BackgroundThe objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group – Bone Tumor Study Group (GSF-GETO) national registry.MethodsAll patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed.ResultsTwenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9–72). The median number of previous lines of chemotherapy was 3 (range 1–8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5 % of patients (95 % Confidence Interval (CI) [20–52.8]). The median Progression-Free Survival (PFS) was 3 months (95 % CI [2–5.4]) for patients treated by sirolimus and 1.8 months (95 % CI [1.3–2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15 %. The median Overall Survival (OS) was 6.8 months (95 % CI [4.7–12.1]), and one-year OS was 24 %. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95 % CI [1.05–7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6 % of cases respectively.ConclusionOff-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.

Although previous estimation methods were useful for estimating FFM at discharge, an equation adapted to present populations of preterm infants with "modern" neonatal care and nutritional practices is required for accuracy.

This cohort study aimed to evaluate the impact of an individualised nutritional care approach combining standardised fortification with adjustable fortification on postnatal growth and body composition in extremely low birth weight (ELBW) infants. We included ELBW infants admitted to a neonatal intensive care unit and still hospitalised at 35 weeks postmenstrual age (PMA). The fortification of human milk was standardised (multicomponent fortifier) between 70 mL/kg/day and full enteral feeding, and then individualised using adjustable fortification. When weight gain was below 20 g/kg/day, protein or energy was added when serum urea was below or above 3.5 mmol/L, respectively. Postnatal growth failure (PNGF) was defined as being small for gestational age at discharge and/or when the Z-score loss between birth and discharge was higher than 1. Body composition was assessed between 35 and 41 weeks of PMA. Among the 310 ELBW infants included, the gestational age of birth was 26.7 ± 1.8 weeks, and the birth weight was 800 ± 128 g. The mean Z-score difference between birth and discharge was moderately negative for the weight (−0.32), more strongly negative for length (−1.21), and almost nil for head circumference (+ 0.03). Only 27% of infants presented PNGF. At discharge, fat mass was 19.8 ± 3.6%. Multivariable analysis showed that the proportion of preterm formula received and gestational age at birth were independently associated with the percentage of fat mass.  Conclusion: The individualised nutritional care approach applied herein prevented postnatal weight loss in most infants, limited length growth deficit, and supported excellent head circumference growth. What is Known:• At least half of extremely low birth weight infants are small for gestational age at discharge and postnatal growth deficit has been associated with impaired neurocognitive and renal development.• Human milk is the main milk used in neonatology and, although fortification of human milk is a standard of care, there is no consensus regarding the optimal fortification strategy to be adopted. What is New:• Using an approach combining standardised fortification followed by individualised adjustable fortification limited postnatal growth deficit for body weight and head circumference. Postnatal growth failure is not a fatality in extremely low birth weight infants.• Each additional gestational age week at birth resulted in a decrease in fat mass percentage at discharge, which was higher than in foetuses of the same gestational age, likely representing a necessary adaptation to extra-uterine life.