Enteral Nutrition in Pediatric High-risk Head and Neck Cancer Patients Receiving Proton Therapy: Identifying Risk Factors and Quality of Life Concerns to Optimize Care.

BACKGROUND: Radiotherapy for pediatric head and neck tumors often results in mucositis and pain, limiting oral intake and compromising patients' nutrition. There are little pediatric data available regarding enteral tube use and risk factors. Our objective was to estimate nutrition needs, identify risk factors contributing to nutritional decline and explore quality of life measures regarding enteral nutrition during proton radiotherapy. PROCEDURE: Nutritional metrics and status were collected throughout radiation treatment for 32 patients. We surveyed patients/caregivers about their perceptions of enteral nutrition. Risk factors for progression to non-oral nutrition or >5% weight loss were evaluated using univariate analysis. RESULTS: Patients who received any esophageal radiation or >30 Gy mean dose to the pharyngeal constrictors were more likely to experience >5% weight loss. These patients, as well as those who received a mean dose >30 Gy to the oropharynx or concurrent chemotherapy, were also more likely to require non-oral supplementation. Patients expressed the importance of maximizing nutrition and feared pain associated with a tube placement. CONCLUSIONS: Pediatric patients with head and neck cancer can be risk-stratified based on clinical and dosimetric factors. This data, combined with parent and patient perceptions, is key to the development of rational guidelines.

Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.

Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1-5 and 8-12 of each 28-day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m(2) and topotecan 1 mg/m(2) ; (2) sorafenib 150 mg/m(2) and topotecan 1.4 mg/m(2) ; and (3) sorafenib 200 mg/m(2) and topotecan 1.4 mg/m(2) . Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration-time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m(2) twice daily orally on days 1-28 combined with topotecan 1.4 mg/m(2) once daily on days 1-5 and 8-12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied.

Treatment of relapsed precursor-B acute lymphoblastic leukemia with intensive chemotherapy: POG (Pediatric Oncology Group) study 9411 (SIMAL 9).

Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%±6.2%) or overall survival (41.6%±6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia.

Effect of oral arginine supplementation on exhaled nitric oxide concentration in sickle cell anemia and acute chest syndrome.

INTRODUCTION: Decreased exhaled nitric oxide levels (FE(NO)) have been described in patients with sickle cell disease (SCD) and a history of acute chest syndrome (ACS) when compared with non-ACS controls. Oral arginine supplementation has been shown to increase FE(NO) in healthy participants, but its effect in SCD patients is not known. OBJECTIVE: To determine the effect of oral arginine intake on FENO in sickle cell patients with and without history of ACS, and in healthy controls. HYPOTHESIS: No differences in the FE(NO) increase were seen in SCD patients with a history of ACS (ACS+) compared with healthy controls (HC) and SCD patients without history of ACS (ACS-). MATERIALS AND METHODS: ACS+ (n=6), ACS- (n=9), and HC (n=7) patients were studied. At baseline, and after the administration of escalating doses of oral L-arginine (0.1, 0.2, and 0.4 g/kg), serial measurements were made of the following: FE(NO), plasma concentrations of arginine, ornithine, citrulline, aspartate, glutamate, arginine/ornithine ratio, nitrite, nitrate, heart rate (HR), respiratory rate (RR), blood pressure (BP), oxygen saturation (SpO2), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). MAIN RESULTS: At baseline, FE(NO) did not differ among the groups. ACS- and ACS+ groups were deficient in arginine, and had decreased FEV1, FVC, and SaO2 when compared with HC patients. After arginine supplementation, FE(NO), arginine, ornithine, citrulline, nitrite, and the arginine/ornithine ratio increased similarly in all groups. Changes from baseline for HR, BP, SpO2, RR, FEV1, and FVC were minimal and similar in all groups. CONCLUSIONS: In contrast to our earlier study, ACS+ patients had similar FE(NO) values when compared with ACS- and HC patients. All SCD patients were arginine deficient at baseline and showed impairment in respiratory physiology when compared with HC patients. After arginine supplementation, FE(NO) concentration increased in all groups to a similar degree, and lung function and physiologic parameters were minimally affected. The physiologic significance of alterations in FE(NO) in SCD patients and its relationship to ACS predilection requires further delineation.

Factors influencing complementary and alternative medicine use in a multisite pediatric oncology practice.

PURPOSE: Complementary and alternative medicine (CAM) use in children is common although estimates of prevalence vary widely. We studied CAM use in our multisite pediatric oncology practice and evaluated factors influencing CAM use. PATIENTS AND METHODS: We conducted an anonymous cross-sectional survey of 274 parents of children treated at the combined Nemours oncology practice in Florida and Delaware. Prevalence of CAM use was determined and binary logistic regression was used to evaluate factors related to CAM use in children. RESULTS: The prevalence of CAM use among children and parents was 24.5% and 66.7%, respectively. Intensity of parent's use of CAM and geographic region were significantly associated with CAM use in children. The odds of CAM use in children increased with increasing use among parents. When parents used 6 or more therapies children were 33 times more likely to use CAM compared with those whose parents did not use CAM (odds ratio=33.3; 95% confidence interval, 10.4-106.2, P<0.01). Children in Florida were more likely to use CAM compared with children in Delaware (odds ratio=3.0; 95% confidence interval, 1.6-5.8, P<0.01). CONCLUSIONS: These results indicate that children's use of CAM is significantly related to the intensity of parent's use regardless of parent's race, sex, education, household income, or child's sex or age. Clinicians should consider parental use and intensity of CAM use. Assessing CAM use should include classifications established by the National Center for CAM and a standard format for inquiring about CAM use should be developed.