Increasing frequency of reirradiation studies in radiation oncology: systematic review of highly cited articles. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study. Colorectal Cancer Pelvic Recurrences: Determinants of Resectability Reirradiation for rectal cancer and surgical resection after ultra high doses. Quality of life in patients with urinary diversion after operation for locally advanced rectal cancer. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. Curative Potential of Multimodality Therapy for Locally Recurrent Rectal Cancer Radiation therapy quality assurance in clinical trials--Global Harmonisation Group. Chemotherapy with preoperative radiotherapy in rectal cancer. Improved survival with preoperative radiotherapy in resectable rectal cancer. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Once-daily reirradiation for rectal cancer in patients who have received previous pelvic radiotherapy.
OBJECTIVES Identification of the most influential scientific publications and directions of mainstream reirradiation research . METHODS A systematic search of the data base Scopus ( Elsevier B.V. , www . scopus .com ) was performed , which focused on the time period 1998 - 2010 . Patterns of citation were analysed ( total number of citations accumulated independently of their origin and proportion of highly cited articles , arbitrarily defined as those with ≥50 citations ) . RESULTS Up to 64 articles were published each year . Numbers increased over time , especially after the year 2007 . Among all 76 articles with at least 50 citations , 28 ( 37 % ) focused on head and neck cancer , 27 ( 36 % ) on brain tumours including metastases , and 5 ( 7 % ) on bone metastases . Most articles evaluated external beam approaches while 10 ( 13 % ) focused on brachytherapy . Many of the often quoted publications reported on  stereotactic and /or intensity-modulated radiotherapy  . Two ( 3 % ) reported on r and omised clinical studies and 10 ( 13 % ) on non-r and omised prospect i ve clinical studies ( single institution or cooperative group ) . Only two articles ( 3 % ) reported on experimental animal studies . CONCLUSIONS The number of published reirradiation studies has increased in recent years . Many studies examined highly conformal and precise radiotherapy , in particular of brain and head and neck tumours . Given that few r and omised clinical trials were published , efforts to increase this type of research activity are warranted PURPOSE The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence . However , a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis . In these patients , local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity . The aim of this multicenter phase II study is to evaluate the response rate , resectability rate , local control , and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis . METHODS AND MATERIAL S Patients with histologically proven pelvic recurrence of rectal carcinoma , with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses < or = 55 Gy ; age > or = 18 years ; performance status ( PS ) ( Karnofsky ) > or = 60 , and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation . Radiotherapy was delivered to a planning target volume ( PTV2 ) including the gross tumor volume ( GTV ) plus a 4-cm margin , with a dose of 30 Gy ( 1.2 Gy twice daily with a minimum 6-h interval ) . A boost was delivered , with the same fractionation schedule , to a PTV1 including the GTV plus a 2-cm margin ( 10.8 Gy ) . During the radiation treatment , concurrent chemotherapy was delivered ( 5-fluorouracil , protracted intravenous infusion , 225 mg/m(2)/day , 7 days per week ) . Four to 6 weeks after the end of chemoradiation , patients were evaluated for tumor resectability , and , when feasible , surgical resection of recurrence was performed between 6 - 8 weeks from the end of chemoradiation . Adjuvant chemotherapy was prescribed to all patients , using Raltitrexed , 3 mg/square meter ( sm ) , every 3 weeks , for a total of 5 cycles . Patients were staged using the computed tomography (CT)-based F-classification ( F0 : no side-wall involvement ; F1 , F2 , F3 : 1 , 2 , and 3 - 4 side-walls involved , respectively ) . Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group ( RTOG ) criteria . RESULTS Fifty-nine patients ( 38 male , 21 female ; median age , 62 years ; range , 43 - 77 years ) were enrolled in the study , by 12 different Italian radiotherapy departments . Previous surgery was anterior resection in 45 patients ( 76.3 % ) and abdominal-perineal resection in 14 patients ( 23.7 % ) ; previous radiotherapy dosage ranged between 30 and 55 Gy ( median , 50.4 Gy ) ; the median interval between prior radiation therapy to the onset of reirradiation was 27 months ( range , 9 - 106 months ) ; 44 patients ( 74.6 % ) had received some form of previous chemotherapy ( concurrent and /or adjuvant ) . Fifty-one of 59 patients ( 86.4 % ) completed chemoradiation without treatment interruptions : 6 patients ( 10.2 % ) had temporary treatment interruption due to toxicity or patient compliance , and 2 patients ( 3.4 % ) had definitive treatment interruption . The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1 % . No patient developed Grade 4 acute toxicity . After chemoradiation , 5 patients ( 8.5 % ) had complete response ( CR ) , 21 patients ( 35.6 % ) had partial response ( PR ) , 31 patients ( 52.6 % ) had no change ( NC ) and 2 patients ( 3.4 % ) showed progressive disease ( PD ) . Overall , the response rate ( PR + CR ) was 44.1 % ( 95 % confidence interval , 29.0 - 58.9 % ) . Twenty of 24 patients ( 83.3 % ) with pelvic pain before treatment had symptomatic response .  Tumor resection was performed in 30 of 59 patients ( 50.8 % ) including 2 local excisions , 4 anterior resections , 18 abdominoperineal resections , and 6 other . Surgical resection result ed as R0 and R1 in 21 patients ( 35.6 % ) and 3 patients ( 5.1 % ) , respectively . The possibility of radical resection was influenced by tumor response to chemoradiation ( PD/NC : 7/33 ; PR/CR : 14/26 ; p = 0.009 ) . Thirty-three patients received adjuvant chemotherapy , which was completed in 30 ( 50.8 % ) . At a median follow-up of 36 months ( range , 9 - 69 months ) , 28 patients ( 47.5 % ) developed local recurrence or tumor progression in the unresected pelvic disease and 18 patients ( 30.5 % ) developed distant metastasis . Seven patients showed late toxicity , including 2 skin fibrosis , 2 impotence , 2 urinary complications requiring nephrostomy , and 1 small bowel fistula requiring surgical diversion . Overall median survival was 42 months . Five-year actuarial survival was 39.3 % ; 66.8 % in R0 resected patients and 22.3 % in patients treated without surgery or undergoing subtotal tumor removal . Local control and disease-free survival were significantly correlated with the interval between surgical treatment for primary tumor and local recurrence ( p = 0.028 and p = 0.003 , respectively ) . Radical resection significantly influenced local control , disease-free survival , and overall survival ( p = 0.010 , p = 0.010 , and p = 0.050 respectively ) . The multivariate analysis confirmed the impact of surgery-relapse interval on local control ( p = 0.016 ) and disease-free survival ( p = 0.002 ) , and confirmed the correlation between R0 surgery with local control and disease-free survival ( p = 0.016 ) . CONCLUSIONS Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications . Pain control was excellent . The overall 5-year survival was 39 % . Despite 87.4 % of patients having F1 - 3 stage disease , approximately one-third ( 35 % ) achieved R0 resection , and two-thirds of patients in this cohort of patients were alive at the 5-year mark . However , further studies using innovative treatment algorithms are warranted to , hopefully , improve the local tumor response and control PURPOSE This study was design ed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy .  METHODS Review of a prospect i ve data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal ( n = 101 ) and colon ( n = 18 ) cancer between January 1994 and November 2000 . R0 resection was achieved in 61 patients . This group was compared with patients in which an R1 ( n = 38 ) , R2 ( n = 7 ) , or palliative procedure ( n = 13 ) was performed . Variables evaluated included : tumor location , features of the primary tumor , and preoperative findings on computed tomography , magnetic resonance imaging , and history/physical . Tumor location was established by review of operative/pathologic reports and classified as axial ( anastomotic/perineal ) , anterior ( bladder/genitourinary organs ) , posterior ( presacral ) , or lateral ( pelvic sidewall ) . RESULTS When recurrence was confined to the axial location only , or axial and anterior locations , R0 resection was achieved significantly more often than when other locations were involved ( P < 0.001 , P = 0.003 , respectively ) . When a lateral component was present , R0 resection was achieved significantly less often than when there was no lateral component ( P = 0.002 ) . For patients with available preoperative computed tomography and /or magnetic resonance imaging results ( n = 70 ) , the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified ( P = 0.004 ) . CONCLUSIONS Pelvic recurrences confined to the axial location , or axial and anterior locations , are more likely to be completely resectable ( R0 ) than those involving the pelvic sidewall . Efforts to enhance preoperative identification and imaging of these patients are clearly justified PURPOSE Local recurrence of rectal cancer following high-dose pelvic radiation presents a difficult management challenge . Conventional wisdom suggests that reirradiation should be avoided and radical pelvic surgery is hazardous after ultra high-dose radiation . METHODS AND MATERIAL S In a unique Phase I/II pilot study , 32 patients with recurrent rectal cancers following previous pelvic radiation underwent planned reirradiation to the pelvis .  Initial radiation doses had ranged from 30 - 64.87 Gy ( median dose 45 Gy ) . Seventeen patients underwent reirradiation followed by radical resection . Fifteen patients were reirradiated for palliative relief of symptoms . Treatment techniques consisted of two lateral fields ( 7 x 7 to 12 x 10 cm ) encompassing the tumor with 2 cm margins . Reirradiation doses ranged from 19.80 - 47.66 Gy , ( median 34.2 Gy ) . Patients also received concurrent low-dose continuous infusion chemotherapy , ( 5-FU 200 - 300 mg/day ) . Total cumulative radiation doses ranged from 70.6 to 111.6 Gy . RESULTS Treatment was well tolerated . Four patients had radiation interrupted/discontinued for diarrhea or leukopenia . Follow-up ranges from 6 months to 36 months . No late sequelae of radiation have been observed to date . Seventeen patients underwent surgical exploration 6 - 8 weeks following reirradiation . Two patients had extensive disease and were not resected . Fifteen patients underwent radical resection of residual tumor ( 4 posterior exenterations , 6 APR , 3 transanal abdominal transanal proctocolectomy with coloanal anastomosis ( TAATA ) , and 2 LAR ) . No patients died postoperatively . No excessive edema , hemorrhage , or adhesions were observed . Two patients developed pelvic abscess and one developed a coloanal stricture . Eleven of 15 resected patients are alive from 6 to 36 months with a 2-year survival of 66 % . Of the patients treated palliatively , symptomatic relief was observed in 13/15 patients . No objective complete response was observed , but 6/15 patients had measurable partial response . Median survival in this group was 14 months . CONCLUSION Based on this experience , we believe that in selected patients radical surgical resection after cumulative ultra high doses ( 70 - 90 Gy ) of radiation can be performed safely . A viable anastomosis is also possible in spite of these high doses . Planned reirradiation for palliative relief of symptoms can be effective without unusual risks of complication . Long-term effects of such ultra high dose radiation and surgery continue to be monitored AIMS When locally advanced or recurrent rectal cancer involves the bladder or prostate , curative treatment often requires pelvic exenteration . The aim was to assess the quality of life ( QoL ) in disease-free patients with urinary diversion after extensive surgery for advanced rectal cancer . METHODS Twelve patients with urinary diversion ( cases ) were compared with 25 r and omly selected patients given the same treatment , but without urinary diversion ( controls ) .  An age- and gender-adjusted general population was identified ( reference ) . QoL was assessed with the EORTC question naires QLQ-C30 , QLQ-CR38 , and parts  of the QLQ-BLM30 . RESULTS The cases did not report significantly worse overall QoL than the controls or the reference population . Both cases and controls had low mean scores of sexual function , and high mean scores of male sexual problems . In the nine cases that had two stomas , overall QoL was not worse than in the control or reference groups . CONCLUSIONS Tumour-free patients did not report worse QoL scores than the controls or the general population , despite most having two stomas and low sexual function . Fear of reducing the patient 's QoL should not be a major contraindication when surgery with urinary diversion is warranted to obtain curative resection 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 Objective To assess the results of multimodality therapy for patients with recurrent rectal cancer and to analyze factors predictive of curative resection and prognostic for overall survival . Summary Background Data Locally recurrent rectal cancer is a difficult clinical problem , and radical treatment options with curative intent are not generally accepted . Methods A total of 394 patients underwent surgical exploration for recurrent rectal cancer . Ninety were found to have unresectable local or extrapelvic disease and 304 underwent resection of the recurrence . The latter patients were prospect ively followed to determine long-term survival and factors influencing survival . Results Overall 5-year survival was 25 % . Curative , negative resection margins were obtained in 45 % of patients ; in these patients a 5-year survival of 37 % was achieved , compared to 16 % ( P < .001 ) in patients with either microscopic or gross residual disease . In a logistic regression analysis , initial surgery with end-colostomy and symptomatic pain ( both univariate ) and increasing number of sites of the recurrent tumor fixation in the pelvis ( multivariate ) were associated with palliative surgery . Overall survival was significantly decreased for symptomatic pain ( P < .001 ) and more than one fixation ( P = .029 ) . Survival following extended resection of adjacent organs was not different from limited resection ( 28 % vs. 21 % , P = .11 ) . Patient demographics and factors related to the initial rectal cancer did not affect outcome . Perioperative mortality was only 0.3 % , but significant morbidity occurred in 26 % of patients , with pelvic abscess being the most common complication . Conclusions This study demonstrates that many patients with locally recurrent rectal cancer can be resected with negative margins . Long-term survival can be achieved , especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis , provided no gross residual disease remains Participation in large multi-centre clinical trials aids establishment of the safety and efficacy of new cancer treatments and methods . Oncology clinical trials have contributed to improved local control , overall survival and quality of life for patients with varying disease types [ 1 ] . Radiation Therapy is indicated in the course of treatment for more than 50 % of all cancer patients [ 2,3 ] and consequently a high percentage of oncology clinical trials include radiotherapy within their treatment schema . Collaboration between global clinical trial groups and organisations has increased the number of patient records available for analysis permitting faster recruitment [ 4 ] , broader acceptance and wider impact of trial results . Global cooperation is also essential in the environment of rare cancers [ 5 ] , in order to be able to create sufficiently large patient data sets within a reasonable recruitment period . A successful example is the EORTC 26981/National Cancer Institute of Canada ( NCIC ) CE3 intergroup trial , where 573 Glioblastoma patients were r and omised within 20 months [ 6 ] , despite the low prevalence of the disease among the general population . Globally , clinical trial groups and organisations have independently implemented their own Radiation Therapy ( RT ) Quality Assurance ( QA ) programs within their corresponding large multicentre clinical trials . Various trial groups have reported that the implementation of RTQA procedures enhanced protocol compliance [ 7–13 ] . In four Radiation Therapy Oncology Group ( RTOG ) studies compliance with the study protocol was enhanced by incorporating pre-treatment review of RT planning [ 8 ] . A Trans-Tasman Radiation Oncology Group ( TROG ) QA audit identified a reduction in unacceptable protocol violations due to three main factors , among which was the QA procedure itself [ 7 ] . More recently , strict RTQA procedures have been shown by TROG to have impacted on both trial protocol compliance as well as general clinical practice in prostate RT [ 9 ] . For several EORTC studies it has been shown that centres which previously participated in a Dummy Run ( DR ) were significantly more likely to be successful at subsequent DR attempts and delivery of protocol -compliant RT [ 10 ] . Additionally , the impact of RTQA on actual clinical trial outcome has been recently demonstrated in the setting of various cancer sites [ 11 ] , stressing its importance and correlation with survival [ 12,13 ] . However , the various approaches as to how RTQA in clinical trials is performed , evaluated and described are diverse , making analysis and inter-trial comparisons of RTQA results challenging . This hampers cooperation between trial groups and impedes the exchange and interpretation of RTQA data . The costs of running an RTQA program have also increased with the introduction of new advanced technologies . This increases the need to make RTQA more efficient and streamline the QA workload dem and ed of clinical centres recruiting into international trials [ 14,15 ] . As shown by Pettersen et al [ 4 ] these RTQA efforts can potentially reduce the number of patients required for trials which could lead to further substantial savings and faster availability of results . The need for a global forum on harmonisation of RTQA within clinical trials thus became apparent . After initial discussion s in Goteborg during ESTRO 27 in 2008 the Global Clinical Trials RTQA Harmonisation Group ( GHG ) was formally established in 2010 . The goals of the GHG are : Collate , homogenise and distribute information regarding the RTQA st and ards of the clinical trial groups , Provide a platform for prospect i ve discussion s on new RTQA procedures , software tools , guidelines and policies of trial groups and Provide a framework to endorse existing and future RTQA procedures and guidelines across various trial groups . Each organisation will have the opportunity to endorse RTQA procedures from other organisations and thus accept them much faster in future collaborative trials . In Table 1 the human re sources and number of intergroup trials of the steering committee members of the GHG are given . Further information about terms of reference and current and future projects can be found on its website : www.RTQAHarmonisation.org . Table 1 RTQA within each of the current GHG steering committee members as of August 2013 . All RTQA groups and organisations participate in international collaborative work to some degree , although there are differences between the USA and all other groups . These differences can be explained by the differences in the funding levels and that most USA RTQA groups only work with NCI funded clinical trials mainly operated in North America [ 16 ] . Recently , the North American RTQA organisations have joined forces in the new Imaging and Radiation Oncology Core ( IROC ) group . The dedicated human re sources also vary significantly , most likely due to differences in the QA philosophy of the funding agencies and their commitment to RTQA , although most of the GHG members have at least one Radiation Oncologist , one Medical Physicist and one Radiation Technologist dedicated full time to RTQA . Until now the GHG has contributed to the harmonisation of naming conventions [ 17 ] , strategies to develop an efficient evidence -based clinical trials RTQA system [ 14 ] and the development of a global model for the international recognition of the activities of national and regional Dosimetry Audit Networks [ 18 ] . Currently , each trial group has defined its own RTQA procedures [ 10,19–24 ] that differ significantly in number , naming conventions and implementation methods [ 22,25–31 ] . The GHG is addressing this by collating all RTQA procedures of each member , comparing them and proposing common , harmonised names and procedures . Although RTQA has been proven to be effective , international differences hamper intergroup collaboration . The Global Clinical Trials RTQA Harmonisation Group has been established to reduce those differences , capitalise on the range of expertise available internationally , increase the power of RT clinical trials , deliver consistency in the reporting of trial quality factors and facilitate the undertaking of effective multi-national trials and data analysis . Although important progress has already been made , many challenges remain to be addressed 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 ] . ) BACKGROUND Adjuvant radiotherapy for rectal cancer has been extensively studied , but no trial has unequivocally demonstrated improved overall survival with radiotherapy , despite a reduction in the rate of local recurrence . METHODS Between March 1987 and February 1990 , we r and omly assigned 1168 patients younger than 80 years of age who had resectable rectal cancer to undergo preoperative irradiation ( 25 Gy delivered in five fractions in one week ) followed by surgery within one week or to have surgery alone .  RESULTS The irradiation did not increase postoperative mortality . After five years of follow-up , the rate of local recurrence was 11 percent ( 63 of 553 patients ) in the group that received radiotherapy before surgery and 27 percent ( 150 of 557 ) in the group treated with surgery alone ( P<0.001 ) . This difference was found in all subgroups defined according to Dukes ' stage . The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgery group and 48 percent in the surgery-alone group ( P=0.004 ) . The cancer-specific survival rates at nine years among patients treated with curative resection were 74 percent and 65 percent , respectively ( P=0.002 ) . CONCLUSIONS A short-term regimen of high-dose preoperative radiotherapy reduces rates of local recurrence and improves survival among patients with resectable rectal cancer BACKGROUND The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision ( TME ) . Long-term results are reported after a median follow-up of 12 years . METHODS Between Jan 12 , 1996 , and Dec 31 , 1999 , 1861 patients with resectable rectal cancer without evidence of distant disease were r and omly assigned to TME preceded by 5 × 5 Gy radiotherapy or TME alone ( ratio 1:1 ) . R and omisation was based on permuted blocks of six with stratification according to centre and expected type of surgery . The primary endpoint was local recurrence , analysed for all eligible patients who underwent a macroscopically complete local resection .  FINDINGS 10-year cumulative incidence of local recurrence was 5 % in the group assigned to radiotherapy and surgery and 11 % in the surgery-alone group ( p<0·0001 ) . The effect of radiotherapy became stronger as the distance from the anal verge increased . However , when patients with a positive circumferential resection margin were excluded , the relation between distance from the anal verge and the effect of radiotherapy disappeared . Patients assigned to radiotherapy had a lower overall recurrence and when operated with a negative circumferential resection margin , cancer-specific survival was higher . Overall survival did not differ between groups . For patients with TNM stage III cancer with a negative circumferential resection margin  , 10-year survival was 50 % in the preoperative radiotherapy group versus 40 % in the surgery-alone group ( p=0·032 ) . INTERPRETATION For all eligible patients , preoperative short-term radiotherapy  reduced 10-year local recurrence by more than 50 % relative to surgery alone without an overall survival benefit . For patients with a negative resection margin , the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival , which was nullified by an increase in other causes of death , result ing in an equal overall survival . Nevertheless , preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and TNM stage III . Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains . FUNDING The Dutch Cancer Society , the Dutch National Health Council , and the Swedish Cancer Society INTRODUCTION The purpose of this study is to assess the efficacy and toxicity using once-daily reirradiation for patients with rectal cancer having received previous pelvic radiotherapy . METHOD Between June 1997 and June 2008 , 56 patients were identified having received previous pelvic radiotherapy and received reirradiation for rectal cancer . Reirradiation intent was palliative in 43 patients , and preoperative/postoperative in 13 patients . Eighty per cent of patients received concurrent chemotherapy ( n = 45 ) . RESULTS The median dose-fractionation reirradiation schedule was 39.6 Gy in 22 fractions once daily ( range 20 - 39.6 Gy ) , and the median cumulative radiation dose was 87.3 Gy . Seven patients experienced a grade 3 acute toxicity , with no grade 4 event . Fifty-one patients ( 91 % ) completed the treatment and five patients required a treatment break . The overall symptomatic response rate was 88 % at three months post-reirradiation . There was one late effect of skin ulceration among patients reirradiated palliatively . Median overall survival was 39 months in patients undergoing radical surgery versus 15 months in patients reirradiated palliatively ( P < 0.001 ) . CONCLUSION Once-daily reirradiation to a total dose of ≤39.6 Gy is relatively safe in the treatment of patients with rectal cancer after previous pelvic radiotherapy . It is effective in symptom control and provides an additional option in management of local recurrence
BACKGROUND Many patients with rectal cancer receive radiotherapy as a component of primary multimodality treatment .
Although local recurrence is infrequent , reirradiation may be needed to improve resectability and outcomes .
This systematic review investigated the effects of reirradiation in terms of feasibility , toxicity , and long-term outcomes .