ABSTRACT
Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive and therapy-resistant pediatric central nervous system (CNS) tumors that have three histological patters: embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. We present a case of ETMR in an 18-year-old woman with DICER1 syndrome. This report confirms the important role of DNA-methylation analysis in the classification of CNS embryonal tumors and the importance of investigating somatic and germline DICER1 mutations in all CNS embryonal tumors.
Subject(s)
DEAD-box RNA Helicases , Neoplasms, Germ Cell and Embryonal , Ribonuclease III , Humans , Female , Ribonuclease III/genetics , DEAD-box RNA Helicases/genetics , Adolescent , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/pathology , DNA MethylationABSTRACT
OBJECTIVE: Treatment response and prognosis in glioblastoma (GBM) tumours can differ among patients, highlighting the growing relevance of genetic biomarkers to differentiate glioblastoma sub-types. The biomarker isocitrate dehydrogenase (IDH1) is currently receiving considerable attention. The objective of this work was to analyse the clinical and prognostic differences between glioblastomas with and without the IDH1 mutation. METHODS: A retrospective study was performed on patients with GBM who underwent surgery between 2007 and 2012. The inclusion criteria were: patient age between 18-85 years who underwent surgery for the first time with complete macroscopic resection, complete adjuvant treatment with chemotherapy and radiotherapy, and a Karnofsky performance score>70. RESULTS: A total of 61 patients (36 males/25 famales) were included and with a mean age of 62.3 years. An IDH1mutation was found in 14 patients (23%). Median survival in patients with the IDH1 mutation (IDH1-m) was 23.6 months compared with 11.9 months in those with the wild type IDH1 (IDH1-wt) (P=.028). Disease onset in IDH1-m patients tended to be at a younger age, 58.7 vs. 63.4 years, but this difference was not statistically significant. CONCLUSION: Glioblastomas with IDH1-m should be considered a different entity from the IDH1-wt, as their natural history and prognosis differ. In the near future we should be classified glioblastomas based on the presence of the IDH1 mutation.
Subject(s)
Brain Neoplasms/genetics , Glioblastoma/genetics , Isocitrate Dehydrogenase/genetics , Mutation , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Combination chemotherapy has been the mainstay of treatment for extensive stage small celI lung cancer (SCLC) over the last 30 years even though it only gives a short prolongation in median survival time. The main goal for these patients should be palliation with the aim of improving their quality of life. OBJECTIVES: To evaluate the effectiveness of chemotherapy in extensive SCLC compared with best supportive care (BSC) or placebo treatment. SEARCH STRATEGY: MEDLINE (1966 to July 2008), EMBASE (1974 to week 31, 2008), and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2008). Experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials in which any chemotherapy treatment was compared with placebo or BSC in patients with extensive SCLC, as first or second therapy at relapse. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study quality. We resolved disagreements by discussion. Additional information was obtained from one study author. MAIN RESULTS: Two studies were included for first-line chemotherapy. A total of 65 patients were randomised to receive either placebo or ifosfamide. Ifosfamide gave an extra mean survival of 78.5 days compared with placebo. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group.Two studies were included for second-line chemotherapy at relapse. A total of 531 patients were randomised to receive either methotrexate-doxorubicin or symptomatic treatment, or to receive oral topotecan versus BSC. The methotrexate-doxorubicin treatment gave a median survival of 63 days longer than in the symptomatic treatment group, and 21 days longer for patients allocated to receive four or eight cycles of first-line chemotherapy, respectively.Treatment with topotecan gave a median survival of 84 days longer than in the BSC group (log-rank P = 0.01). The adjusted hazard ratio for overall survival was 0.61 (95% CI, 0.43 to 0.87). Partial or complete response in the methotrexate-doxorubicin group was 22.3%. Five patients (7%, 95% CI, 2.33 to 15.67) showed a partial response with topotecan. Toxicity was worst in the chemotherapy group. Quality of life was better in the topotecan group. AUTHORS' CONCLUSIONS: Chemotherapeutic treatment prolongs survival in comparison with placebo in patients with advanced SCLC. Nevertheless, the impact of first-line chemotherapy on quality of life and in patients with poor prognosis is unknown. Well-designed, controlled trials are needed to further evaluate the risks and benefits of different chemotherapeutic schedules in patients with advanced SCLC.