***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 
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    ***EXAMPLES*** 
    Input: PURPOSE Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer ; however , it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer . METHODS AND MATERIAL S We analyzed EGFR , KRAS , BRAF , and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor ( EGFR ) and Phosphatase and tensin homolog ( PTEN ) expression status with immunohistochemistry in tumor sample s of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (  preoperative chemoradiation with irinotecan and capecitabine ; n=44 ) or the ERBIRIX trial ( preoperative chemoradiation with irinotecan and capecitabine plus cetuximab ; n=38 ) . Both trials were similarly design ed except for the administration of cetuximab ; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m2 weekly and 1650 mg/m2/day , respectively , for 5 days per week . In the ERBIRIX trial , cetuximab was additionally given with a loading dose of 400 mg/m2 on 1 week before radiation , and 250 mg/m2 weekly thereafter . RESULTS Baseline characteristics before chemoradiation were similar between the 2 trial cohorts . A KRAS mutation in codon 12 , 13 , and 61 was noted in 15 ( 34 % ) patients in the IRIX cohort and 5 ( 13 % ) in the ERBIRIX cohort ( P=.028 ) . Among 62 KRAS wild-type cancer patients , major pathologic response rate , disease-free survival and pathologic stage did not differ significantly between the 2 cohorts . No mutations were detected in BRAF exon 11 and 15 , PIK3CA exon 9 and 20 , or EGFR exon 18 - 24 in any of the 82 patients , and PTEN and EGFR expression were not predictive of clinical outcome . CONCLUSIONS In patients with KRAS wild-type locally advanced rectal cancer , the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab Purpose Preoperative chemoradiation ( CRT ) for locally advanced rectal adenocarcinoma achieves pathologic complete response ( pCR ) in 8–20 % of patients . Mutations in critical cancer genes may contribute to lack of pCR . We retrospectively evaluated our institutional experience to determine potential mutational and clinical predictors of pCR in patients treated with CRT .  Methods Patients with locally advanced rectal adenocarcinoma treated with preoperative CRT ( n = 79 ) were identified . A clinical cancer genotyping assay evaluated 140 hotspot mutation sites across 15 cancer genes in 47 patients with sufficient tissue . Mutational profiles were compared in pre- and post-CRT specimens and with pCR rate . Clinical variables were evaluated using logistic regression . Results Genotyping identified mutations in KRAS ( 43 % ) , APC ( 17 % ) , BRAF ( 4 % ) , NRAS ( 4 % ) , PIK3CA ( 4 % ) , and TP53 ( 11 % ) . In the entire cohort , 21.5 % had a pCR . No patients with BRAF , NRAS , APC , or TP53 achieved a pCR . pCR rate was 23.5 % ( 4/17 ) in wild-type tumors versus 3.3 % ( 1/30 ) in those with a mutation . There was no difference in the mutation rates in pre- versus post-CRT specimens . On univariate analysis , clinical predictors of pCR included post-RT carcinoembriogenic antigen level of ≤2.5 and smaller tumor size . No patients with a pCR developed recurrence . Conclusion Patients without mutations in commonly mutated cancer genes may be associated with a higher likelihood of having a pCR after preoperative CRT . This should be confirmed in a prospect i ve study Purpose For years , 5-fluorouracil ( 5-FU ) has been the backbone of radiochemotherapy ( RCT ) of locally advanced rectal cancer . Its main target , thymidylate synthase ( TS ) , is speculated to be an important biomarker for response prediction and long-term prognosis . In this study , we analyzed TS expression in the rectal cancer tissue of 208 patients to evaluate its predictive/prognostic potential . Methods All patients included were diagnosed with locally advanced adenocarcinoma of the rectum ( UICC II and III ) and were treated within r and omized clinical trials of the German Rectal Cancer Study Group . Preoperative RCT ( 50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin ) was administered in 167 patients followed by surgical resection with total mesorectal excision ( TME ) . Another 41 patients received postoperative RCT .  TS levels and further clinicopathological parameters were assessed in univariate and multivariate analyses . Additionally , a TS gene polymorphism was analyzed with respect to the intratumoral protein levels . Results Low TS expression in pretreatment biopsies correlated with impaired patient survival ( p = 0.015 ) . Analysis of a 28-bp repeat revealed a correlation between the * 3/*3 genotype and high TS expression in pretherapeutic biopsies . In this study , a correlation of TS expression and grade of RCT -induced tumor regression was not found . Histopathological examination confirmed a complete tumor remission in 16 patients (9.6%).Analyses of the resection specimen indicated an unfavorable prognosis for patients with low intratumoral TS expression in case of detected lymph node metastases ( p = 0.04 ) . Conclusions TS can serve as a prognostic biomarker indicating an unfavorable prognosis for patients with low TS expression Purpose Patients with locally advanced T3 rectal tumors who present with complete pathologic response to preoperative chemoradiation have a low rate of local recurrence and an excellent prognosis . Predictive markers for complete pathologic response are needed with the perspective of improving individualized treatment of these patients . This study was design ed to investigate the predictive value of a new combination of three gene polymorphisms : thymidylate synthase , epidermal growth factor receptor Sp1 - 216 , and epidermal growth factor A61 G . Methods Pretreatment blood sample s from 60 patients with locally advanced T3 rectal tumors were analyzed for thymidylate synthase , epidermal growth factor receptor Sp1 - 216 , and epidermal growth factor A61 G gene polymorphisms by polymerase chain reaction . Treatment consisted of preoperative radiotherapy ( total dose 65 Gy ) and concomitant chemotherapy ( Uftoral ) followed by total mesorectal excision eight weeks after treatment . Pathologic response was evaluated according to the tumor regression grade system . Results Thirty percent ( 18/60 ) of patients presented with complete pathologic response . Patients with thymidylate synthase genotype 2/2 had a significantly higher rate of complete pathologic response with 53 percent ( 8/15 ) compared with 22 percent in the 2/3 or 3/3 group . When combining thymidylate synthase and epidermal growth factor A61 G genotype analysis , a small subgroup with a complete pathologic response rate of 100 percent was identified . Only a minor proportion of the complete responders were identified by this combination . Adding the epidermal growth factor receptor Sp1 - 216 genotype analysis , a complete pathologic response rate of 64 percent in the combination group was found compared with 21 percent and an 87 percent risk of being a noncomplete responder in the noncombination group . Conclusions A promising new combination of predictive markers for complete pathologic response was presented and warrants further investigation in prospect i ve clinical trials AIMS The identification of predictive markers of response to chemoradiotherapy treatment remains a promising approach for patient management in order to obtain the best response with minor side effects . Initially , we investigated whether the analysis of several markers previously studied and others not yet evaluated could predict response to 5-fluorouracil- and capecitabine-based neoadjuvant treatment in locally advanced rectal cancer . METHODS & MATERIAL S We studied germline and tumoral sample s of 65 stage II/III rectal patients . A panel of pharmacogenetic markers was genotyped in paired peripheral blood sample s and rectal cancer tumors . RESULTS Our results seem to confirm the previously described association of thymidylate synthase and the prediction of chemoradiotherapy response in rectal cancer . However , it failed to confirm the clinical utility proposed for XRCC1 , ERCC1 , ERCC2 , MTHFR and EGFR polymorphisms in blood/germline sample s. Subsequently , with the aim of improving prediction of individual response and assessing the role of studied polymorphisms in response to treatment , we determined if changes in tumor response to these markers could predict clinical outcome . We found a high degree of changes between germline and tumor sample s , mainly somatic mutations without microsatellite instability , and a minor frequency of loss-of-heterozygosity events . In tumoral sample s , XRCC1 appeared to be significantly associated ( p = 0.006 ) with downstaging of the tumor ( odds ratio : 7.93 ; 95 % CI : 1.03 - 60.83 ) , but the increasing of TYMS low-expression alleles contradict the previous results observed in germline sample s. CONCLUSION The detection of somatic mutations in rectal cancer tumors led us to re-evaluate the utility of the tests performed in blood sample s for these polymorphisms in rectal cancer . Furthermore , studies aim ed at assessing the influence of pharmacogenetic markers in treatment response performed in blood sample s should take into account the particular pattern of hypermutability present in each tumor type . We hypothesize that different patterns of hypermutability present in each tumor type would be related to the different results in association studies related to response to the treatment The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma ( cT3 - 4 cN0 - 1 cM0 ) after multimodal treatment ( radiochemotherapy±surgical resection )  , and the presence of genetic polymorphisms in genes involved in folate metabolism . In total , 68 patients who took part in a prospect i ve multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy , optionally followed by surgery . DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes ( MTHFR C677 T , MTR A2756 G , TS t and em repeat polymorphism ) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy . The genotypes were correlated with tumour response to polychemotherapy , radiochemotherapy and with overall survival . Tumours with the MTR wild-type genotype ( 2756AA ) showed a median survival time of 16 months , whereas tumours with an MTR variant genotype ( 2756AG/2756GG ) showed a median survival time of 42 months ( P=0.0463 ) . No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene . Among tumours treated with radiochemotherapy and subsequent resection , MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype ( P=0.0442 ) . In contrast , no significant relationship between clinical ly determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed . In conclusion , pretherapeutic determination of the MTR A2756 G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas . Determination of MTHFR C677 T and TS t and em repeat polymorphism has no predictive value PURPOSE Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog ( PTEN ) ( deleted on chromosome 10 ) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer . The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer ( LARC ) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown . METHODS AND MATERIAL S We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy ( 45 Gy plus 5.4 Gy ) in patients with LARC ( stage uT3/4 or uN+ ) . The status of KRAS and BRAF mutations was determined with direct sequencing , and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies . Tumor regression was evaluated by using st and ardized regression grading , and disease-free survival ( DFS ) was calculated according to the Kaplan-Meier method . RESULTS A total of 57 patients were available for analyses . A total of 31.6 % of patients carried mutations in 
    Output:
    
Among 24 and 14 genetic markers reported for rectal and esophageal cancers , respectively , significant associations in meta-analyses were demonstrated for the following markers .
In esophageal cancer , successful therapy appeared to correlate with wild-type TP53 .