Risk Factors for GI Adverse Events in a Phase III Randomized Trial of Bevacizumab in First-Line Therapy of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study

Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P \u3c .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). Conclusion History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy

Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer

OBJECTIVE: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D). METHODS: Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n = 30). Patients were treated until progression or unacceptable toxicity. All were followed for survival. RESULTS: No dose limiting toxicities were observed and serum GAS6 was completely suppressed across the three dose levels evaluated. AVB-500 + PAC yielded better clinical activity than AVB-500 + PLD with an ORR of 34.8% (8/23, 2 complete responses) and median DoR, PFS, and OS of 7.0, 3.1, and 10.3 months, respectively. Subgroup analyses showed AVB-500 + PAC patients who had no prior bevacizumab or whose AVB-500 trough levels were \u3e13.8 mg/L exhibited the best clinical response. The ORR and median PFS and OS in patients with these characteristics were ≥50%, ≥7.5 months, and ≥19 months, respectively. Given AVB-500 nor the combination with chemotherapy was expected to cause DLTs, the RP2D of AVB-500 was 15 mg/kg identified using an MIDD approach. CONCLUSION: AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients. Subgroup analyses identified a population of PROC patients who may benefit the most from AVB-500 treatment, which will be further assessed in an ongoing Phase 3 PROC trial

Multioccupant Activity Recognition in Pervasive Smart Home Environments

been the center of lot of research for many years now. The aim is to recognize the sequence of actions by a specific person using sensor readings. Most of the research has been devoted to activity recognition of single occupants in the environment. However, living environments are usually inhabited by more than one person and possibly with pets. Hence, human activity recognition in the context of multi-occupancy is more general, but also more challenging. The difficulty comes from mainly two aspects: resident identification, known as data association, and diversity of human activities. The present survey paper provides an overview of existing approaches and current practices for activity recognition in multi-occupant smart homes. It presents the latest developments and highlights the open issues in this field

The effect of bioturbation in pelagic sediments: Lessons from radioactive tracers and planktonic foraminifera in the Gulf of Aqaba, Red Sea

Studies of recent environmental perturbations often rely on data derived from marine sedimentary records. These records are known to imperfectly inscribe the true sequence of events, yet there is large uncertainty regarding the corrections that should be employed to accurately describe the sedimentary history. Here we show in recent records from the Gulf of Aqaba, Red Sea, how events of the abrupt disappearance of the planktonic foraminifer Globigerinoides sacculifer, and episodic deposition of the artificial radionuclide137Cs, are significantly altered in the sedimentary record compared to their known past timing. Instead of the abrupt disappearance of the foraminifera, we observe a prolonged decline beginning at core depth equivalent to ∼30 y prior to its actual disappearance and continuing for decades past the event. We further observe asymmetric smoothing of the radionuclide peak. Utilization of advection–diffusion–reaction models to reconstruct the original fluxes based on the known absolute timing of the events reveal that it is imperative to use a continuous function to describe bioturbation. Discretization of bioturbation into mixed and unmixed layers significantly shifts the location of the modeled event. When bioturbation is described as a continuously decreasing function of depth, the peak of a very short term event smears asymmetrically but remains in the right depth. When sudden events repeat while the first spike is still mixed with the upper sediment layer, bioturbation unifies adjacent peaks. The united peak appears at an intermediate depth that does not necessarily correlate with the timing of the individual events. In a third case, a long lasting sedimentary event affected by bioturbation, the resulting peak is rather weak compared to the actual event and appears deeper in the sediment column than expected based on the termination of the event. The model clearly shows that abrupt changes can only endure in the record if a thick sediment layer settled on the sediment–water interface at once or if bioturbation rates decreased to very low values for a prolonged period of time. In any other case smearing by bioturbation makes an abrupt event appear to have started shortly before the real timing and end long after its true termination

Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens

Hypersensitivity reactions (HSRs) to paclitaxel are frequently encountered in patients receiving this antitumour drug. Administration of histamine H1- and H2-receptor antagonists and corticosteroids has been shown to reduce significantly the risk of developing an HSR in patients receiving taxanes. In this case report, we describe the fatal outcome of an HSR in a patient receiving paclitaxel despite short-course premedication. The level of evidence supporting the short-course i.v. premedication schedule is challenged, as it is not compatible with the pharmacokinetic properties of dexamethasone

Update on rare epithelial ovarian cancers: based on the Rare Ovarian Tumors Young Investigator Conference

There has been significant progress in the understanding of the pathology and molecular biology of rare ovarian cancers, which has helped both diagnosis and treatment. This paper provides an update on recent advances in the knowledge and treatment of rare ovarian cancers and identifies gaps that need to be addressed by further clinical research. The topics covered include: low-grade serous, mucinous, and clear cell carcinomas of the ovary. Given the molecular heterogeneity and the histopathological rarity of these ovarian cancers, the importance of designing adequately powered trials or finding statistically innovative ways to approach the treatment of these rare tumors has been emphasized. This paper is based on the Rare Ovarian Tumors Conference for Young Investigators which was presented in Tokyo 2015 prior to the 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG)

Participatory action research in two communities in Bolivia and the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66665/2/10.1177_002087289203500214.pd

The ISB Cancer Genomics Cloud: A Flexible Cloud-Based Platform for Cancer Genomics Research.

The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute to explore new approaches to computing on large cancer datasets in a cloud environment. With a focus on Data as a Service, the ISB-CGC offers multiple avenues for accessing and analyzing The Cancer Genome Atlas, TARGET, and other important references such as GENCODE and COSMIC using the Google Cloud Platform. The open approach allows researchers to choose approaches best suited to the task at hand: from analyzing terabytes of data using complex workflows to developing new analysis methods in common languages such as Python, R, and SQL; to using an interactive web application to create synthetic patient cohorts and to explore the wealth of available genomic data. Links to resources and documentation can be found at www.isb-cgc.or