Contouring variation affects estimates of normal tissue complication probability for breast fibrosis after radiotherapy

Tanwiwat Jaikuna, Eliana vasquez Osorio, David Azria, Jenny Chang-Claude, Maria carmen De santis, Sara Gutiérrez-Enríquez, Marcel Van herk, Peter Hoskin, Maarten Lambrecht, Zoe Lingard, Petra Seibold, Alejandro Seoane, Elena Sperk, R paul Symonds, Christopher j. Talbot, Tiziana Rancati, Tim Rattay, Victoria Reyes, Barry s. Rosenstein, Dirk De ruysscherAna Vega, Liv Veldeman, Adam Webb, Catharine m.l. West, Marianne c. Aznar

Research output: Contribution to journalArticlepeer-review


Background and Purpose: Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis.
Materials and methods: 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression.
Results: There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (-3.92%, IQR 4.00, p<0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from “skin” contours showed higher agreement with observed events.
Conclusion: Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models.
Original languageEnglish
Article number103578
JournalThe Breast
Early online date11 Sept 2023
Publication statusE-pub ahead of print - 11 Sept 2023


  • Inter-observer variation
  • Late effects
  • Fibrosis
  • Breast cancer
  • NTCP modelling


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