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• W4249280944 abstract "CNS OncologyVol. 2, No. 3 News & ViewsFree AccessJournal Watch: Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of CNS oncology.Maura Massimino & Larry JunckMaura MassiminoFondazione Istituto di Ricovero e Cura a Carattere Scientifico Instituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, ItalySearch for more papers by this author & Larry JunckUniversity of Michigan Health System, Department of Neurology, Ann Arbor, MI, USASearch for more papers by this authorPublished Online:14 May 2013https://doi.org/10.2217/cns.13.16AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Craniospinal irradiation remains the mainstay in medulloblastoma treatment for patients older than 3 years. Reducing doses to 23.4 Gy and new technologies, such as conformal radiotherapy, have maintained the same therapeutic results, and there is evidence of less neurocognitive morbidity in children treated with lower doses. Some studies have reported an estimated loss of 4.3 IQ points per year and a 10–15 IQ point benefit in younger children treated with a reduced dose of craniospinal radiation [1]. Despite these premises, this paper demonstrates that, in a total of 110 patients and 192 assessments, although patients were treated with 23.4 Gy craniospinal irradiation followed by two different types of adjuvant chemotherapies, longitudinal models created for all of the assessments revealed significantly lower full IQs in patients following treatment. The IQ decline was even more severe for children starting from higher baseline intellectual levels or for those experiencing mutism after surgery. Another risk factor, previously shown in other studies, was younger age at diagnosis [2]. The authors conclude that more studies are required to improve the intellectual outcome of children affected by medulloblastoma.– Written by Maura MassiminoReferences1 Mulhern RK, Kepner JL, Thomas PR et al. Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J. Clin. Oncol.16,1723–1728 (1998).Crossref, Medline, CAS, Google Scholar2 Ris MD, Packer R, Goldwein J et al. Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children’s Cancer Group study. J. Clin. Oncol.19,3470–3476 (2001).Crossref, Medline, CAS, Google ScholarThe aim of this paper was to retrospectively collect all of the cases of tumors originating in the cerebellopontine angle among all of those originating in the posterior fossa. The authors retrieved 26 cerebellopontine tumors out of 267 posterior fossa tumors, with 69% of the cerebellopontine tumors comprising malignant tumors. The authors also defined the main defining features of this malignant subgroup as hydrocephalus at presentation, plastic feature of the tumor along the cisternal spaces, encasement of major arteries and widening of lateral recesses. Owing to the importance of the cerebellopontine angle, neurological postoperative deficits were very common and often permanent. Cerebellopontine angle, therefore, represents a very critical site for both quod vitam and quod valetudinem prognosis, different to the middle posterior fossa where benign tumors (i.e., pilocytic astrocytoma) are more common.– Written by Maura MassiminoWhole-genome or whole-exome sequencing was performed on 17 meningiomas, followed by focused sequencing on an additional 48 tumors (grades I–III). Meningiomas were found to have simple genomes with few mutations. NF2 was inactivated in 43% of tumors and epigenetic modifiers were altered in an additional 8%. A total of 190 other genes were mutated, of which six had mutation rates statistically above baseline. Of these six genes, four (NF2, KDM5C, SMO and AKT1) had previously been implicated in cancer, while two (RGPD3 and CD300C) had not. Five patients had mutations in AKT1 and three in SMO. Tumors with alterations in AKT1, mTOR and SMO were demonstrated to be markers of activation in their corresponding pathways. Tumors with mutated AKT1/mTOR and SMO were predominantly meningothelial, while NF2-altered tumors were predominantly fibroblastic or transitional. These findings suggest that meningiomas have heterogeneous mutations that correspond to their histopathology and could be potential targets for treatment.– Written by Larry JunckThe authors performed genome-wide genotyping and exome sequencing on 50 grade I–II meningiomas, followed by targeted analysis in a confirmation set of 250 meningiomas of various grades. Chromosome 22 loss was the most common event (149 tumors) and, in 108 of these tumors, NF2 mutations were present. TRAF7 was mutated in 72 tumors, and the majority of these also had mutations in KLF4 or AKT. A total of 11 tumors had mutations in SMO, and most of these had no mutations in the other four genes mentioned above. Tumors with chromosome 22 loss with or without NF2 mutation predominated in parieto-occipital cerebral regions, lateral or posterior skull base and the spine, and were more likely to be of a high tumor grade. Tumors without chromosome 22 loss or NF2 mutation predominated in the medial skull base. Those with the SMO L412F mutation (n = 5) were all in the medial anterior skull base. These findings identify distinct meningioma subtypes and provides important new information about their genetic makeup.– Written by Larry JunckThis article provides health-related quality of life results from a Phase III trial of 359 patients, comparing adjuvant whole-brain radiotherapy (WBRT) with observation of a limited number of brain metastases in patients with stable solid tumors after being treated with either surgery or radiosurgery. Health-related quality of life was assessed at baseline, at 8 weeks, and then every 3 months with the C30 questionnaire and Brain Cancer Module. Compliance was 88% at baseline but only 45% at 1 year. In general, patients in the observation arm had better scores than those who received WBRT. Differences that were statistically significant and the authors found to be clinically relevant included global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months and fatigue at 8 weeks. Together with the primary study, which indicated no survival benefit with WBRT, these results support deferring WBRT for patients with a limited number of brain metastases who undergo resection or radiosurgery for all identified lesions.– Written by Larry JunckFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.FiguresReferencesRelatedDetails Vol. 2, No. 3 Follow us on social media for the latest updates Metrics Downloaded 184 times History Published online 14 May 2013 Published in print May 2013 Information© Future Medicine LtdPDF download" @default.
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