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.