Skip to main content

Advertisement

SpringerLink
Log in

Management of gastrointestinal perforation related to radiation

  • Review Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Perforation of gastrointestinal (GI) tract is a rare, but serious complication of abdominopelvic irradiation, and it can even occur several years after radiotherapy. As one of the symptoms of radiation enteropathy, it shares common features with other chronic complications and has its own characteristic at the same time. It has been reported that some systematic therapies, such as sorafenib and bevacizumab, could add the risk of radiation-induced GI perforation. The potential mechanisms of aggravated GI injury may be exacerbation of epithelial cell damage, microvascular damage or subsequent inflammatory response. The complicated situation makes it almost impossible to set uniform dose constraints for GI perforation prevention. The majority of cancer patients with GI perforation require emergency surgery, and there is no high quality evidence for supporting the use of any prevention measures. In this review, we summarize the clinical manifestation, risk factors, mechanism, and therapy of radiation-induced GI perforation. A comprehensive treatment plan is crucial to improve the quality of life for cancer survivors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Qi WX, Sun YJ, Tang LN et al (2014) Risk of gastrointestinal perforation in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis. Crit Rev Oncol Hematol 89:394–403

    Article  PubMed  Google Scholar 

  2. Bottoni C, Scambia G, Fagotti A et al (2018) The safety of bevazicumab for the treatment of ovarian cancer. Expert Opin Drug Saf 17:1107–1113

    Article  CAS  PubMed  Google Scholar 

  3. Andreyev J (2005) Gastrointestinal complications of pelvic radiotherapy: are they of any importance? Gut 54:1051–1054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yamashita H, Nakagawa K, Tago M et al (2006) Small bowel perforation without tumor recurrence after radiotherapy for cervical carcinoma: report of seven cases. J Obstet Gynaecol Res 32:235–242

    Article  PubMed  Google Scholar 

  5. Ramirez PT, Levenback C, Burke TW et al (2001) Sigmoid perforation following radiation therapy in patients with cervical cancer. Gynecol Oncol 82:150–155

    Article  CAS  PubMed  Google Scholar 

  6. Harb AH, Abou FC, Sharara AI (2014) Radiation enteritis. Curr Gastroenterol Rep 16:383

    Article  PubMed  Google Scholar 

  7. Teo MT, Sebag-Montefiore D, Donnellan CF (2015) Prevention and management of radiation-induced late gastrointestinal toxicity. Clin Oncol (R Coll Radiol) 27:656–667

    Article  CAS  Google Scholar 

  8. Andreyev HJ, Vlavianos P, Blake P et al (2005) Gastrointestinal symptoms after pelvic radiotherapy: role for the gastroenterologist? Int J Radiat Oncol Biol Phys 62:1464–1471

    Article  PubMed  Google Scholar 

  9. Andreyev J (2007) Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients. Lancet Oncol 8:1007–1017

    Article  PubMed  Google Scholar 

  10. Pathak R, Shah SK, Hauer-Jensen M (2019) Therapeutic potential of natural plant products and their metabolites in preventing radiation enteropathy resulting from abdominal or pelvic irradiation. Int J Radiat Biol 95:493–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Isohashi F, Yoshioka Y, Mabuchi S et al (2013) Dose-volume histogram predictors of chronic gastrointestinal complications after radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer. Int J Radiat Oncol Biol Phys 85:728–734

    Article  PubMed  Google Scholar 

  12. Shadad AK, Sullivan FJ, Martin JD et al (2013) Gastrointestinal radiation injury: symptoms, risk factors and mechanisms. World J Gastroenterol 19:185–198

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kelly P, Das P, Pinnix CC et al (2013) Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 85:e143–e149

    Article  PubMed  Google Scholar 

  14. George G, Lewis S, Chopra S et al (2020) A retrospective study of the dosimetric parameters and duodenal toxicity in patients with upper gastrointestinal and gynaecological cancers treated with radiation therapy. Clin Oncol (R Coll Radiol) 32:e53–e59

    Article  CAS  Google Scholar 

  15. Verma J, Sulman EP, Jhingran A et al (2014) Dosimetric predictors of duodenal toxicity after intensity modulated radiation therapy for treatment of the para-aortic nodes in gynecologic cancer. Int J Radiat Oncol Biol Phys 88:357–362

    Article  PubMed  Google Scholar 

  16. Vargas C, Martinez A, Kestin LL et al (2005) Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy. Int J Radiat Oncol Biol Phys 62:1297–1308

    Article  PubMed  Google Scholar 

  17. Jadon R, Higgins E, Hanna L et al (2019) A systematic review of dose-volume predictors and constraints for late bowel toxicity following pelvic radiotherapy. Radiat Oncol 14:57

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yeoh EK, Krol R, Dhillon VS et al (2016) Predictors of radiation-induced gastrointestinal morbidity: a prospective, longitudinal study following radiotherapy for carcinoma of the prostate. Acta Oncol 55:604–610

    Article  CAS  PubMed  Google Scholar 

  19. Carrington R, Staffurth J, Warren S et al (2015) The effect of dose escalation on gastric toxicity when treating lower oesophageal tumours: a radiobiological investigation. Radiat Oncol 10:236

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Yoon H, Oh D, Park HC et al (2013) Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma. Strahlenther Onkol 189:541–546

    Article  CAS  PubMed  Google Scholar 

  21. Chopra S, Dora T, Chinnachamy AN et al (2014) Predictors of grade 3 or higher late bowel toxicity in patients undergoing pelvic radiation for cervical cancer: results from a prospective study. Int J Radiat Oncol Biol Phys 88:630–635

    Article  PubMed  Google Scholar 

  22. Pollom EL, Deng L, Pai RK et al (2015) Gastrointestinal toxicities with combined antiangiogenic and stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 92:568–576

    Article  PubMed  PubMed Central  Google Scholar 

  23. Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14:1860–1869

    Article  PubMed  Google Scholar 

  24. Inoue T, Kinoshita H, Komai Y et al (2012) Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma. World J Surg Oncol 10:167

    Article  PubMed  PubMed Central  Google Scholar 

  25. Barney BM, Markovic SN, Laack NN et al (2013) Increased bowel toxicity in patients treated with a vascular endothelial growth factor inhibitor (VEGFI) after stereotactic body radiation therapy (SBRT). Int J Radiat Oncol Biol Phys 87:73–80

    Article  CAS  PubMed  Google Scholar 

  26. Brade AM, Ng S, Brierley J et al (2016) Phase 1 trial of sorafenib and stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 94:580–587

    Article  CAS  PubMed  Google Scholar 

  27. Muraoka T, Tsukuda K, Toyooka S et al (2011) Ileal perforation induced by acute radiation injury under gefitinib treatment. Int J Clin Oncol 16:774–777

    Article  CAS  PubMed  Google Scholar 

  28. Mach CM, Urh A, Anderson ML (2014) Bowel perforation associated with temsirolimus use in a recently irradiated patient. Am J Health Syst Pharm 71:919–923

    Article  CAS  PubMed  Google Scholar 

  29. Anker CJ, Grossmann KF, Atkins MB et al (2016) Avoiding severe toxicity from combined braf inhibitor and radiation treatment: consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG). Int J Radiat Oncol Biol Phys 95:632–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tang T, Abu-Sbeih H, Luo W et al (2019) Upper gastrointestinal symptoms and associated endoscopic and histological features in patients receiving immune checkpoint inhibitors. Scand J Gastroenterol 54:538–545

    Article  CAS  PubMed  Google Scholar 

  31. Tree AC, Jones K, Hafeez S et al (2018) Dose-limiting urinary toxicity with pembrolizumab combined with weekly hypofractionated radiation therapy in bladder cancer. Int J Radiat Oncol Biol Phys 101:1168–1171

    Article  CAS  PubMed  Google Scholar 

  32. Luke JJ, Lemons JM, Karrison TG et al (2018) Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol 36:1611–1618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Stansborough RL, Bateman EH, Al-Dasooqi N et al (2018) Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity. Int J Radiat Biol 94:645–655

    Article  CAS  PubMed  Google Scholar 

  34. Francois A, Milliat F, Guipaud O et al (2013) Inflammation and immunity in radiation damage to the gut mucosa. Biomed Res Int 2013:123241

    PubMed  PubMed Central  Google Scholar 

  35. Hasleton PS, Carr N, Schofield PF (1985) Vascular changes in radiation bowel disease. Histopathology 9:517–534

    Article  CAS  PubMed  Google Scholar 

  36. Bentzen SM (2006) Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 6:702–713

    Article  CAS  PubMed  Google Scholar 

  37. Hong S, Gu Y, Gao Z et al (2014) EGFR inhibitor-driven endoplasmic reticulum stress-mediated injury on intestinal epithelial cells. Life Sci 119:28–33

    Article  CAS  PubMed  Google Scholar 

  38. Karamchandani DM, Chetty R (2018) Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists' perspective. J Clin Pathol 71:665–671

    Article  CAS  PubMed  Google Scholar 

  39. Takatori K, Terashima K, Yoshida R et al (2014) Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer. J Gastroenterol 49:1074–1080

    Article  CAS  PubMed  Google Scholar 

  40. Lawrie TA, Green JT, Beresford M et al (2018) Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers. Cochrane Database Syst Rev 1:D12529

    Google Scholar 

  41. Klopp AH, Yeung AR, Deshmukh S et al (2018) Patient-reported toxicity during pelvic intensity-modulated radiation therapy: NRG oncology-RTOG 1203. J Clin Oncol 36:2538–2544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Samuelian JM, Callister MD, Ashman JB et al (2012) Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 82:1981–1987

    Article  PubMed  Google Scholar 

  43. Rao AD, Feng Z, Shin EJ et al (2017) A novel absorbable radiopaque hydrogel spacer to separate the head of the pancreas and duodenum in radiation therapy for pancreatic cancer. Int J Radiat Oncol Biol Phys 99:1111–1120

    Article  PubMed  PubMed Central  Google Scholar 

  44. Reyngold M, Parikh P, Crane CH (2019) Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results. Radiat Oncol 14:95

    Article  PubMed  PubMed Central  Google Scholar 

  45. Henson CC, Burden S, Davidson SE et al (2013) Nutritional interventions for reducing gastrointestinal toxicity in adults undergoing radical pelvic radiotherapy. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009896.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  46. Wedlake LJ (2018) Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy. Proc Nutr Soc 77:357–368

    Article  PubMed  Google Scholar 

  47. Langsenlehner T, Renner W, Gerger A et al (2011) Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients. Strahlenther Onkol 187:784–791

    Article  PubMed  Google Scholar 

  48. Thurner EM, Krenn-Pilko S, Langsenlehner U et al (2014) Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy. Strahlenther Onkol 190:304–309

    Article  PubMed  Google Scholar 

  49. Kroeze SG, Fritz C, Hoyer M et al (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev 53:25–37

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by Jinan Science and Technology Development Project (No. 201907122).

Author information

Author notes

  1. Yuping Sun, Ligang Xing have contributed the same.

Authors and Affiliations

  1. Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong First Medical University, No. 105, Jie Fang Road, Jinan, 250013, Shandong, China

    Yawen Zheng, Wei Gao & Yuping Sun

  2. Department of Radiation Oncology, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, No. 440 Jiyan Road, Jinan, 250117, Shandong, China

    Yawen Zheng & Ligang Xing

  3. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Yawen Zheng & Denial E. Spratt

Authors
  1. Yawen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denial E. Spratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ligang Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yuping Sun or Ligang Xing.

Ethics declarations

Conflict of interest

No author has any conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, Y., Gao, W., Spratt, D.E. et al. Management of gastrointestinal perforation related to radiation. Int J Clin Oncol 25, 1010–1015 (2020). https://doi.org/10.1007/s10147-020-01662-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-020-01662-5

Keywords

Search

Navigation