Abstract

Purpose:The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor‐control‐probability(TCP) with an acceptable normal‐tissue‐complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose‐based plans. PET image is incorporated to evaluate gain in TCP for dose escalation.Methods:We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on the targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise‐linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET‐image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV‐dose, and two variations (37Gy‐boost to BTV vs 40Gy‐boost) to PET‐image‐pockets.Results:TCP for standard clinical plans range from 59.4% ‐ 63.6%. TCP for dose‐based PET‐guided escalated‐dose‐plan ranges from 63.8%–98.6% for all patients; whereas TCP‐optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy‐boosted vs 40Gy‐boosted. There is no increase in rectum and bladder dose among all plans.Conclusion:Optimizing TCP directly results in highly conformed treatment plans. The TCP‐optimized plan is individualized based on the biological PET‐image of the patients. The TCP‐optimization framework is generalizable and has been applied successfully to other external‐beam delivery modalities. A clinical trial is on‐going to gauge the clinical significance.Partially supported by the National Science Foundation.

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