LUMINOS-102: Lerapolturev with and without α-PD- 1 in unresectable α-PD- 1 refractory melanoma

Lerapolturev (lera, formerly PVSRIPO) is a novel poliovirus based intratumoral immunotherapy that infects both cancer cells and antigen-presenting cells (APCs) via CD155, the poliovirus receptor. Lera has direct anticancer effects while also generating type I/III interferon-dominated inflammation and anti-tumor T-cell priming and activation via infection of local APCs. LUMINOS-102 (NCT04577807) is a multi-center, open-label, two-arm randomized Phase 2 study investigating the efficacy and safety of lera ± α-PD- 1 in patients with unresectable melanoma who failed prior α-PD- 1 therapy. Cross-over to the α-PD- 1 arm is permitted after progression, PR for ≥6 mo or 6 mo on treatment with SD. The maximum initial lera dose was 6x108 TCID50 /visit every 3 or 4 weeks (Q3/4 W). As of March 2022, the maximum lera dose was increased to 1.6 x 109 TCID50/visit, every week (QW) for 7 weeks (induction), followed by Q3/4 W dosing (maintenance). As of 20-Jun- 2022, 21 participants (10 male, 11 female, median 64 yrs) received lera (n = 14 at initial dose, Q3/4 W; n = 4 at increased dose, Q3/4 W; n = 3 at increased dose, QW) ± αPD-1. Five patients are currently on treatment. With the initial regimen, no objective responses and a CBR of 7% were observed. However, with the higher dose regimen, 1 complete response and a CBR of 71% (5/7) has been observed. Two of 4 participants with stable disease have evidence of response (1 with resolution of uninjected lung metastasis, 1 with decreased PET signal in injected and uninjected lesions receiving combination therapy). The only treatment related AE in \u3e1 pt was fatigue (19%, all grade 1 or 2). No dose-limiting toxicities or treatment-related SAEs were reported. Multiplex-IF analysis of on-treatment tumor biopsies will be presented. Lera ± αPD-1 is well tolerated, with early signs of efficacy at the higher dose level. Enrollment and randomization are ongoing

Safety and Efficacy of Donor T Cells Engineered with Herpes Simplex Virus Thymidine-Kinase Suicide Gene (TK Cells) Given after T-Cell Depleted (TCD) Haploidentical Hematopoietic Transplantation (Haplo-HSCT): Results of a 14-Year Follow-Up in 45 Patients

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An unloading foam model to constrain Etna's 11-13 January 2011 lava fountaining episode

International audienceThe 11–13 January 2011 eruptive episode at Etna volcano occurred after several months of increasing ash emissions from the summit craters, and was heralded by increasing SO2 output, which peaked at ∼5000 megagrams/day several hours before the start of the eruptive activity. The eruptive episode began with a phase of Strombolian activity from a pit crater on the eastern flank of the SE‐Crater. Explosions became more intense with time and eventually became transitional between Strombolian and fountaining, before moving into a lava fountaining phase. Fountaining was accompanied by lava output from the lower rim of the pit crater. Emplacement of the resulting lava flow field, as well as associated lava fountain‐ and Strombolian‐phases, was tracked using a remote sensing network comprising both thermal and visible cameras. Thermal surveys completed once the eruptive episode had ended also allowed us to reconstruct the emplacement of the lava flow field. Using a high temporal resolution geostationary satellite data we were also able to construct a detailed record of the heat flux during the fountain‐fed flow phase and its subsequent cooling. The dense rock volume of erupted lava obtained from the satellite data was 1.2 × 106 m3; this was emplaced over a period of about 6 h to give a mean output rate of ∼55 m3 s−1. By comparison, geologic data allowed us to estimate dense rock volumes of ∼0.85 × 106 m3 for the pyroclastics erupted during the lava fountain phase, and 0.84–1.7 × 106 m3 for lavas erupted during the effusive phase, resulting in a total erupted dense rock volume of 1.7–2.5 × 106 m3 and a mean output rate of 78–117 m3 s−1. The sequence of events and quantitative results presented here shed light on the shallow feeding system of the volcano

Differential impact of cognitive computing augmented by real world evidence on novice and expert oncologists

Abstract Introduction Cognitive computing point‐of‐care decision support tools which ingest patient attributes from electronic health records and display treatment options based on expert training and medical literature, supplemented by real world evidence (RWE), might prove useful to expert and novice oncologists. The concordance of augmented intelligence systems with best medical practices and potential influences on physician behavior remain unknown. Methods Electronic health records from 88 breast cancer patients evaluated at a USA tertiary care center were presented to subspecialist experts and oncologists focusing on other disease states with and without reviewing the IBM Watson for Oncology with Cota RWE platform. Results The cognitive computing “recommended” option was concordant with selection by breast cancer experts in 78.5% and “for consideration” option was selected in 9.4%, yielding agreements in 87.9%. Fifty‐nine percent of non‐concordant responses were generated from 8% of cases. In the Cota observational database 69.3% of matched controls were treated with “recommended,” 11.4% “for consideration”, and 19.3% “not recommended.” Without guidance from Watson for Oncology (WfO)/Cota RWE, novice oncologists chose 75.5% recommended/for consideration treatments which improved to 95.3% with WfO/Cota RWE. The novices were more likely than experts to choose a non‐recommended option (P < .01) without WfO/Cota RWE and changed decisions in 39% cases. Conclusions Watson for Oncology with Cota RWE options were largely concordant with disease expert judged best oncology practices, and was able to improve treatment decisions among breast cancer novices. The observation that nearly a fifth of patients with similar disease characteristics received non‐recommended options in a real world database highlights a need for decision support