Background: Currently, radiation-oncologists generally evaluate a single treatment plan for each patient that is possibly adapted by the planner prior to final approval. There is no systematic exploration of patient-specific trade-offs between planning aims, using a set of treatment plans with a-priori defined (slightly) different balances. To this purpose, we developed an automated workflow and explored its use for prostate cancer. Materials and Methods: For each of the 50 study patients, seven plans were generated, including the so-called clinical plan, with currently clinically desired ≥99% dose coverage for the low-dose planning target volume (PTVLow). The six other plans were generated with different, reduced levels of PTVLow coverage, aiming at reductions in rectum dose and consequently in predicted grade≥2 late gastro-intestinal (GI) normal tissue complication probabilities (NTCPs), while keeping other dosimetric differences small. The applied NTCP model included diabetes as a non-dosimetric predictor. All plans were generated with a clinically applied, in-house developed algorithm for automated multi-criterial plan generation. Results: With diabetes, the average NTCP reduced from 24.9 ± 4.5% for ≥99% PTVLow coverage to 17.3 ± 2.6% for 90%, approaching the NTCP (15.4 ± 3.0%) without diabetes and full PTVLow coverage. Apart from intended differences in PTVLow coverage and rectum dose, other differences between the clinical plan and the six alternatives were indeed minor. Obtained NTCP reductions were highly patient-specific (ranging from 14.4 to 0.1%), depending on patient anatomy. Even for patients with equal NTCPs in the clinical plan, large differences were found in NTCP reductions. Conclusions: A clinically feasible workflow has been proposed for systematic exploration of patient-specific trade-offs between various treatment aims. For each patient, automated planning is used to generate a limited set of treatment plans with Bijman et al. Automated Planning for Trade-Off Exploration well-defined variations in the balances between the aims. For prostate cancer, trade-offs between PTVLow coverage and predicted GI NTCP were explored. With relatively small coverage reductions, significant NTCP reductions could be obtained, strongly depending on patient anatomy. Coverage reductions could also make up for enhanced NTCPs related to diabetes as co-morbidity, again dependent on the patient. The proposed system can play an important role in further personalization of patient care.

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Keywords personalized radiotherapy, automated multi-criterial treatment planning, normal tissue complication probability (NTCP), prostate cancer, gastro-intestinal
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Journal Frontiers in Oncology
Bijman, R, Rossi, L, Sharfo, A.W., Heemsbergen, W, Incrocci, L, Breedveld, S, & Heijmen, B.J.M. (2020). Automated Radiotherapy Planning for Patient-Specific Exploration of the Trade-Off Between Tumor Dose Coverage and Predicted Radiation-Induced Toxicity-A Proof of Principle Study for Prostate Cancer. Frontiers in Oncology, 10. doi:10.3389/fonc.2020.00943