• Risk of major cardiac events following adjuvant proton versus photon radiation therapy for patients with thymic malignancies

      Vogel, J.; Lin, L.; Simone, C.B., II (Taylor and Francis Ltd, 2017)
      Background: While often managed with surgery alone, patients with thymic malignancies with high-risk features may benefit from adjuvant radiation therapy but are at risk for late toxicities. Previously, the risk of major cardiac events (MCEs) was reported to increase by 7% per one Gray (Gy) to the heart. In this study, we compare dose to organs at risk (OARs) with intensity-modulated (IMRT) versus proton beam therapy (PBT). We hypothesize a decrease risk of predicted MCEs with PBT. Material and methods: Patients requiring adjuvant therapy for thymic malignancies were treated with double scattered proton beam therapy (DS-PBT). Clinical backup IMRT plans were generated. Predicted MCEs were calculated based on median dose to the heart. A Wilcoxon rank sum test was used for statistical comparisons. Results: Twenty-two consecutive patients were evaluated. DS-PBT resulted in statistically significant decreases in dose to the heart, lungs, left ventricle, esophagus, and spinal cord (all p ≤ .01). The increase in risk of MCEs from 0 to ≥20 years was lower with PBT (74% versus 135%, p = .04). Discussion: DS-PBT results in decreased dose to OARs and may reduce the risk of MCEs compared with IMRT. Long-term follow-up is required to assess for clinical benefit from DS-PBT.
    • Safety and Immunogenicity of an AS03B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study

      Lin, L.; Lyke, K.E.; Koren, M.; Jarman, R.G.; Eckels, K.H.; Lepine, E.; McArthur, M.A.; Currier, J.R.; Friberg, H.; Moris, P.; et al. (American Society of Tropical Medicine and Hygiene, 2020)
      Dengue disease and its causative agents, the dengue viruses (DENV-1–4), cause high morbidity in tropical and subtropical regions. We evaluated three dosing regimens of the investigational tetravalent AS03B-adjuvanted dengue-purified inactivated vaccine (DPIV+AS03B). In this phase 1/2, observer-blind, placebo-controlled study (NCT02421367), 140 healthy adults were randomized 1:1:2 to receive DPIV+AS03B according to the following regimens: 0–1 month (M), 0–1–6 M, or 0–3 M. Participants received DPIV+AS03B or placebo at M0, M1, M3, and M6 according to their dosing schedule. Primary objectives were 1) to evaluate the safety of DPIV+AS03B for 28 days (D) after each dose; 2) to demonstrate the added value of a booster dose (0–1–6 M versus 0–1 M) based on neutralizing antibody titers to each DENV type (DENV-1–4) at 28 D after the last dose; and, if this objective was met, 3) to demonstrate the benefit of a longer interval between the first and second doses (0–1 M versus 0–3 M). Adverse events (AEs) within 7 D after vaccination tended to be more frequent after DPIV+AS03B doses than placebo; the number of grade 3 AEs was low (£ 4.5% after DPIV+AS03B; £ 2.9% after placebo), with no obvious differences across groups. Within 28 D following each dose, the frequency of unsolicited AEs after DPIV+AS03B appeared higher for three-dose (0–1–6 M) than two-dose (0–1 M and 0–3 M) regimens. No serious AEs were considered related to vaccination, and no potential immune-mediated diseases were reported during the study. All three schedules were well tolerated. Both primary immunogenicity objectives were demonstrated. The 0–3 M and 0–1–6 M regimens were more immunogenic than the 0–1 M regimen.