Table 4 Summary of colorectal cancer practice-defining RT clinical trials

From: Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie?

Trial name (first author) Tumour site Trial methodology Practice-defining trial results Publications of trial results Publications related to trial conduct Evidence of practice change
Short course hypofractionated radiotherapy trials in rectal cancer
 Dutch TME Trial (Kapiteijn) Rectal Pre-operative short course radiotherapy 25 Gy in five fractions followed by total mesorectal excision (TME) surgery vs. TME surgery alone. Randomised 1861 patients. Reduced local recurrence rates. No difference in overall survival. 90, 190 191,192,193,194,195,196,197,198,– 199 International: ESMO.92 NCCN.200 UK: NICE.97
 MRC CR07 (Sebag-Montefiore) Rectal Pre-operative short course radiotherapy 25 Gy in five fractions followed by surgery vs. surgery with highly selective post-operative chemoradiotherapy 45 Gy in 25 fractions with concurrent fluorouracil. Randomised 1350 patients. Reduced local recurrence rates and improved disease-free survival in the pre-operative radiotherapy arm. No difference in overall survival. 91 201, 202 International: ESMO.92 NCCN.200 UK: NICE.97
Long-course radiotherapy ± concurrent chemotherapy trials rectal cancer
 EORTC 22921 (Bosset) Rectal Pre-operative RT vs. pre-operative chemoRT vs. pre-operative RT and post-operative chemotherapy vs. pre-operative chemoRT and post-operative chemotherapy in locally advanced rectal cancer. Radiotherapy 45 Gy in 25 fractions. Concurrent chemotherapy 5FU and leucovorin D1-5, 29–33. Randomised 1011 patients. Reduced local recurrence when concurrent 5FU/LV was added in the first and fifth week of radiotherapy. No difference in overall survival. 93 NA International: ESMO.92 NCCN.200 UK: NICE.97
 EORTC 9203 (Gerard) Rectal Pre-operative RT vs. pre-operative chemoRT. Randomised 733 patients. Reduced local recurrence when concurrent 5FU/LV was added in the first and fifth week of radiotherapy. No difference in overall survival. 94 NA International: ESMO.92 NCCN.200 UK: NICE.97
 German Rectal Cancer Trial (Sauer) Rectal Pre-operative CRT (50.4 Gy) with post-operative CRT (55.8 Gy) with concurrent 5FU infusion weeks 1 and 5. Randomised 823 patients. Reduced local recurrence, acute and late toxicity with pre-op CRT. No difference in overall survival. 95 NA International: ESMO.92 NCCN.200 UK: NICE.97
 NSABP R03 (Roh) Rectal Pre-operative CRT (50.4 Gy) with post-operative CRT (50.4 Gy) with concurrent 5FU LV D1-5, 29–33 in locally advanced rectal cancer. Randomised 267 patients. Improved disease-free survival in favour of pre-op CRT. 96 NA International: ESMO.92 NCCN.200 UK: NICE.97
Short-course hypofractionated vs. long-course concurrent chemoradiotherapy trials in rectal cancer
 Polish trial (Bujko) Rectal Pre-operative short course RT (25 Gy in five fractions) with pre-op CRT (50.4 Gy) and 5FU LV D1-5 and 29–33. Randomised 312 patients. Comparable local recurrence overall survival and toxicity for the two treatment regimens. 99 NA International: ESMO.92 UK: NICE.97
 TROG (Ngan) Rectal Pre-operative short course RT (25 Gy in five fractions) with pre-op chemoRT (50.4 Gy) and 5FU LV D1-5 and 29–33. Randomised 312 patients. Comparable local recurrence overall survival and toxicity for the two treatment regimens. 100 NA International: ESMO.92 UK: NICE.97
Concurrent and additional cisplatin in anal cancer
 ACT-2 (James) Anal Fluorouracil with mitomycin (MMC/FU), to fluorouracil with cisplatin, with or without maintenance doses at weeks 11 and 14. Randomised 940 patients. No improvement in 3-year progression-free survival or in complete response rates by substituting mitomycin for cisplatin, nor by adding maintenance therapy. ACT2 used a shrinking field two phase protocol and this become standard radiotherapy practice in the UK. 107, 203 204, 205 International: ESMO.104 NCCN.206
 RTOG 98-11 (Ajanani) Anal Neoadjuvant and concurrent cisplatin 5FU vs. concurrent Mitomycin C and 5FU in patients with anal cancer. Randomised 644 patients. MMC 5FU CRT remains the standard of care. Neoadjuvant and concurrent cisplatin and 5FU resulted in inferior outcomes disease-free and overall survival. 105, 207 208, 209 International: ESMO.104 NCCN.206
 ACCORD 03 (Peiffert) Anal Standard vs. high-dose boost and with or without neoadjuvant cisplatin 5FU chemotherapy. Randomised 307 patients. Higher dose boost and neoadjuvant chemotherapy did not improve cancer outcomes. 106 NA International: NCCN.206
Optimising chemoradiotherapy for anal cancer
 EXTRA (Glynne-Jones) Anal Single arm phase II trial of Mitomycin C capecitabine and radiotherapy (50.4 Gy in 28 F). Entered 31 patients. Acceptable rates of acute toxicity and radiotherapy compliance. Showed that capecitabine can be used instead of 5U with MMC and RT. 108 NA International: ESMO.104 NCCN.206
 RTOG 0529 (Kachnic) Anal Single arm phase II trial if IMRT (54 Gy in 28 F to GTV and 42 Gy in 28 F to CTV) with Mitomycin C and 5FU. Entered 63 patients. Effective and well-tolerated treatment regimen. Supported the introduction if IMRT for a rare cancer. 109 NA International: ESMO104
  1. ESMO European Society for Medical Oncology, NCCN National Comprehensive Cancer Network, NICE National Institute for Health and Care Excellence