***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 & AIMS Adjuvant 5-fluorouracil (5-FU)-based chemotherapy is st and ard treatment for stage C colorectal cancer ( CRC ) . Approximately 12 % of CRCs are characterized by microsatellite instability ( MSI ) , a hallmark of a DNA mismatch repair defect . We investigated the safety of adjuvant 5-FU-based chemotherapy for MSI(+ ) CRC and compared the prognosis of MSI(+ ) and MSI(- ) CRC patients receiving adjuvant therapy . METHODS Previously , a prospect i ve series consisting of 1044 consecutive CRCs has been collected and the MSI status of each sample determined . Patients with stage C cancer who had received adjuvant chemotherapy ( n = 95 ) were followed up for 7 - 63 months ( median , 31 months ) after surgery . RESULTS No unexpected or serious adverse effects were observed when 5-FU-based chemotherapy was used as adjuvant treatment for MSI(+ ) CRC . Three- year recurrence-free survival was 90 % and 43 % in the MSI(+ ) ( n = 11 ) and MSI(- ) ( n = 84 ) groups , respectively ( P = 0.020 ) . CONCLUSIONS Adjuvant 5-FU-based chemotherapy is feasible for both MSI(+ ) and MSI(- ) CRCs , and patients with MSI(+ ) CRC who receive adjuvant therapy have an excellent prognosis PURPOSE It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity , cost , and inconvenience . We investigated the usefulness of defective mismatch repair ( dMMR ) , BRAF , and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy . PATIENTS AND METHODS Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients r and omly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy  in the Quick and Simple and Reliable ( QUASAR ) trial . RESULTS Twenty-six percent of 695 right-sided colon , 3 % of 685 left-sided colon , and 1 % of 407 rectal tumors were dMMR . Similarly , 17 % of right colon , 2 % of left colon , and 2 % of rectal tumors were BRAF mutant . KRAS mutant tumors were more evenly distributed : 40 % right colon , 28 % left colon , and 36 % rectal tumors . Recurrence rate for dMMR tumors was half that for MMR-proficient tumors ( 11 % [ 25 of 218 ] v 26 % [ 438 of 1,695 ] recurred ; risk ratio [ RR ] , 0.53 ; 95 % CI , 0.40 to 0.70 ; P < .001 ) . Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors ( 28 % [ 150 of 542 ] v 21 % [ 219 of 1,041 ] ; RR , 1.40 ; 95 % CI , 1.12 to 1.74 ; P = .002 ) but did not differ significantly between BRAF mutant and wild-type tumors ( P = .36 ) . No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR , KRAS , or BRAF status . The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy . CONCLUSION MMR assays identify patients with a low risk of recurrence . KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy PURPOSE Colorectal cancer ( CRC ) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss . These characteristics may classify CRC into subsets of distinct clinical behaviors . PATIENTS AND METHODS We studied two of these genomic defects-mismatch repair deficiency ( MMR-D ) and loss of heterozygosity  at chromosomal location 18q (18qLOH)-in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer . These trials included prospect i ve secondary analyses to determine the relationship between these markers and treatment outcome . A total of 1,852 patients were tested for MMR status and 955 ( excluding patients with MMR-D tumors ) for 18qLOH .  RESULTS Compared with stage III , more stage II tumors were MMR-D ( 21.3 % v 14.4 % ; P < .001 ) and were intact at 18q ( 24.2 % v 15.1 % ; P = .001 ) . For the combined cohort , patients with MMR-D tumors had better 5-year disease-free survival ( DFS ; 0.76 v 0.67 ; P < .001 ) and overall survival ( OS ; 0.81 v 0.78 ; P = .029 ) than those with MMR intact ( MMR-I ) tumors . Among patients with MMR-I tumors , the status of 18q did not affect outcome , with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 ( P = .18 ) for DFS and 0.81 versus 0.77 ( P = .18 ) for OS . CONCLUSION We conclude that MMR-D tumor status , but not the presence of 18qLOH , has prognostic value for stages II and III colon cancer PURPOSE The role of high-degree microsatellite instability ( MSI-H ) as a marker to predict benefit from adjuvant chemotherapy remains unclear . PATIENTS AND METHODS To help define its impact , we conducted an analysis of National Surgical Adjuvant Breast and Bowel Project ( NSABP ) patients who were r and omly assigned to a surgery-alone group ( untreated cohort ) and patients assigned to an adjuvant fluorouracil ( FU ) -treated group ( treated cohort ) .  MSI-H and other potential markers were assessed ( TGF-BRII , p53 , thymidylate synthase , and Ki67 ) . RESULTS In all , 98 ( 18.1 % ) of 542 patients exhibited MSI-H , and there was a strong inverse relationship between MSI-H and mutant p53 status ( P < .001 ) . The prognostic analyses showed increased recurrence-free survival ( RFS ) for MSI-H patients versus MSS/MSI-L patients ( P = .10 ) , but showed no difference in overall survival ( OS ; P = .67 ) . There was a potential interaction between MSI-H and mutant p53 in terms of improved RFS ( P = .03 ) . In the predictive marker analysis , we observed no interaction between MSI status and treatment for either RFS ( P = .68 ) or OS ( P = .62 ) . Hazard ratios ( HR ) for RFS for MSI-H versus MSS/MSI-L patients were 0.77 ( 95 % CI , 0.40 to 1.48 ) in the untreated- patients group and 0.60 ( 95 % CI , 0.30 to 1.19 ) in the treated- patients group . HRs for OS were 0.82 ( 95 % CI , 0.44 to 1.51 ) and 1.02 ( 95 % CI , 0.56 to 1.85 ) for the respective groups . There was a trend toward improved RFS in patients with MSI-H and mutant p53 . CONCLUSION These results do not support the use of MSI-H as a predictive marker of chemotherapy benefit PURPOSE Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability ( MSI-H ) or defective DNA mismatch repair ( dMMR ) have improved survival and receive no benefit from fluorouracil ( FU ) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair ( pMMR ) tumors . We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer . METHODS MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously r and omly assigned to FU-based therapy ( either FU + levamisole or FU + leucovorin ; n = 229 ) versus no postsurgical treatment ( n = 228 ) . Data were subsequently pooled with data from a previous analysis . The primary end point was disease-free survival ( DFS ) . RESULTS Overall , 70 ( 15 % ) of 457 patients exhibited dMMR . Adjuvant therapy significantly improved DFS ( hazard ratio [ HR ] , 0.67 ; 95 % CI , 0.48 to 0.93 ; P = .02 ) in patients with pMMR tumors . Patients with dMMR tumors receiving FU had no improvement in DFS ( HR , 1.10 ; 95 % CI , 0.42 to 2.91 ; P = .85 ) compared with those r and omly assigned to surgery alone . In the pooled data set of 1,027 patients ( n = 165 with dMMR ) , these findings were maintained ; in patients with stage II disease and with dMMR tumors , treatment was associated with reduced overall survival ( HR , 2.95 ; 95 % CI , 1.02 to 8.54 ; P = .04 ) . CONCLUSION Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy . These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making BACKGROUND Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors . We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer . METHODS Tumor specimens were collected from patients with colon cancer who were enrolled in r and omized trials of fluorouracil-based adjuvant chemotherapy .  Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers . RESULTS Of 570 tissue specimens , 95 ( 16.7 percent ) exhibited high-frequency microsatellite instability . Among 287 patients who did not receive adjuvant therapy  , those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability ( hazard ratio for death , 0.31 [ 95 percent confidence interval , 0.14 to 0.72 ] ; P=0.004 ) . Among patients who received adjuvant chemotherapy  , high-frequency microsatellite instability was not correlated with increased overall survival ( hazard ratio for death , 1.07 [ 95 percent confidence interval , 0.62 to 1.86 ] ; P=0.80 ) . The benefit of treatment differed significantly according to the microsatellite-instability status ( P=0.01 ) . Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability , according to a multivariate analysis adjusted for stage and grade ( hazard ratio for death , 0.72 [ 95 percent confidence interval , 0.53 to 0.99 ] ; P=0.04 ) . By contrast , there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability . CONCLUSIONS Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability 
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In both treated and untreated patients , high‐level MSI improved disease‐free survival compared with low‐level MSI , suggesting a prognostic role but not supporting the hypothesis of a predictive effect of MSI .