Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource-limited setting.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03). CONCLUSIONS: Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric Peruvian patients.

BACKGROUND: A high frequency of primary central nervous system (CNS) sarcomas was observed in Peru. This article describes the clinical characteristics, biological characteristics, and outcome of 70 pediatric patients. METHODS: Data from 70 pediatric patients with primary CNS sarcomas diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling from 28 tumors and gene panel sequencing from 27 tumors were available. RESULTS: The median age of the patients was 6 years (range, 2-17.5 years), and 66 of 70 patients had supratentorial tumors. DNA methylation profiling classified 28 of 28 tumors as primary CNS sarcoma, DICER1 mutant. DICER1 mutations were found in 26 of 27 cases, TP53 mutations were found in 22 of 27 cases, and RAS-pathway gene mutations (NF1, KRAS, and NRAS) were found in 19 of 27 tumors, all of which were somatic (germline control available in 19 cases). The estimated incidence in Peru was 0.19 cases per 100,000 children (<18 years old) per year, which is significantly higher than the estimated incidence in Germany (0.007 cases per 100,000 children [<18 years] per year; P < .001). Patients with nonmetastatic disease (n = 46) that were treated with a combination therapy had a 2-year progression-free survival (PFS) rate of 58% (95% CI, 44%-76%) and a 2-year overall survival rate of 71% (95% CI, 57%-87%). PFS was the highest in patients treated with chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) after upfront surgery followed by radiotherapy and ICE (2-year PFS, 79% [59%-100%], n = 18). CONCLUSIONS: Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course. A combination of surgery, chemotherapy, and radiotherapy seems beneficial. An underlying cancer predisposition syndrome explaining the increased incidence in Peruvian patients has not been identified so far. LAY SUMMARY: A high incidence of primary pediatric central nervous system sarcomas in the Peruvian population is described. Using sequencing technologies and DNA methylation profiling, it is confirmed that these tumors molecularly belong to the recently proposed entity "primary central nervous system sarcomas, DICER1 mutant." Unexpectedly, DICER1 mutations as well as all other defining tumor mutations (TP53 mutations and RAS-pathway mutations) were not inherited in all 19 patients where analyzation was possible. These tumors have an aggressive clinical course. Multimodal combination therapy based on surgery, ifosfamide, carboplatin, and etoposide chemotherapy, and local radiotherapy leads to superior outcomes.

Dolor agudo neonatal con estímulos dolorosos repetitivos, estudio randomizado comparando tres métodos analgésicos no farmacológicos / Neonatal acute pain with repetitive painful stimuli, randomized trial comparing three analgesic non pharmacological methods

Introducción: La analgesia no farmacología es raramente utilizada en las unidades de neonatología. Los estímulos dolorosos repetitivos tienen efectos negativos a largo plazo. Objetivos: Verificar que los métodos analgésicos no farmacológicos son afectivos en estímulos dolorosos repetitivos; determinar cuál método es más efectivo. Material y método; Se realice un ensayo clínica, randomizado, con tres grupos formados de manera aleatoria, con recién nacidos sanos a termino por grupo. Fueron sometidos a tres estímulos dolorosos durante los tres primero días de vida (vacuna contra hepatitis B, BCG y muestra para grupo sanguíneo). El primer grupo (A) recibió lactancia materna y contacto piel como método analgésico no farmacológico durante el estímulo doloroso, el grupo (B) recibió dextrosa al 10 por ciento y el grupo (C) una tetina sin nada. Se utilizó la escala para el Dolor Agudo Neonatal (DAN, Carbajal y col.) y la Escala ABC (Bellieni y col.) para la cuantificación del dolor. Fueron comparados los 3 grupos en cada uno de los tres estímulos repetitivos. Resultados: Para ambas escalas el grupo B expresó menor dolor en los tres estímulos, con 97,5 por ciento de NO DOLOR vs 87,5 por ciento (A) y 85 por ciento (C) (p<0.036) en la escala ABC, y 95 por ciento vs 85 por ciento (A) y 70 por ciento (C) para la categoría NO DOLOR con a categoría DAN (p<0.022). Esta diferencia se mantuvo en las otras categorías de dolor. Se observó que el efecto analgésico es mayor con el estimulo repetitivos. Siendo la categoría NO DOLOR en el grupo B para el primer estimulo 70 por ciento, 85 por ciento en el segundo y 95 por ciento en el tercero (p<0.020). Este efecto se observó también en los grupos A y C. Conclusiones: la dextrosa al 10 por ciento tuvo mayor efecto analgésico comparada con los otros grupos. Los métodos analgésicos no farmacológicos estudiados aumentan su efectividad con estimulo dolorosos repetitivos.

Introduction: Non pharmacological methods are rarely used in neonatal units. repeated painful stimuli have long noxious effects. Objective: To verify the effectiveness of non pharmacological methods in repeated painful procedures; to determine which method is more effective. Material and methods: We conducted a randomized controlled trial. Newborns were randomly assigned into 3 groups (n=40 per group). All of them underwent painful procedures during the first 3 days of life (hepatitis B, BCG and blood sample for determine group and factor). Group A received breast feeding and skin to skin contact as non pharmacological method during the painful stimuli, group B receive dextrose 10 por ciento and group C only suction. Douleur Aigue Nouveauûne scores (DAN, Carvajal et al.) and ABC scale (Bellieni et al.) were used to assess neonatal pain. The 3 groups were compared in each stimulus to determine the most effective method, and the effectiveness in repeated painful stimuli. Results: Group B showed the most analgesic effect in the stimuli, with 97, 5 percent for NO PAIN vs. 87, 5 percent (A) and 85 percent (C) (p<0,036) with ABC scale, and 95 percent vs. 85 (A) and 70 percent (C) for NO PAIN with DAN scale (p<0,022). This difference was constant with all categories of pain. We observed that analgesic effect is greater in repeated painful stimuli. NO PAIN category was 70 percent in group B in the first stimuli, 85 percent in the second and 95 percent in third (9<0,020). This effect was also observed in groups A and C. Conclusions: Dextrose 10 percent seems to offer the best analgesic effect compared with breast feeding and suction. Non pharmacological methods studied increase their effectiveness in repeated painful stimuli.

Comparación de tres géneros musicales como método analgésico no farmacológico: estudio randomizado ciego simple / Comparison of three musical genders as a non pharmacological method: randomized simple blind trial

Objetivo: Comparación de tres géneros musicales como método analgésico no farmacológico para la determinación del género musical que posee mayor efecto analgésico entre niños de 2 a 11 años de edad. Material y Métodos: 150 niños participantes en una campaña de despistaje de anemia realizada en el Hospital Nacinal Arzobispo Laoyza, fueron agrupados aleatoriamente en 4 grupos con 3 distintos géneros musicales y un grupo control (A=Mozart; B=Daddy Yankee; C=Marc Anthony; D= sin estímulo musical). Los niños fueron expuestos a 2 minutos de música o silencio, realizándose el estímulo doloroso (punción para la toma de muestra) a los 60 segundos. Se evaluó la intensidad del dolor según dos escalas: CHEOPS y Autoinforme (según el grupo etario: 2-6 años y 7-11 años, respectivamente); además, se midió la frecuencia cardíaca y saturación de oxígeno, un minuto antes, durante y un minuto después del estímulo doloroso. Se utilizó para el análisis, la pureba de Kruskal-Wallis (prueba no paramétrica). Resultados: El grupo C (Marc Anthony) mostró mayor efecto analgésico al ser comparado con los grupos A y D, al utilizar la escala de Autoinforme (p:0,03); no hubo diferencia significativa con el grupo B. Al comparar los géneros musicales en el grupo etáreo menor (2-6 años, CHEOPS), se encontró un mayor efecto analgésico en el grupo A (Mozart), aunque sin significancia estadística (p: 0,859). Se encontró también mayores niveles de dolor en los grupos B y C. No se hallo diferencia significativa al comparar las curvas de saturación de oxígeno ni frecuencia cardiaca entre los grupos. Conclusiones: La salsa parece otorgar un mayor efecto analgésico en los niños entre 7 y 11 años al ser evaluados con la escala de Autoinforme, comparándolos con los otros géneros musicales y el control; mientras que en los niños entre 2 y 6 años, al ser evaluados con la escala de CHEOPS, ...

Objetive: To compare three music genders as a non pharmacological analgesic method to determine which one has the most analgesic effect in children between 2 and 11 years old. Material and Methods: our study population was a hundred and fifty children who participated on an anemia screening campaign held at the Hospital Nacional Arzobispo Loayza. They were grouped randomly in 4 groups with 3 different musical genders and 1 control group (A=Mozart; B=Daddy Yankee; C=Marc Anthony; D=no musical stimuli). The pain level was assessed by 2 scales: The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Self assessment Scale (the younger age group from 2 to 6 years old, the older age group from 7 to 11 years old respectably), it was also measured heart rate and oxygen saturation 60 seconds before painful stimuli, during stimuli and 30 and 60 seconds post-stimuli. The Kruskal-Wallis Test (non parametric test) was used to analyze the results we obtained. Results: When Self-assessment scale was used, Group C (Marck Anthony) showed the most analgesic effect, compared to groups A and D (p: 0,03); on the other side there was nor significant effect with Group B. When the 3 musical genders where compared in the younger age group (from 2 to 6 years old, CEHOPS), it was found that Group A (Mozart) had the best analgesic effect, even though it did not have any statistic significance (p:0,859). It was also found higher pain levels in Group B and C. No statistical significant difference was found when Oxygen Saturation curves where compared between the four groups, neither heart rate curves. Conclusions: Salsa seems to offer the best analgesic effects in children from 7 to 11 years old, when self-assessment scale was used. Children from 2 to 6 years old were evaluated by CHEOPS scale. We found out that without any statistical significance classical music seems to have the best analgesic effect during painful stimuli.