***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: OBJECTIVE To study the complication rate , local recurrence rate , and survival after total pelvic exenteration for primary advanced and recurrent rectal cancer . DESIGN Prospect i ve study . SETTING Tertiary referral university hospital , Norway . SUBJECTS 25 patients who were operated on for primary advanced and 22 for recurrent rectal cancer since 1991 ; 42 men and 5 women , mean age 64 years ( range 44 - 78 ) . All had preoperative irradiation of 46 - 50 Gy .  MAIN OUTCOME MEASURES Incidence of major complications , and actuarial 5-year survival and local recurrence rate . RESULTS Twenty patients had  RO resection in the primary group versus seven in the recurrent group . No R2 resections were done in the primary group compared with four in the recurrent group . Half the primary cases ( n = 13 ) had abdominoperineal resections . Hartmann 's procedures were common in both groups ( n = 8 in each ) . Postoperative mortality at 30 days was 4 % ( n = 2 ) and in-hospital 13 % ( n = 6 ) . 18 patients had major complications and 12 were reoperated on . Overall 5-year actuarial survival for 43 patients without distant metastases was 28%-those with primary tumours 36 % , and those with recurrent tumours 18%-similar to the figures for RO and R1 resections . Actuarial local recurrence at 5 years for primary cancers was 18 % compared with 68 % for recurrent cancers , again nearly identical to the figures for R0/R1 operations ( p = 0.008 and p = 0.03 ) . CONCLUSION Some patients with advanced rectal cancer either primary or recurrent may benefit from simultaneous en-bloc cystectomy . The higher postoperative morbidity and mortality indicate the need for well-defined indications for this procedure and the necessity for thorough preoperative staging PURPOSE To evaluate the diagnostic performance of quantitative apparent diffusion coefficient ( ADC ) measurements , in the assessment of the therapeutic response to chemo-radiation therapy ( CRT ) in patients with locally advanced rectal cancer , by analyzing post CRT values of ADC , in relation to tumor regression grade ( TRG ) obtained by histopathologic evaluation of the rectal specimen . METHODS This prospect i ve study was approved by an Institutional Review Board , and informed consent was obtained from all patients . Thirty-one patients with locally advanced rectal cancer underwent pre and post CRT MR imaging at 1.5 T .  ADC values were measured in regions of interest ( ROIs ) drawn independently by two radiologists , blinded to the pathology results , on three slices of the pre and post CRT DW-MR image sets with the corresponding T2 weighted images ( T2WI ) available for anatomic reference . The two readers ' measurements were compared for differences in ADC values , inter-observer variability ( measured as the intraclass correlation coefficient ; ICC ) and the ADC distributions of responders vs non-responders . The diagnostic performance of ADC in the prediction of the response to CRT was evaluated by calculating the area under the ROC curve ( AUC ) and the optimal cut-off values . Sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) were assessed . RESULTS The two readers showed an overall strong agreement in measuring ADC values . For both readers , no differences in ADC pre-treatment measurements were observed between responders and non-responders . For reader 1 , the post-CRT ADC and the ΔADC presented the higher AUC ( 0.823 and 0.803 , respectively ) , while Δ%ADC provided the lower AUC value ( 0.682 ) . The optimal cutoff point was 1.294 s/mm(2 ) for post-CRT measures ( sensitivity=86.4 % , specificity=66.7 % , PPV=86.4 % , NPV=66.7 % ) , 0.500 for ΔADC ( sensitivity=81.8 % , specificity=66.7 % , PPV=85.7 % , NPV=60.0 % ) and 59.3 % for Δ%ADC ( sensitivity=63.4 % , specificity=66.7 , PPV=82.4 % , NPV=42.9 % ) . Similar results were observed for reader 2 , with better performance obtained with the ADC post-CRT ( AUC of 0.833 ) and an optimal cut off of 1.277 × 10(-3)s/mm(2 ) . CONCLUSION Post-CRT ADC measurements are reliable and reproducible and may be used as a non-invasive tool to evaluate response to therapy as post-CRT ADC values and ΔADC presented good diagnostic performance to select responder patients OBJECTIVE To identify the MRI parameters which best predict complete response ( CR ) to neoadjuvant chemoradiotherapy ( CRT ) in patients with locally advanced rectal cancer ( LARC ) and to assess their diagnostic performance . METHODS This was a prospect i ve study of pre- and post-CRT MRI and diffusion-weighted imaging ( DWI ) of 64 patients with LARC who underwent neoadjuvant CRT and subsequent surgery .  Histopathological tumour regression grade was the reference st and ard . Multivariate regression analysis was performed to identify the best MRI predictors of CR to neoadjuvant CRT , and their diagnostic performance was assessed . RESULTS The study cohort comprised 48 males and 16 females ( n = 64 ) , with mean age of 49.48 ± 14.3 years , range of 23 - 74 years . 11 patients had pathological complete response . The following factors predicted CR on univariate analysis : low initial ( pre-CRT ) tumour volume on T2 weighted high-resolution ( HR ) images and DWI , tumour volume-reduction rate ( TVRR ) of > 95 % on DWI and CR on post-CRT DWI ( ydwiT0 ) as assessed by the radiologist . However , the best MRI predictors of CR on multivariate regression analysis were CR on post-CRT DWI ( ydwiT0 ) as assessed by the radiologist and TVRR of > 95 % on DWI , and these parameters had an area under the curve ( 95 % confidence interval ) of 0.881 ( 0.74 - 1.0 ) and 0.843 ( 0.7 - 0.98 ) , respectively . The sensitivity , specificity , positive-predictive value , negative-predictive value and accuracy of DWI in predicting CR was 81.8 % , 94.3 % , 75 % , 96.1 % and 76 % ; the sensitivity , specificity and accuracy of TVRR of > 95 % as a predictor of CR was 80 % , 84.1 % and 64.1 % , respectively ; however , this difference was not statistically significant . The interobserver agreement was substantial for ydwiT0 . CONCLUSION Visual assessment of CR on post-CRT DWI and TVRR of > 95 % on DWI were the best predictors of CR after neoadjuvant CRT in patients with LARC , and the former being more practical can be used in daily practice . ADVANCES IN KNOWLEDGE In rectal cancer , ydwiT0 as assessed by the radiologist was the best and most practical imaging predictor of CR and scores over st and ard T2W HR images The effects of vascular endothelial growth factor ( VEGF ) blockade on the vascular biology of human tumors are not known . Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion , vascular volume , microvascular density , interstitial fluid pressure and the number of viable , circulating endothelial and progenitor cells , and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients . These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors Purpose The aim of the present study is to prospect ively evaluate the prognostic value of previously defined [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography ( FDG PET ) criteria of early metabolic response in patients with locally advanced rectal cancer ( LARC ) after long-term follow-up . Methods Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin , raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy . FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy ( CRT ) treatment . Total mesorectal excision ( TME ) was carried out 8 weeks after completion of CRT . A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG st and ardized uptake value ( SUVmean ) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade ( TRG ) and survival . Results Twenty-two metabolic responders showed complete ( TRG1 ) or subtotal tumour regression ( TRG2 ) and demonstrated a statistically significantly higher 5-year relapse-free survival ( RFS ) compared with the 20 non-responders ( 86 vs 55 % , p = .014 ) who showed TRG3 and TRG4 pathologic responses . A multivariate analysis demonstrated that early ∆SUVmean was the only pre-surgical parameter correlated to the likelihood of recurrence ( p = .05 ) . Conclusion This study is the first prospect i ve long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool . Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC Oxaliplatin ( OXA ) , raltitrexed ( RTX ) , 5-fluorouracil ( FU ) and folinic acid ( FA ) have shown activity in metastatic colorectal cancer , radioenhancing effect and synergism when combined . We evaluated a chemotherapy ( CT ) combination of OXA , RTX and FU/FA during preoperative radiotherapy ( RT ) in locally advanced rectal cancer ( LARC ) patients . Fifty-one patients with LARC at high risk of recurrence ( T4 , N+ or T3N0 ⩽5 cm from anal verge and /or circumferential resection margin ⩽5 mm ) received three biweekly courses of CT during pelvic RT ( 45 Gy ) . Surgery was planned 8 weeks after CT-RT . Recommended doses ( RDs ) determined during phase I were utilised in the subsequent phase II trial , where the rate of tumour regression grade ( TRG ) 1 or 2 was the main end point . No toxic deaths occurred , and severe toxicity was easily managed . In phase II , RDs delivered in 31 patients were OXA 100 mg m−2 and RTX 2.5 mg m−2 on day 1 , and FU 900 mg m−2 and LFA 250 mg m−2 on day 2 . Main severe toxicities by patients were grade 4 neutropenia ( 23 % ) and grade 3 diarrhoea ( 19 % ) . In 71 % ( 95 % confidence limits , 52–86 % ) of patients , TRG1 ( 13 ) or TRG2 ( 9 ) was obtained . All patients are alive and recurrence-free after a median follow-up of 29 months . Combination of OXA , RTX and FU/FA with pelvic RT has an acceptable toxicity and a high clinical activity in LARC and should be studied further in patients at high risk of recurrence Purpose Prediction of rectal cancer response to preoperative , neo-adjuvant chemo-radiation therapy ( CRT ) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches . Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up , but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT , when restaging the patient before surgery . Fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG-PET ) is a promising tool for monitoring the effect of anti-tumour therapy . The aim of this study was to prospect ively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT . Methods Forty-four consecutive patients with locally advanced ( cT3–4 ) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospect i ve study . Treatment consisted of external beam intensified radiotherapy ( 50 Gy to the posterior pelvis , 56 Gy to the tumour ) , chemotherapy ( in most cases PVI 5-FU at 300 mg/m2 per day ) and , 8–10 weeks later , surgery with curative intent . All patients underwent FDG-PET/CT both before CRT and 5–6 weeks after completing CRT . One patient died before surgery because of acute myocardial infa rct ion , and was therefore excluded from further analysis . Semi-quantitative measurements of FDG uptake ( SUVmax ) , absolute difference ( ΔSUVmax ) and percent SUVmax difference ( Response Index , RI ) between pre- and post-CRT PET scans were considered . Results were correlated with pathological response , assessed both by histopathological staging of the surgical specimens ( pTNM ) and by the tumour regression grade ( TRG ) according to M and ard ’s criteria ( patients with TRG1–2 being defined as responders and patients with TRG3–5 as non-responders ) . Results Following neo-adjuvant CRT 
    Output:
    
ROC curves analysis demonstrated that multimodal imaging integrating morphological and functional MRI features had the best accuracy both in term of sensitivity and specificity to evaluate preoperative therapy response in LARC .
DCE-MRI following to PET/CT showed high diagnostic accuracy and their results are also more reliable than conventional MRI and DWI alone .
Conclusions Morphological MRI is the modality of choice for rectal cancer staging permitting a correct assessment of the disease extent , of the lymph node involvement , of the mesorectal fascia and of the sphincter complex for surgical planning .