12024 Background: Cardio-oncology rehabilitation holds significant importance for lung cancer survivors, particularly those diagnosed at an early stage requiring lobectomy, where the maximal oxygen uptake peak (VO2PEAK) stands out as a robust prognositic predictor. Home-based cardiac telerehabilitation serves as a substitute for traditional center-based rehabilitation, demonstrating higher participation and completion rates. Despite the potential benefits, wearable devices and mobile apps, which offer tailored video guides, real-time monitoring, individualized safety alerts, and exercise-specific feedback, have not gained widespread adoption in clinical practice. Here, we present findings on the efficacy, safety, and compliance of a 3-month cardio-oncology rehabilitation program based on digital therapeutics (DTx) for lung cancer survivors. Methods: Early-stage lung cancer survivors post-lobectomy, not requiring radiotherapy or chemotherapy, were randomly assigned to receive cardiac telerehabilitation or usual care for 5 months. For pts in the telerehabilitation group, exercise prescriptions with video guides and real-time HR monitoring were implemented using the R Plus Health APP, a software as medical device approved by CFDA for remote cardiac rehab. The AI-driven prescriptions were generated based on CPET, modified by physiologists, and dynamically optimized according to feedback. Pts in the usual care group received routine instructions. Outcome measurements included VO2PEAK (primary outcome), FEV1, DLCO, cardiac function, safety, compliance, and scales assessing symptoms (MDASI), psychology (HADS), sleep (PSQI), fatigue (MSFI-SF), and quality of life (QLQ-C30). Results: 40 of 47 (85%) pts completed the trial (22 in the telerehabilitation group and 18 in the usual care group). Pts in the telerehabilitation group engaged in exercise an average of 3.3 times per week. The average exercise duration was 151.4 min per week, with an average effective exercise duration (when the required heart rate was reached) of 92.3 min per week. The average prescription compliance rate (effective exercise duration/lower limit of prescription duration) was 101.2%. Cardiac telerehabilitation was associated with a higher average VO2PEAK improvement (3.660±3.232 vs 1.088±3.230 mL/Kg/min, p=0.023), better alleviation of affective interference (-0.883±1.500 vs 0.208±1.222, p=0.048), higher quality of life improvement (16.250±23.017 vs 1.042±13.903, p=0.027), fatigue (-0.889±15.960 vs 1.389±12.087, p=0.024), daytime dysfunction (-0.550±0.686 vs 0.000±0.516, p=0.015), and more anxiety relief (-0.314±0.444 vs -0.054±0.295, p=0.048) compared with usual care. Other efficacy outcomes did not show significant differences between the two groups. No exercise-related adverse events occurred during the intervention. Conclusions: DTx-based cardio-oncology rehabilitation demonstrated improvements in cardiorespiratory fitness and reductions in affective interference and anxiety among lung cancer survivors, indicating high compliance and safety. Clinical trial information: ChiCTR2200064000.