Prognostic value of hemogram parameters in osteosarcoma: The French OS2006 experience.

BACKGROUND: Previous studies have shown that neutrophil-to-lymphocyte (NLR) ratio at diagnosis and early lymphocytes recovery on doxorubicin-based chemotherapy, may impact the outcome in patients with osteosarcoma (OST). This study aimed to evaluate the prognostic value of hemogram parameters in patients with OST treated with high-dose methotrexate and etoposide/ifosfamide (M-EI) chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed the prognostic value of various hemogram parameters at diagnosis and during therapy in a large consecutive cohort of patients with OST included in the French OS2006 trial and treated with M-EI chemotherapy. RESULTS: A total of 164 patients were analyzed. The median age was 14.7 years (interquartile range [IQR]: 11.7-17). Median follow-up was 5.6 years (IQR: 3.3-7.7 years). Three-year event-free survival (EFS) and overall survival (OS) were 71.5% (95% confidence interval [CI]: 64%-78%) and 86.4% (95% CI: 80%-91%), respectively. In univariate analysis, blood count parameters at diagnosis and early lymphocyte recovery at Day 14 were not found prognostic of survival outcomes. By contrast, an increase of NLR ratio at Day 1 of the first EI chemotherapy (NLR-W4) was associated with reduced OS in univariate (p = .0044) and multivariate analysis (hazards ratio [HR] = 1.3, 95% CI: 1.1-1.5; p = .002), although not with EFS. After adjustment on histological response and metastatic status, an increase of the ratio NLR-W4 of 1 was associated with an increased risk of death of 30%. CONCLUSIONS: We identified NLR-W4 as a potential early biomarker for survival in patients with OST treated with M-EI chemotherapy. Further studies are required to confirm the prognostic value of NLR and better identify immune mechanisms involved in disease surveillance.

Alveolar soft part sarcomas in young patients: The French national NETSARC+ network experience.

BACKGROUND AND AIMS: Alveolar soft part sarcoma (ASPS) is an ultra-rare chemo-resistant sarcoma in children, occurring preferentially in young adults. We aimed to describe and compare its clinical presentation and behaviour in children and young adults to determine whether the same therapeutic strategy should be addressed for both populations. METHODS: National retrospective multicentre study of children (0-18 years) vs. young adults (19-30 years) included in the "ConticaBase" sarcoma database, treated for ASPS between 2010 and 2019 with pathology reviewed via the NETSARC + network. RESULTS: Overall, 45 patients were identified, 19 children (42%) and 26 young adults (58%). All ASPS diagnoses were confirmed with TFE3 rearrangement by immunohistochemistry or FISH. All clinical characteristics were balanced between both populations with frequent metastases at diagnosis (8/19 vs. 10/26). The therapeutic strategy was based on surgery (17/19 vs. 21/26), radiotherapy (8/19 vs. 12/26) ± systemic treatment (8/19 vs. 9/26). In patients with initially localized disease, metastatic relapse occurred only in adults (8/16), whereas metastatic progression was present in both metastatic groups (5/8 vs. 8/10). After a median follow-up of 5.2 years (range, 0.2-12.2), 5-year EFS was 74% [95%CI, 56-96] vs. 47% [30-74] (p = 0.071) respectively, and 5-year OS was 95% [85-100] vs. 85% [70-100] (p = 0.84). For localized tumours, 5-year MFS was 100% [100-100] vs. 60% [39-91] (p = 0.005). The 5-year OS of all patients with metastasis at diagnosis was 80.2% (62.2%-100%). CONCLUSIONS: ASPS appears to have the overall same clinical characteristics, but a more aggressive behaviour in young adults than in children. However, despite frequent metastases at diagnosis, long-term survival is high in both groups. Overall, the same therapeutic strategies may be considered for both populations.

Biological sample collection to advance research and treatment: a Fight Osteosarcoma Through European Research (FOSTER) and Euro Ewing Consortium (EEC) statement.

Osteosarcoma and Ewing sarcoma are bone tumours mostly diagnosed in children, adolescents and young adults. Despite multi-modal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been ground-breaking. Better understanding of biological subgroups, the role of the tumour immune microenvironment, factors that promote metastasis and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic and clinically linked biological analysis of patient samples but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage and analysis of patient samples. Two international panels of scientists, clinicians and patient and parent advocates have formed the Fight Osteosarcoma Through European Research (FOSTER) consortium and the Euro Ewing Consortium (EEC). The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, liquid biopsy tubes), handling and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonisation with practical, legal and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration and improve outcomes.

Prenatal diagnosis of an adrenal mature teratoma mimicking a neuroblastoma.

Teratomas are defined by the presence of cell types from different germ layers, they typically involve the gonads or the sacrococcygeal region and are rarely retroperitoneal. Prenatally detected adrenal teratomas are extremely uncommon. Aim of this paper is to share our experience with an adrenal antenatal mass initially diagnosed as a left adrenal neuroblastoma that turned out to be a mature teratoma after microscopical examination. We present the case of a male fetus with antenatal diagnosis of a left adrenal cystic image at the 22nd week of amenorrhea. The fetal magnetic resonance imaging showed a non-calcified cystic mass of the left adrenal gland, compatible with a neuroblastoma. At birth an ultrasound confirmed the presence of an anechogenic lesion of the left adrenal gland. The infant was closely monitored during his first year and in the absence of significant regression of the adrenal mass, it was decided to perform a laparoscopic left adrenalectomy. Unexpectedly, the final pathological diagnosis was mature cystic adrenal teratoma. In conclusion, an adrenal mass diagnosed antenatally is generally a hemorrhage or a neuroblastoma. Adrenal teratomas are very rare and those diagnosed antenatally even more. At present, we have no clinical, biological, or radiological evidence to suspect them before surgical removal. There are only two other cases of unexpected adrenal teratoma in infants described in Literature.

Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project.

BACKGROUND: Adolescents (15-19 years) with sarcoma are known to have significantly worse survival than children (0-14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma. METHODS: A retrospective national population-based observational study with documented somatic genetic analyses was conducted between 2011 and 2016 of all patients aged from 0 to 17 years with a diagnosis of sarcoma using the National Registry of Childhood Cancers Database. RESULTS: A total of 1637 children (0-9years: 40%), preadolescents (10-14years: 35%) and adolescents (15-17 years: 25%) with a diagnosis of bone (N = 845) or soft-tissue (N = 792) sarcoma were included. Adolescents had significantly worse outcome for undifferentiated small round cell sarcoma (USRCS), alveolar rhabdomyosarcoma (ARMS), and epithelioid sarcoma. Five-year overall survivals were worse among CIC-rearranged USRCS cases (47% [95%CI:21-69]) as compared to other USRCS, and PAX3::FOXO1 ARMS patients (44% [95%CI:32-55]) as compared to other ARMS. Adjusting for stage and genomic-profiling status, adolescents with USRCS were 1.6-fold more likely to die than children (P = 0.05), while the difference in survival between age of ARMS patients was weaken. Indeed, the prevalence of PAX3::FOXO1 increased significantly with age. CONCLUSION: Age was an independent prognostic factor of outcome only in patients with USRCS, while the association between age and survival of patients with ARMS could be partly explained by differences in prevalence of PAX3::FOXO1.