Download PDF
Clin Colon Rectal Surg 2024; 37(04): 239-247
DOI: 10.1055/s-0043-1770718
Review Article

The Role of Intraoperative Radiotherapy Treatment of Locally Advanced Rectal Cancer

Sudha R. Amarnath
1   Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Intraoperative radiation therapy (IORT) has been used in the treatment of locally advanced and recurrent rectal cancers for the last several decades. Given the heterogeneity of patients treated and different indications for use and dosing at different institutions, it has been difficult to discern if IORT adds any appreciable benefit to standard of care therapies. Herein, the rationale for IORT in rectal cancer is discussed along with the most modern and best available data in 2023. IORT is likely indicated in patients with locally advanced and locally recurrent rectal cancer with threatened margins (R0 or R1 resection) to help improve local control. High-quality imaging and multidisciplinary discussion are necessary to ensure optimal patient selection. Appropriate counseling of the patient and excellent team communication are of the utmost importance given the challenging nature of these cases and the prognostic implications of R1 and R2 resections in this patient population.

Keywords

intraoperative radiotherapy - intraoperative radiation therapy - rectal cancer


Publication History

Article published online:
19 July 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023; 73 (03) 233-254
    CrossrefPubMedGoogle Scholar
  • 2 Haddock MG. Irradiation of very locally advanced and recurrent rectal cancer. Semin Radiat Oncol 2016; 26 (03) 226-235
    CrossrefPubMedGoogle Scholar
  • 3 van der Valk MJM, Hilling DE, Bastiaannet E. et al; IWWD Consortium. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 2018; 391 (10139): 2537-2545
    CrossrefPubMedGoogle Scholar
  • 4 Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1988; 13 (04) 245-252
    CrossrefPubMedGoogle Scholar
  • 5 Kapiteijn E, Marijnen CA, Nagtegaal ID. et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345 (09) 638-646
    CrossrefPubMedGoogle Scholar
  • 6 Sauer R, Becker H, Hohenberger W. et al; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351 (17) 1731-1740
    CrossrefPubMedGoogle Scholar
  • 7 Sauer R, Liersch T, Merkel S. et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012; 30 (16) 1926-1933
    CrossrefPubMedGoogle Scholar
  • 8 Conroy T, Bosset JF, Etienne PL. et al; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22 (05) 702-715
    CrossrefPubMedGoogle Scholar
  • 9 Bahadoer RR, Dijkstra EA, van Etten B. et al; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22 (01) 29-42
    CrossrefPubMedGoogle Scholar
  • 10 Dijkstra EA, Nilsson PJ, Hospers GAP. et al; and collaborative investigators. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared to long-course chemoradiotherapy and surgery - a five-year follow-up of the RAPIDO trial. Ann Surg 2023
    PubMedGoogle Scholar
  • 11 Jin J, Tang Y, Hu C. et al. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol 2022; 40 (15) 1681-1692
    CrossrefPubMedGoogle Scholar
  • 12 Garcia-Aguilar J, Patil S, Gollub MJ. et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 2022; 40 (23) 2546-2556
    CrossrefPubMedGoogle Scholar
  • 13 Habr-Gama A, São Julião GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am 2015; 29 (01) 135-151
    CrossrefPubMedGoogle Scholar
  • 14 Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião GP, Gama-Rodrigues J. Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum 2009; 52 (12) 1927-1934
    CrossrefPubMedGoogle Scholar
  • 15 Dijkstra EA, Mul VEM, Hemmer PHJ. et al. Re-irradiation in patients with recurrent rectal cancer is safe and feasible. Ann Surg Oncol 2021; 28 (09) 5194-5204
    CrossrefPubMedGoogle Scholar
  • 16 Dagoglu N, Nedea E, Poylin V, Nagle D, Mahadevan A. Post operative stereotactic radiosurgery for positive or close margins after preoperative chemoradiation and surgery for rectal cancer. J Gastrointest Oncol 2016; 7 (03) 315-320
    CrossrefPubMedGoogle Scholar
  • 17 Debove C, Maggiori L, Chau A, Kanso F, Ferron M, Panis Y. What happens after R1 resection in patients undergoing laparoscopic total mesorectal excision for rectal cancer? A study in 333 consecutive patients. Colorectal Dis 2015; 17 (03) 197-204
    CrossrefPubMedGoogle Scholar
  • 18 Sebag-Montefiore D, Stephens RJ, Steele R. et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 2009; 373 (9666): 811-820
    CrossrefPubMedGoogle Scholar
  • 19 Gunderson LL, Nelson H, Martenson JA. et al. Locally advanced primary colorectal cancer: intraoperative electron and external beam irradiation +/- 5-FU. Int J Radiat Oncol Biol Phys 1997; 37 (03) 601-614
    CrossrefPubMedGoogle Scholar
  • 20 Wiig JN, Giercksky KE, Tveit KM. Intraoperative radiotherapy for locally advanced or locally recurrent rectal cancer: does it work at all?. Acta Oncol 2014; 53 (07) 865-876
    CrossrefPubMedGoogle Scholar
  • 21 Haddock MG. Intraoperative radiation therapy for colon and rectal cancers: a clinical review. Radiat Oncol 2017; 12 (01) 11
    CrossrefPubMedGoogle Scholar
  • 22 Fahy MR, Kelly ME, Power Foley M, Nugent TS, Shields CJ, Winter DC. The role of intraoperative radiotherapy in advanced rectal cancer: a meta-analysis. Colorectal Dis 2021; 23 (08) 1998-2006
    CrossrefPubMedGoogle Scholar
  • 23 Liu B, Ge L, Wang J. et al. Efficacy and safety of intraoperative radiotherapy in rectal cancer: a systematic review and meta-analysis. World J Gastrointest Oncol 2021; 13 (01) 69-86
    CrossrefPubMedGoogle Scholar
  • 24 Masaki T, Matsuoka H, Kishiki T. et al. Intraoperative radiotherapy for resectable advanced lower rectal cancer-final results of a randomized controlled trial (UMIN000021353). Langenbecks Arch Surg 2020; 405 (03) 247-254
    CrossrefPubMedGoogle Scholar
  • 25 Khan Z, Rooney MK, Das P. et al. Intraoperative radiation after pelvic short course radiation-based total neoadjuvant therapy for patients with rectal adenocarcinoma at high risk for local recurrence. Clin Colorectal Cancer 2022; 21 (03) 204-211
    CrossrefPubMedGoogle Scholar
  • 26 Hagemans JAW, van Rees JM, Alberda WJ. et al. Locally recurrent rectal cancer; long-term outcome of curative surgical and non-surgical treatment of 447 consecutive patients in a tertiary referral centre. Eur J Surg Oncol 2020; 46 (03) 448-454
    CrossrefPubMedGoogle Scholar
  • 27 Mirnezami R, Chang GJ, Das P. et al. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol 2013; 22 (01) 22-35
    CrossrefPubMedGoogle Scholar
  • 28 Ansell J, Perry WRG, Mathis KL. et al. Re-resection of microscopically positive margins found on intraoperative frozen section analysis does not result in a survival benefit in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. Dis Colon Rectum 2022; 65 (09) 1094-1102
    CrossrefPubMedGoogle Scholar
  • 29 National Comprehensive Cancer Network. Rectal Cancer (Version 2). 2023. Accessed April 20, 2023 at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf
    PubMed
  • 30 Calvo FA, Sole CV, Rutten HJ. et al. ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in primary locally advanced rectal cancer. Clin Transl Radiat Oncol 2020; 25: 29-36
    CrossrefPubMedGoogle Scholar
  • 31 Calvo FA, Sole CV, Rutten HJ. et al. ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in locally recurrent rectal cancer. Clin Transl Radiat Oncol 2020; 24: 41-48
    CrossrefPubMedGoogle Scholar
  • 32 Fadel MG, Ahmed M, Malietzis G. et al. Oncological outcomes of multimodality treatment for patients undergoing surgery for locally recurrent rectal cancer: a systematic review. Cancer Treat Rev 2022; 109: 102419
    CrossrefPubMedGoogle Scholar