Relapse primary central nervous system lymphoma successfully consolidated with allogeneic stem cell transplantation with thiotepa/busulfan/fludarabine conditioning

Primary central nervous system lymphoma (PCNSL) is generally characterized by a poor prognosis and frequent relapsing disease. Consolidation therapy in the upfront setting usually consists of an autologous stem cell transplantation. We report the case of a 19-year-old Caucasian male who had previously undergone an allogeneic stem cell transplantation with complete engraftment for the treatment of juvenile myelomonocytic leukemia when he was 1 year old. He presented with two episodes of (donor-derived) PCNSL from allogeneic stem cells; however, after induction chemotherapy, he failed to harvest stem cells for the consolidation with autologous stem cell transplantation. He was consolidated successfully with a second allogeneic stem cell transplantation with another donor after conditioning with thiotepa, busulfan, and fludarabine

Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors

Isocitrate Dehydrogenase Mutant Grade II and III Glial Neoplasms

Mutations in isocitrate dehydrogenase (IDH) 1 or IDH2 occur in the majority of adult low-grade gliomas and, less commonly, in cholangiocarcinoma, chondrosarcoma, acute myeloid leukemia, and other human malignancies. Cancer-associated mutations alter the function of the enzyme, resulting in production of R(-)-2-hydroxyglutarate (R-2-HG) and broad epigenetic dysregulation. Small molecule IDH inhibitors have received regulatory approval for the treatment of IDH mutant (mIDH) leukemia and are under development for the treatment of mIDH solid tumors. This article provides a current view of IDH mutant adult astrocytic and oligodendroglial tumors, including their clinical presentation and treatment, and discusses novel approaches and challenges toward improving the treatment of these tumors

How we treat patients with leptomeningeal metastases

The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options in

Association Between Supratotal Glioblastoma Resection and Patient Survival: A Systematic Review and Meta-Analysis

- BACKGROUND: Gross total resection (GTR) of the contrast enhancing (CE) area will improve the survival of patients with glioblastoma (GBM). However, GBM can infiltrate into the brain parenchyma, beyond the CE margins. It remains unclear whether resection beyond the CE area (supratotal resection [SPTR]) can improve survival without causing additional neurological deficits. The aim of the present meta-analysis was to study the association between SPTR and overall survival of patients of GBM. - METHODS: Embase, PubMed, and other literature databases were searched for eligible studies until August 2018. Studies involving patients with GBM that had compared SPTR with GTR were included in the present study. The main outcome was overall survival, presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and median overall survival differences with the 95% CIs. - RESULTS: The meta-analysis, which included 6 studies and 1168 unique patients with GBM, showed that compared with GTR, SPTR of GBM resulted in a 53% lower risk of mortality at any time during follow-up (HR, 0.47; 95% CI, 0.31e 0.72; P [ 0.0005). The median overall survival of the SPTR group was 6.4 months (95% CI, 3.2e9.7) longer than the GTR group (P [ 0.0001). Reports on postoperative deficits were limited, and the quality of evidence was moderate to very low. - CONCLUSIONS: Compared with GTR, SPTR of GBM resulted in a lower risk of mortality and longer median overall survival. However, the quality of evidence of the available studies was poor. Therefore, it remains unclear whether SPTR is safe and actually improves the survival of patients with GBM. Future prospective trials and a standardized definition of SPTR are needed

Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in metastatic colorectal cancer.

In a phase I study of weekly administered cisplatin combined with oral etoposide, we observed a partial response in 4 out of 11 patients with metastatic colorectal cancer. Subsequently, we performed a phase II study to investigate the activity of this combination as first-line treatment in this disease. Fourteen patients with metastatic colorectal cancer were enrolled in this study. Treatment consisted of cisplatin, administered in 3% sodium chloride, at a dose of 70 mg m-2 on days 1, 8 and 15 and days 29, 36 and 43 combined with oral etoposide 50 mg absolute dose daily on days 1-15 of both courses. Patients with stable disease or better continued treatment with etoposide 50 mg m-2 orally on days 1-21 every 28 days. A partial response was observed in two patients with liver metastases (14%; 95% confidence limits 2-42%) for 30 and 32 weeks. Five patients had stable disease. Toxicity consisted mainly of anaemia, leucocytopenia, nausea and vomiting. Tinnitus was reported by six patients. The activity of the combination cisplatin-oral etoposide in the schedule is only minimal in metastatic colorectal cancer

Predictive and prognostic markers in neurooncology

Abstract Over the past few years molecular assays have been introduced to aid in typing and grading of gliomas. This is the result of improved understanding of these tumors at the molecular level. In particular, the presence or absence of combined 1p/19 loss in oligodendroglial tumors, epidermal growth factor receptor amplification, epidermal growth factor receptor vIII mutations in grade III tumors and glioblastoma multiforme, and MGMT promoter gene methylation in glioblastoma multiforme are now being used to tailor treatment decisions in patients. However, the application of these tests is far from straightforward, and certain standards are required before any test can be introduced in the daily management of patients. Some of these requirements concern inter-and intratest variability, including whether a test gives the same results if repeated in the same or in another laboratory or when different methodologies are used (e.g. loss of heterozygosity vs fluorescence in situ hybridization and a polymerase chain reaction-based test vs immunohistochemistry). The sensitivity and specificity of a test (or negative and positive predictive value) indicate the likelihood that the test results are positive if the disease is present and the likelihood that the disease is present if the test results are positive. Studies on these test characteristics usually require the presence of a gold standard to which new tests should be compared. Last but not least there is the question of what added value the test has; this criterion determines the clinical usefulness of the assay and why some recently introduced molecular assays need to be scrutinized

Hybrid quantum computing with ancillas

In the quest to build a practical quantum computer, it is important to use efficient schemes for enacting the elementary quantum operations from which quantum computer programs are constructed. The opposing requirements of well-protected quantum data and fast quantum operations must be balanced to maintain the integrity of the quantum information throughout the computation. One important approach to quantum operations is to use an extra quantum system - an ancilla - to interact with the quantum data register. Ancillas can mediate interactions between separated quantum registers, and by using fresh ancillas for each quantum operation, data integrity can be preserved for longer. This review provides an overview of the basic concepts of the gate model quantum computer architecture, including the different possible forms of information encodings - from base two up to continuous variables - and a more detailed description of how the main types of ancilla-mediated quantum operations provide efficient quantum gates.Comment: Review paper. An introduction to quantum computation with qudits and continuous variables, and a review of ancilla-based gate method