Added text to state that although most neuroblastoma tumors are initially sensitive to chemotherapy, many relapse in local and/or metastatic sites. Modern genetic analysis, including deep whole-genome sequencing of primary and relapsed neuroblastomas from the same patients, revealed many new mutations and complex clonal evolution of pre-existing minor subclones. The most common new mutations found were in the RAS-MAPK pathway (cited Eleveld et al. and Schramm et al. as references 29 and 30, respectively).
Revised text to state that the International Neuroblastoma Risk Group Staging System (INRGSS) has predictive value for patients with lower-stage disease, with a 5-year event-free survival (EFS) of 90% and overall survival (OS) of 98% for stage L1 patients, compared with an EFS of 79% and OS of 89% for stage L2 patients. Also added text to state that among INRG stage L2 children, International Neuroblastoma Staging System (INSS) stage 2 patients do significantly better than do INSS stage 3 patients in 5-year OS (cited Monclair et al. as reference 24).
Added text to state that a meta-analysis of stage 3 versus stage 4 neuroblastoma patients, at all ages combined, found an advantage for gross-total resection over subtotal resection in stage 3 neuroblastoma only, not stage 4 (cited Mullassery et al. as reference 21). Also added text to state that a small study suggested that after neoadjuvant chemotherapy, completeness of resection was affected by the number of image-defined risk factors remaining (cited Irtan et al. as reference 22).
Revised text about the randomized study that was performed to compare high-dose therapy with purged autologous bone marrow transplant (ABMT) to clarify the randomization and to update the survival statistics.
Added text to state that an updated Cochrane review evaluated three randomized clinical trials comparing ABMT with standard chemotherapy. EFS was significantly better for ABMT, but there was no statistically significant difference in OS (cited Yalçin et al. as reference 20).
Added text to state that the ch14.18 antibody has been approved by the U.S. Food and Drug Administration.
Added text to state that modern comprehensive molecular analysis comparing primary and relapsed neuroblastoma from the same patients revealed extensive clonal enrichment and several new mutations, with many tumors showing new or clonal-enriched mutations in the RAS-MAPK pathway. This was true for patients with both high-risk and low-risk tumors at diagnosis (cited Eleveld et al. and Schramm et al. as references 3 and 4, respectively).
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
weblog.maimonides.edu/farmacia/archives/UM_Informe_Autoevaluacion_FyB.pdf - //
weblog.maimonides.edu/farmacia/archives/0216_Admin_FarmEcon.pdf - //
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