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Phys Med Biol. 2015 May 21;60(10):3999-4013. doi: 10.1088/0031-9155/60/10/3999. Epub 2015 Apr 28.

Risk-optimized proton therapy to minimize radiogenic second cancers.

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The University of Texas Health Science Center Houston, Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Oncology, Section of Radiotherapy, Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark.


Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment planning utilized a combination of a commercial treatment planning system and an in-house risk-optimization algorithm. When normal-tissue dose constraints were incorporated in treatment planning, the risk model that incorporated the effects of fractionation, initiation, inactivation, repopulation and promotion selected a combination of anterior and lateral beams, which lowered the relative risk by 21% for the bladder and 30% for the rectum compared to the lateral-opposed beam arrangement. Other results were found for other risk models.

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