The high cure rates of Hodgkin lymphoma (HL) make this oncological disease among those with the greatest number of long‐term survivors. This single‐institution study including 383 HL patients with up ...to 45 years of follow‐up, analyses the morbidity and mortality of this population after treatments in comparison with the overall Spanish population, and investigates whether it has changed over time stratifying by periods of time, as a consequence of therapeutic optimization. The median age was 34.8 years (range 15–87) with median overall survival of 30 years, significantly higher in women (HR 0.58, 95% CI 0.42–0.79) (p = 0.0002). 185 late‐stage diseases were noted (35% patients), cardiovascular disease (CVD) being the most frequent (23.2%). 30% of patients developed at least one second malignant neoplasm (SMN) to give a total of 174 SMNs. 20.9% of the patients died from HL and 67.0% died from non‐HL causes (32.2% from SMN, 17% from CVD). The overall standardized mortality ratio (SMR) was 3.57 (95% CI: 3.0–4.2), with striking values of 7.73 (95% CI: 5.02–8.69) and of 14.75 (95% CI: 11.38–19.12) for women and patients <30 years at diagnosis, respectively. Excluding HL as the cause of death, the SMRs of those diagnosed before 2000 and from 2000 were proved to be similar (3.88 vs 2.73), maintaining in this last period an unacceptable excess of mortality due to secondary toxicity in patients cured of HL. Our study confirm that HL treatment substantially reduces the life expectancy of patients cured of HL. In recent periods, despite therapeutic optimization, deaths from toxicity continue to occur, mainly from CVD and SMN. Risk‐factor monitoring should be intensified, prevention programs developed, and therapeutic optimization of LH investigated, especially in two vulnerable groups: those aged <30 years at diagnosis, and women.
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.
We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies.
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.
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.
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.
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•Hepatoblastoma (HB) involves global dysregulation of RNA editing, including in the tumor suppressor BLCAP.•Overexpression of a 300 kb region within the 14q32 DLK1/DIO3 locus is a new hallmark of HB.•We identified 2 epigenomic HB subtypes -Epi-CA and Epi-CB- with distinct degrees of DNA hypomethylation and CpG island hypermethylation.•The molecular risk stratification of HB, based on the 14q32-signature and epigenomic subtypes, is associated with patient outcomes.•The enzyme CHKA could be a novel therapeutic target for patients with HB.
El Colegio Montepríncipe trabaja en la educación de niños, niñas y adolescentes con diagnóstico de cáncer; apuesta por la no interrupción de su vida escolar en su aspecto académico y, cuando es ...posible, social. Cuenta, para ello, con un equipo multidisciplinar formado por profesionales de la docencia, psicología y musicoterapia y con personas voluntarias. Este equipo está integrado en el funcionamiento sanitario de la Unidad de Hematología y Oncología Pediátrica del Hospital Universitario Montepríncipe. En este artículo se describe el funcionamiento del colegio en el hospital y cómo este permite integrar la enfermedad en la vida normal de estos grupos afectados por tal diagnóstico. Para valorar dicho objetivo, se ha llevado a cabo un estudio experimental longitudinal cuantitativo, en el que se tuvo en cuenta la asistencia diaria al colegio. Se contó con un promedio de 36 estudiantes a lo largo de cinco cursos académicos (2012-2017) en los que se comprobó que la asistencia diaria al colegio era del 90 % (esta no es obligatoria), y se mantenía constante a lo largo de estos años. Además, se midió el rendimiento académico de una selección de estudiantes para comprobar que la asistencia al colegio era eficaz. En este caso, la muestra real la formaron 14 sujetos y se compararon las notas medias de las asignaturas de Lengua y Matemáticas antes del diagnóstico y después de terminar el curso en el hospital. Los resultados mostraron que el rendimiento aumentaba como promedio un punto por asignatura. De los resultados se podría concluir que la asistencia diaria al colegio en el hospital ayuda a integrar la enfermedad en la vida normal de cada paciente e incluso a mejorar sus resultados académicos.
ObjectivesTo gather insights on the disease experience of patients with heart failure (HF) with reduced ejection fraction (HFrEF), and assess how patients’ experiences and narratives related to the ...disease complement data collected through standardised patient-reported outcome measures (PROMs). Also, to explore new ways of evaluating the burden experienced by patients and caregivers.DesignObservational, descriptive, multicentre, cross-sectional, mixed-methods study.SettingSecondary care, patient’s homes.ParticipantsTwenty patients with HFrEF (New York Heart Association (NYHA) classification I–III) aged 38–85 years.MeasuresPROMs EuroQoL 5D-5L (EQ-5D-5L) and Kansas City Cardiomyopathy Questionnaire and patient interview and observation.ResultsA total of 20 patients with HFrEF participated in the study. The patients’ mean (SD) age was 72.5 (11.4) years, 65% were male and were classified inNYHA functional classes I (n=4), II (n=7) and III (n=9). The study showed a strong impact of HF in the patients’ quality of life (QoL) and disease experience, as revealed by the standardised PROMs (EQ-5D-5L global index=0.64 (0.36); Kansas City Cardiomyopathy Questionnaire total symptom score=71.56 (20.55)) and the in-depth interviews. Patients and caregivers often disagreed describing and evaluating perceived QoL, as patients downplayed their limitations and caregivers overemphasised the poor QoL of the patients. Patients related current QoL to distant life experiences or to critical moments in their disease, such as hospitalisations. Anxiety over the disease progression is apparent in both patients and caregivers, suggesting that caregiver-specific tools should be developed.ConclusionsPROMs are an effective way of assessing symptoms over the most recent time period. However, especially in chronic diseases such as HFrEF, PROM scores could be complemented with additional tools to gain a better understanding of the patient’s status. New PROMs designed to evaluate and compare specific points in the life of the patient could be clinically more useful to assess changes in health status.
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