-α ( INF-α ) . The aim of this study was to investigate the efficacy of modulating 5-FU+ LEV by either FA or IFN-α in the adjuvant treatment of high-risk colon cancer . Methods : Patients with curatively resected colon cancer ( stages UICC IIb and III ) were stratified according to T , N , and participating center and r and omized to receive a 12-month treatment using 5-FU + LEV alone or in combination with FA or IFN-α . Results : A total of 855 of 904 entered patients ( 94.6 % ) were eligible . The median follow-up of all eligible patients was 4.6 years . Addition of FA to 5-FU + LEV improved recurrence-free and overall survival in comparison with 5-FU + LEV alone ( P = 0.007 and P = 0.004 , respectively , 1-sided ) . The 5-year overall survival rates were 60.5 % ( 95 % confidence interval , 54.3–66.7 ) and 72.0 % ( 95 % confidence interval , 66.5–77.5 ) for 5-FU + LEV and 5-FU + LEV + FA , respectively . Addition of INF-α showed a tendency to improve recurrence-free survival , however , without altering overall survival . Toxicities ( WHO III + IV ) were generally tolerable except one toxic death in the control arm and were observed in 9.9 % of the patients receiving 5-FU + LEV alone and in 13.3 % and in 30.7 % of patients receiving additional FA and IFN-α , respectively . Conclusions : Addition of IFN-α was associated with increased toxicity without markedly influencing the outcome and should therefore not be recommended for adjuvant treatment . Addition of FA increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points , respectively . 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer The effect of postoperative immunochemotherapy with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) and OK-432 was evaluated as an adjuvant therapy after curative resection for gastric cancer . Immediately after surgery , patients were r and omly allocated to the following three treatments : ( A ) chemotherapy with MMC and 5-FU ( 32 cases ) ; ( B ) chemoimmunotherapy with MMC , 5-FU and OK-432 ( 33 cases ) ; and ( C ) surgery alone as control ( 34 cases ) . There were no significant differences in the background factors influencing survival time among the groups , and there was no dose-distribution of chemotherapeutic agents between groups A and B. While the differences were not statistically significant , the survival rate and disease-free interval of group B were better than those of groups A or C. Side effects such as gastroenteric disorder , leukopenia ( less than 3,000/mm3 ) , thrombocytopenia ( less than 7 X 10(4)/mm3 ) and increase of serum transaminase level ( GPT greater than or equal to 100 units ) were less frequently observed in group B than in group A. The results of the present study seemed to indicate that chemoimmunotherapy with OK-432 may be effective for surgical adjuvant therapy A cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer was carried out by Kondo 's group from July 1974 to December 1977 . A total of 848 patients with gastric cancer underwent curative resection were eligible . Of 848 patients , 819 cases with complete description of patient 's background were evaluable : Group A ( surgery + MMC + 5-FU : chemotherapy ) 253 cases , group B ( surgery + MMC + 5-FU + OK-432 or PSK : immunochemotherapy ) 282 and group C ( surgery alone ) 284 . The 5-year corrected survival rates of total cases using Cox 's proportional hazard model were 76.2 % with group A , 73.6 % with group B and 73.3 % with group C. And the 10-year survival rates were 67.6 % with group A , 64.3 % with group B and 63.9 % with group C. The difference in survival rate among groups A , B and C was not statistically significant . In the evaluation of prognostic factors by Cox 's proportional hazard model , level of curative resection , extent of resection , histological stage and Kajitani 's classification had an influence upon survival rates , in which degrees of metastasis in lymph node and serous infiltration were also involved . The significance of postoperative adjuvant immunochemotherapy has not been clarified Introduction : We developed an innovative approach for malignant pleural mesothelioma ( MPM ) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy ( IMRT ) followed by extrapleural pneumonectomy ( EPP ) . This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy ( SMART ) . Methods : All resectable clinical T1 - 3N0M0 histologically proven , previously untreated MPMs were eligible . Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT . Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings . The primary end point was treatment-related mortality and secondary end points were overall survival , disease-free survival , treatment-related morbidity , and patterns of failure . Results : Targeted accrual of 25 patients was completed between November 2008 and October 2012 . All patients completed SMART . IMRT was well tolerated with no grade 3 + toxicities . EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality . Thirteen patients developed grade 3 + surgical complications . One patient ( 4 % ) died from treatment-related toxicity ( empyema ) during follow-up . All but one patient had stage III or IV disease on final pathologic findings . Five of 13 ypN2 patients received adjuvant chemotherapy . After a median follow-up of 23 months ( range , 6–51 ) , the cumulative 3-year survival reached 84 % in epithelial subtypes compared with 13 % in biphasic subtypes ( p = 0.0002 ) . Conclusions : SMART is feasible in resectable MPM patients . This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes BACKGROUND Many investigators have reported that extended lymph node dissection ( D2 dissection ) is probably an effective procedure . However , the theory that D2 dissection leads to an improvement in survival has not been confirmed in r and omized trials . We attempted to confirm the effectiveness of D2 dissection with gastrectomy for gastric cancer . MATERIAL S AND METHODS Gastric cancer patients ( 1403 ) underwent curative resection by D1 ( 991 patients ) or D2 ( 412 patients ) dissection with gastrectomy .  Survival rates calculated for all patients and subdivided for stage , depth of invasion , and lymph node metastasis were compared between the two groups . The diagnosis of lymph node metastasis was compared between macroscopic and histological findings . RESULTS There was no significant difference in the survival of patients overall . However , in the patients with stage II , T1 or T2 , or N1 disease , the survival of the D2 group was significantly better than that of the D1 group . The false positive rates of lymph node metastasis were 53.3 % in the N1 group , 26.2 % in the N2 group , and 9.2 % in the N3 group . In a considerable proportion of the N1 and N2 patients , histological findings proved more or fewer metastases than macroscopic diagnosis . CONCLUSIONS Metastatic lymph nodes should be resected as far as possible . D2 dissection with gastrectomy is recommended for T1 , N1 or T2 , N1 disease , particularly in younger patients BACKGROUND Adjuvant chemoradiotherapy does not represent the st and ard of care in patients with resected high-risk gastric cancer ; however , results from phase 2 and r and omized trials suggest improvement in overall survival . We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer . DESIGN Pilot study . SETTING University hospital . PATIENTS Twenty-nine patients with T4N+ or any TN23 gastric cancer previously treated with potentially curative surgery were enrolled . All of the patients received combined adjuvant chemotherapy with FOLFOX-4 ( ie , a combination of folinic acid [ leucovorin ] , fluorouracil , and oxaliplatin [ Eloxatin ] ) for 8 cycles and concomitant radiotherapy ( 45 Gy in 25 daily fractions over 5 weeks ) . Radiotherapy was begun after the first 2 cycles of FOLFOX-4 , which was reduced by 25 % during the period of concomitant radiotherapy . MAIN OUTCOME MEASURES Treatment toxic effects according to the National Cancer Institute-Common Toxicity Criteria classification , overall and disease-free survival rates , and identification of prognostic indicators . RESULTS All of the patients completed treatment . Severe hematologic and gastrointestinal toxic effects occurred in 10 % and 33 % , respectively . No acute hepatic or renal toxic effects were observed ; 1 patient experienced severe neurotoxicity . Disease-free and overall survival rates at 1 , 2 , and 3 years were 79 % , 35 % , and 35 % and 85 % , 62.6 % , and 50.1 % , respectively , and were shown to be substantially better than those observed in untreated patients . Long-term outcome was related to TNM stage , basal serum tumor marker level , and , particularly , lymph node ratio . CONCLUSION A multimodal approach with FOLFOX-4 and radiotherapy is feasible and effective for the treatment of patients with resected high-risk gastric cancer PURPOSE Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy , although fewer than 50 % could receive postoperative chemotherapy . We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines . PATIENTS AND METHODS Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction ( AEG II and III ) were r and omly assigned to  preoperative chemotherapy followed by surgery or to surgery alone . To detect with 80 % power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant , 282 events were required . RESULTS This trial was stopped for poor accrual after 144 patients were r and omly assigned ( 72:72 ) ; 52.8 % patients had tumors located in the proximal third of the stomach , including AEG type II and III . The International Union Against Cancer R0 resection rate was 81.9 % after neoadjuvant chemotherapy as compared with 66.7 % with surgery alone ( P = .036 ) . The surgery-only group had more lymph node metastases than the neoadjuvant group ( 76.5 % v 61.4 % ; P = .018 ) . Postoperative complications were more frequent in the neoadjuvant arm ( 27.1 % v 16.2 % ; P = .09 ) . After a median follow-up of 4.4 years and 67 deaths , a survival benefit could not be shown ( hazard ratio , 0.84 ; 95 % CI , 0.52 to 1.35 ; P = .466 ) . CONCLUSION This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit . Possible explanations are low statistical power , a high rate of proximal gastric cancer including AEG and /or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area ( celiac trunc , hepatic ligament , lymph node at a. lienalis ; D2 ) Adenocarcinoma of the pancreas is associated with the worst survival of any form of gastrointestinal malignancy . In spite of the progress in surgical treatment , result ing in increasing resection rates and a decrease in treatment-related morbidity and mortality , the true figures of cure are even today below 3 % . The dissemination of pancreatic cancer behind the local tissue compartments restricts the short-term ( < 3 years ) and long-term outcome for patients who have undergone resection . By histological evaluation , less than 15 % of the patients undergoing R0 resection have a pN0 status , more than 60 % suffer from lymph angiosis carcinomatosa , and more than 50 % suffer extrapancreatic nerve plexus infiltration . Hematoxylin and eosin – negative lymph nodes were found to be cancer positive when reverse transcriptase polymerase chain reaction ( RT- PCR ) or immunostaining was applied to the HE-negative lymph nodes . Cancer of the uncinate process has a very poor prognosis because there are no early symptoms ; vessel wall involvement occurs early and frequently ; a high association of liver metastasis exists as well . Surgery offers a low success rate , but it provides the only chance of cure . Ductal pancreatic cancer is diagnosed in more than 95 % of the cases in an advanced stage ; potentially curative resection can be performed only in about 10%–15 % of these patients . Major contributions of surgery to improved treatment results are the reduction of surgical morbidity — e.g . , early postoperative local and systemic complications— and a decrease of hospital mortality below 3%–5 % . In most recently published prospect i ve trials , R0 resection has been reported to result in an increase in short-term survival beyond that recorded for patients with residual tumor . However , R0 resection fails to improve long-term survival . In many published R0 series , st and ard tissue resection of pancreatic head cancer with the Kausch-Whipple procedure failed to include remote cancer cell – positive tissues in the operative specimen ; e.g. , N2-lymph nodes , nerve plexus , and perivascular extrapancreatic and retropancreatic tissues were not excised . Cancer recurrence after so-called R0 resection with curative intent is frequently the consequence of cancer left behind . Thus , long-term survival ( > 5 years ) is observed in a very small group of patients , contradicting the published 5-year actuarial survival rates of 20%–45 % for resected patients . The assessment of clinical benefit from surgical or medical cancer treatment should therefore be based on several end points , not only on actuarial survival . Publication of actuarial survival figures must include the number of observed ( actual ) survivals , the definition of the subset of patients followed after resection , and the total number of patients in the study group ; anything less is misleading . In reporting pancreatic cancer treatment trial results after oncological resections , more convincing primary end points to evaluate treatment efficacy are median survival ( in months ) , actual survival at 1–5 years , and progression-free survival ( in months ) . In series with multimodality treatment , clinical benefit response as well as quality of life measurements using the EORTC Quality of Life index C30 ( QLQ-C30 ) are of importance in evaluating survival data . Adjuvant treatment improves survival after oncological resection ; however , the short-term and long-term benefit after adjuvant chemotherapy in R0 as well as in R1 - 2 resected patients has not yet been underscored by data from controlled clinical trials . The survival benefit ( median survival time ) of adjuvant chemotherapy or radiochemotherapy has been demonstrated to be 6–10 months . Therefore , after oncological resection of pancreatic cancer each patient should be offered adjuvant treatment . A neoadjuvant treatment protocol for pancreatic cancer , however , has not been established
Furthermore , this therapy could increase the dem and on radiation re sources .
There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria .
For patients unable to undergo radiation , adjuvant chemotherapy alone may be of benefit , particularly for those with lymph-node metastases .
There is insufficient evidence from r and omized trials to recommend neoadjuvant chemotherapy , or neoadjuvant or adjuvant radiotherapy or immunotherapy , either alone or in combination , outside a clinical trial .
OBJECTIVE To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer ( T1 - 4 , N1 - 2 , M0 ) .
OPTIONS Neoadjuvant or adjuvant treatments compared with " curative " surgery alone .
OUTCOMES Overall survival , disease-free survival , and adverse effects .
The radiation fields used can possibly damage the left kidney , result ing in hypertension and other renal problems .