Procarbazine, Lomustine and Vincristine Toxicity in Low-Grade Gliomas

Background: Procarbazine, lomustine, and vincristine (PCV) significantly improve survival outcomes in LGG (low-grade gliomas). Administration of PCV to LGG patients increased tremendously over the past years as it went from 2 patients per year between 2005 and 2012 to 23 patients in 2015 only in our centre. However, serious hematological and non-hematological adverse events may occur. The purpose of this study was to evaluate the toxicity of PCV and its clinical relevance in our practice. Methods: We retrospectively reviewed the charts of 57 patients with LGG who received PCV at the Centre hospitalier de l’Université de Montréal between 1 January 2005 and 27 July 2016. Results: Procarbazine, lomustine, and vincristine were associated with severe hematological toxicity as clinically significant grade 3 anemia, neutropenia, and thrombocytopenia occurred in 7%, 10%, and 28% of patients, respectively. Other frequent adverse events such as the increase of liver enzymes, cutaneous rash, neurotoxicity, and vomiting occurred in 65%, 26%, 60%, and 40% of patients, respectively. Patients with prophylactic trimethoprim/sulfamethoxazole had more grade 3 hematological toxicity with PCV, especially anemia (p = 0.040) and thrombocytopenia (p = 0.003) but we found no increase in PCV toxicity in patients on concurrent anticonvulsants. Patients with grade 3 neutropenia had a significantly lower survival (median survival 44.0 months vs. 114.0 months, p = 0.001). Patients who were given PCV at diagnosis had more grade 3 anemia than those who received it at subsequent lines of treatment (p = 0.042). Conclusion: Procarbazine, lomustine, and vincristine increase survival in LGG but were also associated with major hematologic, hepatic, neurologic, and cutaneous toxicity. Anti-Pneumocystis jiroveci pneumonia (PJP) prophylaxis, but not anticonvulsants, enhances hematologic toxicity

First scattered-light images of the gas-rich debris disk around 49 Ceti

We present the first scattered-light images of the debris disk around 49 ceti, a ~40 Myr A1 main sequence star at 59 pc, famous for hosting two massive dust belts as well as large quantities of atomic and molecular gas. The outer disk is revealed in reprocessed archival Hubble Space Telescope NICMOS F110W images, as well as new coronagraphic H band images from the Very Large Telescope SPHERE instrument. The disk extends from 1.1" (65 AU) to 4.6" (250 AU), and is seen at an inclination of 73degr, which refines previous measurements at lower angular resolution. We also report no companion detection larger than 3 M_Jup at projected separations beyond 20 AU from the star (0.34"). Comparison between the F110W and H-band images is consistent with a grey color of 49 ceti's dust, indicating grains larger than >2microns. Our photometric measurements indicate a scattering efficiency / infrared excess ratio of 0.2-0.4, relatively low compared to other characterized debris disks. We find that 49 ceti presents morphological and scattering properties very similar to the gas-rich HD 131835 system. From our constraint on the disk inclination we find that the atomic gas previously detected in absorption must extend to the inner disk, and that the latter must be depleted of CO gas. Building on previous studies, we propose a schematic view of the system describing the dust and gas structure around 49 ceti and hypothetic scenarios for the gas nature and origin.VORTE