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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 Helicobacter pylori 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 H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival (p = .02) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena. [ABSTRACT FROM AUTHOR]

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. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%; p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155; 5yPFS 78% vs. 67%, p = 0.114). From 2006-2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen. [ABSTRACT FROM AUTHOR]

We investigate whether the inclusion of Cat Bonds in portfolios composed of traditional assets and common factors is beneficial to investors. Various mean‐variance spanning tests performed for the period of 2002 to 2017 show that under different market conditions, the addition of Cat Bonds gives rise to previously unattainable portfolios. Using the Engle (2002) Dynamic Conditional Correlation (DCC) model, we find that including Cat bonds increases significantly the time‐varying Sharpe ratio and the Choueifaty and Coignard (2008) maximum diversification ratio. Cat Bonds provide needed diversification during critical times particularly during episodes of crisis and of high volatility. Under the second‐order stochastic dominance efficiency (SDE) tests, the null hypothesis that portfolios without Cat Bonds are efficient cannot be rejected. Out‐of‐sample analyses indicate that the performance of portfolios with Cat Bonds included varies depending on the performance measures employed, the portfolio construction techniques used and the assets or factors considered. [ABSTRACT FROM AUTHOR]

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. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. Management and outcome: The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. Discussion: Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids. [ABSTRACT FROM AUTHOR]

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. Methods: Thirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP. Adverse events (AEs) were monitored and response to treatment was evaluated. Tumor tissue and peripheral blood were collected at specified time points to characterize tumor immune markers by immunohistochemistry and systemic immune activity by multiplex assays and flow cytometry. Results: Eighty three percent of patients received all 5 cycles of CP and 93% completed ipilimumab induction. Serious AEs occurred in 13% of patients, and no treatment-related deaths were observed. Best Overall Response Rate (BORR) and Disease Control Rate (DCR) were 27 and 57%, respectively. Median overall survival was 16. 2 months. Response to treatment was positively correlated with a higher tumor CD3+ infiltrate (immune score) at baseline. NRAS and BRAF mutations were less frequent in patients who experienced clinical benefit. Assessment of peripheral blood revealed that non-responders had elevated baseline levels of CXCL8 and CCL4, and a higher proportion of circulating late differentiated B cells. Pre-existing high levels of chemokines (CCL3, CCL4 and CXCL8) and advanced B cell differentiation were strongly associated with worse patient overall survival. Elevated proportions of circulating CD8+/PD-1+ T cells during treatment were associated with worse survival. Conclusions: The combination of ipilimumab and CP was well tolerated and revealed novel characteristics associated with patients likely to benefit from treatment. A pre-existing systemic inflammatory state characterized by elevation of selected chemokines and advanced B cell differentiation, was strongly associated with poor patient outcomes, revealing potential predictive circulating biomarkers. [ABSTRACT FROM AUTHOR]

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 post-operative week. It is unclear whether such recommendations are followed. Our objective was to compare our perioperative and long-term pAED use in glioma patients with AAN practice parameters. Methods. Retrospective chart review was performed on 578 glioma patients from 2006 to 2013. Seizures and AED use were assessed at surgery, 3 months postoperatively and death, last visit or 16 months postoperatively. Patients were divided into three groups at surgery: seizure-free with pAED, seizure-free without pAED, and seizure patients. Long-term pAED use was defined as continued use at 3 months postsurgery without seizures. pAEDs efficacy, factors influencing its use, and survival were examined. Results. Out of 578 patients identified, 330 (57.1%) were seizure-naïve preoperatively. There were no significant differences in age, histology, tumor location or resection status between seizure-free populations with and without prophylaxis. Of 330 seizure-naïve patients, 205 (62.1%) received pAEDs at surgery. Ninety-six (46.9%) of those patients were still on pAEDs 3 months postsurgery (median use = 58 days). Rate of long-term prophylaxis use decreased by 13.5% over 6 years (70.3% in 2006; 56.8% in 2012). Phenytoin was preferred in 2006 (98.2%) with increasing use of levetiracetam over 6 years (44.6% in 2012). The only predictive factor for pAED use was complete resection (P = .0069). First seizure prevalence was similar in both seizure-free populations (P = .91). The seizure population had more men (P = .007), younger patients (P < .0001), lower-grade gliomas (P = .0003) and survived longer (P = .001) compared with seizure-free populations. Conclusions. In our center, long-term prophylactic AED use is high, deviating from current AAN Guidelines. Corrective measures are warranted. [ABSTRACT FROM AUTHOR]

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-2 β to identify schedule and dose for patients with metastatic RCC. Results: Doses of IFN 9 MIU/MG98 125 mg/m2 for a continuous schedule and IFN 9 MIU/MG98 200 mg/m2 for an intermittent schedule were considered the MTDs. Treatment resulted in one PR and eight SD. Conclusion: MG98 combined with IFN was safe and resulted in clinical activity. [ABSTRACT FROM AUTHOR]