Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose–based and dose–volume–based normal tissue complication probability models

Söhn, Matthias; Yan, Di; Liang, Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

doi:10.1016/j.ijrobp.2006.10.014

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Volume 67, Issue 4 , Pages 1066-1073, 15 March 2007

Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose–based and dose–volume–based normal tissue complication probability models

Presented in part at the 48th Annual American Society for Therapeutic Radiology and Oncology Meeting (ASTRO), Philadelphia, PA, Nov. 5–9, 2006.

Matthias Söhn, Dipl. Phys.
- Section for Biomedical Physics, University Hospital for Radiation Oncology, Tübingen, Germany
- Reprint requests to: Matthias Söhn, Dipl. Phys., Section for Biomedical Physics, University Hospital for Radiation Oncology, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; Tel: (+49) 7071-2986061; Fax: (+49) 7071-295920
Di Yan, D.Sc.
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI
Jian Liang, Ph.D.
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI
Elisa Meldolesi, M.D.
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI
Carlos Vargas, M.D.
- Radiation Oncology, University of Florida, Gainesville, FL
Markus Alber, Ph.D.
- Section for Biomedical Physics, University Hospital for Radiation Oncology, Tübingen, Germany

Received 6 September 2006; received in revised form 2 October 2006; accepted 9 October 2006. published online 26 January 2007.

Purpose: Accurate modeling of rectal complications based on dose–volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)–based and dose–volume–based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding.

Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD, (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose– and (6) cutoff dose–logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation.

Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models.

Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose–volume–based cutoff-dose models performed worse.

Keywords: Prostate cancer, Rectal toxicity, Normal tissue complication probability, Volume effects, Dose–volume histograms, Equivalent uniform dose