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Background Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG-PET/CT (PET-CT)) use is increasing. The aim of this study was to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008. Methods Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared. Results Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0–5) with PET-CT and 1.72 (range 0–5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease. Conclusion PET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement.

Infants (12 months) with rhabdomyosarcoma have historically had poorer outcome than the older age groups. We present outcomes for infants and young children aged 12-36 months with localised rhabdomyosarcoma with a particular emphasis on infants.All children less than 36 months of age enrolled on the EpSSG RMS 2005 study for localised disease are included. Treatment comprised chemotherapy, local surgery and/or radiation therapy adapted to risk group and age. Main outcome measures were event free survival (EFS) and overall survival (OS).Outcome data were available for 485/490 patients aged less than 36 months, 110 were infants. Infants received chemotherapy according to the risk group with no toxic deaths. Radiotherapy was delivered to 33.6% of infants and 63.5% of 12-36 months old, with respectively 41.7% and 22.2% receiving brachytherapy. Radical surgery was performed in 62% of infants and 57.1% of 12-36 months old. Median follow up for patients who are alive (n = 393) was 72.7 months (range 6.9-158.2). Five-year OS for infants was 88.4% (95%CI 80.3-93.2), which is significantly better than the OS in 12-36 months old patients of 78.0% (95%CI 73.2-82.0; p = 0.0204). Five-year EFS for infants was 72.5% (95%CI 62.8-80.0) compared with 66.1% (95%CI 61.0-70.7; p = 0.2663) for 12-36 months old.Infants treated on RMS 2005 achieved excellent EFS and OS. The EpSSG RMS 2005 chemotherapy regimen, combined with an increase in the application of adequate local therapy, improvements in imaging and supportive care and potentially favourable patients' characteristics may have contributed to these results.

Procedure Congenital rhabdomyosarcoma (RMS) represents a challenging disease due to its characteristics and the difficulties in delivering treatment in this immature population. Methods We analyzed treatment and outcome of patients with congenital RMS, defined as tumor diagnosed in the first 2 months of life, enrolled in the European paediatric Soft tissue sarcoma Study Group protocols. Results Twenty-four patients with congenital RMS were registered. All, except one patient (PAX3-FOXO1-positive metastatic RMS), had favorable histology and localized disease. Three patients had VGLL2-CITED2/NCOA2 fusion. Complete tumor resection was achieved in 10 patients. No radiotherapy was given. Chemotherapy doses were adjusted to age and weight. Only two patients required further dose reduction for toxicity. The 5-year event-free survival (EFS) and overall survival (OS) were 75.0% (95% confidence interval [CI] 52.6-87.9) and 87.3% (95% CI 65.6-95.7), respectively. Progressive disease was the main cause of treatment failure. Conclusion Patients with congenital RMS presented with a favorable disease, allowing weight- and age-adjusted doses of chemotherapy and avoidance of irradiation, without compromising the outcome.

PROCEDURE The survival of children with rhabdomyosarcoma (RMS) has gradually improved as a result of the adoption of multidisciplinary treatments. Dedicated skills and facilities are indispensable and more readily available at reference centers. In this study, we examined the role of centers' experience (based on the number of patients treated) in their management of patients with RMS. METHODS We analyzed 342 patients with localized RMS enrolled in the European RMS 2005 protocol from October 2005 to December 2016 at 31 Italian centers that are part of the Soft Tissue Sarcoma Committee (STSC). We grouped the centers by the number of patients each one enrolled (Group 1: >40; Group 2: 10; and Group 3

BACKGROUND Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age

Introduction:Pleuropulmonary blastoma (PPB) is a rare, aggressive mesenchymal tumor of childhood. The Italian Tumori Rari in Età Pediatrica (TREP) Registry was the first in Europe dedicated to prospective data collection on rare pediatric tumors. We analyzed data from an Italian series of patients with PPB, focusing on the role of the TREP Project.Methods:We considered patients aged 0–14 with histologically confirmed diagnosis, registered in population-based cancer registries (before 2000) or the TREP Registry (2000 to 2014), and analyzed data on clinical characteristics, treatment, and outcome. Event-free survival (EFS) and overall survival (OS) were estimated. Relevant prognostic factors were identified performing a univariate analysis.Results:Thirty-seven cases were included (7 type I, 13 type II, 17 type III). The average diagnosis rate rose from 1.10 to 1.73 cases/year after the TREP Project started. All patients underwent surgery, 33 received chemotherapy, and 9 had radiotherapy. The median follow-up was 8.7 years. For type I, II, and III, respectively, the 5-year OS was 85.7% (33.4–97.9), 52.7% (23.4–75.5), and 57.8% (31.1–77.3); the 5-year EFS was 85.7% (33.4–97.9), 52.7% (23.4–75.5), and 52.9% (27.6–73.0). Favorable prognostic factors for EFS were Intergroup Rhabdomyosarcoma Study (IRS) stage I ( p = 0.03) and T1 tumor ( p = 0.05). A total of 78.3% of patients who had chemotherapy after 2000 received a standardized treatment.Conclusions:The TREP Registry showed an excellent capacity for registering cases of PPB. Patients received homogeneous treatment after the TREP Project started. Long-term outcomes were excellent for type I and unsatisfactory for type II and III. Tumor invasiveness and IRS stage were of prognostic value.

Background: Children with sickle cell disease (SCD) are at increased risk of cerebrovascular events that can impact neurocognitive development and quality of life (Colombatti 2016). Transcranial Doppler ultrasound (TCD) is a validated screening tool to identify pediatric SCD patients with the highest risk of stroke to start on a preventive chronic blood transfusion regimen (Estcourt 2020; Inusa 2019). High TCD velocities are an indication to start disease-modifying treatments or consider disease-curative options in children with SCD (Khemani 2019). However, real-world pediatric data on the correlation between hematological variables and TCD results are scarce (Salama 2020). We aimed to evaluate the distribution of TCD velocities in a pediatric natural history cohort and investigate their correlation with hematological variables and treatments. Methods: We performed a retrospective analysis on data from a prospective pediatric cohort followed from January 1,2009, to December 31, 2020 (censoring date). Standard care includes annual TCD from 2 years of age. We used transcranial Doppler imaging (TCDi) and classified results according to STOP criteria, considering terminal internal carotid artery (TICA) and middle cerebral artery (MCA) time-averaged maximum mean velocities (TAMMVs). Only complete exams with right and left measures available for both vessels were included. Hematological, clinical, and treatment variables were available from the natural history cohort database. Patients were divided according to genotype: HbSS/HbSβ 0 or HbSC/HbSβ +. Two-sample and Welch t-tests for unequal variances were used to compare mean hemoglobin (Hb) values and hemolysis markers in patients with and without abnormal/conditional TCDi results. Fisher and chi-square tests were used to compare categorical variables. Linear regression models were used to assess the effects of MCA and TICA TAMMVs as continuous variables on Hb. Odds ratios (ORs) for neurological events at different Hb levels were estimated using generalized estimated equations (GEE) with a binomial distribution, logistic function, and exchangeable correlation structure, allowing for correlation among repeated observations for the same patient. Multivariable GEE including characteristics and treatment variables were used to evaluate the association between neurological events and Hb. Results: Of the 182 SCD patients in the cohort, 169 had assessments of cerebral vasculopathy, and 155 had evaluable TCDi (583 exams). The median follow-up of the entire cohort was 79.8 months (range: 2.1-298.6 months) (interquartile range [IQR]: 36.9-126.3 months). The median age at the censoring date was 13.4 years (IQR: 9.1-17.5 years); 130 were HbSS/HbSβ 0, and 25 were HbSC/HbSβ +. Basic demographic characteristics of the cohort are in Table 1. The distribution of TCDi results was significantly different between genotypes (P We detected a linear correlation between TICA/MCA TAMMVs and Hb (Figure 1A and 1B). Univariate analysis showed significant inverse correlation between abnormal/conditional TCDi results and Hb considered as a continuous variable (OR: 0.484, P Conclusions: This analysis from our natural history cohort shows a significant inverse correlation between Hb and MCA and TICA velocities, supporting the beneficial effect of higher Hb levels in reducing TAMMV. Disease-modifying therapies increasing Hb and reducing hemolysis could be helpful in reducing TAMMV in children with SCD. Funding: This study was supported by Global Blood Therapeutics. Figure 1 Figure 1. Disclosures Agodoa: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Beaubrun: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Biffi: BlueBirdBio: Consultancy, Other: Advisory Board. Colombatti: Global Blood Therapeutics: Research Funding; Addmedica: Consultancy; Forma Therapeutics: Consultancy; Novartis: Consultancy; NovoNordisk: Consultancy; BlueBirdBio: Consultancy; Global Blood Therapeutics: Consultancy; BlueBirdBio: Research Funding.

Background: Hydroxyurea (HU) and chronic transfusion therapy (CTT) are the only disease modifying therapies (DMTs) currently available as standard of care in the UK and Italy for patients with sickle cell disease (SCD), with hematopoietic stem cell transplant (HSCT) available to a small fraction of patients. Few registries capture long-term follow up of real-world outcomes among patients with SCD and there is a need for natural history studies demonstrating morbidity and mortality under existing standard of care. The East London Newborn Sickle Cohort Study (ELNSCS) at the Royal London Hospital and the Sickle Cell Disease Cohort (SCDC) at the University of Padova (UNIPD) collect biomarker and clinical data on patients followed comprehensively at two expert referral centers and provide an opportunity to understand SCD real-world outcomes. Here, we report severe acute complications under standard of care during years when HU and CTT were widely available and accepted. Methods: Inclusion of patients in the ELNSCS required being born in a designated region in London, diagnosed by newborn screening between 1983-2018 and, for this analysis, followed during 2015-2018. Inclusion in the SCDC required being followed, for this analysis, at the UNIPD during 2016-2019. Analyses were restricted to patients with β Sβ S, β Sβ 0, and, for ELNSCS, β Sβ +. Data were entered into clinical databases at each site and subsequently validated against institutional records. Severe vaso-occlusive events (VOEs) were defined as events requiring admission (inpatient, ED, or hematology day unit) for acute chest syndrome (ACS), acute painful crisis, acute hepatic/splenic sequestration, acute ischaemic stroke, dactylitis and priapism. Statistical analysis was aligned between both sites. Patients were categorized into three mutually exclusive treatment groups (HU, CTT, no treatment) according to treatment during study period. Results: One hundred seventy-two patients in the ELNSCS and 62 patients at UNIPD met study inclusion criteria in the four-year analysis period. HbSS genotype accounted for 161 (93.6%) of ELNSCS cohort and 58 (93.5%) of UNIPD cohort. Median age at study entry was 11.6 (range 0.2 - 31.4) years in the ELNSCS and 7.66 (range 0.12 - 19.96) years at UNIPD. Median age differed across treatment groups; HU group tended to be younger, while CTT group tended to be older. According to institutional standards of care, 47 (27.3%) patients from the ELNSCS and 50 (80.6%) from UNIPD received HU, 53 (30.8%) from the ELNSCS and 8 (12.9%) from UNIPD received CTT, and 72 (41.9%) from the ELNSCS and 4 (6.5%) from UNIPD received no treatment during the four year study period. Differences in treatment allocation reflect slightly different patient populations and approaches to care at the two centers. Severe VOEs persist among patients in all three treatment groups at both sites. Of those receiving HU, 83.0% from the ELNSCS and 68.0% at UNIPD had ≥1 severe VOE, including 21.3% from the ELNSCS and 44.0% at UNIPD experiencing ≥1 ACS event. The rate of severe VOEs in the HU group was 0.75 (range 0 - 39.5) per patient year from the ELNSCS and 0.49 (range 0 - 3.00) per patient year from UNIPD. HU dosing and adherence will be explored using data collected on hematologic parameters. In the ELNSCS, of those receiving CTT, 60.4% experienced ≥1 severe VOE (20.8% had ≥1 ACS event); of those receiving no therapy, 56.9% experienced ≥1 severe VOE (11.1% had ≥1 ACS event). At UNIPD, severe VOEs were observed in 62.5% of the CTT group and 50% of the no treatment group, though sample sizes were very small. C onclusions: Despite receiving expert care in accordance with local and international guidelines at two large academic centers, a significant sub-group of patients continue to experience severe VOEs. Results show that real-world usage of HU and CTT may not be optimized and, even if optimized, some patients may continue to experience severe acute complications including ACS. Both cohorts confirm that implementation of existing standard of care is insufficient to prevent significant morbidity in patients with SCD. Findings suggest the need to introduce DMT early in life to reduce and prevent acute complications and minimize disease progression. There is a persistent need for maximizing effective DMTs, as well as further developing curative therapies such as HSCT and gene therapy for both pediatric and adult patients. Figure 1 Figure 1. Disclosures Colombatti: Novartis: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBirdBio: Membership on an entity's Board of Directors or advisory committees, Research Funding. Chawla: BlueBirdBio: Current Employment. Puri-Sharma: BlueBirdBio: Current Employment. Walls: BlueBirdBio: Current Employment. Kommera: BlueBirdBio: Current Employment. Telfer: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; ApoPharma: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBirdBio: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Terumo: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.