10021 Background: Relapsed or refractory (R/R) solid tumors remain a significant cause of mortality for children. While upfront therapies have been well-studied, the cumulative effects of multiple relapses and salvage regimens is unknown. We describe the disease trajectory in these patients, from the time of first R/R event (on-therapy progression/refractoriness or off-therapy relapse) to time of death or last follow-up. We also analyze whether breaks ( > 30 days) between diagnosis of events and initiation of subsequent therapies have an impact on survival. Methods: We reviewed data from electronic medical records for patients with primary, malignant R/R extracranial solid tumors treated at Texas Children’s Hospital between 2005-2023. Descriptive analysis was performed along with univariate chi-square, one-way ANOVA, and independent sample t-tests. Cox regression analysis was used to evaluate time from first event to death or last known follow-up for each variable described. Analysis was performed with SPSS v29. Results: We reviewed data for 466 patients with R/R solid tumors (female: 47%; median age: 8.66 years; median follow-up after first event: 12.9 months). Most common diagnoses were neuroblastoma (21.5%), rhabdomyosarcoma (19.1%), and osteosarcoma (16.1%). Patients had a median of 3 (interquartile range [IQR]: 1-4) R/R events with a median of 93 (IQR 52-200) days between each event. The most common post-event therapy regimens were intravenous chemotherapy alone (21.4%) or in combination with surgery and/or radiotherapy (19.9%). Deceased patients (n = 339) had a median of 291 (IQR: 127-549) days from first event to death. Increased time from first R/R event to death was associated with a break in disease-directed therapy; type of diagnosis; non-metastatic stage at original diagnosis; type of first event; type of first salvage regimen; and receiving phase 1 therapy. Of 438 patients who received ≥1 salvage therapy regimen, 116 (26.5%) took ≥1 break between an R/R event and subsequent therapy. Reasons for breaks varied relatively evenly between intentional/goal-concordant (e.g., to seek second opinion, to focus on quality of life), and unintentional (e.g., care coordination, care access issues). In a multivariable Cox regression model, taking a > 30 day break in disease-directed therapy was associated with prolonged survival, even after adjusting for number of events and significant covariates (p < 0.05). Conclusions: The prognosis for children with R/R solid tumors is poor. Most children experience multiple R/R events and therapy regimens without a break in therapy. Presence of a > 30 day break between an R/R event and subsequent therapy did not negatively impact survival, implying that time between therapy regimens can safely be offered to some patients to promote quality of life, exploration of goals of care, and thoughtful decision-making, without compromising survival.