Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Heat Transfer Capabilities of Surface Cooling Systems for Inducing Therapeutic Hypothermia.

Therapeutic hypothermia (TH) is used to treat patients with cerebral ischemia. Body surface cooling provides a simple noninvasive method to induce TH. We compared three surface cooling systems (Arctic Sun with adhesive ArcticGel pads [AS]); Blanketrol III with two nonadhesive Maxi-Therm Lite blankets [BL]); and Blanketrol III with nonadhesive Kool Kit [KK]). We hypothesized that KK would remove more heat due to its tighter fit and increased surface area. Eight subjects (four females) were cooled with each system set to 4°C outflow temperature for 120 minutes. Heat loss, skin and esophageal temperature, and metabolic heat production were measured. Skin temperature was higher with KK (p = 0.002), heat loss was lower with KK in the first hour (p = 0.014) but not after 120 minutes. Heat production increased similarly with all systems. Core temperature decrease was greater for AS (0.57°C) than BL (0.14°C; p = 0.035), but not KK (0.24°C; p = 0.1). Each system had its own benefits and limitations. Heat transfer capability is dependent on the cooling pump unit and the design of the liquid-perfused covers. Both Arctic Sun and Blanketrol III cooling/pump units had 4°C output temperatures. However, the Blanketrol III unit had a greater flow rate and therefore more cooling power. The nonadhesive BL and KK covers were easier to apply and remove compared with the adhesive AS pads. AS had an early transient advantage in heat removal, but this effect decreased over the course of cooling, thus minimizing or eliminating any advantage during longer periods of cooling that occur during clinical TH. Clinical Trial Registration number: NCT04332224.

One Cool Guy: Scientific Contributions of John Hayward, Cold Water Pioneer.

John Hayward, PhD (1937-2012), was an early and significant contributor to the understanding of cold water immersion physiology and survival. This article summarizes his work on the 50th anniversary of his first publication in this area. He described areas of high heat loss and emphasized the importance of protecting these areas during cold exposure using the Heat Escape Lessening Posture (HELP) and the potential for heat donation to these areas during rewarming. He described several factors that affect the rate of core cooling, including body composition, behavior (swimming increases cooling whereas the HELP position decreases cooling), wet and wind, and thermal protective garments (dry suits offered much more protection than wet suits). Hayward determined breath-hold duration in children as young as 4 y and had his own heart catheterized for 3 d to complete 3 hypothermia rewarming trials. His work provided early understanding of the cold shock response and ways to mitigate its threat to survival. Hayward provided valuable contributions to prediction models for heat production, heat loss, and core cooling rates in cold water. He also developed a human model for severe hypothermia and patented the UVic Thermofloat Jacket. Finally, as evidence of his stature in the cold physiology community, Hayward was a coauthor of the initial State of Alaska guidelines for the treatment of hypothermia. John Hayward was truly a cold water pioneer.