Background: Tumor Treating Fields (TTFields) therapy is a noninvasive, locoregional modality comprised of electric fields which disrupt critical cellular processes necessary for cancer cell viability and tumor progression. TTFields therapy is FDA approved and CE-marked for glioblastoma, and pleural mesothelioma. Approval for the latter was based on results from the phase 2 STELLAR study (EF-23, NCT02397928), in which the median OS was 18.2 months (95% CI 12.1–25.8) and median PFS was 7.6 months (95% CI 6.7–8.6). As the electrical fields are delivered non-invasively via skin-adhered arrays, the most common adverse events (AEs) are mild-moderate skin reactions which can be effectively managed with appropriate prophylaxis and timely intervention. Here we report a single-center experience of treating and managing TTFields therapy-related AEs in the STELLAR study, based on a center-specific protocol. Methods: The STELLAR study was a multicenter, single-arm, non-randomized, phase 2 study, whereby patients received TTFields therapy (150 kHz, 18 h/day) concomitant with pemetrexed (500 mg/m²) and platinum-based chemotherapy (75 mg/m²). TTFields-therapy AEs were managed and treated using a center-specific protocol (Table). Results: In this single center, 23 patients were treated using the predefined protocol to prevent skin AEs; all were included in the safety analysis. n = 15 (65%) reported a mild-moderate skin AE (n = 12 [52%] medical device site reaction [skin AE], n = 1 [4%] had mild-moderate rash, rash erythematous and skin irritation) in the single center, vs n = 54 (68%) in the overall STELLAR population. n = 2 (9%) in the single site had a severe medical device site reaction, which was comparable with the overall STELLAR study population. Conclusions: A predefined multidisciplinary approach was successful to help prevent mild-moderate skin AEs. Timely and appropriate management of mild/moderate skin AEs can prevent exacerbations. Skin management may support usage, thus optimizing outcomes for patients. Guidelines on preventing skin AEs when using TTFields therapy are available and should be incorporated in a clinical setting. Clinical trial information: NCT02397928.