***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 / AIM To investigate the feasibility and safety of preoperative capecitabine , cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer ( LARC , cT3/T4 ) . PATIENTS AND METHODS 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision . Histopathological response and association with KRAS status was evaluated . RESULTS R0-resection was possible in 27 of 31 ( 86 % ) patients . No complete pathological remission was observed . Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity . KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage . CONCLUSION Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission . Treatment tolerability was excellent and toxicity remained low . KRAS status did not influence treatment outcomes . Capecitabine in combination with radiotherapy remains a st and ard therapy for locally advanced rectal cancer Background We investigated tumor regression grading ( TRG ) as a prognostic marker and individual-level surrogate for disease-free survival ( DFS ) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 r and omized trial . Methods TRG was recorded prospect ively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy ( CRT ) with or without oxaliplatin .  Multivariable analysis was performed using Cox regression models adjusted for treatment arm , resection status , and pathologic stage . Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria ( PC1 - 4 ) . All statistical tests were two-sided . Results With a median follow-up of 50 months , the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS ( 75.9 % , 95 % CI = 72.3 to 79.5 , vs 71.3 % , 95 % CI = 67.6 to 74.9 , P = .04 , PC 1 ) and a shift toward more advanced TRG groups ( P < .001 , PC 2 ) compared with CRT with fluorouracil alone . The three-year DFS was 64.6 % ( 95 % CI = 57.3 to 71.9 ) , 77.6 % ( 95 % CI = 74.5 to 80.7 ) , and 92.3 % ( 95 % CI = 88.4 to 96.2 ) for TRG 0 + 1 ( poor regression ) , TRG 2 + 3 ( intermediate regression ) , and TRG 4 ( complete regression ) , respectively ( P < .001 , PC 3 ) . TRG constituted an independent prognostic factor for DFS ( TRG 2 + 3 vs TRG 0 + 1 , HR = 0.68 , 95 % CI = 0.51 to 0.90 , P = .007 ) . Due to multicollinearity , TRG 4 and pathologic stage could not be tested within the same model . The treatment effect on DFS was captured by TRG , satisfying individual-level PC4 . Conclusions Higher TRG after preoperative CRT predicted a favorable long-term outcome . At the individual patient level , TRG was a surrogate marker for DFS . Further phase III trials are needed to vali date TRG as a surrogate at trial level BACKGROUND PARP inhibitors are currently evaluated in combination with radiotherapy and /or chemotherapy . As sensitizers , PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic ( PD ) assays . Current clinical PD-assays partly fail to provide such sensitivities . The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development . MATERIAL AND METHODS P BMC s of healthy individuals and of olaparib and radiotherapy treated lung cancer patients were collected for ELISA-based PD-assays . RESULTS PAR-signal amplification by ex vivo irradiation enabled an extended quantification range for PARP inhibitory activities after ex vivo treatment with inhibitors . This " radiation-enhanced-PAR " ( REP ) assay provided accurate IC50 values thereby also revealing differences among healthy individuals . Implemented in clinical radiotherapy combination Phase I trials , the REP-assay showed sensitive detection of PARP inhibition in patients treated with olaparib and establishes strong PARP inhibitory activities at low daily doses . CONCLUSIONS Combination trials of radiotherapy and novel targeted agent(s ) often require different and more sensitive PD assessment s than in the monotherapy setting . This study shows the benefit and relevance of sensitive and adapted PD-assays for such combination purpose s and provides proof of clinical ly relevant cellular PARP inhibitory activities at low daily olaparib doses PURPOSE To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers . METHODS AND MATERIAL S One hundred six patients with T3/T4 distal rectal cancers were r and omized in a phase 2 study . Patients received either continuous venous infusion ( CVI ) of 5-Fluorouracil ( 5-FU ) , 225 mg/m(2 ) per day , 7 days per week plus pelvic hyperfractionated radiation ( HRT ) , 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers ( Arm 1 ) , or CVI of 5-FU , 225 mg/m(2 ) per day , Monday to Friday , plus irinotecan , 50 mg/m(2 ) once weekly × 4 , plus pelvic radiation therapy ( RT ) , 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers ( Arm 2 ) . Surgery was performed 4 to 10 weeks later . RESULTS All eligible patients ( n=103 ) are included in this analysis ; 2 ineligible patients were excluded , and 1 patient withdrew consent . Ninety-eight of 103 patients ( 95 % ) underwent resection . Four patients did not undergo surgery for either disease progression or patient refusal , and 1 patient died during induction chemotherapy . The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2 . The pathological complete response ( pCR ) rates were 30 % in Arm 1 and 26 % in Arm 2 . Locoregional recurrence rates were 16 % in Arm 1 and 17 % in Arm 2 . Five-year survival rates were 61 % and 75 % and Disease-specific survival rates were 78 % and 85 % for Arm1 and Arm 2 , respectively . Five second primaries occurred in patients on Arm 1 , and 1 second primary occurred in Arm 2 . CONCLUSIONS High rates of disease-specific survival were seen in each arm . Overall survival appears affected by the development of unrelated second cancers . The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival The Stockholm III Trial r and omized patients with primary operable rectal cancers to either short‐course radiotherapy ( RT ) with immediate surgery ( SRT ) , short‐course RT with surgery delayed 4–8 weeks ( SRT‐delay ) or long‐course RT with surgery delayed 4–8 weeks . This preplanned interim analysis examined the pathological outcome of delaying surgery BACKGROUND Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy  , to potentially avoid morbidity and side-effects of rectal excision . The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer . METHODS We did a prospect i ve , r and omised , open-label , multicentre , phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer . Patients aged 18 years and older with stage T2T3 lower rectal carcinoma , of maximum size 4 cm , who had a good clinical response to neoadjuvant chemoradiotherapy ( residual tumour ≤2 cm ) were central ly r and omly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery . R and omisation , which was done via the internet , was not stratified and used permuted blocks of size eight . In the local excision group , a completion total mesorectal excision was required if tumour stage was ypT2 - 3 . The primary endpoint was a composite outcome of death , recurrence , morbidity , and side-effects at 2 years after surgery , to show superiority of local excision over total mesorectal excision in the modified intention-to-treat ( ITT ) population ( expected proportions of patients having at least one event were 25 % vs 60 % for superiority ) . This trial was registered with Clinical Trials.gov , number NCT00427375 . FINDINGS From March 1 , 2007 , to Sept 24 , 2012 , 186 patients received chemoradiotherapy and were enrolled in the study . 148 good clinical responders were r and omly assigned to treatment , three were excluded ( because they had metastatic disease , tumour > 8 cm from anal verge , and withdrew consent ) , and 145 were analysed : 74 in the local excision group and 71 in the total mesorectal excision group . In the local excision group , 26 patients had a completion total mesorectal excision . At 2 years in the modified ITT population , one or more events from the composite primary outcome occurred in 41 ( 56 % ) of 73 patients in the local excision group and 33 ( 48 % ) of 69 in the total mesorectal excision group ( odds ratio 1·33 , 95 % CI 0·62 - 2·86 ; p=0·43 ) . In the modified ITT analysis , there was no difference between the groups in all components of the composite outcome , and superiority was not shown for local excision over total mesorectal excision . INTERPRETATION We failed to show superiority of local excision over total mesorectal excision , because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects , and compromised the potential advantages of local excision . Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy . FUNDING National Cancer Institute of France , Sanofi , Roche Pharma Background There is increasing interest in nonoperative management ( NOM ) for rectal cancer with complete clinical response ( cCR ) after neoadjuvant chemoradiation ( nCRT ) . Objective The aim of this systematic review was to summarize the available data on NOM , with the intention of formulating st and ardized protocol s on which to base future investigations . Methods A systematic review following the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines was conducted . A highly sensitive literature search identified all relevant studies published between January 2004 and December 2016 . Data extraction and quality assessment was performed independently by two authors , and resolved by consensus with a third review er . Results In total , 15 studies , including 920 patients , met the inclusion criteria ; 575 ( 62.5 % ) of these patients underwent NOM after cCR , with the remaining patients forming a surgical control group . The weighted mean follow-up was 39.4 ( 12.7 ) months in the NOM group and 39.8 ( 5.1 ) months in the surgery group . The pooled regrowth rate in the NOM group was 21.3 % at a mean of 15.6 ( 7.0 ) months . Surgical salvage was possible and was undertaken in 93.2 % of these patients . Overall survival in the NOM group was 91.7 % , while disease-free survival was 82.7 % . For the comparison proctectomy group , pooled rates of local recurrence , overall survival , and disease-free survival were 8.4 , 92.4 , and 87.5 % , respectively . Conclusion NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT . Before such a strategy can be widely implemented , further prospect i ve data are required with st and ardized definitions , diagnostic criteria , and management protocol s , with an emphasis on shared patient – provider decision making and patient-centered outcomes BACKGROUND Further optimisation of present st and ard chemoradiation is needed in patients with locally advanced rectal cancer .  Veliparib , an oral poly(ADP-ribose ) polymerase inhibitor , has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in pre clinical models . We aim ed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy . METHODS This phase 1b , open-label , multicentre , dose-escalation study was done at six hospitals ( one in Australia and five in the USA ) . Patients were eligible if they were aged 18 years or more and were newly diagnosed 
    Output:
    
The oral derivative capecitabine has practical advantages over 5-fluorouracil , with equal efficacy , but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in r and omized clinical assessment .