Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

OBJECTIVE: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns. BACKGROUND: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear. METHODS: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant. RESULTS: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used. CONCLUSIONS: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Patterns of recurrence after intracranial stereotactic radiosurgery for brain-only metastases from non-small cell lung cancer and the impact of upfront thoracic therapy with synchronous presentation.

Background: We characterized long-term organ-specific patterns of recurrence, time to progression (TTP) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with brain-only metastases treated with single-fraction stereotactic radiosurgery (SRS) and analyzed the impact of upfront thoracic therapy (UTT) in those with synchronous presentation of primary NSCLC and brain metastases. Methods: The clinical records of 137 patients with brain metastases from NSCLC treated with intracranial SRS, and no other metastatic sites, were retrospectively reviewed. Patients with available follow-up imaging (n=124) were analyzed for patterns of recurrence; all were analyzed for OS. Results: The majority of first distant recurrences were in brain and thoracic sites, while extra-thoracic sites were relatively uncommon. After median follow-up of 16.0 months, 24.8% did not develop recurrence outside of brain and/or thoracic sites and 43.5% were free of distant extracranial recurrence. Whole brain radiotherapy (WBRT) and UTT, but not systemic therapy, altered patterns of recurrence and intracranial or extracranial TTP. Multivariable analysis revealed UTT, but not systemic therapy or WBRT, was associated with more favorable OS [hazard ratio (HR) 0.515, P=0.029] among 88 patients with synchronous presentation. Within the subgroup of thoracic stage III patients (n=69), those treated with UTT experienced remarkable median extracranial TTP and OS of 19.3 and 22.7 months, respectively. Conclusions: First and cumulative recurrences in patients treated with intracranial SRS for NSCLC metastases limited to brain are most often in the brain and thorax. Long-term survival is possible, regardless of thoracic stage, and is dependent on UTT among other factors.

Factors Predictive of Improved Outcomes With Multimodality Local Therapy After Palliative Chemotherapy for Stage IV Esophageal Cancer.

OBJECTIVES: We reviewed survival outcomes and factors associated with improved outcomes for patients with stage IVB esophageal cancer who received multimodality therapy with initial chemotherapy followed by concurrent chemoradiation (CRT)±surgery. METHODS: We retrospectively identified 96 patients with stage IVB esophageal carcinoma (with positive nonregional lymph nodes and/or distant organ metastasis) treated at a single institution with chemotherapy followed by concurrent CRT, with or without surgery. The Cox proportional hazard model was used to test associations between overall survival (OS), disease-free survival (DFS), locoregional relapse, distant metastasis-free survival, and potential predictive factors. RESULTS: Median patient age at diagnosis was 59 years. The median OS time among all patients was 21.0 months, and 1-, 2-, and 5-year OS rates were 84.4%, 46.8%, and 17.9%, respectively; corresponding DFS time and rates were 8.1 months and 37%, 24.6%, and 24.6%, respectively. On multivariate analysis, factors that predicted improved OS with aggressive multimodal therapy included young age; lack of anorexia, fatigue at diagnosis; distant nodal metastasis without organ metastasis at diagnosis; and radiographic response to initial chemotherapy. A subset of 14 patients who had surgery after chemotherapy and concurrent CRT also had better median OS (not reached vs. 20 mo for 82 patients who did not receive surgery, P=0.001), DFS (14.6 vs. 5.9 mo, P=0.021), and distant metastasis-free survival (26.7 vs. 9.2 mo, P=0.042). CONCLUSIONS: Aggressive local therapy with radiation and potentially surgery after initial palliative chemotherapy can improve prognosis for a select group of patients with stage IVB esophageal cancer.

Improved survival endpoints with adjuvant radiation treatment in patients with high-risk early-stage endometrial carcinoma.

PURPOSE/OBJECTIVE(S): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. METHODS AND MATERIALS: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. RESULTS: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. CONCLUSION: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma. Furthermore, adjuvant RT is an independent predictor for RFS, DSS, and OS in this group of patients. These findings need validation from a prospective randomized study.