***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: PURPOSE Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer . We took advantage of PETACC-3 , an adjuvant trial with 3,278 patients with stage II to III colon cancer , to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting . PATIENTS AND METHODS  Formalin-fixed paraffin-embedded tissue blocks ( n = 1,564 ) were prospect ively collected and DNA was extracted from tissue sections from 1,404 cases . Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction .  Survival analyses were based on univariate and multivariate proportional hazard regression models . RESULTS KRAS and BRAF tumor mutation rates were 37.0 % and 7.9 % , respectively , and were not significantly different according to tumor stage . In a multivariate analysis containing stage , tumor site , nodal status , sex , age , grade , and microsatellite instability ( MSI ) status , KRAS mutation was associated with grade ( P = .0016 ) , while BRAF mutation was significantly associated with female sex ( P = .017 ) , and highly significantly associated with right-sided tumors , older age , high grade , and MSI-high tumors ( all P < 10(-4 ) ) . In univariate and multivariate analysis , KRAS mutations did not have a major prognostic value regarding relapse-free survival ( RFS ) or overall survival ( OS ) . BRAF mutation was not prognostic for RFS , but was for OS , particularly in patients with MSI-low ( MSI-L ) and stable ( MSI-S ) tumors ( hazard ratio , 2.2 ; 95 % CI , 1.4 to 3.4 ; P = .0003 ) . CONCLUSION In stage II-III colon cancer , the KRAS mutation status does not have major prognostic value . BRAF is prognostic for OS in MS-L/S tumors BACKGROUND Despite their low risk for recurrence , many women with endometrial adenocarcinoma receive postoperative radiation therapy ( RT ) . This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics ( FIGO ) stages IB , IC , and II ( occult disease ) . METHODS Four hundred forty-eight consenting patients with " intermediate risk " endometrial adenocarcinoma were r and omized after surgery to either no additional therapy ( NAT ) or whole pelvic radiation therapy ( RT ) .  They were followed to determine toxicity , date and location of recurrence , and overall survival . A high intermediate risk ( HIR ) subgroup of patients was defined as those with ( 1 ) moderate to poorly differentiated tumor , presence of lymphovascular invasion , and outer third myometrial invasion ; ( 2 ) age 50 or greater with any two risk factors listed above ; or ( 3 ) age of at least 70 with any risk factor listed above . All other eligible participants were considered to be in a low intermediate risk ( LIR ) subgroup . RESULTS Three hundred ninety-two women met all eligibility requirements ( 202 NAT , 190 RT ) . Median follow-up was 69 months . In the entire study population , there were 44 recurrences and 66 deaths ( 32 disease or treatment-related deaths ) , and the estimated 2-year cumulative incidence of recurrence ( CIR ) was 12 % in the NAT arm and 3 % in the RT arm ( relative hazard ( RH ) : 0.42 ; P=0.007 ) . The treatment difference was particularly evident among the HIR subgroup ( 2-year CIR in NAT versus RT : 26 % versus 6 % ; RH=0.42 ) . Overall , radiation had a substantial impact on pelvic and vaginal recurrences ( 18 in NAT and 3 in RT ) . The estimated 4-year survival was 86 % in the NAT arm and 92 % for the RT arm , not significantly different ( RH : 0.86 ; P=0.557 ) . CONCLUSIONS Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence , but should be limited to patients whose risk factors fit a high intermediate risk definition 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 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 THERE IS GROWING AWARENESS THAT THE RESULTS OF r and omized clinical trials might not apply in a straightforward way to individual patients , even those within the trial . Although r and omization theoretically ensures the comparability of treatment groups overall , there remain important differences between individuals in each treatment group that can dramatically affect the likelihood of benefiting from or being harmed by a therapy . Averaging effects across such different patients can give misleading results to physicians who care for individual , not average , patients . The limitations of subgroup analyses — the conventional means for exploring differences in treatment effect based on patient characteristics — are well-appreciated . Because patients in trials , as in clinical practice , have many attributes that can affect the likelihood of treatment being beneficial or harmful , exploring each of these attributes “ one variable at a time ” ( eg , male vs female , old vs young ) risks spurious false-positive subgroup results from chance fluctuations . Furthermore , although patients have simultaneous multiple characteristics that can affect the likelihood of the outcome and the effect of therapy , one-variable-at-a-time comparisons are fundamentally limited because they compare groups that vary only on a single factor , usually result ing in the subgroups being more similar than different 
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Yes , the data confirm that the risks of adjuvant pelvic radiation therapy  outweigh the benefits for patients with these very favorable tumors .