Prevalence and characterization of breakthrough pain in cancer patients with proctalgia treated with 3D pelvic radiotherapy

  • V. T. FerreroEmail author
  • M. M. Oset
  • J. P. Masferrer
  • E. H. Pardo
  • E. J. Sorolla
  • S. C. Largo
  • the PrevaDIOR Study Group
Research Article



Radiotherapy-induced dysfunction of the gastrointestinal tract is common in cancer patients and has a significant impact on their quality of life. In this study, we investigated the prevalence of breakthrough cancer pain (BTcP) in patients undergoing 3D pelvic radiotherapy and who had proctalgia.


This observational, multicenter, cross-sectional epidemiological study was performed in 13 Spanish hospitals. Data were obtained on the presence and characteristics of BTcP, demographics, common comorbidities, and treatments prescribed to the patients.


The prevalence of BTcP in patients undergoing pelvic 3D external radiotherapy with proctalgia (N = 105) was 48.6% (95% CI 39.0–58.1%). BTcP was further characterized in 59 patients. The mean (± SD) intensity of the BTcP episodes was 7.45 ± 1.47 in a visual analog scale. We found several statistically significant associations between the descriptive variables of BTcP with demographic and clinical variables associated with the tumor or the patient, such as an increased number of BTcP episodes per day depending on the presence or absence of diabetes (p = 0.001, Chi-square) or time to the onset of pain relief depending on the location of the tumor (p = 0.019, Chi-square). Fentanyl was the drug of choice in BTcP episodes for 95% of the patients.


This study demonstrated a high prevalence of BTcP prevalence in cancer patients undergoing pelvic 3D radiotherapy and with proctalgia. Although the variables determining the onset of BTcP are still unclear, our results could help in the design of future clinical studies addressing the treatment of BTcP in these patients.


Pelvic 3D radiotherapy Proctalgia Breakthrough pain 



The PrevaDIOR Study Group is formed by Vicente Tormo and Marta Marcos (Hospital Universitario San Juan de Alicante, Alicante, Spain); José Pardo and Neus Aymar (Hospital Universitari Son Espases, Palma de Mallorca, Spain); Eduardo Hortelano and Amanda Flaquer (Hospital Universitario de Araba, Vitoria, Spain); Esther Jordá (Hospital Clínico Universitario de Valencia, Valencia, Spain); Sofía Córdoba and Juan Antonio Corona (Hospital Clínico San Carlos, Madrid, Spain); Carlos Ferrer, Alicia Francés, Virginia Morillo and Ana Bouche (Consorcio hospitalario Provincial de Castellón, Castellón, Spain); Susana Marín, María Cambray, Montse Ventura and Hector Pérez (Institut Catalá D’Oncologia L’Hospitalet, Hospitalet, Spain); Ruth Hernandez, José Javier Martín, Leonardo Lorenzo and Claudio Fuentes (Hospital Universitario Nuestra Señora de la Candelaria); Mercedes Zurita and Rosario del Moral (Complejo Hospitalario Regional Virgen de las Nieves, Granada, Spain); Víctor Muñoz, Alba González, Manuel Enguix and Marta Martinez (Hospital do Meixoeiro, Vigo, Spain); María José Ortíz and María Carmen Fernandez (Hospital Virgen del Rocío, Sevilla, Spain); Enrique Cárdenas and Antonio José Lozano (Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain).

The authors thank Francisco López de Saro (PhD) for medical writing support.


Kyowa Kirin Farmacéutica SLU supported the study. Apices Soluciones SL was contracted by Kyowa Kirin Farmacéutica SLU for the design, monitoring, and statistical analysis. Trialance SCCL was contracted for the production and management of publications.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

This study was approved by the Clinical Research Ethics Committee of the Hospital San Juan of Alicante, Spain, on March 6th, 2017.

Informed consent

All patients participating in this study signed an informed consent.


  1. 1.
    van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan-Heijnen VC, Janssen DJ. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manag. 2016;51(6):1070–90.CrossRefGoogle Scholar
  2. 2.
    Portenoy RK, Forbes K, Lussier D. Difficult pain problems: an integrated approach. In: Doyle D, Hanks G, Cherny N, Caiman K, editors. Textbook of palliative medicine. 3rd ed. New York: Oxford University Press; 2004. p. 438–58.Google Scholar
  3. 3.
    Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G. The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain. 2009;13(4):331–8.CrossRefGoogle Scholar
  4. 4.
    Porta-Sales J, Garzon Rodriguez C, Julia Torras J, Casals Merchán M. Cancer-related breakthrough pain. Med Clin. 2010;135(6):280–5.CrossRefGoogle Scholar
  5. 5.
    Bennett D, Burton AW, Fishman S, Fortner B, McCarberg B, Miaskowski C, et al. Consensus panel recommendations for the assessment and management of breakthrough pain. Part 1 assessment. P&T. 2005;0(5):296–301.Google Scholar
  6. 6.
    Porta-Sales J, Gómez-Batiste X, Tuca-Rodriguez A, et al. WHO analgesic ladder-or lift? Eur J Palliat Care. 2003;10:105–9.Google Scholar
  7. 7.
    Mercadante S, Zagonel V, Breda E, Arcara C, Gebbia V, Porzio G, et al. Breakthrough pain in oncology: a longitudinal study. J Pain Symptom Manag. 2010;40(2):183–90.CrossRefGoogle Scholar
  8. 8.
    Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain. 1999;81(1–2):129–34.CrossRefGoogle Scholar
  9. 9.
    Fortner BV, Okon TA, Portenoy RK. A survey of pain-related hospitalizations, emergency department visits, and physician office visits reported by cancer patients with and without history of breakthrough pain. J Pain. 2002;3(1):38–44.CrossRefGoogle Scholar
  10. 10.
    Abernethy AP, Wheeler JL, Fortner BV. A health economic model of breakthrough pain. Am J Manag Care. 2008;14(5 Suppl 1):S129–40.Google Scholar
  11. 11.
    Ray A, Sarkar B. Small bowel toxicity in pelvic radiotherapy for postoperative gynecological cancer: comparison between conformal radiotherapy and intensity modulated radiotherapy. Asia Pac J Clin Oncol. 2013;9:280–4.CrossRefGoogle Scholar
  12. 12.
    Lan ML, Yu X, Xiao H, Zhou P, Hu N, Li J, Wang G. Clinical outcomes and toxicity of postoperative intensity-modulated versus three-dimensional conformal radiation therapy in patients with cervical cancer. Asia Pac J Clin Oncol. 2016;12:430–6.CrossRefGoogle Scholar
  13. 13.
    Huang CM, Huang MY, Tsai HL, Huang CW, Ma CJ, Lin CH, et al. A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma. J Radiat Res. 2016;10:1–13.Google Scholar
  14. 14.
    Bacon CG, Giovannucci E, Testa M, Glass TA, Kawachi I. The association of treatment-related symptoms with quality of life outcomes for localized prostate carcinoma patients. Cancer. 2002;94(3):862–71.CrossRefGoogle Scholar
  15. 15.
    Bacon CG, Giovannucci E, Testa M, Kawachi I. The impact of cancer treatment on quality of life outcomes for patients with localized prostate cancer. J Urol. 2001;166(5):1804–10.CrossRefGoogle Scholar
  16. 16.
    Hong JJ, Park W, Ehrenpreis ED. Current therapeutic options for radiation proctopathy. Aliment Pharmacol Ther. 2001;15(9):1253–62.CrossRefGoogle Scholar
  17. 17.
    Hayne D, Vaizey CJ, Boulos PB. Anorectal injury following pelvic radiotherapy. Br J Surg. 2001;88(8):1037–48.CrossRefGoogle Scholar
  18. 18.
    Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, EORTC Radiotherapy Group Trial 22921, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23.CrossRefGoogle Scholar
  19. 19.
    Herold DM, Hanlon AL, Hanks GE. Diabetes mellitus: a predictor for late radiation morbidity. Int J Radiat Oncol Biol Phys. 1999;43(3):475–9.CrossRefGoogle Scholar
  20. 20.
    Yang TJ, Oh JH, Son CH, Apte A, Deasy JO, Wu A, Goodman KA. Predictors of acute gastrointestinal toxicity during pelvic chemoradiotherapy in patients with rectal cancer. Gastrointest Cancer Res. 2013;6(5–6):129–36.Google Scholar
  21. 21.
    Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: symptoms, risk factors and mechanisms. World J Gastroenterol. 2013;19(2):185–98.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyHospital Universitary de Sant Joan D’AlacantAlicanteSpain
  2. 2.Department of Radiation OncologyHospital Universitari Son EspasesPalma de MallorcaSpain
  3. 3.Department of Radiation OncologyHospital Universitario de ArabaVitoriaSpain
  4. 4.Department of RadiotherapyHospital Clínico Universitario de ValenciaValenciaSpain
  5. 5.Department of Radiation OncologyHospital Clínico San CarlosMadridSpain

Personalised recommendations