We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.
Recent studies have shown that isocitrate dehydrogenase1 ⁄ 2 (IDH1 ⁄ 2) mutations occur frequently in secondary glioblastoma. This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in secondary glioblastoma. Searches for IDH1 and IDH2 mutations, 1p19q codeletion, MGMT promoter methylation, and p53 expression were carried out in a series of 86 secondary glioblastomas and correlated with progression-free survival and overall survival. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58 ⁄ 79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression-free survival in univariate (P < 0.001, P < 0.001, P = 0.003, respectively) and multivariate analysis (P < 0.001, P < 0.001, P = 0.035, respectively). IDH mutation (P = 0.001) and MGMT promoter methylation (P = 0.011) were correlated with a higher rate of objective response to temozolomide. Further analysis of response to temozolomide showed that patients with both IDH mutation and MGMT promoter methylation had the best response rate to temozolomide. IDH mutation appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. Use of IDH status combined with MGMT promoter status as a stratification factor seems appropriate in future clinical trials involving temozolomide for the treatment of patients with secondary glioblastoma. (Cancer Sci 2012; 103: 269-273) G lioblastomas (GBMs), the most common and malignant primary brain tumors in adults, may develop rapidly after a short history and without evidence of less malignant precursor lesions (primary GBM, pGBM), or through progression from low-grade or anaplastic gliomas (secondary GBM, sGBM).(1-3)In GBM, the clinical value of O(6)-methylguanine DNA methyltransferase (MGMT) promotor methylation status in predicting benefit from alkylating agents has been validated by several clinical trials, both in patients treated with nitrosourea and in those with temozolomide (TMZ). (4,5) In the European Organization for Research and Treatment of Cancer (EORTC) ⁄ National Cancer Institute of Canada (NCIC) 26981 ⁄ 22981 trial evaluating the effect of radiotherapy plus concomitant and adjuvant TMZ versus radiotherapy alone in GBM, methylation of MGMT promotor emerged as the strongest predictor for outcome and benefit from chemotherapy.(6,7) However, all of these studies were based on newly diagnosed GBMs, most of which were pGBMs. So far, there is no clear evidence that MGMT promotor methylation plays the same role in sGBMs, as these two subtypes constitute distinct disease entities and develop through different genetic pathways. (2,3,8) In 2008, a genome-wide sequencing study identified somatic mutations on codon 132 in a gene encoding isocitrate dehydrogenase-1 (IDH1) in 12% s...
Statement of translational relevance:Disease recurrence after curative resection for hepatocellular carcinoma (HCC) patients Experimental Design:In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE (n=140) or no adjuvant treatment (control; n = 140) groups.The primary endpoint was recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients' outcomes. Results:Patients who received adjuvant TACE had a significantly longer RFS than Conclusion:For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy, our study showed adjuvant TACE significantly reduced tumor recurrence, improved RFS and OS, and the procedure was well tolerated.
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