***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer .  Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties . Therefore , these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases . PATIENTS AND METHODS Forty patients with rectal cancer ( T3-T4 and /or N+ ) received radiotherapy ( 1.8 Gy , 5 days a week over 5 weeks , total dose 45 Gy , 3D conformational technique ) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation . Surgery was performed 6 - 8 weeks after completion of radiotherapy . The main end points were safety and efficacy as assessed by the pathological complete response ( pCR ) . RESULTS The most frequent grade 3/4 adverse event was diarrhea , occurring in 30 % of patients . pCR was found in five ( 14 % ) patients . According to Dworak 's classification , good regression was found in six ( 18 % ) additional patients . CONCLUSIONS Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer Background There is common belief among some medical research ers that if a potential surrogate endpoint is highly correlated with a true endpoint , then a positive ( or negative ) difference in potential surrogate endpoints between r and omization groups would imply a positive ( or negative ) difference in unobserved true endpoints between r and omization groups . We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each r and omization group . Methods We use a graphical approach . The vertical axis is the unobserved true endpoint and the horizontal axis is the  potential surrogate endpoint  . Perfect correlation within each r and omization group implies that , for each r and omization group , potential surrogate and true endpoints are related by a straight line . In this scenario the investigator does not know the slopes or intercepts . We consider a plausible example where the slope of the line is higher for the experimental group than for the control group . Results In our example with unknown lines , a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups . Thus the potential surrogate endpoints give the wrong inference . Similar results hold for binary potential surrogate and true outcomes ( although the notion of correlation does not apply ) . The potential surrogate endpointwould give the correct inference if either ( i ) the unknown lines for the two group coincided , which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group , which is called the Prentice Criterion or ( ii ) if one could accurately predict the lines based on data from prior studies . Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within r and omized groups does not guarantee correct inference based on a potential surrogate endpoint . Even in early phase trials , investigators should not base conclusions on potential surrogate endpoints in which the only validation is high correlation with the true endpoint within a group PURPOSE To evaluate the activity and safety of preoperative radiotherapy ( RT ) and concurrent capecitabine and oxaliplatin ( XELOX-RT ) plus four cycles of adjuvant XELOX in patients with rectal cancer . PATIENTS AND METHODS One hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT ( 50.4 Gy in 28 fractions ) . Capecitabine was administered concurrently at 1,650 mg/m2 on days 1 to 14 and 22 to 35 , and oxaliplatin was administered at 50 mg/m2 on days 1 , 8 , 22 , and 29 . Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT . Four cycles of adjuvant XELOX ( capecitabine 1,000 mg/m2 bid on days 1 to 14 ; oxaliplatin 130 mg/m2 on day 1 ) were administered . The main end points were activity as assessed by the pathologic complete response ( pCR ) rate and the feasibility of postoperative XELOX chemotherapy .  RESULTS After XELOX-RT , 103 of 104 eligible patients underwent surgery ; pCR was achieved in 17 patients ( 16 % ) , one patient had ypT0N1 disease , and 53 patients showed tumor regression of more than 50 % of the tumor mass . R0 resections were achieved in 95 % of patients , and sphincter preservation was accomplished in 77 % . Full-dose preoperative XELOX-RT was administered in 96 % . Grade 3 or 4 diarrhea occurred in 12 % of patients . Postoperative complication occurred in 43 % of patients . Sixty percent of patients received all four cycles of adjuvant XELOX , with sensory neuropathy ( 18 % ) and diarrhea ( 12 % ) being the main grade 3 or 4 toxicities . CONCLUSION Preoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment . This regimen is proposed for phase III evaluation comparing st and ard fluorouracil-based treatment with XELOX- based multimodality treatment PURPOSE The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy ( CT-RT ) regimens in T3 - 4 Nx M0 resectable rectal cancer . Clinical results are reported after follow-up of 3 years . PATIENTS AND METHODS Between November 2005 and July 2008 , a total of 598 patients were r and omly assigned to preoperative CT-RT with CAP45 ( 45-Gy RT for 5 weeks with concurrent capecitabine ) or CAPOX50 ( 50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin ) . Total mesorectal excision was planned 6 weeks after CT-RT . The primary end point was sterilization of the operative specimen , which was achieved in 13.9 % versus 19.2 % of patients , respectively ( P = .09 ) . Clinical results were analyzed for all r and omly assigned patients according to the intention-to-treat principle . RESULTS At 3 years , there was no significant difference between CAP45 and CAPOX50 ( cumulative incidence of local recurrence , 6.1 % v 4.4 % ; overall survival , 87.6 % v 88.3 % ; disease-free survival , 67.9 % v 72.7 % ) . Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group . Bowel continence , erectile dysfunction , and social life disturbance were not different between groups . In multivariate analysis , the sterilization rate ( Dworak score ) of the operative specimen was the main significant prognostic factor ( hazard ratio , 0.32 ; 95 % CI , 0.21 to 0.50 ) . CONCLUSION At 3 years , no significant difference in clinical outcome was achieved with the intensified CAPOX regimen . When compared with other recent r and omized trials , these results indicate that concurrent administration of oxaliplatin and RT is not recommended PURPOSE To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer . PATIENTS AND METHODS Seven hundred forty-seven patients with resectable , locally advanced ( cT3 - 4 and /or cN1 - 2 ) adenocarcinoma of the mid-low rectum were r and omly assigned to receive pelvic radiation ( 50.4 Gy in 28 daily fractions ) and concomitant infused fluorouracil ( 225 mg/m(2)/d ) either alone ( arm A , n = 379 ) or combined with oxaliplatin ( 60 mg/m(2 ) weekly × 6 ; arm B , n = 368 ) . Overall survival is the primary end point . A protocol -planned analysis of response to preoperative treatment is reported here . RESULTS Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone ( 24 % v 8 % of treated patients ; P < .001 ) . In arm B , 83 % of the patients treated with oxaliplatin had five or more weekly administrations . Ninety-one percent , compared with 97 % in the control arm , received ≥ 45 Gy ( P < .001 ) . Ninety-six percent versus 95 % of patients underwent surgery with similar rates of abdominoperineal resections ( 20 % v 18 % , arm A v arm B ) . The rate of pathologic complete responses was 16 % in both arms ( odds ratio = 0.98 ; 95 % CI , 0.66 to 1.44 ; P = .904 ) . Twenty-six percent versus 29 % of patients had pathologically positive lymph nodes ( arm A v arm B ; P = .447 ) , 46 % versus 44 % had tumor infiltration beyond the muscularis propria ( P = .701 ) , and 7 % versus 4 % had positive circumferential resection margins ( P = .239 ) . Intra-abdominal metastases were found at surgery in 2.9 % versus 0.5 % of patients ( arm A v arm B ; P = .014 ) . CONCLUSION Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy  significantly increases toxicity without affecting primary tumor response . Longer follow-up is needed to assess the impact on efficacy end points PURPOSE Neoadjuvant chemoradiotherapy is considered a st and ard approach for T3 - 4 M0 rectal cancer . In this situation , we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin . PATIENTS AND METHODS We r and omly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2 ) twice daily 5 days per week ( Cap 45 ) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2 ) twice daily 5 days per week and oxaliplatin 50 mg/m(2 ) once weekly ( Capox 50 ) . The primary end point was complete sterilization of the operative specimen ( ypCR ) . RESULTS Five hundred ninety-eight patients were r and omly assigned to receive Cap 45 ( n = 299 ) or Capox 50 ( n = 299 ) . More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group ( 25 v 1 % ; P < .001 ) . Surgery was performed in 98 % of patients in both groups . There were no differences between groups in the rate of conservative surgery ( 75 % ) or postoperative deaths at 60 days ( 0.3 % ) . The ypCR rate was 13.9 % with Cap 45 and 19.2 % with Capox 50 ( P = .09 ) . When ypCR was combined with yp few residual cells , the rate was respectively 28.9 % with Cap 45 and 39.4 % with Capox 50 ( P = .008 ) . The rate of positive circumferential rectal margins ( between 0 and 2 mm ) was 19.3 % with Cap 45 and 9.9 % with Capox 50 ( P = .02 ) . CONCLUSION The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation . Cap 50 merits investigation for T3 - 4 rectal cancers AIM To evaluate the activity , safety and long-term survival of patients after preoperative oxaliplatin and 5-fluorouracil chemoradiation therapy in locally advanced rectal cancer ( LARC ) . PATIENTS AND METHODS Patients with resectable , T3 - 4 and /or nodal involvement rectal adenocarcinoma were treated with oxaliplatin 60 mg/m(2 ) weekly and 5-fluorouracil 200 mg/m(2)/d infused continuously for five days , over a period of five weeks , and radiotherapy ( 45 Gy/25 fractions ) . The primary end-point was pathological complete response ( ypCR ) . Safety , overall survival ( OS ) and relapse-free survival ( RFS ) were secondary end-points . RESULTS Sixty-six patients were treated .  Grade 1 - 2 diarrhea was the most common adverse event . The ypCR rate was 16.7 % ( 95 % confidence interval=7.7 - 25.7 % ) . After a median follow-up of 73.5 months , 23 patients ( 34.8 % ) had experienced relapse . Five-year actuarial RFS and OS rates were 64 % and 73 % , respectively . Five-year actuarial RFS was 91.7 % in the ypCR group versus 57.8 % in non-ypCR cases . CONCLUSION Long-term local control and survival after this very well-tolerated regimen appear encouraging BACK 
    Output:
    
Grade 3 - 4 acute toxicity and grade 3 - 4 diarrhea was considerably higher for OX/FU compared with FU alone .
In conclusion , the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible .
LARC patients are likely to benefit from CRT regimens with OX