serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors.

The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of on outcomes and microbiome composition.

Adult Medulloblastoma Demographic, Tumor and Treatment Impact since 2006: A Canadian University Experience.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017.

Very high-dose methylprednisolone for treatment of nivolumab-induced limbic encephalitis: A case report.

Introduction: Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis.

Case Report: We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks.

Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors.

: The gut microbiota has been shown to be an important determinant of the efficacy of immune checkpoint inhibitions (ICI) in cancer. Several lines of evidence suggest that antibiotic (ATB) usage prior to or within the first month of ICI initiation negatively impacts clinical outcomes. : We examined patients with advanced melanoma treated with an anti-PD-1 monoclonal antibody (mAb) or an anti-CTLA-4 mAb alone or in combination with chemotherapy.

Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma.

Background: Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers.

Efficiency of Crizotinib on an ALK-Positive Inflammatory Myofibroblastic Tumor of the Central Nervous System: A Case Report.

Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are rare entities that have a predilection for local recurrences. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby present the case of a patient diagnosed with a left parieto-occipital IMT that recurred after multiple surgeries and radiotherapy.

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome.

Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99).

Prophylactic anticonvulsants for gliomas: a seven-year retrospective analysis.

Background: The American Academy of Neurology (AAN) does not recommend routine use of prophylactic antiepileptic drugs (pAEDs) in patients with newly diagnosed brain tumors. If used in the perioperative setting, discontinuation is suggested after the first postoperative week. It is unclear whether such recommendations are followed.

Interleukin-21 has activity in patients with metastatic melanoma: a phase II study.

Purpose: We report a multicenter phase II study of patients with metastatic melanoma (MM), evaluating the efficacy, toxicity, progression-free survival (PFS), immunogenicity, and biomarker profile of interleukin-21 (IL-21).

Patients And Methods: Patients with no prior systemic therapy and with limited-disease MM were treated with IL-21 by using three different dosing regimens. Cohort 1 received 50 μg/kg per day by outpatient intravenous bolus injection for 5 days of each week during weeks 1, 3, and 5 of an 8-week cycle.

MG98, a second-generation DNMT1 inhibitor, in the treatment of advanced renal cell carcinoma.

Background: In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production.

Methods: This multicenter study explored two schedules of MG98 with Interferon-α-2β to identify schedule and dose for patients with metastatic RCC.

A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression.

This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the Ras-MAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study.

Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study.

PURPOSE Concomitant temozolomide (TMZ)/radiotherapy followed by adjuvant TMZ has increased survival in patients with glioblastoma multiforme (GBM). However, few options are effective for patients who experience treatment failure. We conducted a multicenter, phase II study to assess the efficacy and safety of continuous dose-intense TMZ for recurrent GBM.

A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation.

Purpose: We undertook a phase I/II study of the EGFR/erbB2 inhibitor lapatinib in patients with recurrent glioblastoma multiforme (GBM) to determine response rate, pharmacokinetics (PK) and recommended dose in patients taking enzyme-inducing anti-epileptic drugs (EIAEDs) and to explore relationships of molecular genetics to outcome.

Methods: Recurrent GBM patients taking EIAEDs were enrolled on the phase I portion (starting dose of lapatinib 1,000 mg po bid). In the absence of dose-limiting toxicity (DLT), escalation continued in cohorts of three patients.

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

Background: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years.

Methods: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide.

Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3.

Background: A randomised trial published by the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) Clinical Trials Group (trial 26981-22981/CE.3) showed that addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma significantly improved survival. We aimed to undertake an exploratory subanalysis of the EORTC and NCIC data to confirm or identify new prognostic factors for survival in adult patients with glioblastoma, derive nomograms that predict an individual patient's prognosis, and suggest stratification factors for future trials.

A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trial.

To assess the response rate and toxicity of the kinesin spindle protein (KSP) inhibitor, ispinesib, in malignant melanoma. Seventeen patients were enrolled from April to November 2005. Ispinesib was administered as a 1-hour infusion at a dose of 18 mg/m2 once every 3 weeks until disease progression.

A phase I study of T900607 given once every 3 weeks in patients with advanced refractory cancers; National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) IND 130.

Background: T900607 is a novel tubulin active agent which disrupts microtubule polymerization by a unique mechanism of action. This phase I trial was conducted to determine the maximum tolerated dose, recommended phase II dose, pharmacokinetic properties and toxicities of this agent.

Patients And Methods: Patients with advanced and/or metastatic solid malignancies were enrolled, for an open dose escalation of T900607 administered intravenously over 30 minutes every 21-days.

Phase II study of perifosine in previously untreated patients with metastatic melanoma.

Purpose: To assess the response rate and toxicity of the alkylphosphocholine analogue, perifosine, in patients with metastatic or recurrent malignant melanoma.

Patients And Methods: Patients had histologically proven, unidimensionally measurable disease which was incurable by standard therapy. Prior adjuvant immunotherapy was allowed but patients had not received prior chemotherapy.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.

Background: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.

A phase II study of topotecan in patients with anaplastic oligodendroglioma or anaplastic mixed oligoastrocytoma.

To determine the efficacy and toxicity of a novel chemotherapeutic approach with topotecan, a camptothecin analog, for progressive or recurring anaplastic oligodendroglioma or mixed oligoastrocytoma.Patients from seven centers with recurrent or progressive disease were treated with topotecan, 1.5 mg/m(2) intravenously (i.

Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group.

Objectives: To determine the tolerability and efficacy of daily oral marimastat (BB-2516 in patients with metastatic melanoma and to determine the matrix metalloproteinase (MMP) activity, tumour necrosis, peri- and intra-tumoral fibrosis and tumor inflammation in pre- and post-treatment tumor biopsies.

Patients And Methods: Patients with measurable metastatic melanoma who had received no more than one prior chemotherapy regimen and lesions accessible for biopsy were eligible. The first 18 were treated with 100 mg p.

Phase I and pharmacokinetic study of novel L-nucleoside analog troxacitabine given as a 30-minute infusion every 21 days.

Purpose: Troxacitabine (Troxatyl, BCH-4556; BioChem Pharma Inc, Basingstoke, United Kingdom) is a novel synthetic L-nucleoside analog with activity against a broad range of human tumors in preclinical models. Preclinical toxicity suggested a predictable toxicity profile consistent with an agent of this class, with evidence of interspecies differences. We conducted a phase I study of troxacitabine given as a 30-minute infusion once every 21 days.