Background/Objectives: Psychological distress is a significant concern among cancer patients, negatively affecting their quality of life and adherence to treatment. The Cancer Patient Empowerment Program (CancerPEP) was developed as a comprehensive, home-based intervention aimed at reducing psychological distress by incorporating physical activity, dietary guidance, and social support. This study aimed to evaluate the feasibility, accrual and attrition rates, safety, and effectiveness of the CancerPEP intervention, with and without the biofeedback device, on psychological distress from baseline to 6 months, specifically focusing on the effects of group randomization and the difference between pre- and post-intervention results. Methods: This single-site, crossover randomized clinical trial included 104 cancer patients who were randomized to receive the CancerPEP intervention, with or without a Heart Rate Variability (HRV) biofeedback monitor. At 6 months, participants who did not receive the device were allowed to use one until the end of the year, while those who did receive the device were followed up to 12 months. Randomization was stratified by the presence or absence of clinically significant psychological distress and metastatic status. Psychological distress was assessed using the Kessler Psychological Distress Scale (K10) at baseline, 6 months, and 12 months. The primary endpoint was the presence of nonspecific psychological distress, as measured by the K10 scale at 6 months from the trial start, based on group randomization. A secondary exploratory analysis assessed psychological distress at baseline, 6 months, and 12 months for both groups, while controlling for group randomization and prognostic covariates. Prognostic covariates included age; comorbidities; time between diagnosis and randomization; treatment modality; relationship status; and use of prescribed medications for anxiety, depression, or both. An exploratory sub-analysis was conducted for the breast cancer subgroup, based on the sample size available after recruitment. The trial is registered at ClinicalTrials.gov (NCT05508412). Results: The provision of the HRV biofeedback monitor in conjunction with the CancerPEP intervention did not significantly affect the primary outcome in either the full sample or the breast cancer subgroup, indicating that the HRV biofeedback provision was not beneficial in this trial. No self-reported or otherwise discovered adverse events at the 6-month mark were observed. About 10% of participants were lost to follow-up in both the early and late HRV monitor provision groups. Participation in the CancerPEP program led to a significant reduction in psychological distress over time. The odds of psychological distress were significantly higher at the start of the trial than at the end of the intervention (aOR = 2.64, 95% CI: 1.53–4.56) or 6 months after the intervention (aOR = 2.94, 95% CI: 1.62–5.30). Similarly, in the breast cancer subgroup, distress was higher at the trial’s start than at 6 months, i.e., after the intervention (aOR = 2.25, 95% CI: 1.24–4.08), or at the end of the trial at 12 months (aOR = 2.73, 95% CI: 1.35–5.52). Conclusions: CancerPEP significantly reduces psychological distress in cancer patients, with consistent improvements noted across various cancer types and stages, including benefits specifically for breast cancer patients. These findings build upon the success of the Prostate Cancer Patient Empowerment Program (PC-PEP), indicating that a similar comprehensive intervention can be advantageous for all cancer patients and may be further tailored to address specific needs. With its holistic approach—encompassing physical, dietary, and psychosocial support—CancerPEP shows promise as a vital component of survivorship care. Ongoing 24-month evaluations will yield critical data on its long-term benefits. Additionally, a randomized trial with a control group (usual care without intervention) for breast cancer patients is currently under way and could potentially guide the integration of CancerPEP into standard oncology care to enhance patient outcomes and quality of life.

Online adaptive radiation (ART) is a novel treatment approach that allows for a new daily treatment plan based on cone beam CT (CBCT) imaging. This daily adaptation facilitates precise tumor and organ-at-risk (OAR) localization and minimizes the impact of interfractional motion, allowing for planning target volume (PTV) margin reduction. Isotropic PTV margins for localized non-stereotactic adaptive prostate radiation performed on an ETHOS linear accelerator with HyperSight have been reduced from standard 7 mm to 5 mm. This study assesses the impact of margin reduction by evaluating the dose metrics of patient reference plans, as well as daily treated plans, for 7 mm vs 5 mm PTV margins. Patients with prostate cancer receiving moderately hypofractionated adaptive radiation were initially treated with a 7 mm PTV margin (n = 10). This retrospective study generated 5 mm PTV margin treatment plans (n = 10) for these patients for comparison. In addition, a full adaptive 20 fraction treatment course was simulated with margin reduction to identify differences not recognized with reference plan comparison alone. Bladder V40.8 and V48.6 but not V60 were significantly reduced in 5 mm treatment plans compared to 7 mm treatment plans. However, when daily treated plan data was examined bladder V60 was lower for the 5 mm PTV case. Similarly, rectum doses V24.6-V57 but not V60 were significantly reduced in 5 mm PTV margin treatment plans. Further differences were identified when looking at the daily treated plan data as opposed to simply comparing reference plans. In the era of online ART, with significant data available, such as daily treated plan dosimetry, analysis of reference plans alone may not be sufficient. PTV margin reduction, made possible due to the use of online ART, reduced the volume of bladder and rectum receiving <60 Gy, which may reduce toxicity and secondary malignancy risk.