Research Progress of Preoperative Radiotherapy for Rectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DU Bingqing , ZHONG Xiaogang , MAI Wei ,  HUANG Shunrong.

Department of Gastroenterology Surgery， The People’s Hospital of Guangxi Zhuang Autonomous Region， Nanning 530021， Guangxi Zhuang Autonomous Region， China;

Corresponding author：

HUANG Shunrong., Email: shunronghuanggx@163.com

Keywords：

Rectal cancer; Preoperative radiotherapy; Short-course radiotherapy; Conventionally radiotherapy; Local recurrence rate; Radiosensitivity; Gene expression profiling

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Objective 　To summarize the current advancement of preoperative radiotherapy for rectal cancer.
Methods 　Relevant literatures about current advancement of preoperative radiotherapy for rectal cancer published domesticly and abroad recently were collected and reviewed.
Results 　The lower local recurrence rate and longer disease-free survival time were observed in preoperative radiotherapy， compared with postoperative radiotherapy for rectal cancer. The recurrence rate was higher in short-course radiotherapy， compared with conventionally radiotherapy for stageⅢrectal cancer， but there was no significant difference for stageⅡrectal cancer. The biology molecular such as p53， CEA， Cox-2， EGFR， and VEGF had shown to be radiosensitive.
Conclusions 　The proposal of preoperative radiotherapy for rectal cancer， could be prone to conventionally radiotherapy. There are more screening targets for preoperative radiotherapy in extensive exploration of diverse radiosensitivity. Biology molecular， developed gene expression profiling， and gene chips for rectal cancer may contribute to the individualization treatment.

Citation： DU Bingqing,ZHONG Xiaogang,MAI Wei,HUANG Shunrong.. Research Progress of Preoperative Radiotherapy for Rectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(12): 1357-1361. doi: Copy

1.	Nelson H， Petrelli N， Carlin A， et al. Guidelines 2000 for colon and rectal cancer surgery[J]. Natl Cancer Inst， 2001， 93(8)：583-596.
2.	Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma[J]. N Engl J Med， 1985， 312(23)：1465-1472.
3.	Camma C， Giunta M， Fiorica F， et al. Preoperative radiotherapy for resectable rectal cancer： a meta-analysis[J]. JAMA， 2000， 284(8)：1008-1015.
4.	Engstrom PF， Arnoletti JP， Benson AB 3rd， et al. NCCN Clinical Practice Guidelines in Oncology： rectal cancer[J]. J Natl Compr Canc Netw， 2009， 7(8)：838-881.
5.	Yeh CH， Chen MF， Lai CH， et al. Comparison of treatmentresults between surgery alone， preoperative short course radiotherapy， or long-course concurrent chemoradiotherapy in locallyadvanced rectal cancer[J]. Int J Clin Oncol， 2012， 17(5)：482-490.
6.	Tiv M， Puyraveau M， Mineur L， et al. Long-term quality of life in patients with rectal cancer treated with preoperative-radiotherapywithin a randomized trial[J]. Cancer Radiother， 2010， 14(6-7)：530-534.
7.	Sauer R， Becker H， Hohenberger W， et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med， 2004， 351(17)：1731-1740.
8.	van Giin W， Marijinen CA， Naqteqaal ID， et al. Preoperativeradiotherapy combined with total mesorectal excision for resectable rectal cancer：12-year follow-up of the multicentre， rando-mised controlled TME trial[J]. Lancet Oncol， 2011， 12(6)：575-582.
9.	Sebag-Montefiore D， Steele R， Quirke P， et al. Routine short course pre-op radiotherapy or selective post-op chemoradiotherapyfor resectable rectal cancer? Preliminary results of the MRC CR07randomised trial[J]. J Clin Oncol， 2006， 24(18)：3511-3514.
10.	Marijnen CA， Nagtegaal ID， Klein Kranenbarg E， et al. No downstaging after short-term preoperative radiotherapy in rectal cancer patients[J]. J Clin Oncol， 2001， 19(7)：1976-1984.
11.	Francois Y， Nemoz CJ， Baulieux J， et al. Infuence of the interval between preoperative radiation therapy and surgery on downstaging and the rate of sphincter sparing surgery for rectal cancer：the Lyon R9001 randomized trial[J]. J Clin Oncol， 1999， 17(8)：2396-2402.
12.	Pach R， Kuliq J， Richter P， et al. Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer-treatment results at 5-year follow-up[J]. Lanqenbecks Arch Surg， 2012， 397(5)：801-807.
13.	Pollack J， Holm T， Cedermark B， et al. Long-term effect ofpreoperative radiation therapy on anorectal function[J]. DisColon Rectum， 2006， 49(3)：345-352.
14.	Sauer R， Becker H， Hohenberger W， et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med， 2004， 351(17)：1731-1740.
15.	Bujko K， Nowacki MP， Nasierowska-Guttmejer A， et al. Sphincterpreservation following preoperative radiotherapy for rectal cancer：report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy[J]. Radiother Oncol， 2004， 72(1)：15-24.
16.	Eitta MA， EI-Wahidi GF， Fouda MA， et al. Preoperativeradiotherapy in resectable rectal cancer：a prospective randomized study of two different approaches[J]. Jegypt Nati Canc Inst， 2010， 22(3)：155-164.
17.	Klenova A， Parvanova V， Georqiev R， et al. Preoperative radiotherapy in rectal cancer：treatment results of three different dose regimens[J]. J Buon， 2006， 11(2)：161-166.
18.	Bosset JF， Collette L， Calais G， et al. Chemothrapy with preoperative radiotherapy in rectal cancer[J]. N Engl J Med， 2006， 355(11)：1114-1123.
19.	Gerard JP， Bonnetain F， Conroy T， et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers：results of the FFCD9203[J]. Clin Oncol， 2006， 24(28)：4620-4625.
20.	Rouanet P， Rivoire M， Lelong B， et al. Sphincter preserving surgery after preoperative treatment for ultra-low rectal carcinoma. A French multicenter prospective trial： GRECCAR 1[J]. Proc Am Soc Clin Oncol， 2006， 24(18)：3527-3530.
21.	Stojanovic S， Popov I， Radosevic-Jelic L， et al. Preoperativeradiotherapy with capecitabine and mitomycin C in locallyadvanced rectal carcinoma[J]. Cancer Chemother Pharmacol， 2011， 68(3)：787-793.
22.	Das P， Skibber JM， Rodriquez-Bigas MA， et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation[J]. Cancer， 2007， 109(9)：1750-1755.
23.	吴文铭，邱辉忠，吴斌，等. 临床病理指标预测直肠癌新辅助治疗效果初探[J]. 中华外科杂志， 2010，48(5)：348-352.
24.	Ishihara S， Watanabe T， Kiyomatsu T， et al. Prognostic signifi-cance of response to preoperative radiotherapy， lymph nodemetastasis， and CEA level in patients undergoing total mesorectal excision of rectal cancer[J]. Int J Colorectal Dis， 2010， 25(12)：1417-1425.
25.	Korkeila EA， Syrjanen K， Bendardaf R， et al. Preoperativeradiotherapy modulates ezrin expression and its value as apredictive marker in patients with rectal cancer[J]. Hum Pathol， 2011， 42(3)：384-392.
26.	Shinto E， Hashiquchi Y， Ueno H， et al. Pretreatment CD133 and cyclooxygenase-2 expression as the predictive markers of the pathological effect of chemoradiotherapy in rectal cancer patients[J]. Dis Colon Rectum， 2011， 54(9)：1006-1098.
27.	Min BS， Choi YJ， Pvo HR， et al. Cyclooxygenase-2 expression in pretreatment biopsy as a predictor of tumor responses afterpreoperative chemoradiation in rectal cancer[J]. Arch Surg， 2008， 143(11)：1091-1097.
28.	Zlobec L， Vuonq T， Compton CC， et al. Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy[J]. Br J Cancer， 2008， 98(2)：450-456.
29.	Unsal Kilic D， Uner A， Akyurek N， et al. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy[J]. Int J Radiat Oncol Biol Phys， 2007， 67(1)：196-203.
30.	Moureau-Zabotto L， Farnault B， de Chaisemartin C， et al.Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer[J]. Int J Radiat Oncol Biol Phys， 2011， 80(2)：483-491.
31.	Yasuda K， Nirei T， Sunami E， et al. Density of CD4+ and CD8+ T lymphocytes in biopsy samples can be a predictor of pathologicalresponse to chemoradiotherapy (CRT) for rectal cancer[J]. RadiatOncol， 2011， 6：49.
32.	Kitayama J， Yasuda K， Kawai K， et al. Circulating lymphocyte is an important determinant of the effectiveness of preoperative rediotherapy in advanced rectal cancer[J]. BMC Cancer， 2011， 11：64.
33.	Chang GJ， Rodriguez-Bigas MA， Eng C， et al. Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome[J]. Cancer， 2009， 115(23)：5432-5440.
34.	Hu-Lieskovan S， Vallbohmer D， Zhang W， et al. EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients[J]. Clin Cancer Res， 2011， 17(15)：5161-5169.
35.	Kobunai T， Watanabe T， Fukusato T， et al. REG4， NEIL2， and BIRC5 gene expression correlates with gamma-radiation sensitivityin patients with rectal cancer receiving radiothrapy[J]. Anticancer， 2011， 31(12)：4147-4153.
36.	Watanabe T， Komuro Y， Kiyomatsu T， et al. Prediction ofsensitivity of rectal cancer cells in response to preoterativeradiotherapy by DNA microarray analysis of gene expressionprofiles[J]. Cancer Res， 2006， 66(7)：3370-3374.

1. Nelson H， Petrelli N， Carlin A， et al. Guidelines 2000 for colon and rectal cancer surgery[J]. Natl Cancer Inst， 2001， 93(8)：583-596.
2. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma[J]. N Engl J Med， 1985， 312(23)：1465-1472.
3. Camma C， Giunta M， Fiorica F， et al. Preoperative radiotherapy for resectable rectal cancer： a meta-analysis[J]. JAMA， 2000， 284(8)：1008-1015.
4. Engstrom PF， Arnoletti JP， Benson AB 3rd， et al. NCCN Clinical Practice Guidelines in Oncology： rectal cancer[J]. J Natl Compr Canc Netw， 2009， 7(8)：838-881.
5. Yeh CH， Chen MF， Lai CH， et al. Comparison of treatmentresults between surgery alone， preoperative short course radiotherapy， or long-course concurrent chemoradiotherapy in locallyadvanced rectal cancer[J]. Int J Clin Oncol， 2012， 17(5)：482-490.
6. Tiv M， Puyraveau M， Mineur L， et al. Long-term quality of life in patients with rectal cancer treated with preoperative-radiotherapywithin a randomized trial[J]. Cancer Radiother， 2010， 14(6-7)：530-534.
7. Sauer R， Becker H， Hohenberger W， et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med， 2004， 351(17)：1731-1740.
8. van Giin W， Marijinen CA， Naqteqaal ID， et al. Preoperativeradiotherapy combined with total mesorectal excision for resectable rectal cancer：12-year follow-up of the multicentre， rando-mised controlled TME trial[J]. Lancet Oncol， 2011， 12(6)：575-582.
9. Sebag-Montefiore D， Steele R， Quirke P， et al. Routine short course pre-op radiotherapy or selective post-op chemoradiotherapyfor resectable rectal cancer? Preliminary results of the MRC CR07randomised trial[J]. J Clin Oncol， 2006， 24(18)：3511-3514.
10. Marijnen CA， Nagtegaal ID， Klein Kranenbarg E， et al. No downstaging after short-term preoperative radiotherapy in rectal cancer patients[J]. J Clin Oncol， 2001， 19(7)：1976-1984.
11. Francois Y， Nemoz CJ， Baulieux J， et al. Infuence of the interval between preoperative radiation therapy and surgery on downstaging and the rate of sphincter sparing surgery for rectal cancer：the Lyon R9001 randomized trial[J]. J Clin Oncol， 1999， 17(8)：2396-2402.
12. Pach R， Kuliq J， Richter P， et al. Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer-treatment results at 5-year follow-up[J]. Lanqenbecks Arch Surg， 2012， 397(5)：801-807.
13. Pollack J， Holm T， Cedermark B， et al. Long-term effect ofpreoperative radiation therapy on anorectal function[J]. DisColon Rectum， 2006， 49(3)：345-352.
14. Sauer R， Becker H， Hohenberger W， et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med， 2004， 351(17)：1731-1740.
15. Bujko K， Nowacki MP， Nasierowska-Guttmejer A， et al. Sphincterpreservation following preoperative radiotherapy for rectal cancer：report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy[J]. Radiother Oncol， 2004， 72(1)：15-24.
16. Eitta MA， EI-Wahidi GF， Fouda MA， et al. Preoperativeradiotherapy in resectable rectal cancer：a prospective randomized study of two different approaches[J]. Jegypt Nati Canc Inst， 2010， 22(3)：155-164.
17. Klenova A， Parvanova V， Georqiev R， et al. Preoperative radiotherapy in rectal cancer：treatment results of three different dose regimens[J]. J Buon， 2006， 11(2)：161-166.
18. Bosset JF， Collette L， Calais G， et al. Chemothrapy with preoperative radiotherapy in rectal cancer[J]. N Engl J Med， 2006， 355(11)：1114-1123.
19. Gerard JP， Bonnetain F， Conroy T， et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers：results of the FFCD9203[J]. Clin Oncol， 2006， 24(28)：4620-4625.
20. Rouanet P， Rivoire M， Lelong B， et al. Sphincter preserving surgery after preoperative treatment for ultra-low rectal carcinoma. A French multicenter prospective trial： GRECCAR 1[J]. Proc Am Soc Clin Oncol， 2006， 24(18)：3527-3530.
21. Stojanovic S， Popov I， Radosevic-Jelic L， et al. Preoperativeradiotherapy with capecitabine and mitomycin C in locallyadvanced rectal carcinoma[J]. Cancer Chemother Pharmacol， 2011， 68(3)：787-793.
22. Das P， Skibber JM， Rodriquez-Bigas MA， et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation[J]. Cancer， 2007， 109(9)：1750-1755.
23. 吴文铭，邱辉忠，吴斌，等. 临床病理指标预测直肠癌新辅助治疗效果初探[J]. 中华外科杂志， 2010，48(5)：348-352.
24. Ishihara S， Watanabe T， Kiyomatsu T， et al. Prognostic signifi-cance of response to preoperative radiotherapy， lymph nodemetastasis， and CEA level in patients undergoing total mesorectal excision of rectal cancer[J]. Int J Colorectal Dis， 2010， 25(12)：1417-1425.
25. Korkeila EA， Syrjanen K， Bendardaf R， et al. Preoperativeradiotherapy modulates ezrin expression and its value as apredictive marker in patients with rectal cancer[J]. Hum Pathol， 2011， 42(3)：384-392.
26. Shinto E， Hashiquchi Y， Ueno H， et al. Pretreatment CD133 and cyclooxygenase-2 expression as the predictive markers of the pathological effect of chemoradiotherapy in rectal cancer patients[J]. Dis Colon Rectum， 2011， 54(9)：1006-1098.
27. Min BS， Choi YJ， Pvo HR， et al. Cyclooxygenase-2 expression in pretreatment biopsy as a predictor of tumor responses afterpreoperative chemoradiation in rectal cancer[J]. Arch Surg， 2008， 143(11)：1091-1097.
28. Zlobec L， Vuonq T， Compton CC， et al. Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy[J]. Br J Cancer， 2008， 98(2)：450-456.
29. Unsal Kilic D， Uner A， Akyurek N， et al. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy[J]. Int J Radiat Oncol Biol Phys， 2007， 67(1)：196-203.
30. Moureau-Zabotto L， Farnault B， de Chaisemartin C， et al.Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer[J]. Int J Radiat Oncol Biol Phys， 2011， 80(2)：483-491.
31. Yasuda K， Nirei T， Sunami E， et al. Density of CD4+ and CD8+ T lymphocytes in biopsy samples can be a predictor of pathologicalresponse to chemoradiotherapy (CRT) for rectal cancer[J]. RadiatOncol， 2011， 6：49.
32. Kitayama J， Yasuda K， Kawai K， et al. Circulating lymphocyte is an important determinant of the effectiveness of preoperative rediotherapy in advanced rectal cancer[J]. BMC Cancer， 2011， 11：64.
33. Chang GJ， Rodriguez-Bigas MA， Eng C， et al. Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome[J]. Cancer， 2009， 115(23)：5432-5440.
34. Hu-Lieskovan S， Vallbohmer D， Zhang W， et al. EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients[J]. Clin Cancer Res， 2011， 17(15)：5161-5169.
35. Kobunai T， Watanabe T， Fukusato T， et al. REG4， NEIL2， and BIRC5 gene expression correlates with gamma-radiation sensitivityin patients with rectal cancer receiving radiothrapy[J]. Anticancer， 2011， 31(12)：4147-4153.
36. Watanabe T， Komuro Y， Kiyomatsu T， et al. Prediction ofsensitivity of rectal cancer cells in response to preoterativeradiotherapy by DNA microarray analysis of gene expressionprofiles[J]. Cancer Res， 2006， 66(7)：3370-3374.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progress of Preoperative Radiotherapy for Rectal Cancer

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