Article a new epigenetic model to stratify glioma patients according to their immunosuppressive state

Gliomas are the most common primary neoplasm of the central nervous system. A promising frontier in the definition of glioma prognosis and treatment is represented by epigenetics. Further-more, in this study, we developed a machine learning classification model based on epigenetic data (CpG probes) to separate patients according to their state of immunosuppression. We considered 573 cases of low-grade glioma (LGG) and glioblastoma (GBM) from The Cancer Genome Atlas (TCGA). First, from gene expression data, we derived a novel binary indicator to flag patients with a favorable immune state. Then, based on previous studies, we selected the genes related to the immune state of tumor microenvironment. After, we improved the selection with a data-driven procedure, based on Boruta. Finally, we tuned, trained, and evaluated both random forest and neural network classifiers on the resulting dataset. We found that a multi-layer perceptron network fed by the 338 probes selected by applying both expert choice and Boruta results in the best performance, achieving an out-of-sample accuracy of 82.8%, a Matthews correlation coefficient of 0.657, and an area under the ROC curve of 0.9. Based on the proposed model, we provided a method to stratify glioma patients according to their epigenomic state

A novel comprehensive clinical stratification model to refine prognosis of glioblastoma patients undergoing surgical resection

Despite recent discoveries in genetics and molecular fields, glioblastoma (GBM) prognosis still remains unfavorable with less than 10% of patients alive 5 years after diagnosis. Numerous studies have focused on the research of biological biomarkers to stratify GBM patients. We addressed this issue in our study by using clinical/molecular and image data, which is generally available to Neurosurgical Departments in order to create a prognostic score that can be useful to stratify GBM patients undergoing surgical resection. By using the random forest approach [CART analysis (classification and regression tree)] on Survival time data of 465 cases, we developed a new prediction score resulting in 10 groups based on extent of resection (EOR), age, tumor volumetric features, intraoperative protocols and tumor molecular classes. The resulting tree was trimmed according to similarities in the relative hazard ratios amongst groups, giving rise to a 5-group classification tree. These 5 groups were different in terms of overall survival (OS) (p < 0.000). The score performance in predicting death was defined by a Harrell\u2019s c-index of 0.79 (95% confidence interval [0.76\u20130.81]). The proposed score could be useful in a clinical setting to refine the prognosis of GBM patients after surgery and prior to postoperative treatment

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Updating and inhibition processes in working memory: a comparison between Alzheimer's type dementia and frontal lobe focal damage

6nonenoneBORGO F; GIOVANNINI L; MORO R; SEMENZA C.; ARCICASA M; ZARAMELLA MBorgo, F; Giovannini, L; Moro, R; Semenza, Carlo; Arcicasa, M; Zaramella, M

Radiotherapy and concomitant Docetaxel in very high risk prostatic cancer our esperience in the first 30 patients

High-risk prostate cancer patients (cT3, N1, PSA 65 20 ng/ml and/or Gleason score 658) have a 5-year biochemical failure rate after surgery or radiation of 50% or higher. In this group of patients hormonal therapy (HT) is currently the best systemic treatment option in association with radiotherapy (RT). Due to the heterogeneity of prostate cancer (CaP) cells and attempt to improve the outcome with RT, weekly chemotherapy (CHT) during RT, in localized, high-risk CaP is being explored. Docetaxel has demonstrated a significant anti-tumor effect and impact on survival in hormone refractory CaP and can increase the sensitivity of tumor cells to radiation injury. Patients and Methods: From 2005 to 2010, 30 very high risk patients (pts) were treated with high dose of RT and concomitant Docetaxel. Of these, 17/30 (Group 1) underwent surgery before RT and they were all characterized by pathological advanced disease; 13/30 (Group 2) underwent radical RT and they all presented a clinically advanced disease. Group 1 median age was 65 years (range 57-80); the pathological Gleason Score (pGS) was 8 in 4 and 9 in 13 pts; the pTNM was pT2c in 2, pT3a in 3, pT3b in 10 and pT4 in 2 pts. Nodes were positive in 3 pts; surgical positive margins were found in 6 cases. PSA median level, at diagnosis, was 18 (range 4.25-56.3) and PSA prior to RT was 0.65 ng/ml (range 0.01-4.22); RT median dose, was 70 Gy (range 66-76). Group 2 median age was 73 years (range 65-81); the bioptic GS was 7 in 1, 8 in 4, 9 in 7 pts and 10 in 1 case; cTNM was T3 in 8 and T2 in 5 pts; PSA median level at diagnosis was 9,3 (range 5,27-71,3) and PSA prior to RT was 0,51 ng/ml (0,05-3,83); RT median dose was 80 Gy (range 76-80). Docetaxel was administered in a standard weekly dose (30 mg for pts with m2=2). Median cycles of CHT was 7 (range 2-8). All pts began HT before and during RT and continued the treatment for 2 years after RT. Results: The median follow up was of 36 months (8-60). Only 6 pts, after a median period of 14 months, presented a recurrent disease (locally or/and to the bones). Median PSA at 3 months after RT was 0.04 (0.01-1.1) ng/ml, and at the last follow up was 0.04 (0.01-1.9). As to the toxicity: gastrointestinal grade I was complained by 18/30 and urological grade I by 12/30 pts. Two patients had to stop CHT infusion after two cycles for systemic toxicity. Conclusion: These preliminary data confirm the feasibility and the tolerability of weekly Docetaxel in combination with RT in men with high risk of disease progression. No pts suffered a performance status worsening during the scheduled treatment. At the median follow up of 36 months, only 20% of pts were relapsed. An increase number of recruited pts and a longer follow up are necessary to confirm the validity of these preliminary results

Multimodal treatment for high-risk locally-advanced prostate cancer following radical prostatectomy and extended lymphadenectomy

The aim of this study was to prospectively evaluate the safety and oncologic outcomes of multimodal treatment in high risk-locally advanced prostate cancer patients (PCa)