Reirradiation for Locally Recurrent Rectal Cancer: A Review

Abstract

Among patients diagnosed with locoregionally advanced rectal cancer requiring neoadjuvant therapy and proctectomy, approximately 5 to 10% will develop pelvic recurrences which are associated with significant morbidity and mortality. After standard neoadjuvant chemoradiotherapy and proctectomy, pelvic recurrences are typically unresectable or borderline-resectable, necessitating consideration of reirradiation using conformal external beam techniques and/or intraoperative radiotherapy to achieve margin-negative resection. Given the heterogeneity of pelvic recurrences in combination with altered pelvic anatomy and adjacent radiosensitive organs, there remains significant uncertainty regarding optimal patient selection, reirradiation techniques, organ tolerances with cumulative radiotherapy doses, and the use of intraoperative radiotherapy. In this article, we review the available evidence supporting the efficacy, toxicity, and techniques of reirradiation with photons, particle therapy, intraoperative radiotherapy, and stereotactic body radiotherapy (SBRT). We highlight the consistent prognostic relevance of surgical resection, techniques to limit toxicity with reirradiation, and contemporary uncertainties regarding the roles of sequential multiagent chemotherapy, particle therapy, SBRT, and intraoperative radiotherapy boost.

Keywords

locally recurrent rectal cancer - reirradiation - hyperfractionation

Publikationsverlauf

Eingereicht: 26. Januar 2025

Angenommen: 06. März 2025

Artikel online veröffentlicht:
29. April 2025

• References

• 1 Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024; 74 (01) 12-49
• 2 Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology 2020; 158 (02) 341-353
• 3 Amarnath SR. The role of intraoperative radiotherapy treatment of locally advanced rectal cancer. Clin Colon Rectal Surg 2023; 37 (04) 239-247
• 4 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
• 5 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
• 6 Dijkstra EA, Nilsson PJ, Hospers GAP. et al; Collaborative Investigators. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared with long-course chemoradiotherapy and surgery: a 5-year follow-up of the RAPIDO trial. Ann Surg 2023; 278 (04) e766-e772
• 7 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
• 8 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
• 9 Regan SN, Hendren S, Krauss JC, Crysler OV, Cuneo KC. Treatment of locally recurrent rectal cancer: a review. Cancer J 2024; 30 (04) 264-271
• 10 Beyond TMEC. Beyond TME Collaborative. Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br J Surg 2013; 100 (08) E1-E33
• 11 Guren MG, Undseth C, Rekstad BL. et al. Reirradiation of locally recurrent rectal cancer: a systematic review. Radiother Oncol 2014; 113 (02) 151-157
• 12 Lee J, Kim CY, Koom WS, Rim CH. Practical effectiveness of re-irradiation with or without surgery for locoregional recurrence of rectal cancer: a meta-analysis and systematic review. Radiother Oncol 2019; 140: 10-19
• 13 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
• 14 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
• 15 Mohiuddin M, Ahmad NR. Pre-operative chemoradiation for advanced rectal cancer. Int J Radiat Oncol Biol Phys 1993; 25 (05) 923-924
• 16 Mohiuddin M, Marks GM, Lingareddy V, Marks J. Curative surgical resection following reirradiation for recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1997; 39 (03) 643-649
• 17 Mohiuddin M, Marks G, Marks J. Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer 2002; 95 (05) 1144-1150
• 18 Haddock MG, Gunderson LL, Nelson H. et al. Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients. Int J Radiat Oncol Biol Phys 2001; 49 (05) 1267-1274
• 19 Valentini V, Morganti AG, Gambacorta MA. et al; Study Group for Therapies of Rectal Malignancies (STORM). Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: a multicentric phase II study. Int J Radiat Oncol Biol Phys 2006; 64 (04) 1129-1139
• 20 Tao R, Tsai CJ, Jensen G. et al. Hyperfractionated accelerated reirradiation for rectal cancer: an analysis of outcomes and toxicity. Radiother Oncol 2017; 122 (01) 146-151
• 21 Kramer S. Reirradiation: indications–technique–results. Prog Radiat Ther 1962; 2: 195-214
• 22 Pryzant RM, Wendt CD, Delclos L, Peters LJ. Re-treatment of nasopharyngeal carcinoma in 53 patients. Int J Radiat Oncol Biol Phys 1992; 22 (05) 941-947
• 23 Laramore GE, Griffin TW, Parker RG, Gerdes AJ. The use of electron beams in treating local recurrence of breast cancer in previously irradiated fields. Cancer 1978; 41 (03) 991-995
• 24 Green N, Melbye RW. Lung cancer: retreatment of local recurrence after definitive irradiation. Cancer 1982; 49 (05) 865-868
• 25 Lingareddy V, Ahmad NR, Mohiuddin M. Palliative reirradiation for recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1997; 38 (04) 785-790
• 26 Valentini V, Morganti AG, De Franco A. et al. Chemoradiation with or without intraoperative radiation therapy in patients with locally recurrent rectal carcinoma: prognostic factors and long term outcome. Cancer 1999; 86 (12) 2612-2624
• 27 Sun DS, Zhang JD, Li L, Dai Y, Yu JM, Shao ZY. Accelerated hyperfractionation field-involved re-irradiation combined with concurrent capecitabine chemotherapy for locally recurrent and irresectable rectal cancer. Br J Radiol 2012; 85 (1011): 259-264
• 28 Cai G, Zhu J, Hu W, Zhang Z. Accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation: results of a phase II study. Radiat Oncol 2014; 9: 278
• 29 Das P, Delclos ME, Skibber JM. et al. Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation. Int J Radiat Oncol Biol Phys 2010; 77 (01) 60-65
• 30 Ng MK, Leong T, Heriot AG, Ngan SY. Once-daily reirradiation for rectal cancer in patients who have received previous pelvic radiotherapy. J Med Imaging Radiat Oncol 2013; 57 (04) 512-518
• 31 Youssef FF, Parikh PJ, DeWees TA. et al. Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who have received prior pelvic radiation therapy. Adv Radiat Oncol 2016; 1 (02) 94-100
• 32 Matsuyama T, Yamauchi S, Masuda T. et al; Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. Treatment and subsequent prognosis in locally recurrent rectal cancer: a multicenter retrospective study of 498 patients. Int J Colorectal Dis 2021; 36 (06) 1243-1250
• 33 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
• 34 Nordkamp S, Voogt ELK, van Zoggel DMGI. et al. Locally recurrent rectal cancer: oncological outcomes with different treatment strategies in two tertiary referral units. Br J Surg 2022; 109 (07) 623-631
• 35 Haddock MG. Intraoperative radiation therapy for colon and rectal cancers: a clinical review. Radiat Oncol 2017; 12 (01) 11
• 36 Bussières E, Gilly FN, Rouanet P. et al. Recurrences of rectal cancers: results of a multimodal approach with intraoperative radiation therapy. French Group of IORT. Intraoperative radiation therapy. Int J Radiat Oncol Biol Phys 1996; 34 (01) 49-56
• 37 Haddock MG, Miller RC, Nelson H. et al. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. Int J Radiat Oncol Biol Phys 2011; 79 (01) 143-150
• 38 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
• 39 Buchberger DS, Videtic GMM. Stereotactic body radiotherapy for the management of early-stage non-small-cell lung cancer: a clinical overview. JCO Oncol Pract 2023; 19 (05) 239-249
• 40 Lax I, Blomgren H, Näslund I, Svanström R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol 1994; 33 (06) 677-683
• 41 Blomgren H, Lax I, Näslund I, Svanström R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol 1995; 34 (06) 861-870
• 42 Kim MS, Choi C, Yoo S. et al. Stereotactic body radiation therapy in patients with pelvic recurrence from rectal carcinoma. Jpn J Clin Oncol 2008; 38 (10) 695-700
• 43 Defoe SG, Bernard ME, Rwigema JC, Heron DE, Ozhasoglu C, Burton S. Stereotactic body radiotherapy for the treatment of presacral recurrences from rectal cancers. J Cancer Res Ther 2011; 7 (04) 408-411
• 44 Dagoglu N, Mahadevan A, Nedea E, Poylin V, Nagle D. Stereotactic body radiotherapy (SBRT) reirradiation for pelvic recurrence from colorectal cancer. J Surg Oncol 2015; 111 (04) 478-482
• 45 Smith T, O'Cathail SM, Silverman S. et al. Stereotactic body radiation therapy reirradiation for locally recurrent rectal cancer: outcomes and toxicity. Adv Radiat Oncol 2020; 5 (06) 1311-1319
• 46 Johnstone P, Okonta L, Aitken K. et al. A multicentre retrospective review of SABR reirradiation in rectal cancer recurrence. Radiother Oncol 2021; 162: 1-6
• 47 Robinson M, O'Cathail S, Duffton A, Aitken K, Muirhead R. Potential for isotoxic re-irradiation stereotactic ablative body radiotherapy in locally recurrent rectal cancer. Clin Oncol (R Coll Radiol) 2022; 34 (09) 571-577
• 48 Koroulakis A, Molitoris J, Kaiser A. et al. Reirradiation for rectal cancer using pencil beam scanning proton therapy: a single institutional experience. Adv Radiat Oncol 2020; 6 (01) 100595
• 49 Takagawa Y, Suzuki M, Seto I. et al. Proton beam reirradiation for locally recurrent rectal cancer patients with prior pelvic irradiation. J Radiat Res 2024; 65 (03) 379-386
• 50 Habermehl D, Wagner M, Ellerbrock M. et al. Reirradiation using carbon ions in patients with locally recurrent rectal cancer at HIT: first results. Ann Surg Oncol 2015; 22 (06) 2068-2074
• 51 Barcellini A, Vitolo V, Cobianchi L. et al. Re-irradiation with carbon ion radiotherapy for pelvic rectal cancer recurrences in patients previously irradiated to the pelvis. In Vivo 2020; 34 (03) 1547-1553
• 52 Cai X, Li P, Zhao J. et al. Definitive carbon ion re-irradiation with pencil beam scanning in the treatment of unresectable locally recurrent rectal cancer. J Radiat Res 2023; 64 (06) 933-939
• 53 Chung SY, Takiyama H, Kang JH. et al. Comparison of clinical outcomes between carbon ion radiotherapy and X-ray radiotherapy for reirradiation in locoregional recurrence of rectal cancer. Sci Rep 2022; 12 (01) 1845
• 54 Jeans EB, Ebner DK, Takiyama H. et al. Comparing oncologic outcomes and toxicity for combined modality therapy vs. carbon-ion radiotherapy for previously irradiated locally recurrent rectal cancer. Cancers (Basel) 2023; 15 (11) 3057
• 55 Denost Q, Frison E, Salut C. et al; On Behalf the GRECCAR Group. A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer - GRECCAR 15 trial protocol. Colorectal Dis 2021; 23 (07) 1909-1918
• 56 PelvEx C. Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II). BJS Open 2021; 5 (03)
• 57 Cercek A, Lumish M, Sinopoli J. et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022; 386 (25) 2363-2376
• 58 Xia F, Wang Y, Wang H. et al. Randomized Phase II trial of immunotherapy-based total neoadjuvant therapy for proficient mismatch repair or microsatellite stable locally advanced rectal cancer (TORCH). J Clin Oncol 2024; 42 (28) 3308-3318