Personalized mid-course FDG-PET based adaptive treatment planning for non-small cell lung cancer using machine learning and optimization.

Objective. Traditional radiotherapy (RT) treatment planning of non-small cell lung cancer (NSCLC) relies on population-wide estimates of organ tolerance to minimize excess toxicity. The goal of this study is to develop a personalized treatment planning based on patient-specific lung radiosensitivity, by combining machine learning and optimization.Approach. Sixty-nine non-small cell lung cancer patients with baseline and mid-treatment [18]F-fluorodeoxyglucose (FDG)-PET images were retrospectively analyzed. A probabilistic Bayesian networks (BN) model was developed to predict the risk of radiation pneumonitis (RP) at three months post-RT using pre- and mid-treatment FDG information. A patient-specific dose modifying factor (DMF), as a surrogate for lung radiosensitivity, was estimated to personalize the normal tissue toxicity probability (NTCP) model. This personalized NTCP was then integrated into a NTCP-based optimization model for RT adaptation, ensuring tumor coverage and respecting patient-specific lung radiosensitivity. The methodology was employed to adapt the treatment planning of fifteen NSCLC patients.Main results. The magnitude of the BN predicted risks corresponded with the RP severity. Average predicted risk for grade 1-4 RP were 0.18, 0.42, 0.63, and 0.76, respectively (p< 0.001). The proposed model yielded an average area under the receiver-operating characteristic curve (AUROC) of 0.84, outperforming the AUROCs of LKB-NTCP (0.77), and pre-treatment BN (0.79). Average DMF for the radio-tolerant (RP grade = 1) and radiosensitive (RP grade ≥ 2) groups were 0.8 and 1.63,p< 0.01. RT personalization resulted in five dose escalation strategies (average mean tumor dose increase = 6.47 Gy, range = [2.67-17.5]), and ten dose de-escalation (average mean lung dose reduction = 2.98 Gy [0.8-5.4]), corresponding to average NTCP reduction of 15% [4-27].Significance. Personalized FDG-PET-based mid-treatment adaptation of NSCLC RT could significantly lower the RP risk without compromising tumor control. The proposed methodology could help the design of personalized clinical trials for NSCLC patients.