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Background: The prognosis for children with recurrent solid tumors generally is poor. Targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor A with everolimus and bevacizumab, respectively, synergistically improves progression-free survival and is well tolerated in adults with solid tumors.Methods: In the current phase 1 study, a total of 15 children with recurrent or refractory solid tumors were treated with bevacizumab and everolimus to establish the maximum tolerated dose, toxicity, and preliminary antitumor response (ClinicalTrials.gov identifier NCT00756340). The authors also evaluated everolimus-mediated inhibition of the mTOR pathway in the peripheral blood mononuclear cells of treated patients.Results: Tumors predominantly were soft tissue and/or bone sarcomas (8 cases) and brain tumors (5 cases). The first 2 patients enrolled at dose level 1 (10 mg/kg of bevacizumab and 4 mg/m2 of everolimus) experienced dose-limiting toxicities (DLTs). The next 5 patients were enrolled at dose level 0 (8 mg/kg of bevacizumab and 4 mg/m2 of everolimus), and DLTs occurred in 2 patients. The authors then modified the protocol to permit expansion of dose 0, and 8 additional patients were added, with no DLTs reported. Of all the patients, stable disease occurred in 4 patients (30.8%; median, 2 courses), and progressive disease occurred in 9 patients (69.2%). Overall survival was 0.59 years (95% CI, 0.24-1.05 years). The mTOR biomarker phospho-4EBP1 Thr/37/46 significantly decreased from baseline to day 27 in peripheral blood mononuclear cells (P = .045). Phospho-AKT levels also decreased from those at baseline.Conclusions: The maximum tolerated dose of cotreatment with bevacizumab and everolimus was 8 mg/kg of bevacizumab and 4 mg/m2 of everolimus in a 4-week cycle for children with recurrent solid tumors. [ABSTRACT FROM AUTHOR]

Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies. Cohorts of 3–6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Talazoparib was administered on days 1–6, and intravenous irinotecan and oral temozolomide were administered on days 2–6, of a 21-day course. Serum for talazoparib and irinotecan pharmacokinetics was obtained during course 1. UGT1A1 polymorphism and Schlafen family member 11 (SLFN11) immunohistochemical staining were performed. Forty-one patients (20 males; median age, 14.6 years; 24 with recurrent disease) were evaluable for dose escalation. Twenty-nine and 12 patients were treated on arm A and arm B, respectively, for a total of 208 courses. The most common diagnosis was Ewing sarcoma (53%). The most common ≥grade III haematologic toxicities in arms A and B included neutropenia (78% and 31%, respectively) and thrombocytopenia (42% and 31%, respectively). In arms A and B, febrile neutropenia (24% and 14%, respectively) and diarrhoea (21% and 7%, respectively) were the most common ≥grade III non-hematologic toxicities. Six patients (Ewing sarcoma [5 patients] and synovial sarcoma [1 patient]) had a response (1 with a complete response, 5 with a partial response). The objective response rates were 10.3% (arm A) and 25% (arm B). Pharmacokinetic testing demonstrated no evidence of drug-drug interaction between talazoparib and irinotecan. UGT1A1 was not related to response. SLFN11 positivity was associated with best response to therapy. The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted. • Talazoparib with irinotecan and temozolomide is tolerated in paediatric patients. • There was no drug-drug interaction between talazoparib and irinotecan. • UGT1A1 status was significantly associated with a course 1 dose-limiting toxicity. • Schlafen family member 11 positivity was associated with best response to therapy. • This regimen had clinical benefit in patients with Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Background: A variety of terms and attitudes surround palliative sedation (PS) with little research devoted to hospice and palliative care (HPC) clinicians' perceptions and experiences with PS. These factors may contribute to the wide variability in the reported prevalence of PS. Objective: This study was designed to better identify hospice and palliative care (HPC) clinician attitudes toward, and clinical experiences with palliative sedation (PS). Methods: A 32-question survey was distributed to members of the American Academy of Hospice and Palliative Medicine ( n = 4678). The questions explored the language clinicians use for PS, and their experiences with PS. Results: Nine hundred thirty-six (20% response rate) responded to the survey. About 83.21% preferred the terminology of PS compared with other terms. A majority felt that PS is a bioethically appropriate treatment for refractory physical and nonphysical symptoms in dying patients. Most felt PS was not an appropriate term in clinical scenarios when sedation occurred as an unintended side effect from standard treatments. Hospice clinicians use PS more consistently and with less distress than nonhospice clinician respondents. Benzodiazepines (63.1%) and barbiturates (18.9%) are most commonly prescribed for PS. Conclusion: PS is the preferred term among HPC clinicians for the proportionate use of pharmacotherapies to intentionally lower awareness for refractory symptoms in dying patients. PS is a bioethically appropriate treatment for refractory symptoms in dying patients. However, there is a lack of clear agreement about what is included in PS and how the practice of PS should be best delivered in different clinical scenarios. Future efforts to investigate PS should focus on describing the clinical scenarios in which PS is utilized and on the level of intended sedation necessary, in an effort to better unify the practice of PS. [ABSTRACT FROM AUTHOR]

Keywords: American Society of Anesthesiology Physical Status (ASA-PS) score; anesthesiology; enucleation; oncology; pediatric oncology; retinoblastoma EN American Society of Anesthesiology Physical Status (ASA-PS) score anesthesiology enucleation oncology pediatric oncology retinoblastoma 491 493 3 03/30/21 20210401 NES 210401 An American Society of Anesthesiology-Physical Status (ASA-PS) score is assigned to patients prior to undergoing anesthesia as a means of quantifying the impact of a patient's comorbidities. ASA-PS scores were summarized to create a single, summarized median (S SB M sb ) ASA-PS score for the pre-enucleation and the post-enucleation set of anesthetics for each patient. Pre-enucleation S SB M sb ASA-PS scores were compared with post-enucleation S SB M sb ASA-PS scores to determine if removal of localized cancer influenced ASA-PS assigning practices. [Extracted from the article]

Abstract: Background: Cyclic vomiting syndrome (CVS) is often triggered by stress. Patients report high degrees of psychological distress due to CVS, but there is limited data on factors associated with psychological distress. We sought to determine the degree of psychological distress and its correlation with clinical characteristics in CVS. Methods: The Brief Symptom Inventory (BSI), a validated tool to determine psychological distress, was administered prospectively to patients. The control population consisted of 719 normal subjects. Student's t test was used to compare means, and logistic regression analysis was performed to identify predictors of a GSI score ≥63, indicating high degrees of psychological distress. Scores for the regression predictors were calculated using the maximum likelihood estimate for the logistic regression model and was called the DAME score (depression, age 25‐35, chronic marijuana use, and interepisodic GI symptoms). Key Results: Of 87 patients, 60% were female, 92% were caucasian, and mean age was 37 years. Forty‐one percent of patients had high degrees of psychological distress with the highest scores for somatization. Independent predictors of psychological distress included depression, young age (25‐35 years), chronic marijuana use, and interepisodic dyspepsia (called the DAME score). A score of ≥7 accurately predicted psychological distress in >88% of patients. Conclusions & Inferences: Psychological distress is common in CVS and can be predicted accurately using our proposed DAME score. Whether psychological distress is a cause or an effect of CVS needs to be determined. Addressing psychological distress can potentially improve overall healthcare outcomes in CVS. [ABSTRACT FROM AUTHOR]