NN bundle method applied to cosmology: an improvement in computational times

In the last few years, there has been significant progress in the development of machine learning methods tailored to astrophysics and cosmology. Among the various methods that have been developed, there is one that allows to obtain a bundle of solutions of differential systems without the need of using traditional numerical solvers. We have recently applied this to the cosmological scenario and showed that in some cases the computational times of the inference process can be reduced. In this paper, we present an improvement to the neural network bundle method that results in a significant reduction of the computational times of the statistical analysis. The novelty of the method consists in the use of the neural network bundle method to calculate the luminosity distance of type Ia supernovae, which is usually computed through an integral with numerical methods. In this work, we have applied this improvement to the Starobinsky $f(R)$ model, which is more difficult to integrate than the $f(R)$ models analyzed in our previous work. We performed a statistical analysis with data from type Ia supernovae of the Pantheon+ compilation and cosmic chronometers to estimate the values of the free parameters of the Starobinsky model. We show that the statistical analyses carried out with our new method require lower computational times than the ones performed with both the numerical and the neural network method from our previous work. This reduction in time is more significant in the case of a difficult computational problem such as the one we address in this work.Comment: 11 pages, 3 figures, 2 tables, to be submitted to PR

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG).

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future

Detection of N-Glycolyl GM3 Ganglioside in Neuroectodermal Tumors by Immunohistochemistry: An Attractive Vaccine Target for Aggressive Pediatric Cancer

The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy

Global effect of the COVID-19 pandemic on paediatric cancer care: a cross-sectional study

BACKGROUND: Although mortality due to COVID-19 has been reportedly low among children with cancer, changes in health-care services due to the pandemic have affected cancer care delivery. This study aimed to assess the effect of the COVID-19 pandemic on childhood cancer care worldwide. METHODS: A cross-sectional survey was distributed to paediatric oncology providers worldwide from June 22 to Aug 21, 2020, through the St Jude Global Alliance and International Society for Paediatric Oncology listservs and regional networks. The survey included 60 questions to assess institution characteristics, the number of patients diagnosed with COVID-19, disruptions to cancer care (eg, service closures and treatment abandonment), adaptations to care, and resources (including availability of clinical staff and personal protective equipment). Surveys were included for analysis if respondents answered at least two thirds of the items, and the responses were analysed at the institutional level. FINDINGS: Responses from 311 health-care professionals at 213 institutions in 79 countries from all WHO regions were included in the analysis. 187 (88%) of 213 centres had the capacity to test for SARS-CoV-2 and a median of two (range 0-350) infections per institutution were reported in children with cancer. 15 (7%) centres reported complete closure of paediatric haematology-oncology services (median 10 days, range 1-75 days). Overall, 2% (5 of 213) of centres were no longer evaluating new cases of suspected cancer, while 43% (90 of 208) of the remaining centers described a decrease in newly diagnosed paediatric cancer cases. 73 (34%) centres reported increased treatment abandonment (ie, failure to initiate cancer therapy or a delay in care of 4 weeks or longer). Changes to cancer care delivery included: reduced surgical care (153 [72%]), blood product shortages (127 [60%]), chemotherapy modifications (121 [57%]), and interruptions to radiotherapy (43 [28%] of 155 institutions that provided radiotherapy before the pandemic). The decreased number of new cancer diagnoses did not vary based on country income status (p=0·14). However, unavailability of chemotherapy agents (p=0·022), treatment abandonment (p<0·0001), and interruptions in radiotherapy (p<0·0001) were more frequent in low-income and middle-income countries than in high-income countries. These findings did not vary based on institutional or national numbers of COVID-19 cases. Hospitals reported using new or adapted checklists (146 [69%] of 213), processes for communication with patients and families (134 [63%]), and guidelines for essential services (119 [56%]) as a result of the pandemic. INTERPRETATION: The COVID-19 pandemic has considerably affected paediatric oncology services worldwide, posing substantial disruptions to cancer diagnosis and management, particularly in low-income and middle-income countries. This study emphasises the urgency of an equitably distributed robust global response to support paediatric oncology care during this pandemic and future public health emergencies. FUNDING: American Lebanese Syrian Associated Charities. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section

Treatment of nonmetastatic unilateral retinoblastoma in children

IMPORTANCE: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. OBJECTIVE: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. DESIGN, SETTING, AND PARTICIPANTS: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. INTERVENTIONS: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10mg/m2/d], and vincristine sulfate [0.05mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500mg/m2/d, days 1 and 2] and etoposide [100mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. MAIN OUTCOMES AND MEASURES: Probability of event-free survival (extraocular relapse and death from any cause were considered events). RESULTS: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95%CI, 0.94-0.99), and the probability of overall survival was 0.98 (95%CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). CONCLUSIONS AND RELEVANCE: Adjuvant therapymay be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.Fil: Pérez, Verónica. Hospital San Juan de Dios; ChileFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rey, Guadalupe. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Parareda Salles, Andreu. Hospital Sant Joan de Déu; EspañaFil: Kopp, Katherine. Hospital Dr. Luis Calvo Mackenna Hospital; ChileFil: Dabezies, Agustín P.. Hospital Pereyra Rossell; UruguayFil: Dufort, Gustavo. Hospital Pereyra Rossell; UruguayFil: Zelter, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: López, Juan P.. Hospital Calvo Mackenna; ChileFil: Urbieta, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Alcalde Ruiz, Elisa. Hospital Dr. Luis Calvo Mackenna Hospital; ChileFil: Catala Mora, Jaume. Hospital Sant Joan de Déu; EspañaFil: Suñol, Mariona. Hospital Sant Joan de Déu; EspañaFil: Ossandon, Diego. Hospital San Juan de Dios; ChileFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Dávila, María T. G.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Reaman, Gregory. Center for Drug Evaluation and Research; Estados UnidosFil: Ravindranath, Yaddanapudi. Children’s Hospital of Michigan; Estados UnidosFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Metastatic deaths in retinoblastoma patients treated with intraarterial chemotherapy (ophthalmic artery chemosurgery) worldwide.

Ophthalmic artery chemosurgery [OAC, intra-arterial chemotherapy (IAC)] was introduced in 2006 as treatment modality for intraocular retinoblastoma. The purpose of this commentary is to retrospectively review the incidence of metastatic deaths in retinoblastoma patients treated with OAC worldwide over a 10 year period. Retrospective data regarding metastatic deaths was collected from six international retinoblastoma centers (New York City USA, Philadelphia USA, Sao Paulo Brazil, Siena Italy, Lausanne Switzerland and Buenos Aires Argentina). All retinoblastoma patients from these centers (naive and recurrent, unilateral and bilateral) treated with OAC/IAC since 2006 have been included in this study. Data regarding number of patients, number of OAC/IAC infusions, number unilateral and bilateral, number treated for naive disease or salvage and number of metastatic deaths have been assessed. Over a 10-year period of time 1139 patients received OAC/IAC for 4396 infusions. At last follow-up there were only three metastatic deaths (all treated in Buenos Aires). The current survey assessed the recorded risk of metastatic deaths in six retinoblastoma centers worldwide in children with retinoblastoma (unilateral or bilateral) treated with OAC/IAC as primary or secondary therapy. Overall, the observed risk for metastatic deaths from retinoblastoma was &lt;1% in OAC/IAC treated children

The Global COVID-19 Observatory and Resource Center for Childhood Cancer: A response for the pediatric oncology community by SIOP and St. Jude Global

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute.Fil: Mukkada, Sheena. St Jude Children's Research Hospital; Estados UnidosFil: Bhakta, Nickhill. St Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Hospital Sant Joan de Déu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chen, Yichen. St Jude Children's Research Hospital; Estados UnidosFil: Vedaraju, Yuvanesh. St Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R. St Jude Children's Research Hospital; Estados UnidosFil: Muniz Talavera, Hilmarie. St Jude Children's Research Hospital; Estados UnidosFil: Ranadive, Radhikesh. St Jude Children's Research Hospital; Estados UnidosFil: Metzger, Monika. St Jude Children's Research Hospital; Estados UnidosFil: Friedrich, Paola. St Jude Children's Research Hospital; Estados UnidosFil: Agulnik, Asya. St Jude Children's Research Hospital; Estados UnidosFil: Jeha, Sima. St Jude Children's Research Hospital; Estados UnidosFil: Lam, Catherine G.. St Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Moreira, Daniela. St Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor M. St Jude Children's Research Hospital; Estados UnidosFil: Sullivan, Michael. University of Melbourne; AustraliaFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; CanadáFil: Caniza, Miguela A.. St Jude Children's Research Hospital; Estados UnidosFil: Devidas, Meenakshi. St Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. UCL Great Ormond Street Institute of Child Health; Reino UnidoFil: Rodriguez Galindo, Carlos. St Jude Children's Research Hospital; Estados Unido

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute.Fil: Mukkada, Sheena. St Jude Children's Research Hospital; Estados UnidosFil: Bhakta, Nickhill. St Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Hospital Sant Joan de Déu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chen, Yichen. St Jude Children's Research Hospital; Estados UnidosFil: Vedaraju, Yuvanesh. St Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R. St Jude Children's Research Hospital; Estados UnidosFil: Muniz Talavera, Hilmarie. St Jude Children's Research Hospital; Estados UnidosFil: Ranadive, Radhikesh. St Jude Children's Research Hospital; Estados UnidosFil: Metzger, Monika. St Jude Children's Research Hospital; Estados UnidosFil: Friedrich, Paola. St Jude Children's Research Hospital; Estados UnidosFil: Agulnik, Asya. St Jude Children's Research Hospital; Estados UnidosFil: Jeha, Sima. St Jude Children's Research Hospital; Estados UnidosFil: Lam, Catherine G.. St Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Moreira, Daniela. St Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor M. St Jude Children's Research Hospital; Estados UnidosFil: Sullivan, Michael. University of Melbourne; AustraliaFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; CanadáFil: Caniza, Miguela A.. St Jude Children's Research Hospital; Estados UnidosFil: Devidas, Meenakshi. St Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. UCL Great Ormond Street Institute of Child Health; Reino UnidoFil: Rodriguez Galindo, Carlos. St Jude Children's Research Hospital; Estados Unido