standard management for locally advanced rectal cancer ( larc ) involves preoperative chemoradiotherapy ( crt ) and radical surgery . however , this level of treatment may be unnecessary for a subgroup of larc patients . previous reports have shown that approximately 20% of larc patients experience a complete tumor response to preoperative crt . post - crt nonoperative management of these patients may prevent morbidities associated with radical surgery . to our knowledge , this case report firstly presents the favorable long - term outcomes of a larc patient who underwent definitive aim crt . a radiotherapy ( rt ) dose of 64.8 gy was prescribed , which was higher than conventional ( 50.4 gy ) preoperative aim rt . the regimen of concurrent chemotherapy was the same as that used in preoperative aim crt : 2 cycles of 5-fluorouracil and leucovorin . this patient is alive after 4 years with no evidence of recurrence or severe toxicity . the long - term outcomes of this case indicate the feasibility of definitive high - dose rt with concurrent chemotherapy for larc . standard management for locally advanced rectal cancer ( larc ; stage ii or iii ) consists of preoperative ( rather than postoperative ) chemoradiotherapy ( crt ) , radical transabdominal surgery , and postoperative chemotherapy . this multimodal combined treatment plan has significantly improved disease control and patient survival , but has inevitably been accompanied by an increase in morbidities and functional deterioration . to decrease suffering from treatment sequelae , research to individualize treatments for larc patients that is , from postoperative to preoperative has allowed for the classification of larc patients based on the tumor response to preoperative crt . whether the tumor regresses post - crt or not , the tumor is removed surgically ; however , long - term outcomes are strongly correlated with the degree of crt - induced tumor regression . the crt response reflects tumor behavior and has become a key factor in introducing personalized treatments for larc . for example , conservative local excision or a nonoperative watch - and - wait approach has been investigated to avoid the morbidities associated with radical surgery in selected larc patients whose tumors show a complete or near - complete response to crt . this study presents a case of larc in a patient who refused surgery , received definitive high - dose radiotherapy ( rt ) with concurrent chemotherapy , and showed a complete tumor response with long - term disease - free survival . a 73-year - old man visited the hospital in september 2011 because of hematochezia , which had started 3 days before . the serum carcinoembryonic antigen level was 6.31  ng / ml ( normal range 05.0  ng / ml ) . nothing was palpated upon digital rectal examination , but colonoscopy showed an ulcerofungating mass ( fig . 1a ) , with the distal end located 10  cm from the anal verge . pelvic computed tomography ( ct ) and magnetic resonance imaging indicated a 4-cm - long irregular shaped eccentric enhancing wall thickening with perirectal fat infiltration ( fig . 1c ) , and 7 enlarged ( short - axis diameter 5  mm ) mesorectal lymph nodes . f - fluorodeoxyglucose positron emission tomography - ct revealed a hypermetabolic lesion in the rectum , with a maximum standardized uptake value of 8.3 , and several perirectal lymphadenopathies with mild fluorodeoxyglucose uptake . the pretreatment clinical stage was determined to be t3n2bm0 ( iiic ) according to the american joint committee on cancer staging , 7 ed . the institutional review board ( soonchunhyang university cheonan hospital ) waived the approval , as this is a retrospective case report . colonoscopy before ( a ) and 1 year after chemoradiotherapy ( b ) . computed tomography before ( c ) and 3 months after chemoradiotherapy ( d ) . the patient refused surgery despite explanations to him that surgical resection was the standard definitive treatment . rt with a radiation dose higher than that of standard preoperative rt was prescribed as definitive treatment . for rt simulation , a contrast - enhanced planning ct scan was performed using a 16-slice ct scanner ( brilliance ct big bore ; philips medical systems , cleveland , oh ) . axial ct images were obtained at 5-mm intervals and imported to the eclipse rt planning system ( varian medical systems , inc . , target delineation followed the recommendations of the international commission on radiation units and measurements reports no . the initial clinical target volume ( ctv ) encompassed the gross mural tumor , involved lymph nodes , mesorectum , presacral space , and the internal iliac and distal common iliac lymphatics . the planning target volume was generated by the addition of a 5-mm isotropic set - up margin to the ctv . the small bowel , bladder , and femur head were outlined as organs at risk . most of the small bowel was displaced from the pelvic cavity by the belly board . a 3-dimensional conformal plan was developed using a 6-mv photon posterior - anterior field and 15-mv photon opposed lateral fields with 45 degree wedges . the plan was normalized such that 95% of the planning target volume received 100% of the prescription dose . boost ctv included the gross mural tumor , involved lymph nodes , and adjacent mesorectum . the boost plan was composed of four 15-mv photon fields : anterior / posterior right / left oblique fields . rt was performed on a novalis tx system ( varian medical systems , palo alto , ca and brainlab , feldkirchen , germany ) . patient set - up was verified weekly before treatment using an electronic portal imaging device . chemotherapy was administered concurrently with rt , using 5-fluorouracil and leucovorin , and consisted of 2 cycles of a bolus infusion of 5-fluorouracil ( 450  mg / m / d ) and leucovorin ( 20  mg / m / d ) for 5 days during the 15 and 2428 fractions of rt . the patient was admitted to the hospital during concurrent crt , but on other days , rt alone was performed during the outpatient visits . volume histogram : boost planning target volume ( red ) , bladder ( yellow ) , small bowel ( blue ) , left ( dark green ) , and right ( green ) femur head . follow - up evaluation for rectal cancer patients consisted of physical and digital rectal examinations , complete blood cell counts , liver function tests , and measurement of carcinoembryonic antigen levels every 3 months for the first 2 years and every 6 months thereafter . three months after crt completion , the mass or stenosis was not palpated on digital rectal examination . 1b ) , and biopsy of a scar revealed no tumor cells , but revealed chronic nonspecific proctitis . treatment toxicity involved nausea and fatigue during crt and defecation difficulty during the early follow - ups ; however , these subsided with conservative management . four years after treatment , the patient is alive with no evidence of disease and no severe complications . crt , involving a higher than conventional preoperative rt dose , eradicated all of the tumor cells . a complete response by crt represents low biologic tumor aggressiveness , and the patient survived with no tumor relapse or serious toxicity . standard treatment for this patient would be a combination of preoperative crt and radical surgery . surgical resection has played a major role in the treatment of rectal cancer , whereas crt is considered a neoadjuvant or adjuvant therapy . however , surgical resection is also a major contributor to the morbidities induced by combined treatments . this technique removes a circumferential envelope of perirectal tissue in its entirety and significantly reduces local recurrence rates compared with the historical blunt dissection . however , various perioperative complications are associated with this procedure , such as infection , pelvic sepsis , vascular or ureteral injury , anastomotic leak , and wound complications . the mortality rate after total mesorectal excision is at least 2% even in fit patients , and over one - third of patients report some degree of urologic and sexual dysfunction and fecal incontinence . a permanent colostomy , inducing significant physical and psychological morbidity , is required in 10% to 30% of rectal cancer patients . rt decreases local recurrence rates compared with total mesorectal excision alone , and this effect is more pronounced when given preoperatively versus postoperatively . in addition to this long - term benefit , preoperative crt results in the complete regression of tumors in approximately 20% of patients . such findings challenge the routine use of radical resection in all larc patients . for selected patients showing a remarkable crt response , investigators have explored post - crt nonoperative management , also called a watch - and - wait approach , with surgery reserved as salvage therapy . individualized strategies investigated for larc patients also include selective use of rt to evade radiation toxicity , which exacerbates surgical morbidities . however , for those patients in whom rt performs a definitive role and completely eradicates the tumor , selective use of surgery ( or deferral of surgery ) results in fewer morbidities because surgery is the main cause of morbidities following combined multimodal treatments . nonoperative management of this patient was not determined after identifying a crt response , but rather was decided before treatment due to the refusal of surgery . however long - term follow - up outcomes indicate that this nonoperative approach is feasible . nonoperative management or a watch - and - wait approach was pioneered by habr - gama and her colleagues in brazil . they published a series of retrospective studies including hundreds of patients with mainly t3 or n1 mid / low rectal tumors . according to their latest publication , this approach resulted in a 5-year rate of local recurrence that was  not amenable to salvage  as low as 6% . early tumor regrowth ( within the initial 12 months of follow - up ) occurred in up to 19% of patients ; however , 94% of these patients were able to undergo salvage surgery , with a 75% sphincter preservation rate . after 12 months post - crt , an additional 11% of patients developed local recurrence , but salvage was feasible in 91% , with sphincter preservation in 35% . systemic relapse rates were not different between patients with and without local recurrence ( 18% vs. 13% , p  =  0.6 ) , and the 3-year disease - free and overall survival rates were 78% and 88% , respectively , which are comparable to outcomes after standard treatments including crt and surgical resection . these outcomes , including those from a small series prospective trial in the netherlands , were achieved after a conventional preoperative crt regimen , with a typical rt dose of 50.4 gy . a more intensified crt regimen may further increase the number of candidates recommended for a watch - and - wait approach and could further reduce recurrence rates . in the present study , appelt et al showed a significant dose-response relationship for larc regression in the range of 50.4 to 70 gy . in this study , recently , the outcomes of a prospective observational study in which patients with t23n0 - 1m0 distal rectal cancer were managed with high - dose crt and a watchful waiting strategy have been reported . sixty - five gy rt was composed of 60 gy external beam rt and 5 gy endorectal brachytherapy boost . of 51 eligible patients , 40 ( 78.4% ) had a clinical complete response and were allocated to observation . cumulative local recurrence rates in the observance groups after 1 and 2 years were 15.5% and 25.9% , respectively . no unexpected serious adverse reactions or treatment - related deaths occurred , and ultimately , more than half of all patients were managed nonsurgically . the current case used external beam rt only ; however , it suggests that high - dose rt may increase the chances of a complete response and preclude surgical resection , without serious side effects . newer technologies such as intensity - modulated rt and proton therapy may allow for a safe increase in the radiation dose for treatment of rectal cancer , which could thereby expand the patient group suitable for nonsurgical strategies and improve the long - term outcomes of patients treated by such strategies . bypassing definitive surgery , which has long been the standard treatment for larc , represents a radical change in the practice . currently , limitations persist in terms of crt response evaluation and appropriate candidate selection . however , this alternative option is of particular concern in elderly or medically inoperable patients who are at higher risk of significant morbidity ( including permanent stoma ) and mortality associated with radical surgery . if biomolecular strategies are developed to accurately select tumors with a high susceptibility to rt , high - dose crt may become a valid option as definitive treatment . continuing evolution of rectal cancer treatment , especially for distal rectal cancer , may mimic that of anal cancer , for which crt is the standard definitive treatment .
abstractbackground : standard management for locally advanced rectal cancer ( larc ) involves preoperative chemoradiotherapy ( crt ) and radical surgery . 
 however , this level of treatment may be unnecessary for a subgroup of larc patients . 
 previous reports have shown that approximately 20% of larc patients experience a complete tumor response to preoperative crt . 
 post - crt nonoperative management of these patients may prevent morbidities associated with radical surgery . to our knowledge 
 , this case report firstly presents the favorable long - term outcomes of a larc patient who underwent definitive aim crt.methods:the patient was 73 years old , and staging workups revealed t3n2bm0 rectal adenocarcinoma . 
 he agreed to receive crt , but refused surgery . 
 a radiotherapy ( rt ) dose of 64.8 gy was prescribed , which was higher than conventional ( 50.4 gy ) preoperative aim rt . 
 the regimen of concurrent chemotherapy was the same as that used in preoperative aim crt : 2 cycles of 5-fluorouracil and leucovorin.results:three months after crt completion , a complete tumor response was identified clinically . 
 colonoscopic biopsy after 1 year showed no tumor cells . 
 this patient is alive after 4 years with no evidence of recurrence or severe toxicity.conclusion:the long - term outcomes of this case indicate the feasibility of definitive high - dose rt with concurrent chemotherapy for larc .