COLLECTIVE REVIEW NO\'EA.IBLI< 75, L O I 3 p~~ -

Short-course Radiation Versus Long-Course Chemoradiation for

Rectal Cancer

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1. Minsky BD. Short-course radiation versus long-course chemoradiation for rectal cancer: making progress. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 201 2;30(31):3777-8.

2. Colorectal Cancer Collaborative Group: Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001, 358:1291-1304. '

3. David Sebag-Montefiore GR. Choosing between short-course preoperative radiotherapy and long-course chemoradiation therapy. Current Colorectal Cancer Reports 5(4): 232-9.

4. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. The New England journal of medicine. 1997;336(14):980-7

5. Sauer R, Fietkau R, Wittekind C, Rodel C, Martus P, Hohenberger W, et al. Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2003;5(5):406-15.

6. Bujko K, Bujko M. Point: short-course radiation therapy is preferable in the neoadjuvant treatment of rectal cancer. Seminars in radiation oncology. 201 1 ;21(3): 220-7.

7. Minsky BD. Counterpoint: long-course chemoradiation is preferable in the neoadjuvant treatment of rectal cancer. Seminars in radiation oncology. 201 1 ;21(3): 228-33.

8. Mohiuddin M, Marks J, Marks G. Management of rectal cancer: short- vs. long- course preoperative radiation. International journal of radiation oncology, biology, physics: 2008;72(3):636-43.

9. Tiefenbacher U, Wenz F. [Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer]. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft [et all. 2001 ;177(12):682-4.

10.Chan AK, Wong AO, Langevin J, et al. Preoperative chemoradiotherapy and pelvic radiation for tethered or fixedrectal cancer: a phase II dose escalation study. Int J Ra- diat Oncol Biol Phys 2000; 48 (3): 843-56.

11 .Ahmad NR, Marks G, Mohiuddin M. High-dose pre-operative radiation for cancer of the rectum: impact ofradiation dose on patterns of failure and survival. lntJ Radiat Oncol Biol Phys 1993; 27: 773-8.

12.Mohiuddin M, Winter K, Mitchell E, et al. Randomizedphase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation TherapyOncology Group Trial 0012. J Clin Oncol 2006; 24 (4):650-5.

13.Fortier GA, Constable WC, Meyers H, et al. Preoperativeradiation therapy for rectal cancer. Arch Surg 1 986; 121 : I 380-4.

14.Peeters KC, van de Velde CJ, Leer JW, et al.: Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients-a Dutch colorectal cancer group study. J Clin Oncol 2005, 23:6199-6206.

15.Marijnen CA, van de Velde CJ, Putter H, et al.: Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2005,23:1847-1858.

16.Marijnen CA, Kapiteijn E, van de Velde CJ, et al.: Acute side effects and complications after short-term preoperative radiotherapy combined with total * ,

mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002, 20:817-825.

17.McLachlan S, Fisher R, McLure B, et al.: A comparison of quality of life in patients with T3 rectal cancer receiving short course versus long course radiation. A Trans- Tasman Radiation Oncology Group Trial (TROG 01.04) [abstract]. J Clin Oncol 2008, 26:4097.

18.Siegel R, Burock S, Wernecke KD, et al.: Preoperative short- course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer 2009, 9:50.

19.Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJ, Beets-Tan RG, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPID0 trial. BMC cancer. 201 3;13:279.