Beating the odds: extreme long-term survival with glioblastoma

摘要: See the article by Gerber et al, on pages 1186–1195. Amongst all cancers, diagnosis of glioblastoma multiforme (GBM) portends one most malevolent clinical prognoses. Median survival is only nine months, rising to 15–16 months for those receiving standard care surgery and adjuvant chemoradiation.1–3 Nevertheless, GBMs exhibit a substantial degree heterogeneity in both their molecular profiles. Several dozen somatic genetic events have been identified as likely “drivers” GBM tumorigenesis, individual can contain countless combinations these.4 methylation profiles tend divide into two major classes which themselves associate with presence or absence IDH1/2 mutations.5 also be sorted at least four based upon expression profiles, each these enriched specific epigenetic features.6 Beyond this, intratumoral heterogeneity, this itself varies between tumors.7 Clinically, varying responses treatment, 12% patients who receive chemoradiation surviving years after diagnosis.8 Initial investigations factors influencing differential advanced age, pre-existing neurologic impairment, poor functional status worse outcome patients.9 Furthermore, extent resection, either initial tumor recurrence, has clearly shown an important predictor survival.10,11 These features integrated prognostic model.12 More recently, several signatures predict favorable patient response treatment well overall gliomas. include chromosomal arm-level such loss 1p 19q,13 silencing MGMT through methylation,14 mutations,15 signatures.16 Regions instability credited prognosis patients.17 However, few studies focused that extreme long-term survival. disease course qualitatively different from vast majority patients. For example, half survived will survive more.18 Do simply associated good population, does relate set disease? A detailed answer question potential not enable refinement classes, but indicate therapeutic strategies convert more survivors. In “Transcriptomal diversity survivors”, colleagues begin address question. Their study evaluated patterns past years, using data single institution (MSKCC) extending results larger TCGA REMBRANDT databases. They found survivors frequently MGMT, suggesting responsiveness temozolomide contributor Surprisingly, however, they did identify preponderance IDH-mutant tumors among survivors. no relationship membership expression-based subclasses determined TCGA. Similarly, defining association increased any groups.6 Although start, leaves questions unaddressed. First, because are definition rare, small number could included study. It generate cohorts obtain sufficient power detect robust differences extremely general population. Additionally, were assessed may determining Chief epigenetic, determine uniformity cells within tumor.19,20 Moreover, need continued reassessment our evolve. The inability show improvements targeted therapeutics, despite wealth druggable targets GBMs, great failing field. Hopefully, greater understanding why some so long us why, best efforts, do not.