Application of high-dose-rate endorectal brachytherapy in the treatment of locally advanced rectal cancer

Abstract

Purpose: This study evaluates the efficacy, toxicity, and survival impact of high-dose-rate endorectal brachytherapy (HDR-EBT) as neoadjuvant therapy for locally advanced rectal cancer.

Methods: A review of 16 studies from PubMed, Embase, and Web of Science (1990–2023) was conducted.

Results: Patients treated with HDR-EBT alone had a pathological complete response (pCR) rate of 23.7%–35.3% (mean: 24.3%), anal preservation rate of 12.2%–74.9% (mean: 41.8%), and 5-year progression-free survival rate of 64.6%–65.4% (mean: 65.3%). When combined with concurrent long-term radiotherapy and chemotherapy, pCR rates improved from 18.1%–55.0% (mean: 31.0%), with anal preservation rates of 39.6%–51.4% (mean: 45.3%). However, overall survival did not significantly improve.

Conclusion: Integrating advanced techniques such as intensity-modulated radiation therapy (IMRT) with HDR-EBT shows promise. This approach particularly benefits patients ineligible for surgery or those adopting a watch-and-wait strategy after complete clinical remission, thus highlighting the potential of HDR-EBT in this treatment landscape.

Keywords

High-dose-rate Brachytherapy / Rectal cancer / Systematic review

References

[1] Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. Published online April 5, 2021.

[2] Liao CK, Kuo YT, Lin YC, et al. Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Curr Oncol. 2022; 29(5): 3708-3727.

[3] Stewart AJ, Van Limbergen EJ, Gerard JP, et al. GEC ESTRO ACROP consensus recommendations for contact brachytherapy for rectal cancer. Clin Transl Radiat Oncol. 2021; 33: 15-22.

[4] Shoemaker T, Vuong T, Glickman H, Kaifi S, Famulari G, Enger SA. Dosimetric Considerations for Ytterbium-169, Selenium-75, and Iridium-192 Radioisotopes in High-Dose-Rate Endorectal Brachytherapy. Int J Radiat Oncol Biol Phys. 2019; 105(4): 875-883.

[5] Otter SJ, Stewart AJ, Devlin PM. Modern Brachytherapy. Hematol Oncol Clin North Am. 2019; 33(6): 1011-1025.

[6] Buckley H, Wilson C, Ajithkumar T. High-Dose-Rate Brachytherapy in the Management of Operable Rectal Cancer: A Systematic Review. Int J Radiat Oncol Biol Phys. 2017; 99(1): 111-127.

[7] Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.

[8] Yanagi H, Kusunoki M, Yamamura T. The effectiveness of preoperative intraluminal brachytherapy in preventing wall penetration and nodal involvement of rectal carcinomas. Surg Today. 2000; 30(5): 410-415.

[9] Vuong T, Belliveau PJ, Michel RP, et al. Conformal preoperative endorectal brachytherapy treatment for locally advanced rectal cancer: early results of a phase I/II study. Dis Colon Rectum. 2002; 45(11): 1486-1495.

[10] Jakobsen A, Mortensen JP, Bisgaard C, Lindebjerg J, Hansen JW, Rafaelsen SR. Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost. Int J Radiat Oncol Biol Phys. 2006; 64(2): 461-465.

[11] Vuong T, Devic S, Podgorsak E. High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol (R Coll Radiol). 2007; 19(9): 701-705.

[12] Jakobsen A, Mortensen JP, Bisgaard C, Lindebjerg J, Rafaelsen SR, Bendtsen VO. A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer: a phase II trial. Int J Colorectal Dis. 2008; 23(3): 251-255.

[13] Sun Myint A, Mukhopadhyay T, Ramani VS, et al. Can increasing the dose of radiation by HDR brachytherapy boost following pre operative chemoradiotherapy for advanced rectal cancer improve surgical outcomes?. Colorectal Dis. 2010;12(Suppl 2): 30-36.

[14] Tunio MA, Rafi M, Hashmi A, et al. High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers. World J Gastroenterol. 2010; 16(35): 4436-4442.

[15] Jakobsen A, Ploen J, Vuong T, Appelt A, Lindebjerg J, Rafaelsen SR. Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses. Int J Radiat Oncol Biol Phys. 2012; 84(4): 949-954.

[16] Hesselager C, Vuong T, Påhlman L, et al. Short-term outcome after neoadjuvant high-dose-rate endorectal brachytherapy or short-course external beam radiotherapy in resectable rectal cancer. Colorectal Dis. 2013; 15(6): 662-666.

[17] Appelt AL, Vogelius IR, Pløen J, et al. Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost. Int J Radiat Oncol Biol Phys. 2014; 90(1): 110-118.

[18] Craig-Schapiro R, Kamel IR, Sacerdote M, et al. Radiographic predictors of response to endoluminal brachytherapy for the treatment of rectal cancer. J Radiat Oncol. 2017; 6(3): 287-294.

[19] Garant A, Kavan P, Martin AG, et al. Optimizing treatment sequencing of chemotherapy for patients with rectal cancer: The KIR randomized phase II trial. Radiother Oncol. 2021; 155: 237-245.

[20] Engineer R, Datta D, Gudi S, et al. Dose Escalation Using Magnetic Resonance Guided High-Dose-Rate Endorectal Brachytherapy to Enhance Clinical Response after Neoadjuvant Radiotherapy in Rectal Adenocarcinoma. Int J Radiat Oncol Biol Phys. 2023; 117(2): e295.

[21] Saeedian A, Lashkari M, Ghalehtaki R, et al. Complication and response assessment of high-dose-rate endorectal brachytherapy boost in neo-adjuvant chemoradiotherapy of locally advanced rectal cancer with long-term outcomes. J Contemp Brachytherapy. 2023; 15(2): 117-122.

[22] Breugom AJ, Vermeer TA, van den Broek CB, et al. Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers. Eur J Surg Oncol. 2015; 41(8): 1039-1044.

[23] Vuong T, Devic S. High-dose-rate pre-operative endorectal brachytherapy for patients with rectal cancer. J Contemp Brachytherapy. 2015; 7(2): 183-188.

[24] National Health Commission of the People's Republic of China & Chinese Society of Clinical Oncology. Guidelines for the diagnosis and treatment of colorectal cancer in China (2023 Edition). Chin J Surg.2023; 61(8): 617–644.

[25] Liu S, Jiang T, Xiao L, et al. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021; 26(9): e1555-e1566.

[26] Gerard JP, Barbet N, Schiappa R, et al. Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma (OPERA): a phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023; 8(4): 356-367.

[27] Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012; 99(7): 918-928.

[28] Garant A, Vasilevsky CA, Boutros M, et al. MORPHEUS Phase II-III Study: A Pre-Planned Interim Safety Analysis and Preliminary Results. Cancers (Basel). 2022; 14(15): 3665.

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2025 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.