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Dose-Volume Effects and Risk Factors for Late Diarrhea in Cervix Cancer Patients After Radiochemotherapy With Image Guided Adaptive Brachytherapy in the EMBRACE I Study

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  • Nina B K Jensen
  • Richard Pötter, Medical University Vienna, Vienna
  • ,
  • Sofia Spampinato
  • Lars U Fokdal
  • Cyrus Chargari, Department of Radiotherapy, Gustave-Roussy, Villejuif, France.
  • ,
  • Jacob C Lindegaard
  • Maximilian P Schmid, Medical University Vienna, Vienna
  • ,
  • Alina Sturdza, Medical University Vienna, Vienna
  • ,
  • Ina M Jürgenliemk-Schulz, University Medical Centre Utrecht
  • ,
  • Umesh Mahantshetty, Homi Bhabha Natl Inst, Homi Bhabha National Institute
  • ,
  • Barbara Segedin, Institute of Oncology of Ljubljana, Ljubljana, Slovenia
  • ,
  • Kjersti Bruheim, Oslo University Hospital
  • ,
  • Peter Hoskin, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex
  • ,
  • Bhavana Rai, Postgraduate Institute of Medical Education and Research
  • ,
  • Ericka Wiebe, Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Canada.
  • ,
  • Rachel Cooper, St James's University Hospital
  • ,
  • Elzbieta Van der Steen-Banasik, Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam and Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands.
  • ,
  • Erik Van Limbergen, Leuven Centre for Algology & Pain Management, University Hospitals Leuven, University Hospitals Leuven, Pellenberg, Belgium.
  • ,
  • Marit Sundset, St Olavs Hospital, Trondheim University Hospital
  • ,
  • Bradley R Pieters, Academic Centre for Dentistry Amsterdam, University of Amsterdam and and VU University Amsterdam, Amsterdam
  • ,
  • Remi A Nout, Leiden University Medical Center, University Medical Center Rotterdam
  • ,
  • Christian Kirisits, Medical University Vienna, Vienna
  • ,
  • Kathrin Kirchheiner, Medical University Vienna, Vienna
  • ,
  • Kari Tanderup
  • EMBRACE Collaborative Group

PURPOSE: To evaluate patient- and treatment-related risk factors associated with incidence and persistence of late diarrhea after radiochemotherapy and image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer.

MATERIALS AND METHODS: Of 1416 patients from the EMBRACE I study, 1199 were prospectively evaluated using physician-reported (Common Terminology Criteria for Adverse Events version 3 [CTCAEv3]) assessment for diarrhea; median follow-up 48 months. Patient-reported outcome (EORTC) was available in 900 patients. Incidence of CTCAE G≥2, G≥3, and EORTC "very much" diarrhea was analyzed with Cox proportional hazards regression. Binary logistic regression was used for analysis of persistent G≥1 and EORTC "quite a bit" - "very much" (≥"quite a bit") diarrhea, defined if present in at least half of all follow-ups.

RESULTS: Crude incidences of G≥2 and G≥3 diarrhea were 8.3% and 1.5%, respectively, and 8% of patients reported "very much" diarrhea. Persistent G≥1 and ≥"quite a bit" diarrhea was present in 16% and 7%, respectively. Patient-related risk factors were baseline diarrhea, smoking, and diabetes with hazard ratios of 1.4 to 7.3. Treatment-related risk factors included prescribed dose, V43 Gy, V57 Gy (lymph node boost), and para-aortic irradiation for external beam radiation therapy (EBRT). G≥2 diarrhea at 3 years increased from 9.5% to 19.9% with prescribed dose 45 Gy versus 50 Gy, 8.7% to 14.0% with V43 Gy <2500 cm3 versus >3000 cm3 and 9.4% to 19.0% with V57 Gy <165 cm3 versus ≥165 cm3. Brachytherapy-related bowel and rectum D2cm3 were also associated with diarrhea.

CONCLUSION: Dose and volume effects have been established for late diarrhea after radiochemotherapy and IGABT in both CTCAE and EORTC reporting. The risk of diarrhea was lower with a pelvic EBRT prescription of 45 Gy, and higher with larger lymph node boosts volumes (ie, ≥165 cm3). The importance of EBRT volumes as determinants of late toxicity underline the need for continuous quality assurance of target contouring, dose planning, and conformity. The findings of brachytherapy dosimetric factors related to the intestines may become more important with highly conformal EBRT.

Original languageEnglish
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume109
Issue3
Pages (from-to)688-700
ISSN0360-3016
DOIs
Publication statusPublished - Mar 2021

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