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.
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
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 .