Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background

Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

Methods

This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

Results

The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

Conclusions

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

Plain Language Summary

• Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
• Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
• This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.

     

Recellularizing of human acellular dermal matrices imaged by high‐definition optical coherence tomography

High‐definition optical coherence tomography (HD‐OCT) permits real‐time 3D imaging of the impact of selected agents on human skin allografts. The real‐time 3D HD‐OCT assessment of (i) the impact on morphological and cellular characteristics of the processing of human acellular dermal matrices (HADMs) and (ii) repopulation of HADMs in vitro by human fibroblasts and remodelling of the extracellular matrix by these cells. Four different skin decellularization methods, Dispase II/Triton X‐100, Dispase II/SDS (sodium dodecyl sulphate), NaCl/Triton X‐100 and NaCl/SDS, were analysed by HD‐OCT. HD‐OCT features of epidermal removal, dermo‐epidermal junction (DEJ) integrity, cellularity and dermal architecture were correlated with reflectance confocal microscopy (RCM), histopathology and immunohistochemistry. Human adult dermal fibroblasts were in vitro seeded on the NaCl/Triton X‐100 processed HADMs, cultured up to 19 days and evaluated by HD‐OCT in comparison with MTT proliferation test and histology. Epidermis was effectively removed by all treatments. DEJ was best preserved after NaCl/Triton X‐100 treatment. Dispase II/SDS treatment seemed to remove all cellular debris in comparison with NaCl/Triton X‐100 but disturbed the DEJ severely. The dermal micro‐architectural structure and vascular spaces of (sub)papillary dermis were best preserved with the NaCl/Triton X‐100. The impact on the 3D structure and vascular holes was detrimental with Dispase II/SDS. Elastic fibre fragmentation was only observed after Dispase II incubation. HD‐OCT showed that NaCl/Triton X‐100 processed matrices permitted in vitro repopulation by human dermal fibroblasts (confirmed by MTT test and histology) and underwent remodelling upon increasing incubation time. Care must be taken in choosing the appropriate processing steps to maintain selected properties of the extracellular matrix in HADMs. Processing HADMs with NaCl/Triton X‐100 permits in vitro the proliferation and remodelling activity of human dermal fibroblasts. HD‐OCT provides unique real‐time and non‐invasive 3D imaging of tissue‐engineered skin constructs and complementary morphological and cytological information.     

Transition as a topic in psychiatry training throughout Europe: trainees’ perspectives

European Child & Adolescent Psychiatry - The majority of adolescents with mental health problems do not experience continuity of care when they reach the transition boundary of their child and...     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

MRI-targeted biopsy for detecting prostate cancer: have the guidelines changed our practices and our prostate cancer detection rate?

International Urology and Nephrology - In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious...     

Effects of two 1-year calcium and vitamin D3 treatments on bone remodeling markers and femoral bone density in elderly women

The aim of this study was to compare the effects of a 1-year treatment with calcium and vitamin D₃ combined in a tablet (Orocal^®) with the effects of a reference treatment of calcium administered in a sachet (Ostram^®) and vitamin D₃ as a tablet (Devaron^®) on bone remodeling markers and bone mineral density (BMD) in elderly women. The study population comprised 119 women ?70 years of age, 80% of whom were institutionalized. The women were randomly allocated to receive treatment for 1 year with elemental calcium 0.5 g and vitamin D₃ 400 IU combined in one chewable tablet taken twice daily (group 1) or elemental calcium 0.6 g (1 sachet) and vitamin D₃ 400 IU (1 chewable tablet) taken twice daily (group 2). BMD of the proximal femur was measured at four sites before and after the 1-year treatment period; serum 1–84 intact parathyroid hormone (PTH) concentration, serum 25-hydroxyvitamin D₃ (25[OH]D₃) concentration, and bone alkaline phosphatase activity were measured at baseline and after 6 and 12 months of treatment. At month 12, BMD had increased at all sites in patients in group 1; the increase was statistically significant at the trochanter (2.34%). In group 2, BMD had increased slightly at the femoral neck and decreased slightly at the other sites, without any statistically significant differences. BMD changes were not statistically different between the two groups except at the trochanter, where we observed a 2.34% increase in group 1 versus a 0.32% decrease in group 2. In group 1, PTH decreased significantly from baseline to month 6 (13%) and then did not change significantly from month 6 to month 12. In group 2 the decrease was not statistically significant. In addition, 25(OH)D₃ increased significantly in the two groups from baseline to month 6 (group 1, 107%; group 2, 96%). This significant increase continued but became less marked from month 6 to month 12 (13% and 15%, respectively). Bone alkaline phosphatase values decreased significantly in both groups from baseline to month 6; however, this decrease was significantly greater in group 1 (35%) than in group 2 (22%). From month 6 to month 12, values remained constant in both groups. In this study, results with the calcium and vitamin D₃ combination tablet were comparable to those of the separated calcium and vitamin D₃ supplementation concerning parameters involved in senile osteoporosis. Densitometric data showed some prevention of age-related bone loss; biochemical data showed the correction of vitamin D₃ deficiency and the reduction of PTH secretion, both of which are responsible for increased bone remodeling in the elderly. The results of this study confirm those of previous studies on the effects of calcium and vitamin D₃ supplementation in institutionalized elderly patients.     

Quantification of nucleated red blood cells in allogeneic marrow graft and impact of processing on recovery

BACKGROUND: In allogeneic bone marrow transplantation (BMT), a higher nucleated and CD34+ cell dose has been reported to improve various outcomes. Other cell types, such as lymphocyte subsets, also influenced BMT results. While nucleated red blood cells (NRBCs) represent a subset of bone marrow (BM) cell subpopulation, the question of their quantification in BM grafts and the impact of BM processing on their recovery has not been addressed. STUDY DESIGN AND METHODS: In a prospective study on 77 BM products, NRBCs were enumerated by flow cytometry and the recovery analyzed after manipulation. Because NRBCs could compromise white blood cell count, the impact of NRBC count on CD34+ cell percentage and total nucleated cell (TNC) dose were also determined. RESULTS: The mean percentage of NRBCs in BM grafts was 21.6 percent (range, 7.8%-40.9%). Mean NRBC recoveries after BM concentration or RBC depletion were 98.4 and 28.7 percent, respectively, close to those obtained for TNC cells (88.6 and 31.3%, respectively). When corrected with NRBC count, the mean percentages of corrected CD34+ cell and TNC dose were significantly modified when compared with uncorrected values, whatever the type of BM manipulation. CONCLUSION: Our data show that NRBC quantification might be of importance to improve quality control of BM products and to evaluate the influence of NRBCs cell dose on outcomes after BMT.