A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors

Immunotherapy; Oncolytic herpes virus; Pediatric solid tumorInmunoterapia; Virus del herpes oncolítico; Tumor sólido pediátricoImmunoteràpia; Virus de l'herpes oncolític; Tumor sòlid pediàtricBackground: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non–central nervous system tumors. Methods: T-VEC was delivered by intralesional injection at 106 plaque-forming units (PFU)/ml on the first day, followed by 108 PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST). Results: Fifteen patients were enrolled into two cohorts based on age: cohort A1 (n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 (n = 2) 2 to <12 years old (melanoma, n = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response. Conclusions: T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.This study received funding from Amgen Inc. The funder was involved in the study design; collection, analysis, and interpretation of data; the writing of this article; and the decision to submit it for publication

Guia de pràctica clínica: tractament del dolor oncològic pediàtric

Dolor oncològic pediàtric; Càncer; Tractament; RegistreDolor oncológico pediátrico; Cáncer; Tratamiento; RegistroPediatric oncological pain; Cancer; Treatment; RegistryEl dolor oncològic pediàtric és un problema clínic rellevant a l'Hospital Vall d'hebron i les dades de què es disposa sobre el seu tractament són escasses. Aquest document s'ha desenvolupat per millorar el registre i el tractament del dolor en nens amb càncer atesos a l’Hospital, sobre la base de l’evidència científica de què es disposa. Es pretén aconseguir que, d’una banda, la mesura del dolor es faci de forma regular, amb la metodologia adequada i es registri sistemàticament a la història clínica. De l’altra, utilitzar les estratègies de tractament del dolor, tant farmacològiques com no farmacològiques; més efectives i segures per a aquest tipus de població. La utilització pràctica d’aquesta publicació s’ha de considerar com una guia; no es pretén anteposar-la al judici clínic

Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma

Genètica del càncer; Càncer del SNC; Càncer pediàtricGenética del cáncer; Cáncer del SNC; Cáncer pediátricoCancer genetics; CNS cancer; Paediatric cancerThe molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. CSF ctDNA also characterises the intra-tumour genomic heterogeneity identifying small subclones. ctDNA is abundant in the CSF but barely present in plasma and longitudinal analysis of CSF ctDNA allows the study of minimal residual disease, genomic evolution and the characterisation of tumours at recurrence. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.We would like to thank the patients at the Vall d’Hebron Hospital that were enrolled in the study and their families. The study was undertaken with the support of the Fundación Asociación Española contra el Cáncer (AECC), FERO (EDM), Ramón Areces Foundation, Cellex Foundation, BBVA (CAIMI), the ISCIII, FIS (PI16/01278) and the Juan de la Cierva fellowship (L.E). X.S.P. is supported by Ministerio de Economía y Competitividad (MINECO) SAF2013-45836-R and CIBERONC; A.D.N. is supported by the Department of Education of the Basque Government (grant number PRE_2017_1_0100). We thank CERCA Programme/Generalitat de Catalunya for institutional support