Abstract
With the implementation of total mesorectal excision surgery and neoadjuvant (chemo) radiotherapy, the outcome of rectal cancer patients has improved and a substantial proportion of them have become long-term survivors. These advances come at the expense of radiation- and chemotherapy-related toxicity which remains an underestimated problem. Radiation-induced early toxicity in rectal cancer treatment mainly includes diarrhea, cystitis, and perineal dermatitis, while bowel dysfunction, fecal incontinence, bleeding, and perforation, genitourinary dysfunction, and pelvic fractures constitute the majority of late toxicity. It is now generally accepted that short-course radiotherapy (SCRT) and immediate surgery is associated with less early toxicity compared to conventionally fractionated chemoradiotherapy with delayed surgery. There are no significant differences in late toxicity between both treatment regimens. While there is hardly an increase in early toxicity after preoperative SCRT with immediate surgery, late toxicity is substantial compared to surgery alone. Early toxicity is more frequent when a longer interval between SCRT and surgery is used and is comparable to the toxicity observed with conventionally fractionated radiotherapy except that it occurs after the end of the radiotherapy. So far, randomized phase III trials failed to demonstrate a substantial gain in tumoural response when oxaliplatin or molecular agents are added to the multimodality treatment. Moreover, the addition of these drugs increases toxicity and remains therefore experimental.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- CRT:
-
Chemoradiotherapy
- SCRT:
-
Short-course radiotherapy
- TME:
-
Total mesorectal excision
References
An X, Lin X, Wang FH et al (2013) Short term results of neoadjuvant chemoradiotherapy with fluoropyrimidine alone or in combination with oxaliplatin in locally advanced rectal cancer: a meta analysis. Eur J Cancer 49:843–851
André T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351
Andreyev HJ, Benton BE, Lalji A et al (2013) Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial. Lancet 382:2084–2092
Aschele C, Cionini L, Lonardi S et al (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomised phase III trial. J Clin Oncol 29:2773–2780
Baerlocher MO, Rajan DK, Ing DJ, Rubin BB (2004) Primary stenting of bilateral radiation-induced external iliac stenoses. J Vasc Surg 40:1028–1031
Bentzen SM (2006) Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 6:702–713
Birgisson H, Påhlman L, Gunnarson U, Glimelius B (2005a) Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 23:8697–8705
Birgisson H, Påhlman L, Gunnarsson U, Glimelius B (2005b) Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol 23:6126–6131
Birgisson H, Påhlman L, Gunnarson U, Glimelius B (2008) Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy. Br J Surg 95:206–213
Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123
Brændengen M, Tveit KM, Berglund A et al (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26:3687–3694
Brændengen M, Tveit KM, Bruheim K, Cvancarova M, Berglund Å, Glimelius B (2011) Late patient-reported toxicity after preoperative radiotherapy or chemoradiotherapy in nonresectable rectal cancer: results from a randomized Phase III study. Int J Radiat Oncol Biol Phys 81:1017–1024
Brændengen M, Tveit KM, Hjermstad MJ et al (2012) Health-related quality of life (HRQoL) after multimodal treatment for primarily non-resectable rectal cancer. Long-term results from a phase III study. Eur J Cancer 48:813–819
Bujko K, Nowacki M, Nasierwska-Guttmejer A et al (2006) Long-term results of a randomised trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93:1215–1223
Bujko K, Nowacki M, Nasierwska-Guttmejer A et al (2004) Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy versus conventionally fractionated radiochemotherapy. Radiother Oncol 72:15–24
Chitapanarux I, Chitapanarux T, Traisathit P, Kudumpee S, Tharavichitkul E, Lorvidhaya V (2010) Randomized controlled trial of live Lactobacillus acidophilus plus Bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol 5:31
Chuang VP (1994) Radiation-induced arteritis. Semin Roentgenol 29:64–69
Dahlberg M, Glimelius B, Graf W, Påhlman L (1998) Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study. Dis Colon Rectum 41:543–549
Delia P, Sansotta G, Donato V et al (2007) Use of probiotics for prevention of radiation-induced diarrhea. Tumori 93(Suppl 2):1–6
Denham JW, Hauer-Jensen M, Kron T, Langberg CW (2000) Treatment-time-dependence models of early and delayed radiation injury in rat small intestine. Int J Radiat Oncol Biol Phys 48:871–887
Dewdney A, Cunningham D, Tabernero J et al (2012) Multicenter randomised phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 30:1620–1627
Dörr W, Hendry JH (2001) Consequential late effects in normal tissues. Radiother Oncol 61:223–231
Dörr W, Bertmann S, Hermann T (2005) Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects. Strahlenther Onkol 181:567–573
Fuccio L, Guida A, Andreyev HJ (2012) Management of intestinal complications in patients with pelvic radiation disease. Clin Gastroenterol Hepatol 10:1326–1334
Frykholm GJ, Sintorn K, Montelius A, Jung B, Påhlman L, Glimelius B (1996) Early lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma. Radiother Oncol 38:121–130
Gérard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625
Gérard JP, Azria D, Gourgou-Bourgade S et al (2010) Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28:1638–1644
Gérard JP, Azria D, Gourgou-Bourgade S et al (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomised trial in rectal cancer. J Clin Oncol 30:4558–4565
Goldberg RM, Sargent DJ, Morton RF et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30
Hatfield P, Hingorani M, Radhakrishna G et al (2009) Short-course radiotherapy, with elective delay prior to surgery, in patients with unresectable rectal cancer who have poor performance status or significant co-morbidity. Radiother Oncol 92:210–214
Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1:1479–1482
Holm T, Singnomklao T, Rutqvist LE, Cedermark B (1996) Adjuvant preoperative radiotherapy in patients with rectal carcinoma. Adverse effects during long term follow-up of two randomized trials. Cancer 78:968–976
Joiner M, van der Kogel A (2009) Basic Clinial Radiobiology. Hodder Arnold, London
Kapiteijn E, Marijnen CA, Nagtegaal ID et al., Dutch Colorectal Cancer Group (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646
Marijnen CA, Kapiteijn E, van de Velde CJ et al., Cooperative Investigators of the Dutch Colorectal Cancer Group (2002) 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 20:817–825
Marijnen CA, van de Velde CJ, Putter H et al (2005) Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomised trial. J Clin Oncol 23:1847–1858
Marquardt F, Rödel F, Capalbo G, Weiss C, Rödel C. (2009) Molecular targeted treatment and radiation therapy for rectal cancer. Strahlenther Onkol 185:371–378
Martling A, Holm T, Johansson H, Rutqvist LE, Cedermark B (2001) The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 92:896–902
Ngan S, Fisher R, Mackay J et al (2007) Early adverse events in a randomised trial of short course versus long course preoperative radiotherapy for T3 adenocarcinoma of rectum: a trans-tasman radiation oncology group trial (TROG01.04). Eur J Cancer 5:237(Abstract)
Ngan SY, Burmeister B, Fisher RJ et al (2012) Randomised trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: trans-tasman radiation oncology group trial 01.04. J Clin Oncol 30:3827–3833
Nilsson PJ, van Etten B, Hospers GA et al (2013) Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial. BMC Cancer 13:279
Peeters KC, van de Velde CJ, Leer JW et al (2005) 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 23:6199–6206
Peeters KC, Marijnen CA, Nagtegaal ID et al (2007) The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg 246:693–701
Pettersson D, Cedermark B, Holm T et al (2010) Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg 97:580–587
Pettersson D, Holm T, Iversen H, Blomqvist L, Glimelius B, Martling A (2012) Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer. Br J Surg 99:577–583
Pietrzak L, Bujko K, Nowacki MP et al., Polish Colorectal Study Group (2007) Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiother Oncol 84:217–25
Pollack J, Holm T, Cedermark B et al (2006a) Late adverse effects of short-course preoperative radiotherapy in rectal cancer. Br J Surg 93:1519–1525
Pollack J, Holm T, Cedermark B, Holmström B, Mellgren A (2006b) Long-term effect of preoperative radiation therapy on anorectal function. Dis Colon Rectum 49:345–352
Radu C, Berglund A, Påhlman L, Glimelius B (2008) Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a retrospective study. Radiother Oncol 87:343–349
Rödel C, Liersch T, Becker H et al (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687
Roh MS, Colangelo LH, O’Connell MJ et al (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 31:5124–5130
Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL (2012) Reduced early bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 82:1981–1987
Sauer R, Becker H, Hohenberger W et al., German Rectal Cancer Study Group (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740
Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomised phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933
Schmoll HJ, Haustermans K, Price T et al (2013) Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: response to the local treatment after chemoradiation and surgery as secondary endpoint. Ann Oncol 24:iv11–24
Sebag-Montefiore D, Stephens RJ, Steele R et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820
Siegel R, Burock S, Wernecke KD et al (2009) 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 9:50
Stockholm Rectal Cancer Study Group (1990) Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomised trial. Cancer 66:49–55
Swedish Rectal Cancer Trial (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336:980–987
Tiv M, Puyreveau M, Mineur L et al (2010) Long-term quaity of life in patients with rectal cancer treated with preoperative (chemo)-radiotherapy within a randomized trial. Cancer Radiother 14:530–534
van Gijn W, Marijnen CA, Nagtegaal ID et al., Dutch Colorectal Cancer Group (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12:575–82
Wedlake LJ, Shaw C, Whelan K, Andreyec HJ (2013) Systematic review: the efficacy of nutritional interventions to counteract acute gastrointestinal toxicity during therapeutic pelvic radiotherapy. Aliment Pharmacol Ther 37:1046–1056
Wolff HA, Wagner DM, Conradi LC et al (2012) Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications. Radiother Oncol 102:30–37
Wolff HA, Conradi LC, Beissbarth T et al (2013) Gender affects acute organ toxicity during radiochemotherapy for rectal cancer: long-term results of the German CAO/ARO/AIO-94 phase III trial. Radiother Oncol 108:48–54
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Joye, I., Haustermans, K. (2014). Early and Late Toxicity of Radiotherapy for Rectal Cancer. In: Otto, F., Lutz, M. (eds) Early Gastrointestinal Cancers II: Rectal Cancer. Recent Results in Cancer Research, vol 203. Springer, Cham. https://doi.org/10.1007/978-3-319-08060-4_13
Download citation
DOI: https://doi.org/10.1007/978-3-319-08060-4_13
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-08059-8
Online ISBN: 978-3-319-08060-4
eBook Packages: MedicineMedicine (R0)