Hyperthermia, the procedure of raising the temperature of a part of the entire body above normal for a defined period of time, is applied alone or as an adjunctive treatment to various established cancer treatment modalities such as radiotherapy and chemotherapy. Whole-Body Hyperthermia (WBHT), in contrast to local or regional hyperthermia, represents the only hyperthermia modality available for patients with disseminated malignancies. The biological rationale for the treatment of malignant disease by heat is driven by a number of reasons; a) the survival of cells depends on the temperature and duration of heating in a predictable and repeatable way; b) the tumor cell environment (such as hypoxia, poor nutrition, and low pH) that negatively influences the tumor cell killing by ionizing radiation and some chemotherapy regimens, is beneficially influenced by heat therapy; c) the differential sensitivity of normal and tumor cells to heat is dependent on cell type and environmental conditions; d) heat treatment enhances the biological effect of both radiation and chemotherapy agents. The biological rationale is based on a direct cell-killing effect at temperatures in the range of 41– 42°C. A systematic review of van der Horst et al, 2018, addressed clinical trials that used local or whole-body hyperthermia treatment (at variable temperatures) in pancreatic cancer patients. In those described trials, the weighted estimate of the treated population median overall survival was 11.7 compared to 5.6 for the control cohorts. In addition, locoregional hyperthermia (42-44°C) clinical trials showed that the weighted estimate median overall survival of the treated population was 15 months compared to 9 months in control cohorts. The MATTERS trial is a first in-human clinical investigation in advanced solid cancer patients or pancreatic adenocarcinoma patients (TxNxM1). The justification of the design is based on evaluation of pre-clinical data and clinical evaluation of clinical data, safety and/or performance of similar devices/therapies. The study is a mono-centric, non-randomized trial in which the safety and preliminary efficacy of whole-body hyperthermia will be evidenced. Well designed and performed early-stage correlative studies have the potential to strongly influence further clinical development of oncology clinical trials, and correlative data obtained from early stage trials has the potential to provide important guidance on the design and ultimate success of later stage trials. Blood samples will be collected for analysis of immunological panels (e.g. cytokines, chemokines), exosome research, RNA expression profiles. Urine will be collected for analysis of exosome research. The samples will be collected during different timepoints (before, during and after treatment).

Citation Format: Ivana Gorbaslieva, Dana Mustafa, Robin Colenbier, Marc Peeters, Dirk Ysebaert, Vera Saldien, Luigi Brancato, Oleg Rudenko, Johan Van den Bossche, John Paul Bogers. First in-human, safety and preliminary efficacy study of (neo)adjuvant, model-based, whole-body hyperthermia treatment in advanced solid cancer patients or stage IV (TxNxM1) metastatic pancreatic adenocarcinoma patients: Liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A023.