BackgroundAmide proton transfer‐weighted imaging (APTWI) and multiple models intravoxel incoherent motion (IVIM) based 18F‐FDG PET/MR could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non‐small cell lung cancer (NSCLC) still needs to be further explored.PurposeTo determine whether pretreatment APTWI, mono‐, bi‐, and stretched‐exponential model IVIM, and 18F‐FDG PET‐derived parameters of the primary lesion may be associated with progression‐free survival (PFS) in NSCLC.Study TypeProspective.PopulationSeventy‐seven patients (mean age, 62 years, range, 20–81 years) with 37 men and 40 women were included.Field Strength/Sequence3.0 T 18F‐FDG PET/MRI, single shot echo planar imaging sequences for IVIM and fast spin‐echo sequences with magnetization transfer pulses for APTWI.AssessmentPatient clinical characteristics (age, sex, smoke, subtype, TNM stage, and surgery), PFS (chest CT every 3 months, median follow‐up was 18 months, range, 4–27 months), and APTWI (MTRasym(3.5 ppm)), IVIM (ADCstand, D, D*, f, DDC, and α), and 18F‐FDG PET (SUVmax, MTV, and TLG) parameters were recorded.Statistical TestsProportional hazards model, concordance index, calibration curve, decision curve analysis (DCA), and Log‐rank test. A P value <0.05 was considered statistically significant.ResultsHistological subtype, TNM stage, MTV, D*, and MTRasym(3.5 ppm) were all independent predictors of PFS. A prediction model based on these predictors was developed with a C‐index of 0.895 (95% CI: 0.839–0.951), which was significantly superior to each of the above predictors alone (C‐index = 0.629, 0.707, 0.692, 0.678, and 0.558, respectively). The calibration curve and DCA indicated good consistency and clinical utility of the prediction model, respectively. Log‐rank test results showed a significant difference in PFS between the high‐ and low‐risk groups.Data ConclusionAPTWI and multiple models IVIM based 18F‐FDG PET/MRI can be used for PFS assessment in NSCLC.Evidence Level3Technical EfficacyStage 2