Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. Optimal Timing of Surgery After Chemoradiation for Advanced Rectal Cancer: Preliminary Results of a Multicenter, Nonrandomized Phase II Prospective Trial Timing of Surgery Following Preoperative Therapy in Rectal Cancer: The Need for a Prospective Randomized Trial? Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial Longer Time Interval Between Completion of Neoadjuvant Chemoradiation and Surgical Resection Does Not Improve Downstaging of Rectal Carcinoma Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging? Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): Is it a matter of days? Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer Risk factors for sexual dysfunction after rectal cancer treatment. Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. Chemotherapy with preoperative radiotherapy in rectal cancer. Improved Overall Survival Among Responders to Preoperative Chemoradiation for Locally Advanced Rectal Cancer Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer Rate of Pathologic Complete Response With Increased Interval Between Preoperative Combined Modality Therapy and Rectal Cancer Resection Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks? Optimal Surgery Time After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancers
PURPOSE The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown . The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery . PATIENTS AND METHODS Patients with rectal carcinoma accessible to rectal digital examination , staged T2 to T3 , NX , M0 , were r and omized before radiotherapy ( 39 Gy in 13 fractions ) into two groups : in the short interval ( SI ) group , surgery had to be performed within 2 weeks after completion of radiation therapy , compared with 6 to 8 weeks in the long interval ( LI ) group . Between 1991 and 1995 , 201 patients were enrolled onto the study . RESULTS A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response ( 53 . 1 % in the SI group v 71.7 % in the LI group , P = .007 ) and pathologic downstaging ( 10.3 % in the SI group v 26 % in the LI group , P = .005 ) . At a median follow-up of 33 months , there were no differences in morbidity , local relapse , and short-term survival between the two groups . Sphincter-preserving surgery was performed in 76 % of cases in the LI group versus 68 % in the SI group ( P = 0.27 ) . CONCLUSION A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results . When sphincter preservation is question able , a long interval may increase the chance of a successful sphincter-saving surgery Objective : To determine whether extending the interval between chemoradiation ( CRT ) and surgery , and administering additional chemotherapy during the waiting period has an impact on tumor response , CRT-related toxicity and surgical complications in patients with advanced rectal cancer . Background : Locally advanced rectal cancer is usually treated with preoperative CRT followed by surgery approximately 6 weeks later . The Timing of Rectal Cancer Response to Chemoradiation Consortium design ed a prospect i ve , multicenter , Phase II clinical trial to investigate extending the interval between CRT and surgery , and administering additional chemotherapy during the waiting period . Here , we present preliminary results of this trial , reporting the tumor response , CRT-related toxicity and surgical complications . Methods : Stage II and III rectal cancer patients were treated concurrently with 5-Fluorouracil ( FU ) and radiation for 5 to 6 weeks . Patients in study group ( SG ) 1 underwent total mesorectal excision ( TME ) 6 weeks later . Patients in SG2 with evidence of a clinical response 4 weeks after CRT received 2 cycles of modified FOLFOX-6 ( mFOLFOX-6 ) followed by TME 3 to 5 weeks later . Tumor response , CRT-related toxicity and surgical complications were recorded . Results : One hundred and forty-four patients were accrued . One hundred and thirty-six ( 66 , SG1 ; 70 , SG2 ) were evaluated for CRT-related toxicity . One hundred and twenty-seven ( 60 , SG1 ; 67 , SG2 ) were assessed for tumor response and surgical complications . A similar proportion of patients completed CRT per protocol in both SGs , but the cumulative dose of sensitizing 5-FU and radiation was higher in SG2 . CRT-related toxicity was comparable between SGs . Average time from CRT-to-surgery was 6 ( SG1 ) and 11 weeks ( SG2 ) . Pathologic complete response ( pCR ) was 18 % ( SG1 ) and 25 % ( SG2 ) . Postoperative complications were similar between SGs . Conclusions : Intense neoadjuvant therapy consisting of CRT followed by additional chemotherapy ( mFOLFOX-6 ) , and delaying surgery may result in a modest increase in pCR rate without increasing complications in patients undergoing TME for locally advanced rectal cancer BACKGROUND : In rectal cancer , the st and ard of care after the completion of radiotherapy is surgery at 6 to 8 weeks . However , there is variation regarding the timing of surgery . OBJECTIVE : This investigation aim ed to audit the timing of surgery following radiotherapy and to compare perioperative morbidity and tumor downstaging in patients operated on , before and after the 6- to 8-week window . DESIGN : A retrospective review of rectal cancers treated preoperatively in our cancer network over a 27-month period . The effect of “ time till surgery ” of 6 to 8 weeks , < 6 weeks , and > 8 weeks on T downstaging and nodal downstaging was calculated by univariate and multivariate logistic regression analyses . SETTING : This study was conducted in an oncology tertiary referral center in the Southwest London Cancer Network . PATIENTS : Patients receiving preoperative radiotherapy for primary locally advanced rectal cancer undergoing subsequent surgical resection were eligible . MAIN OUTCOME MEASURES : The primary outcome measurement was time to surgery following the completion of ( chemo ) radiotherapy .  Thirty-day perioperative morbidity and mortality and tumor and nodal downstaging were examined according to the timing of surgery . LIMITATIONS : This study was limited by its nonr and omized retrospective design and the lack of st and ardization of preoperative chemotherapy . RESULTS : Thirty-two ( 34 % ) patients underwent surgery at 6 to 8 weeks , 45 ( 47 % ) at > 8 weeks , and 18 ( 19 % ) at < 6 weeks after radiotherapy . Delay was attributed to scheduling in 87 % of cases and to comorbidities in the remainder . T downstaging occurred in 6 ( 33.3 % ) patients in the < 6 weeks group , in 12 ( 37.5 % ) in the 6 to 8 weeks group , and in 28 ( 62.2 % ) in > 8 weeks group with no significant differences in perioperative morbidity . On multivariate analysis , T downstaging was significantly greater for the > 8 weeks group ( OR , 3.79 ; 95 % CI : 1.11–12.99 ; P = .03 ) . More patients were staged ypT0-T2 , 19 of 45 ( 42 % ) in the > 8 weeks group vs other groups , 14 of 50 ( 28 % , P < .05 ) . CONCLUSIONS : Following radiotherapy , surgery frequently occurs at > 8 weeks and is associated with increased downstaging . The consequences on survival and perioperative morbidity warrant further investigation Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy ( with or without chemotherapy ) and surgical techniques such as total mesorectal excision . However , the contributions of surgery and radiotherapy to outcomes are unclear . We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved . Methods In this prospect i ve study , the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists , using a st and ard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial , which compared short-course ( 5 days ) preoperative radiotherapy and selective postoperative chemoradiotherapy , between March , 1998 , and August , 2005 . All analyses were by intention to treat . This trial is registered , number IS RCT N 28785842 . Findings 128 patients ( 11 % ) had involvement of the circumferential resection margin , and the plane of surgery achieved was classified as good ( mesorectal ) in 604 ( 52 % ) , intermediate ( intramesorectal ) in 398 ( 34 % ) , and poor ( muscularis propria plane ) in 154 ( 13 % ) . We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates . Hazard ratio ( HR ) was 0·32 ( 95 % CI 0·16–0·63 , p=0·0011 ) with 3-year local recurrence rates of 6 % ( 5–8 % ) and 17 % ( 10–26 % ) for patients who were negative and positive for circumferential resection margin , respectively . For plane of surgery achieved , HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 ( 0·16–0·64 ) and 0·48 ( 0·25–0·93 ) , respectively . At 3 years , the estimated local recurrence rates were 4 % ( 3–6 % ) for mesorectal , 7 % ( 5–11 % ) for intramesorectal , and 13 % ( 8–21 % ) for muscularis propria groups . The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups ( p=0·30 for trend ) . Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1 % . Interpretation In rectal cancer , the plane of surgery achieved is an important prognostic factor for local recurrence .  Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups , almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane . The plane of surgery achieved should therefore be assessed and reported routinely . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada Abstract PURPOSE : An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described . Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity . METHODS : Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospect i ve trial with  irinotecan ( 50 mg/m2 ) , 5-fluorouracil ( 225 mg/m2 ) , and concomitant external-beam radiation ( 45–54 Gy ) followed by complete surgical resection of the tumor with total mesorectal excision . The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days . The patients were divided into two groups with 33 eligible patients : Group A ( 4-week to 8-week time interval ; 28–56 days ) and Group B ( 10-week to 14-week interval ; 67–97 days ) . Tumor downstaging was compared between these two groups . The number of patients downstaged by at least one T stage , those downstaged by at least one N stage , those with pathologic complete responses , and those with only residual microscopic tumor foci were compared . Postoperative length of stay , estimated blood loss , perioperative morbidity , and sphincter-sparing procedures were also compared . Chi-squared tests and Student ’s t-test were calculated . RESULTS : Group A had 19 patients , and Group B had 14 patients . Patient demographics were comparable . Mean age was 52 years , and 70 percent of patients were male . There were no deaths . There were no statistical differences in perioperative morbidity , with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B ( P = 0.61 ) . Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B ( P = 0.9 ) . The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B ( P = 0.97 ) , and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B ( P = 0.90 ) . These differences were not statistically significant . CONCLUSIONS : Perioperative morbidity is not affected by longer intervals . A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort The aim of this study was to compare CT , MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer . A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia .  Staging was performed using four-slice CT ( n=23 ) , 1.5-T MRI ( n=10 ) , and 18F-FDG-PET ( n=23 ) before and 2–4 weeks after completion of neoadjuvant treatment . Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake ( st and ard uptake value ) within the tumour for FDG-PET . Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings . Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders . The mean SUV reduction in responders ( 60±14 % ) was significantly higher than in nonresponders ( 37±31 % ; P=0.030 ) . The sensitivity and specificity of FDG-PET in identifying response was 100 % ( CT 54 % , MRI 71 % ) and 60 % ( CT 80 % , MRT 67 % ) . Positive and negative predictive values were 77 % ( CT 78 % , MRI 83 % ) and 100 % ( CT 57 % , MRI 50 % ) ( PET P=0.002 , CT P=0.197 , MRI P=0.500 ) . These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer BACKGROUND AND OBJECTIVES Preoperative chemoradiotherapy for locally advanced rectal cancer is now considered " st and ard of care . " However , the optimal time interval for resection after neoadjuvant therapy is unknown . METHODS Between 11/90 and 11/04 , 107 patients with rectal adenocarcinoma underwent preoperative chemo/RT at the University of Pennsylvania . Fifty-six percent had LAR and 40 % had APR .  Chemotherapy consisted of 5-FU/oxaliplatin in 28 % and 5-FU in 72 % of patients . All patients received preoperative RT . RESULTS A longer time interval between chemo/RT and surgery was associated with tumor downstaging ( OR 1.24 , P = 0.02 ) . A longer time interval was not associated with : nodal downstaging ( OR 1.00 , P = 0.98 ) ; pathologic complete response ( PCR ) ( OR 0.97 , P = 0.80 ) ; likelihood of performing an LAR ( OR 0.90 , P = 0.47 ) ; improved disease free survival ( DFS ) , local control , or distant control ( HR 1.05 , P = 0.49 ; HR 1.14 , P = 0.22 ; HR 1.06 , P = 0.52 , respectively ) . The PCR rate was 34.5 % in the 5-FU/oxaliplatin/radiation group , and 13.7 % in the 5-FU/radiation group . If patients with microscopic CR were excluded , then the PCR rate for 5FU/OX was 21.4 % and for 5-FU was 12.2 % . CONCLUSIONS Time interval between surgery and chemo/RT appeared to have little effect on PCR or LAR rates . Patients receiving 5 FU/oxaliplatin/RT had a high PCR rate . A prospect i ve r and omized trial to test superiority of 5 FU/oxaliplatin is warranted PURPOSE In 1992 , preoperative radiotherapy was considered in France as the st and ard treatment for T3 - 4 rectal cancers . The present r and omized trial compares preoperative radiotherapy with chemoradiotherapy . PATIENTS AND METHODS Patients were eligible if they presented a resectable T3 - 4 , Nx , M0 rectal adenocarcinoma accessible to digital rectal examination .  Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered . Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days , together with leucovorin , was administered during the first and fifth week in the experimental arm . Surgery was planned 3 to 10 weeks after the end of radiotherapy . All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen . The primary end point of the trial was overall survival . RESULTS A total of 733 patients were eligible .  Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy ( 14.6 % v 2.7 % ; P < .05 ) . There was no difference in sphincter preservation . Complete sterilization of the operative specimen was more frequent with chemoradiotherapy ( 11.4 % v 3.6 % ; P < .05 ) . The 5-year incidence of local recurrence was lower with chemoradiotherapy ( 8.1 % v 16.5 % ; P < .05 ) . Overall 5-year survival in the two groups did not differ . CONCLUSION Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3 - 4 , N0 - 2 , M0 adenocarcinoma of the middle and distal rectum We intend to analyse retrospectively whether the time interval ( “ gap duration ” = GD ) between preoperative radiotherapy and surgery  in locally advanced rectal cancer ( LARC ) has an impact on overall survival ( OS ) , cancer specific survival ( CSS ) , disease free survival ( DFS ) and local control ( LC ) .  Two hundred seventy nine patients with LARC were entered in Trial 93 - 01 ( hyperfractionated accelerated radiotherapy 41.6 Gy/26 Fx BID ) shortly followed by surgery . From these 250 patients are fully assessable . The median GD of 5 days was used as a discriminator . The median follow-up for all patients was 39 months . GD > 5 days was a significant discriminator for actuarial 5-years OS ( 69 % vs 47 % , p = 0.002 ) , CSS ( 82 % vs 57 % , p = 0.0007 ) , DFS ( 62 % vs 41 % , p = 0.0003 ) but not for LC ( 93 % vs 90 % , p = non-significant ) . In multivariate analysis , the following factors independently predict outcome ; for OS : age , GD , circumferential margin ( CM ) and nodal stage ( ypN ) ; for CSS : GD , ypN and vascular invasion ( VI ) ; for DFS : CEA , distance to anal verge , GD , ypN and VI ; for LC : CM only . Gap duration predicts survival outcome but not local control . The patients su bmi tted to surgery after a median delay of more than 5 days had a significantly better outcome Objective : Our aims were to ( 1 ) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy ( CMT ) followed by total mesorectal excision ( TME )  , ( 2 ) identify factors predictive of oncologic outcome , and ( 3 ) determine the oncologic significance of the extent of pathologic tumor response . Summary Background Data : Locally advanced ( T3–4 and /or N1 ) rectal adenocarcinoma is commonly treated with preoperative CMT and TME . However , the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown . Methods : Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6 cm from the anal verge ( range 0–15 cm ) were treated with preoperative CMT ( radiation : 5040 centi-Gray ( cGy ) and 5-fluorouracil (5-FU)-based chemotherapy ) followed by TME from 1988 to 2002 . A prospect ively collected data base was queried for long-term oncologic outcome and predictive clinicopathologic factors . Results : With a median follow-up of 44 months , the estimated 10-year overall survival ( OS ) was 58 % and 10 year recurrence-free survival ( RFS ) was 62 % . On multivariate analysis , pathologic response > 95 % , lymphovascular invasion and /or perineural invasion ( PNI ) , and positive lymph nodes were significantly associated with OS and RFS . Patients with a > 95 % pathologic response had a significantly improved OS ( P = 0.003 ) and RFS ( P = 0.002 ) . Conclusions : Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58 % and RFS of 62 % . Patients who achieve a > 95 % response to preoperative CMT have an improved long-term oncologic outcome , a novel finding that deserves further study This study aim ed to identify risk factors for long-term sexual dysfunction ( SD ) after rectal cancer treatment . Patients with resectable rectal cancer were r and omised to total mesorectal excision with or without preoperative radiotherapy ( PRT ) .  Preoperatively and at 3 , 6 , 12 , 18 and 24 months postoperatively , SD scores were filled out in question naires . Possible risk factors for postoperative deterioration of sexual functioning , including patients ' demographics , tumour-specific factors and treatment-related variables , were investigated with univariate and multivariable regression analyses . Increase in general SD , erectile dysfunction and ejaculatory problems were reported by 76.4 , 79.8 and 72.2 percent of the male patients , respectively . Risk factors were nerve damage , blood loss , anastomotic leakage , PRT and the presence of a stoma . In female patients , increase in general SD , dyspareunia and vaginal dryness were reported by 61.5 , 59.1 and 56.6 percent , respectively . This was associated with PRT and the presence of a stoma . SD occurs frequently after rectal cancer treatment and is caused by surgical ( nerve ) damage with an additional effect of PRT . Patients should be informed preoperatively , and education of surgeons in neuroanatomy may provide the key to the improvement of functional outcome PURPOSE Quality assessment and assurance are important issues in modern health care . For the evaluation of surgical procedures , there are indirect parameters such as complication , recurrence , and survival rates . These parameters are of limited value for the individual surgeon , and there is an obvious need for direct parameters . We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a r and omized trial for rectal cancer . PATIENTS AND METHODS The pathology reports of all patients entered onto a Dutch multicenter r and omized trial were review ed . All participating pathologists had been instructed by workshops and videos in order to obtain st and ardized pathology work-up . A three-tiered classification was applied to assess  completeness of the total mesorectal excision ( TME ) . Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment . RESULTS Included were 180 patients . In 24 % ( n = 43 ) , the mesorectum was incomplete . Patients in this group had an increased risk for local and distant recurrence , 36.1 % v. 20.3 % recurrence in the group with a complete mesorectum ( P = .02 ) . Follow-up is too short to observe an effect on survival rates . CONCLUSION A patient 's prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen . We conclude that pathologists are able to judge the quality of TME for rectal cancer . With this direct interdisciplinary assessment instrument , we establish a new role of the pathologist in quality control BACKGROUND Preoperative radiotherapy is recommended for selected patients with rectal cancer . We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy , preoperative chemoradiotherapy , preoperative radiotherapy and postoperative chemotherapy , or preoperative chemoradiotherapy and postoperative chemotherapy . Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks . One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day , both given for 5 days . Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy ; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy . The primary end point was overall survival . RESULTS We enrolled 1011 patients in the trial . There was no significant difference in overall survival between the groups that received chemotherapy preoperatively ( P=0.84 ) and those that received it postoperatively ( P=0.12 ) . The combined 5-year overall survival rate for all four groups was 65.2 % . The 5-year cumulative incidence rates for local recurrences were 8.7 % , 9.6 % , and 7.6 % in the groups that received chemotherapy preoperatively , postoperatively , or both , respectively , and 17.1 % in the group that did not receive chemotherapy ( P=0.002 ) . The rate of adherence to preoperative chemotherapy was 82.0 % , and to postoperative chemotherapy was 42.9 % . CONCLUSIONS In patients with rectal cancer who receive  preoperative radiotherapy , adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival . Chemotherapy , regardless of whether it is administered before or after surgery , confers a significant benefit with respect to local control . ( Clinical Trials.gov number , NCT00002523 [ Clinical Trials.gov ] . ) The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil ( 5-FU ) was predictive for survival among patients with locally advanced rectal cancer .  Preoperative chemoradiation ( CTX/XRT ) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU ( 300 mg/m2/day ) was given to 117 patients . The pretreatment stage distribution , as determined by endorectal ultrasound ( u ) , included uT2N0 in 2 % , uT3N0 in 47 % , uT3N1 in 49 % , and uT4N0 in 2 % of cases ; endorectal ultrasound was not performed in 13 % of cases ( 15 patients ) . Approximately 6 weeks after completion of CTX/XRT , surgery was performed . Adjuvant chemotherapy , consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days , was administered every 28 days for 4 to 6 cycles after surgical resection . Among the 74 patients treated with adjuvant chemotherapy , the preoperative stage of disease was 31 with T3N0 and 43 T3N1 . Median follow-up was 46 months ( range 2 to 89 months ) . The pathologic tumor stages were Tis-2N0 in 26 % , T2N1 in 5 % , T3N0 in 21 % , T3N1 in 15 % , T4N0 in 5 % , and T4N1 in 1 % ; a complete response ( CR ) to preoperative CTX/XRT was pathologically confirmed in 32 ( 27 % ) of patients . Tumor down-staging occurred in 72 ( 62 % ) cases . A sphincter-saving procedure ( SP ) was possible in 59 % of patients . The median DFS and overall survival rates for responders were 46 months and 47 months , respectively ; for non-responders these outcome measures were 38 months and 41 months , respectively . Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT ( p < 0.00001 ) , CR to CTX/XRT ( p < 0.009 ) and SP ( p < 0.012 ) . Likewise , these parameters also significantly influenced DFS rates ( CTX/XRT p < 0.00001 ; CR p < 0.006 ; and SP p < 0.008 ) . Control of pelvic disease was influenced by clinical size ( p < 0.002 ) and SP ( p < 0.016 ) on univariate analysis . On multivariate analysis only clinical size ( p < 0.002 ) continued to be a significant factor for local control . Factors on multivariate analysis that result ed in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT ( p < 0.017 ) and administration of adjuvant chemotherapy ( p < 0.034 ) . Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates . Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in overall survival among patients with locally advanced rectal cancer . Patients who fail to respond to preoperative 5-FU based chemotherapy given concomitantly with radiation have higher rates of distant metastases with adjuvant 5-FU therapy PURPOSE Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes . In patients without residual tumor on imaging and endoscopy ( clinical complete response [ cCR ] ) a wait- and -see-policy ( omission of surgery with follow-up ) might be considered instead of surgery . The purpose of this prospect i ve cohort study was to evaluate feasibility and safety of a wait- and -see policy with strict selection criteria and follow-up . PATIENTS AND METHODS Patients with a cCR after chemoradiotherapy  were prospect ively selected for the wait- and -see policy with magnetic resonance imaging ( MRI ) and endoscopy plus biopsies . Follow-up was performed 3 to 6 monthly and consisted of MRI , endoscopy , and computed tomography scans . A control group of patients with a pathologic complete response ( pCR ) after surgery was identified from a prospect i ve cohort study . Functional outcome was measured with the Memorial Sloan-Kettering Cancer Center ( MSKCC ) bowel function question naire and Wexner incontinence score . Long-term outcome was estimated by using Kaplan-Meier curves . RESULTS Twenty-one patients with cCR were included in the wait- and -see policy group . Mean follow-up was 25 ± 19 months . One patient developed a local recurrence and had surgery as salvage treatment . The other 20 patients are alive without disease . The control group consisted of 20 patients with a pCR after surgery who had a mean follow-up of 35 ± 23 months . For these patients with a pCR , cumulative probabilities of 2-year disease-free survival and overall survival were 93 % and 91 % , respectively . CONCLUSION A wait- and -see policy with strict selection criteria , up-to- date imaging techniques , and follow-up is feasible and results in promising outcome at least as good as that of patients with a pCR after surgery . The proposed selection criteria and follow-up could form the basis for future r and omized studies Abstract Purpose . To investigate the use of FDG-PET/CT before , during and after chemoradiotherapy ( CRT ) and diffusion-weighted magnetic resonance imaging ( DW-MRI ) before CRT for the prediction of pathological response ( pCR ) in rectal cancer patients . Material and methods . Twenty-two rectal cancer patients treated with long course CRT were included . An FDG-PET/CT was performed prior to the start of CRT , after 10 to 12 fractions of CRT and five weeks after the end of CRT . The tumor was delineated using a gradient based delineation method and the maximal st and ardized uptake values ( SUVmax ) were calculated . A DW-MRI was performed before start of CRT . Mean apparent diffusion coefficients ( ADC ) were determined . The ΔSUVmax during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision ( TME ) . Results . ΔSUVmax during and after CRT significantly correlated with the pathological response to treatment ( during CRT : ΔSUVmax = 59 % ± 12 % for pCR vs. 25 % ± 27 % if no pCR , p=0.0036 ; post-CRT : 90 % ± 11 for pCR vs. 63 % ± 22 if no pCR p=0.013 ) . ROC curve analysis revealed an optimal threshold for ΔSUVmax of 40 % during CRT and 76 % after CRT . The initial ADC value was also significantly correlated with pCR ( 0.94 ± 0.12 × 10−3 mm2/s for pCR vs. 1.2 ± 0.24 × 10−3 mm2/s , p=0.002 ) and ROC curve analysis revealed an optimal threshold of 1.06 × 10−3 mm2/s . Combining the provided ΔSUVmax thresholds during and after CRT increased specificity of the prediction ( sensitivity 100 % and specificity 94 % ) . The combination of the thresholds for the initial ADC value and the ΔSUVmax during CRT increased specificity of the prediction to a similar level ( sensitivity of 100 % and specificity of 94 % ) . Conclusions . The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT INTRODUCTION Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy .  Prolongation of the interval between preoperative combined modality therapy and surgery ( RT-surgery interval ) as a means of increasing pathologic complete response rate has not been fully examined . METHODS One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified . All patients had endorectal ultrasound prior to combined modality therapy .  Final pathology reports were review ed for ypT and ypN stage and margin status . Medical records were review ed for sphincter preservation , operative time , estimated blood loss , hospital stay , and morbidity ( overall , anastomotic , and perineal ) . RESULTS A pathologic complete response ( ypT0N0 ) occurred in 24 patients ( 15 percent ) . Median RT-surgery interval was 44 ( range , 15 - 206 ) days . A pathologic complete response occurred in 19 percent of patients with an interval > 44 days , vs. 12 percent in those with an interval ≤44 days ( P = 0.27 ) . Downstaging by three stages occurred more frequently in the long-interval group ( 15 percent vs. 6 percent , P = 0.11 ) . The rates of sphincter preservation , positive margins , estimated blood loss , and operative time were not significantly different . Overall morbidity was similar between groups . CONCLUSIONS Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval . However , sphincter preservation is not increased . Until prospect i ve analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome , the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear PURPOSE To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy ( CRT )  by 2-[fluorine-18 ] fluoro-2-deoxy-d-glucose-labeled positron emission tomography/computed tomography ( [(18)FDG]PET/CT ) imaging and correlate with response to CRT . METHODS AND MATERIAL S Patients with cT2 - 4N0 - 2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT ( 54 Gy , 5-fluouracil-based ) were prospect ively studied ( Clinical Trials.org identifier NCT00254683 ) . All patients underwent 3 PET/CT studies ( at baseline and 6 and 12 weeks from CRT completion ) . Clinical assessment was at 12 weeks . Maximal st and ard uptake value ( SUVmax ) of the primary tumor was measured and recorded at each PET/CT study after 1 h ( early ) and 3 h ( late ) from (18)FDG injection . Patients with an increase in early SUVmax between 6 and 12 weeks were considered " bad " responders and the others as " good " responders . RESULTS Ninety-one patients were included ; 46 patients ( 51 % ) were " bad " responders , whereas 45 ( 49 % ) patients were " good " responders . " Bad " responders were less likely to develop complete clinical response ( 6.5 % vs. 37.8 % , respectively ; P=.001 ) , less likely to develop significant histological tumor regression ( complete or near-complete pathological response ; 16 % vs. 45 % , respectively ; P=.008 ) and exhibited greater final tumor dimension ( 4.3 cm vs. 3.3 cm ; P=.03 ) . Decrease between early ( 1 h ) and late ( 3 h ) SUVmax at 6-week PET/CT was a significant predictor of " good " response ( accuracy of 67 % ) . CONCLUSIONS Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging . Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients Objective : To evaluate the effect of the time interval between chemoradiotherapy ( CRT ) and surgery on CRT response and surgical outcomes . Summary Background Data : Although preoperative CRT is a st and ard component of multimodal treatment for locally advanced rectal cancers , the optimal time for surgery after CRT has yet to be established . This study analyzed outcomes in 397 prospect ively enrolled patients with locally advanced rectal cancer who underwent fractionated CRT involving 50.4 Gy radiotherapy followed by surgical resection between 4 and 8 weeks later . Methods : Patients were divided into 2 groups according to the time that elapsed between CRT and surgery : group A ( 28–41 day interval ) and group B ( 42–56 day interval ) .  CRT responses and surgical outcomes were analyzed . Results : Of the 397 patients , 217 ( 54.7 % ) were in group A and 180 ( 45.3 % ) in group B. The 2 groups were similar in terms of pretreatment characteristics other than a slight difference in mean age ( A : 55.3 years vs. B : 57.5 years , P = 0.042 ) . Analysis of CRT responses showed that the 2 groups were similar in terms of T-level downstaging rate ( A : 47.5 % vs. B : 44.4 % , P = 0.548 ) , volume reduction rate ( A : 34.6 % vs. B : 34.2 % , P = 0.870 ) and complete response rate ( A : 13.8 % vs. B : 15.0 % , P = 0.740 ) . Analysis of surgical outcomes showed that the 2 groups were also similar in terms of sphincter-preservation rate ( A : 83.9 % vs. B : 82.2 % , P = 0.688 ) and anastomosis-related complication rate ( A : 5.5 % vs. B : 3.9 % , P = 0.453 ) . The median follow-up period was 31 months ( range , 5–63 ) , and both groups showed similar local recurrence-free survival rates ( P = 0.1165 ) . Conclusion : The present findings suggest that compared with a 4 to 6 week interval , delaying surgery for 6 to 8 weeks after completion of fractionated radiotherapy with concurrent chemotherapy does not improve CRT response or the sphincter-preservation rate , and does not decrease morbidity or local recurrence
BACKGROUND : Neoadjuvant long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer , with surgery performed after an interval of a number of weeks .
OBJECTIVE : We report an evidence -based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy .