Intensity-modulated Radiotherapy for Anal Cancer: Dose-Volume Relationship of Acute Gastrointestinal Toxicity and Disease Outcomes

Clin Oncol (R Coll Radiol). 2018 Oct;30(10):634-641. doi: 10.1016/j.clon.2018.07.020. Epub 2018 Jul 23.

Abstract

Aims: Intensity-modulated radiotherapy (IMRT) is increasingly used in the treatment delivery of chemoradiotherapy in anal cancer with the ability to reduce toxicity. We report on 4 year outcomes since the introduction of IMRT and identify the most predictive bowel organ at risk that correlates with acute diarrhoea.

Materials and methods: Fifty-eight patients receiving definitive chemoradiotherapy for squamous or basaloid cell anal carcinoma (T1-4NanyM0) were reviewed. Fifty-four per cent of patients had stage III disease and most (79%) were treated with a dose of 54 Gy in 30 fractions. Patient acute gastrointestinal toxicity was recorded using Common Terminology Criteria of Adverse Events (CTCAE) diarrhoea grading. Four different methods of bowel were re-contoured for each patient and correlated with acute diarrhoea. Locoregional control and overall survival were analysed.

Results: CTCAE grade 3 or more diarrhoea occurred in 11/58 patients (19%). Seven patients did not complete treatment; 10 patients (17%) required a treatment break of 3 or more days. 'Bowel cavity' was the best predictor of acute grade 3 toxicity using volume (P = 0.002) or volume to bowel cavity in 5 Gy bins (V5-V50Gy); P < 0.05. Bowel cavity V30Gy ≤ 300 cm3 predicts a 6% grade 3 diarrhoea risk versus > 300 cm3 predicts a 42% risk. Four year progression-free survival was 84% (95% confidence interval 73-92%) and overall survival was 88% (95% confidence interval 75-95%).

Conclusion: Chemoradiation using IMRT provides excellent local control and acceptable acute gastrointestinal toxicity. Bowel cavity is the most sensitive predictor for grade 3 versus grade 0-2 diarrhoea, with any volume receiving 5-50 Gy discriminatory.

Keywords: Anal cancer; diarrhoea; dose–volume relationship; gastrointestinal toxicity; intensity-modulated radiotherapy.

MeSH terms

  • Abdominal Cavity / radiation effects*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Anus Neoplasms / pathology
  • Anus Neoplasms / therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / adverse effects
  • Diarrhea / etiology*
  • Dose Fractionation, Radiation
  • Dose-Response Relationship, Radiation
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Neoplasm Staging
  • Organs at Risk
  • Progression-Free Survival
  • Radiation Dosage
  • Radiation Injuries / etiology*
  • Radiotherapy, Intensity-Modulated / adverse effects*
  • Survival Rate

Substances

  • Mitomycin
  • Fluorouracil