Dynamic changes and outcomes of magnetic resonance imaging in radiotherapy-related rectal injury in cervical cancer

Background: To observe dynamic changes of rectal injury in patients with locally advanced cervical cancer during curative pelvic radiotherapy using magnetic resonance imaging (MRI), and to explore non-invasive radiological methods for assessing radiation-induced rectal injury (RRI). Methods: A retrospective analysis was conducted on pelvic MRI images from 56 patients with locally advanced cervical cancer who underwent radical radiotherapy. MRI scans were conducted at four key stages: before radiotherapy, two weeks after starting external irradiation, upon completing external irradiation, and at the conclusion of brachytherapy. Thickness of the intestinal wall from the anorectal region to the sigmoid take-off at each scanning level was measured by RadiAnt DICOM Viewer software, and the average rectal wall thickness was calculated. Statistical analysis was performed using SPSS 26. Results: Out of the 56 patients undergoing pelvic radiation therapy, 30 (53.6%) reported symptoms of rectal injury, including diarrhea, increased frequency of stools, loose stools, abdominal pain, tenesmus, and difficulty in defecation, typically appearing during the 3rd to 5th week of treatment. Medication-preserved enemas were administered in the 5th week of radiotherapy and at the beginning of brachytherapy. In symptomatic patients, rectal wall thickness at two weeks of radiotherapy (7.76 ± 0.96 mm) was significantly greater than that before radiotherapy (6.98 ± 0.77 mm) (p < 0.01). Thickness continued to increase during external irradiation, reaching its peak at the end of external irradiation (7.99 ± 0.83 mm), followed by a decrease at the end of brachytherapy (7.31 ± 0.81 mm), which was significantly reduced compared with end-of-external-irradiation values (p < 0.01). Conclusions: Patients with locally advanced cervical cancer undergoing pelvic radiotherapy exhibit significant early and time-dependent rectal imaging changes prior to the onset of evident clinical symptoms of RRI. MRI may serve as a sensitive diagnostic tool for the early detection and prediction of radiation-induced rectal injury.

Cervical cancer; Radiotherapy; MRI; Radiation-induced rectal injury

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China, 2022. Journal of the National Cancer Center. 2024; 4: 47–53.

[3] Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chinese Medical Journal. 2022; 135: 584–590.

[4] Mayadev JS, Ke G, Mahantshetty U, Pereira MD, Tarnawski R, Toita T. Global challenges of radiotherapy for the treatment of locally advanced cervical cancer. International Journal of Gynecological Cancer. 2022; 32: 436–445.

[5] Dahiya DS, Kichloo A, Tuma F, Albosta M, Wani F. Radiation proctitis and management strategies. Clinical Endoscopy. 2022; 55: 22–32.

[6] Denton A, Forbes A, Andreyev J, Maher EJ. Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database of Systematic Reviews. 2002; CD003455.

[7] Henson CC, Andreyev HJ, Symonds RP, Peel D, Swindell R, Davidson SE. Late-onset bowel dysfunction after pelvic radiotherapy: a national survey of current practice and opinions of clinical oncologists. Clinical Oncology. 2011; 23: 552–557.

[8] Huang X, Zhong Q, Wang H, Zhao J, Kuang Y, Guan Q, et al. Diverting colostomy is an effective procedure for ulcerative chronic radiation proctitis patients after pelvic malignancy radiation. BMC Surgery. 2020; 20: 267.

[9] Garg AK, Mai WY, McGary JE, Grant WH III, Butler EB, Teh BS. Radiation proctopathy in the treatment of prostate cancer. International Journal of Radiation Oncology, Biology, Physics. 2006; 66: 1294–1305.

[10] Vanneste BG, Van De Voorde L, de Ridder RJ, Van Limbergen EJ, Lambin P, van Lin EN. Chronic radiation proctitis: tricks to prevent and treat. International Journal of Colorectal Disease. 2015; 30: 1293–1303.

[11] Tabaja L, Sidani SM. Management of radiation proctitis. Digestive Diseases and Sciences. 2018; 63: 2180–2188.

[12] Lim K, Small W III, Portelance L, Creutzberg C, Jurgenliemk-Schulz IM, Mundt A, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer. International Journal of Radiation Oncology, Biology, Physics. 2011; 79: 348–355.

[13] Herrmann T, Knorr A, Dorner K. The RTOG/EORTC classification criteria for early and late radiation reactions. Radiobiologia, Radiotherapia. 1987; 28: 519–528. (In German)

[14] Zhu L, Zhu L, Shi H, Wang H, Yan J, Liu B, et al. Evaluating early response of cervical cancer under concurrent chemo-radiotherapy by intravoxel incoherent motion MR imaging. BMC Cancer. 2016; 16: 79.

[15] D'Souza N, de Neree Tot Babberich MPM, d’Hoore A, Tiret E, Xynos E, Beets-Tan RGH, et al. Definition of the rectum: an international, expert-based Delphi consensus. Annals of Surgery. 2019; 270: 955–959.

[16] Ma TH. Interpretation of Chinese expert consensus on multidisciplinary diagnosis and treatment of radiation rectal injury (2021 edition). Chinese Journal of Gastrointestinal Surgery. 2021; 24: 956–961. (In Chinese)

[17] Francois A, Milliat F, Guipaud O, Benderitter M. Inflammation and immunity in radiation damage to the gut mucosa. BioMed Research International. 2013; 2013: 123241.

[18] Hauer-Jensen M, Denham JW, Andreyev HJ. Radiation enteropathy—pathogenesis, treatment and prevention. Nature Reviews Gastroenterology & Hepatology. 2014; 11: 470–479.

[19] Cotti G, Seid V, Araujo S, Souza AH III, Kiss D, Habr-Gama A. Conservative therapies for hemorrhagic radiation proctitis: a review. Revista do Hospital das Clínicas. 2003; 58: 284–292.

[20] Negaard A, Paulsen V, Sandvik L, Berstad AE, Borthne A, Try K, et al. A prospective randomized comparison between two MRI studies of the small bowel in Crohn’s disease, the oral contrast method and MR enteroclysis. European Radiology. 2007; 17: 2294–2301.

[21] Hamama S, Gilbert-Sirieix M, Vozenin MC, Delanian S. Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition. Radiotherapy and Oncology. 2012; 105: 305–312.

[22] de Parades V, Etienney I, Bauer P, Bourguignon J, Meary N, Mory B, et al. Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis—an effective but not risk-free procedure: a prospective study of 33 patients. Diseases of the Colon & Rectum. 2005; 48: 1535–1541.

[23] Swan MP, Moore GT, Sievert W, Devonshire DA. Efficacy and safety of single-session argon plasma coagulation in the management of chronic radiation proctitis. Gastrointestinal Endoscopy. 2010; 72: 150–154.

[24] McCarty TR, Rustagi T. New indications for endoscopic radiofrequency ablation. Clinical Gastroenterology and Hepatology. 2018; 16: 1007–1017.

[25] Ortega MA, Fraile-Martinez O, Garcia-Montero C, Callejon-Pelaez E, Saez MA, Alvarez-Mon MA, et al. A general overview on the hyperbaric oxygen therapy: applications, mechanisms and translational opportunities. Medicina. 2021; 57: 864.

[26] Li N, Tian HL, Chen QY, Yang B, Ma CL, Lin ZL, et al. Efficacy analysis of fecal microbiota transplantation in the treatment of 2010 patients with intestinal disorders. Chinese Journal of Gastrointestinal Surgery. 2019; 22: 861–868. (In Chinese)

[27] Letschert JG. The prevention of radiation-induced small bowel complications. European Journal of Cancer. 1995; 31A: 1361–1365.

[28] Nutting CM, Convery DJ, Cosgrove VP, Rowbottom C, Padhani AR, Webb S, et al. Reduction of small and large bowel irradiation using an optimized intensity-modulated pelvic radiotherapy technique in patients with prostate cancer. International Journal of Radiation Oncology, Biology, Physics. 2000; 48: 649–656.

[29] Kolbl O, Richter S, Flentje M. Influence of treatment technique on dose-volume histogram and normal tissue complication probability for small bowel and bladder. A prospective study using a 3D planning system and a radiobiological model in patients receiving postoperative pelvic irradiation. Journal of Radiation Oncology, Biology, Physics. 2000; 176: 105–111.

[30] Chan P, Yeo I, Perkins G, Fyles A, Milosevic M. Dosimetric comparison of intensity-modulated, conformal, and four-field pelvic radiotherapy boost plans for gynecologic cancer: a retrospective planning study. Radiation Oncology. 2006; 1: 13.

[31] Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020; 126: 4423–4431.

[32] Rodionova OG, Sakun PG, Sheiko EA, Karnaukhova EA, Pustovalova AV, Chalabova TG, et al. Prevention of radiation-induced rectal injuries with perirectal blocks in radiation therapy. Journal of Clinical Oncology. 2022; 40: e17507.