Palliative care for children with central nervous system tumors: results of a Spanish multicenter study.

BACKGROUND: Brain tumors represent the most common cause of cancer-related death in children. Few studies concerning the palliative phase in children with brain tumors are available. OBJECTIVES: (i) To describe the palliative phase in children with brain tumors; (ii) to determine whether the use of palliative sedation (PS) depends on the place of death, the age of the patient, or if they received specific palliative care (PC). METHODS: Retrospective multicenter study between 2010 and 2021, including children from one month to 18 years, who had died of a brain tumor. RESULTS: 228 patients (59.2% male) from 10 Spanish institutions were included. Median age at diagnosis was 5 years (IQR 2-9) and median age at death was 7 years (IQR 4-11). The most frequent tumors were medulloblastoma (25.4%) and diffuse intrinsic pontine glioma (DIPG) (24.1%). Median number of antineoplastic regimens were 2 (range 0-5 regimens). During palliative phase, 52.2% of the patients were attended by PC teams, while 47.8% were cared exclusively by pediatric oncology teams. Most common concerns included motor deficit (93.4%) and asthenia (87.5%) and communication disorders (89.8%). Most frequently prescribed supportive drugs were antiemetics (83.6%), opioids (81.6%), and dexamethasone (78.5%). PS was administered to 48.7% patients. Most of them died in the hospital (85.6%), while patients who died at home required PS less frequently (14.4%) (p = .01). CONCLUSION: Children dying from CNS tumors have specific needs during palliative phase. The optimal indication of PS depended on the center experience although, in our series, it was also influenced by the place of death.

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review.

Introduction: Treatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been developed over the time to maximize survival and minimize side effects. Methods: We performed a systematic literature search in May 2023 using PubMed. We selected all clinical trials articles and multicenter studies focusing on MB. We excluded studies focusing exclusively on infants, adults, supratentorial PNETs or refractory/relapsed tumors, studies involving different tumors or different types of PNETs without differentiating survival, studies including <10 cases of MB, solely retrospective studies and those without reference to outcome and/or side effects after a defined treatment. Results: 1. The main poor-prognosis factors are: metastatic disease, anaplasia, MYC amplification, age younger than 36 months and some molecular subgroups. The postoperative residual tumor size is controversial.2. MB is a collection of diseases.3. MB is a curable disease at diagnosis, but survival is scarce upon relapse.4. Children should be treated by experienced neurosurgeons and in advanced centers.5. RT is an essential treatment for MB. It should be administered craniospinal, early and without interruptions.6. Craniospinal RT dose could be lowered in some low-risk patients, but these reductions should be done with caution to avoid relapses.7. Irradiation of the tumor area instead of the entire posterior fossa is safe enough.8. Hyperfractionated RT is not superior to conventional RT9. Both photon and proton RT are effective.10. CT increases survival, especially in high-risk patients.11. There are multiple drugs effective in MB. The combination of different drugs is appropriate management.12. CT should be administered after RT.13. The specific benefit of concomitant CT to RT is unknown.14. Intensified CT with stem cell rescue has no benefit compared to standard CT regimens.15. The efficacy of intraventricular/intrathecal CT is controversial.16. We should start to think about incorporating targeted therapies in front-line treatment.17. Survivors of MB still have significant side effects. Conclusion: Survival rates of MB improved greatly from 1940-1970, but since then the improvement has been smaller. We should consider introducing targeted therapy as front-line therapy.

Radioterapia paliativa pediátrica / Pediatric palliative radiotherapy

Introducción: La radioterapia es un recurso infrautilizado en los cuidados paliativos pediátricos; sin embargo, tiene utilidad para aliviar diversos síntomas al final de la vida. Pacientes y métodos: Se muestra un estudio retrospectivo de 30 pacientes pediátricos que han recibido radioterapia por motivos paliativos. El objetivo fue revisar si la radioterapia resultó efectiva. Resultados: La radioterapia fue útil para aliviar los síntomas, mostrando una respuesta global en el 85 % de los casos y presentando toxicidades leves. Las respuestas más pobres fueron en gliomas con alivio sintomático en el 56 % de los casos, mostrando toxicidades en el 89 % de los mismos. La necesidad de anestesia supuso un factor de riesgo para el desarrollo de toxicidades. Conclusiones: El uso de la radioterapia paliativa es beneficiosa y debe incluirse en el manejo multidisciplinar del niño en cuidados paliativos. (AU)

Introduction: Radiotherapy is an underutilized resource in pediatric palliative care; however, it has utility in relieving various symptoms at the end of life. Patients and methods: A retrospective study of 30 pediatric patients who received radiotherapy for palliative reasons is reported. The objective was to review whether radiotherapy was effective. Results: Radiotherapy was useful in relieving symptoms, showing an overall response in 85 % of cases and presenting mild toxicities. The poorest responses were found in gliomas, with symptomatic relief in 56 % of cases, showing toxicities in 89 % of cases. The need for anesthesia represented risk factor for the development of toxicities. Conclusions: The use of palliative radiotherapy is beneficial and should be included in the multidisciplinary management of children in palliative care. (AU)

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma.

BACKGROUND: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. METHODS: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. RESULTS: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. CONCLUSIONS: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).

Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors -A Review.

People with Down syndrome have unique characteristics as a result of the presence of an extra chromosome 21. Regarding cancer, they present a unique pattern of tumors, which has not been fully explained to date. Globally, people with Down syndrome have a similar lifetime risk of developing cancer compared to the general population. However, they have a very increased risk of developing certain tumors (e.g., acute leukemia, germ cell tumors, testicular tumors and retinoblastoma) and, on the contrary, there are some other tumors which appear only exceptionally in this syndrome (e.g., breast cancer, prostate cancer, medulloblastoma, neuroblastoma and Wilms tumor). Various hypotheses have been developed to explain this situation. The genetic imbalance secondary to the presence of an extra chromosome 21 has molecular consequences at several levels, not only in chromosome 21 but also throughout the genome. In this review, we discuss the different proposed mechanisms that protect individuals with trisomy 21 from developing solid tumors: genetic dosage effect, tumor suppressor genes overexpression, disturbed metabolism, impaired neurogenesis and angiogenesis, increased apoptosis, immune system dysregulation, epigenetic aberrations and the effect of different microRNAs, among others. More research into the molecular pathways involved in this unique pattern of malignancies is still needed.

Análisis del uso y funciones del silencio en la comunicación de los pro-fesionales sanitarios en una unidad de oncología pediátrica / Analysis of the use and functions of silence in the communication of healthcare professionals in a pediatric oncology unit

Existen diferentes tipos de silencio, con múltiples funciones, y cada uno puede provocar efectos diversos en la comunicación. En el ámbito sanitario una comunicación eficaz es fundamental para lograr que los pacientes comprendan lo que les sucede y se expresen con claridad y confianza ante los profesionales sanitarios. El silencio juega un papel clave en esta comunicación. Objetivo: Desarrollar un instrumento para conocer la importancia que tiene el silencio para los profesionales sanitarios y analizar de qué manera emplean el silencio en su comunicación con los pacientes. Métodos: En el estudio han participado 43 profesionales del ámbito de la Oncología Pediátrica. Este estudio propone una clasificación de los tipos de silencio en la comunicación sanitaria. Resultados: El silencio es heterogéneo y cumple diferentes funciones. Se comprueba que los profesionales sanitarios emplean distintos tipos de silencio, siendo los Silencios Neutros los más utilizados, a continuación, los Silencios Productivos y los menos empleados los Silencios Obstructivos. Aquel que más se usa es el que favorece la atención, el acompañamiento, la reflexión y la expresión, mientras que el silencio de poder y el de desconexión son los menos empleados. Conclusión: El instrumento de evaluación propuesto (Q-SPS) ha presentado buenos niveles de consistencia interna para esta muestra permitiendo establecer un perfil comparativo entre el uso del silencio por parte de los distintos profesionales del ámbito de la salud por lo que podría valorarse una investigación más exhaustiva con mayor volumen de participantes (AU)

There are different kinds of silence and each of them has multiple functions and can cause several effects. Regarding the health field, an effective communication is key to enable the patients to understand the situation and to express themselves with clarity and confidence in front of health professionals. Silence is also key in that communication. Objective: The aim of this study is to know the importance of silence amongst professionals and to analyze the way they use silence in their communication with patients. Methods: 43 professionals belonging to the Pediatric Oncology field have taken part in the study. This study proposes a classification of the kinds of silence referred to health communication and a pilot tool to evaluate the silence in that communication. Results: The outcomes confirm that silence is heterogeneous and fulfils different purposes. It has confirmed that health professionals use different kinds of silence, among which Neutral Silences are the most frequent, followed by Productive Silences and with Obstructive Silences as the least used Moreover, the one more used is that which boosts attention, accompaniment, reflection and expression, whereas the silence of power and the silence of disconnection are the least used.Conclusions: The proposed evaluation tool (Q-SPS) has shown good level of inner consistency for this sample, allowing for setting a comparative profile in the use of silence amongst different health professionals, so a more exhaustive research with a greater volume of participants could be assessed (AU)

Importancia del síndrome de Li-Fraumeni, un síndrome genético de predisposición al cáncer / The importance of Li-Fraumeni syndrome, a hereditary cancer predisposition disorder

El cáncer en pediatría es una entidad infrecuente. Se estima que más de un 10-15 % de los tumores son secundarios a una variante patogénica en un gen de predisposición al cáncer.Se conocen más de 100 genes de predisposición al cáncer y su asociación con síndromes o tumores aislados. Uno de los más descritos es el síndrome de Li-Fraumeni.Los pacientes con este síndrome tienen alto riesgo de desarrollar uno o más tumores. Su conocimiento permite realizar un protocolo de seguimiento del paciente y de sus familiares afectos, con el que detectar precozmente nuevos tumores y disminuir la morbimortalidad del tumor y de su tratamiento.Esta revisión pretende ser una guía útil para el pediatra. Utilizando como caso guía a una familia, se revisarán los motivos de sospecha de un síndrome de Li-Fraumeni, su diagnóstico clínico y genético, y el protocolo de seguimiento de los familiares portadores de la misma mutación

Pediatric cancer is rare. It is estimated that more than 10-15 % of tumors are secondary to a pathogenic variant in a cancer predisposition gene.More than 100 cancer predisposition genes and their association with syndromes or isolated tumors have been identified. Li-Fraumeni syndrome is one of those who have been most widely described.Patients with this syndrome present a high risk of developing one or more tumors. Its knowledge allows to establish a follow-up protocol for the patient and affected family members, so as to detect new tumors in an early manner and reduce tumor- and treatment-related morbidity and mortality.The objective of this review is to offer useful guidelines for pediatricians. Based on a family case, reasons for Li-Fraumeni syndrome suspicion, clinical and genetic diagnosis, and the follow-up protocol of family members who carry the same mutation will be reviewed.

The importance of Li-Fraumeni syndrome, a hereditary cancer predisposition disorder. / Importancia del síndrome de Li-Fraumeni, un síndrome genético de predisposición al cáncer.

Pediatric cancer is rare. It is estimated that more than 10-15 % of tumors are secondary to a pathogenic variant in a cancer predisposition gene. More than 100 cancer predisposition genes and their association with syndromes or isolated tumors have been identified. Li-Fraumeni syndrome is one of those who have been most widely described. Patients with this syndrome present a high risk of developing one or more tumors. Its knowledge allows to establish a follow-up protocol for the patient and affected family members, so as to detect new tumors in an early manner and reduce tumorand treatment-related morbidity and mortality. The objective of this review is to offer useful guidelines for pediatricians. Based on a family case, reasons for Li-Fraumeni syndrome suspicion, clinical and genetic diagnosis, and the follow-up protocol of family members who carry the same mutation will be reviewed.

El cáncer en pediatría es una entidad infrecuente. Se estima que más de un 10-15 % de los tumores son secundarios a una variante patogénica en un gen de predisposición al cáncer. Se conocen más de 100 genes de predisposición al cáncer y su asociación con síndromes o tumores aislados. Uno de los más descritos es el síndrome de Li-Fraumeni. Los pacientes con este síndrome tienen alto riesgo de desarrollar uno o más tumores. Su conocimiento permite realizar un protocolo de seguimiento del paciente y de sus familiares afectos, con el que detectar precozmente nuevos tumores y disminuir la morbimortalidad del tumor y de su tratamiento. Esta revisión pretende ser una guía útil para el pediatra. Utilizando como caso guía a una familia, se revisarán los motivos de sospecha de un síndrome de Li-Fraumeni, su diagnóstico clínico y genético, y el protocolo de seguimiento de los familiares portadores de la misma mutación.

Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications.

BACKGROUND & AIMS: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. METHODS: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. RESULTS: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. CONCLUSIONS: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. LAY SUMMARY: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.

BRAF V600E Detection in Liquid Biopsies from Pediatric Central Nervous System Tumors.

Pediatric Central Nervous System (CNS) tumors are the most fatal cancer diseases in childhood. Due to their localization and infiltrative nature, some tumor resections or biopsies are not feasible. In those cases, the use of minimally invasive methods as diagnostic, molecular marker detection, prognostic or monitoring therapies are emerging. The analysis of liquid biopsies which contain genetic information from the tumor has been much more widely explored in adults than in children. We compare the detection of BRAF V600E targetable mutation by digital-PCR from cell-free-DNA and EV-derived DNA (ctDNA) in serum, plasma and cerebrospinal fluid (CSF) isolated from a cohort of 29 CNS pediatric patients. Here we demonstrate that ctDNA isolated from serum and plasma could be successfully analyzed to obtain tumor genetic information which could be used to guide critical treatment decisions.

Afrontamiento y bienestar psicológico en padres de niños y adolescentes con cáncer durante el tratamiento / Parental coping and psychological well-being in pediatric oncolgy patients while on treatment

Objetivo: explorar la vivencia emocional de los padres de niños y adolescentes con cáncer de un modo más abierto y no exclusivamente centrado en búsqueda de consecuencias negativas para la familia. Método: Se realizó un estudio mixto (cuantitativo y cualitativo) a través de la realización de una entrevista semiestructurada a 30 padres de niños y adolescentes con cáncer en tratamiento en la Unidad de Hematología y Oncología Pediátrica de HM Montepríncipe. Resultados: Se han obtenido 5 temas principales de las entrevistas realizadas a los padres. Los padres de niños con cáncer durante el tratamiento de la enfermedad de su hijo emplean un afrontamiento activo, centrado en el presente que permite la aceptación. Por otro lado, los padres reflejan los modos de expresión emocional, la presencia de valores y crecimiento personal, la actitud de gratitud y el modelo de ayuda que han recibido en el lugar dónde ha sido atendido su hijo. En el modelo teórico se presenta la importancia y consistencia como predictor del bienestar psicológico (crecimiento personal y propósito vital) y la gratitud en esta población. Discusión/conclusiones: En los padres de niños y adolescentes con cáncer se debe favorecer un afrontamiento activo, permitiendo la importancia y consistencia con los valores y generando actitudes de gratitud y confianza que permitirán el crecimiento personal y el propósito vital de las familias, y por lo tanto una adecuada vivencia emocional en los padres resultará un beneficio directo para los hijos

Our objective in this work has been exploring the parents emotional experiences while their children or adolescents with cancer were on treatment. We aproached them openly instead of exclusively focused on the known negative consequences of pediatric cancer in the family. Method: The population study included 30 parents whose children were on treatment at the Pediatric Hematology and Oncology Unit at Universitary HM Monteprincipe hospital. A mixed method study was carried out (quantitative and qualitative) through a semi-structured interview. Results: Five main findings have been obtained from the parent's interviews. Parents of children with cancer use active coping, focused on the present therefore allowing acceptance during treatment of their child’s illness. On the other hand, parents found an enviroment in the Unit in which they could express their emotions, their personal values, and their spiritual grothw. Gratitude towards life and caring was also and important finding in this study. In this theoretical model the comitment with values was a predictor of psychological well-being (personal growth and life sense) as well as gratitude. Discussion / conclusions: Active coping in parents of children and adolescents with cancer, should be encouraged in any Pediatric Oncology Unit, regarding commitment with values and attitudes of gratitude and trust. Gratitude allows personal growth and vital sense within families. An adequate emotional experience in parents results in a direct benefit on their children

Hemophagocytic Lymphohistiocytosis: A Dangerous Intruder in Pediatric Acute Lymphoblastic Leukemia.

Hemophagocytic lymphohistiocytosis (HLH) is a condition caused by a pathologic immune activation, which is responsible for its signs and symptoms. It may also appear as a secondary process caused by malignancy. Developing HLH during treatment for acute lymphoblastic leukemia (ALL) is extremely uncommon, but underdiagnosis may be fatal. Two patients with ALL on chemotherapy maintenance treatment who developed HLH triggered by infection are presented here. We emphasize the importance of being aware of this condition when a patient with ALL in complete remission presents with unexplained hepatomegaly, cytopenia, and fever. Early diagnosis and treatment may be lifesaving.

Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005.

Philadelphia-chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate-dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1-18years were enrolled in three consecutive ALL/SHOP trials (SHOP-94/SHOP-99/SHOP-2005). In the SHOP-2005 trial, imatinib (260mg/m(2) per day) was given on day-15 of induction. Allogeneic haematopoietic stem-cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty-three patients were evaluable (22 boys, median age 6·8years, range, 1·2-15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non-imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow-up of 109 and 39months for the non-imatinib and imatinib cohorts, the 3-year event-free survival (EFS) was 29·6% and 78·7%, respectively (P=0·01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL.

High-dose busulfan and cyclophosphamide as a conditioning regimen for autologous peripheral blood stem cell transplantation in childhood non-Hodgkin lymphoma patients: a long-term follow-up study.

We analyzed the outcome in 22 children with refractory or relapsed non-Hodgkin lymphoma who underwent autologous peripheral blood progenitor cell transplantation between 1994 and 2009. The conditioning regimen used in all patients consisted of busulfan and cyclophosphamide. Median age was 6 years (range 2 to 16 y). The most common histologic subtype was Burkitt lymphoma. Ten patients were in complete remission and 12 in partial remission at the time of transplant. The median dose of CD34+ cells that was infused was 4.6 × 10/kg (range 2.1 to 58.7 × 10/kg). All the patients were engrafted, with a median time for neutrophils and platelets recovery of 11 (range, 8 to 15 d) and 14 (range, 9 to 60 d) days, respectively. Nonhematologic treatment-related toxicity included severe mucositis in 3 patients and hepatic sinusoidal obstruction syndrome in 1 patient. There were no transplant-related mortalities. With a median follow-up of 60 months (range, 4 to 180 d) the disease-free survival was 90 ± 6.5% for the whole group. This retrospective study shows a high long-term survival using busulfan/cyclophosphamide as conditioning regimen in children with refractory or relapsed non-Hodgkin lymphoma.

High-dose busulfan and melphalan as conditioning regimen for autologous peripheral blood progenitor cell transplantation in high-risk neuroblastoma patients.

The aim of this retrospective study was to analyze the outcome and identify risk factors associated with progression-free survival (PFS) in 36 children with high-risk neuroblastoma who underwent autologous peripheral blood progenitor cell (PBPC) transplantation between 1994 and 2010. The conditioning regimen used in all cases consisted of high-dose of busulfan and melphalan. Median age at transplantation was 3 years (range: 0.7-14 years). The median times to neutrophil and platelet engraftment were 11 days (range: 9.16 days) and 13 days (range: 9.33), respectively. Twenty-one patients developed nonhematologic toxicity: 15 patients had mucositis, 4 patients developed an engraftment syndrome, and there were 2 cases of liver toxicity. No toxic deaths were observed. There were 15 patients who relapsed. The median time to relapse was 6 months after the transplant (range: 3-13 months). With a median follow-up of 55 months (range: 4-180 months), the PFS was 57% ± 8.5% for the whole group. In multivariate analysis, age below 3 years (P < .005), complete remission (CR) pretransplantation (P < .07) and 1p germline status (P < .01) were variables associated with better outcomes. Patients who were or achieved early CR following transplantation (3 months posttransplantation) had a probability of PFS of 91% ± 6% as compared to patients who did not (PFS 9% ± 8%) (P < .0001). This retrospective study shows that high dose of busulfan and melphalan as conditioning regimen in children with high-risk neuroblastoma is associated with very low morbidity and no mortality in the authors' hands. Younger patients with no 1p deletions and in first CR at transplantation had the better outcome.

Transgenerational tobacco smoke exposure and childhood cancer: an observational study.

AIM: Although tobacco smoke is an established risk factor for adult cancer, studies of the association between parental smoking and childhood cancer have produced inconsistent results. To investigate the transgenerational relationship between pre-natal and post-natal tobacco smoke exposure from the grandmother's pregnancies until after the post-natal period and childhood cancer. METHODS: Exposure to tobacco smoke was recorded for three generations. Data were collected through personal interviews using the paediatric environmental history, and were compared among 128 children with cancer and 128 matched controls. The contingency tables and a logistic multivariable regression model were used to control for possible confounding factors. RESULTS: Smoke exposure during oogenesis (maternal grandmother smokers)--odds ratio (OR) 2.2 (95% confidence interval (CI) 1.1-4.9)--and during the mother' pregnancies--OR 1.8 (95% CI 1.1-3.3)--were significantly associated with an increased risk of childhood cancer. CONCLUSIONS: Tobacco smoke exposure during the grandmother's and mother's pregnancies increase the risk of cancer in the descendants. The results suggest that the biological plausibility of the association between parental smoking and paediatric cancer can be explained by the large latency period of paediatric carcinogenesis.

Aspectos médicos, psicológicos y sociales del cáncer infantil / Medical, psychological and social aspects in chilhood cancer

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Intrathecal liposomal cytarabine in children under 4 years with malignant brain tumors.

Infants and very young children with malignant brain tumors usually have unfavourable locations and are not candidates for craniospinal irradiation. New therapeutic approaches must be attempted to improve poor survival rates. The primary goal of the present study was to report on the safety profile and toxicity of intrathecal administration of liposomal cytarabine in children <4 years with malignant brain tumors. This is the first study including this group of patients receiving intrathecal liposomal cytarabine. Nine patients with a median age of 26 months were eligible for the study. The diagnoses were ependymoma (3), peripheral neuroectodermic tumor (PNET) (2), meduloblastoma, atypical teratoid rhabdoid tumor (ATRT), cerebral lymphoma, and rhabdomyosarcoma with CNS invasion. Liposomal cytarabine at doses between 20 and 35 mg were administered by lumbar puncture. Dexamethasone was given for arachnoiditis prophylaxis. A total of 44 doses (median = 6) of liposomal cytarabine were administered. Neurological side effects possibly related to liposomal cytarabine were observed in five patients (55.6%). This incidence was higher than previously reported in children older than 3 years. Eight of the patients (89%) experienced an initial improvement of clinical symptoms after initiation treatment, confirmed by MRI. This study demonstrates the feasibility of using intrathecal liposomal cytarabine in children under 4 years of age with malignant brain tumors.

Full breastfeeding and paediatric cancer.

AIM: It has been suggested that there is an inverse association between breastfeeding and the risk of childhood cancer. We investigated the association between full breastfeeding and paediatric cancer (PC) in a case control study in Spain. METHODS: Maternal reports of full breastfeeding, collected through personal interviews using the Paediatric Environmental History, were compared among 187 children 6 months of age or older who had PC and 187 age-matched control siblings. RESULTS: The mean duration of full breastfeeding for cases were 8.43 and 11.25 weeks for controls. Cases had been significantly more often bottle-fed than controls (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.1-2.8). Cases were significantly less breastfed for at least 2 months (OR 0.5; 95% CI 0.3-0.8), for at least 4 months (OR 0.5; 95% CI 0.3-0.8), and for 24 weeks or more (OR 0.5; 95% CI 0.2-0.9). CONCLUSIONS: Breastfeeding was inversely associated with PC, the protection increasing with the duration of full breastfeeding. Additional research on possible mechanisms of this association may be warranted. Meanwhile, breastfeeding should be encouraged among mothers.